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The disease has caused a global pandemic, leading to deaths of thousands of people across the world and thus finding origin of this novel coronavirus is important in responding and controlling the pandemic. Recent research results suggest that bats or pangolins might be the original hosts for the virus based on comparative studies using its genomic sequences. This paper investigates the COVID-19 virus origin by using artificial intelligence (AI) and raw genomic sequences of the virus. More than 300 genome sequences of COVID-19 infected cases collected from different countries are explored and analysed using unsupervised clustering methods. The results obtained from various AI-enabled experiments using clustering algorithms demonstrate that all examined COVID-19 virus genomes belong to a cluster that also contains bat and pangolin coronavirus genomes. This provides evidences strongly supporting scientific hypotheses that bats and pangolins are probable hosts for the COVID-19 virus. At the whole genome analysis level, our findings also indicate that bats are more likely the hosts for the COVID-19 virus than pangolins.", "title": "Origin of Novel Coronavirus (COVID-19): A Computational Biology Study using Artificial Intelligence", "pid": "4dtk1kyh", "bm25_score": 217.2948455810547}, {"text": "Every time a pandemic occurs, dozens of theories emerge to attribute the origin of the event to different facts. The COVID-19 pandemic that has hit virtually all the globe has been no exception. What is known so far about the origin of the virus that causes COVID 19? The first investigations on the origin of this disease have determined that it is a new type of virus, the origin of which is most likely zoonotic.", "title": "[What is the origin of SARS-CoV-2?]", "pid": "dv9m19yk", "bm25_score": 216.84706115722656}, {"text": "The emerging coronavirus disease (COVID-19) swept across the world, affecting more than 200 countries and territories. Genomic analysis suggests that the COVID-19 virus originated in bats and transmitted to humans through unknown intermediate hosts in the Wuhan seafood market, China, in December of 2019. This virus belongs to the Betacoronavirus group, the same group of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV), and for the similarity, it was named SARS-CoV-2. Given the lack of registered clinical therapies or vaccines, many physicians and scientists are investigating previously used clinical drugs for COVID-19 treatment. In this review, we aim to provide an overview of the CoVs origin, pathogenicity, and genomic structure, with a focus on SARS-CoV-2. Besides, we summarize the recently investigated drugs that constitute an option for COVID-19 treatment.", "title": "The Human Coronavirus Disease COVID-19: Its Origin, Characteristics, and Insights into Potential Drugs and Its Mechanisms", "pid": "utsr0zv7", "bm25_score": 216.71575927734375}, {"text": "A novel coronavirus has caused thousands of human infections in China since December 2019, raising a global public health concern. Recent studies (Huang et al ., Chan et al ., and Zhou et al .) have provided timely insights into its origin and ability to spread among humans, informing infection prevention and control practices.", "title": "Unveiling the Origin and Transmission of 2019-nCoV", "pid": "t7gpi2vo", "bm25_score": 216.60903930664062}, {"text": "A novel coronavirus has caused thousands of human infections in China since December 2019, raising a global public health concern. Recent studies (Huang et al., Chan et al., and Zhou et al.) have provided timely insights into its origin and ability to spread among humans, informing infection prevention and control practices.", "title": "Unveiling the Origin and Transmission of 2019-nCoV", "pid": "558awj1m", "bm25_score": 216.60903930664062}, {"text": "", "title": "The proximal origin of SARS-CoV-2", "pid": "beguhous", "bm25_score": 216.56719970703125}, {"text": "The ongoing pandemic of coronavirus disease 2019 (COVID-19), caused by infection with human coronavirus 2019 (HCoV-19 / SARS-CoV-2 / 2019-nCoV), is a global threat to the human population. Here, we briefly summarize the available data for the zoonotic origins of HCoV-19, with reference to the other two epidemics of highly virulent coronaviruses, SARS-CoV and MERS-CoV, which cause severe pneumonia in humans. We propose to intensify future efforts for tracing the origins of HCoV-19, which is a very important scientific question for the control and prevention of the pandemic.", "title": "Zoonotic origins of human coronavirus 2019 (HCoV-19 / SARS-CoV-2): why is this work important?", "pid": "75773gwg", "bm25_score": 216.30349731445312}, {"text": "", "title": "Strategies to trace back the origin of COVID-19", "pid": "u7u75sl0", "bm25_score": 216.17080688476562}, {"text": "In the 5th February 2020 issue of Journal of Medical Virology a paper was published by Giovannetti et al., entitled \"The first two cases of 2019-nCoV in Italy: where they come from?\"1 . In this paper a phylogenetic and evolutionary analysis was applied to the virus identified in the first two subjects diagnosed in Italy with 2019-nCoV infection, recently renamed SARS-CoV-22 , two Chinese spouses arrived in Italy for tourism. The diagnosis was performed by the virology team under direction of Maria R. Capobianchi, at the National Institute of Infectious Diseases (INMI) in Rome, Italy, where the patients are currently hospitalized. This article is protected by copyright. All rights reserved.", "title": "About the origin of the first two Sars-CoV-2 infections in Italy: inference not supported by appropriate sequence analysis.", "pid": "4flvyqgn", "bm25_score": 216.1510772705078}, {"text": "The 2019 novel coronavirus (2019-nCoV) have emerged from Wuhan, China. Studying the epidemic dynamics is crucial for further surveillance and control of the outbreak. We employed a Bayesian framework to infer the time-calibrated phylogeny and the epidemic dynamics represented by the effective reproductive number (Re) changing over time from the genomic sequences available from GISAID. The origin time is estimated to be December 17, 2019 (95% CI: December 5, 2019 – December 23, 2019). The median estimate of Re ranges from 0.2 to 2.2 and changes drastically over time. This study provides an early insight of the 2019-nCoV epidemic.", "title": "Origin time and epidemic dynamics of the 2019 novel coronavirus", "pid": "t1iagum7", "bm25_score": 216.10491943359375}, {"text": "OBJECTIVE: Turkey is one of the latest countries that COVID-19 disease was reported, with the first case on March 11, 2020, and since then, Istanbul became the epicenter of the pandemic in Turkey. Here, we reveal sequences of the virus isolated from three different patients with various clinical presentations. METHODS: Nasopharyngeal swab specimens of the patients were tested positive for the COVID-19 by qRT-PCR. Viral RNA extraction was performed from the same swab samples. Amplicon based libraries were prepared and sequenced using the Illumina NextSeq platform. Raw sequencing data were processed for variant calling and generating near-complete genome sequences. All three genomes were evaluated and compared with other worldwide isolates. RESULTS: The patients showed various clinics (an asymptomatic patient, patient with mild disease, and with severe pulmonary infiltration). Amplicon-based next-generation sequencing approach successfully applied to generate near-complete genomes with an average depth of 2.616. All three viral genomes carried the D614G variant (G clade according to GISAID classification) with implications for the origin of a spread first through China to Europe then to Istanbul. CONCLUSION: Here, we report the viral genomes circulating in Istanbul for the first time. Further sequencing of the virus isolates may enable us to understand variations in disease presentation and association with viral factors if there is any. In addition, the sequencing of more viral genomes will delineate the spread of disease and will guide and ease the necessary measures taken to stem the spread of the novel coronavirus.", "title": "The origin of SARS-CoV-2 in Istanbul: Sequencing findings from the epicenter of the pandemic in Turkey", "pid": "9mrtic2k", "bm25_score": 216.09295654296875}, {"text": "In the 5th February 2020 issue of Journal of Medical Virology a paper was published by Giovannetti et al., entitled \"The first two cases of 2019-nCoV in Italy: where they come from?\"1 . In this paper a phylogenetic and evolutionary analysis was applied to the virus identified in the first two subjects diagnosed in Italy with 2019-nCoV infection, recently renamed SARS-CoV-22 , two Chinese spouses arrived in Italy for tourism. The diagnosis was performed by the virology team under direction of Maria R. Capobianchi, at the National Institute of Infectious Diseases (INMI) in Rome, Italy, where the patients are currently hospitalized. This article is protected by copyright. All rights reserved.", "title": "About the origin of the first two Sars-CoV-2 infections in Italy: inference not supported by appropriate sequence analysis", "pid": "9057d046", "bm25_score": 216.0810089111328}, {"text": "Coronavirus has emerged as a global health threat due to its accelerated geographic spread over the last two decades. This article reviews the current state of knowledge concerning the origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Historically, it has caused two pandemics: severe acute respiratory syndrome and Middle East respiratory syndrome followed by the present COVID-19 that emerged from China. The virus is believed to be acquired from zoonotic source and spreads through direct and contact transmission. The symptomatic phase manifests with fever, cough and myalgia to severe respiratory failure. The diagnosis is confirmed using reverse transcriptase PCR. Management of COVID-19 is mainly by supportive therapy along with mechanical ventilation in severe cases. Preventive strategies form the major role in reducing the public spread of virus along with successful disease isolation and community containment. Development of a vaccine to eliminate the virus from the host still remains an ongoing challenge.", "title": "Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19)", "pid": "3ll2tlzr", "bm25_score": 215.92449951171875}, {"text": "", "title": "Origin and evolution of the 2019 novel coronavirus", "pid": "pl48ev5o", "bm25_score": 215.86172485351562}, {"text": "", "title": "Origin and Evolution of the 2019 Novel Coronavirus", "pid": "h8ahn8fw", "bm25_score": 215.86172485351562}, {"text": "OBJECTIVE SARS-CoV-2 is responsible for the present coronavirus pandemic and some suggestions were made about its possible artificial origin. We, therefore, compared SARS-CoV-2 with such known viruses that were prepared in the laboratory and other relevant natural strains to estimate their genetic relatedness. MATERIALS AND METHODS BLAST and clustalW were used to identify and align viral sequences of SARS-CoV-2 to other animal coronaviruses (human, bat, mouse, pangolin) and related artificial constructs. Phylogenetics trees were then prepared using iTOL. RESULTS Our study supports the notion that known artificial coronaviruses, including the chimeric SL-SHC014-MA15 synthesized in 2015, differ too much from SARS-CoV-2 to hypothesize an artificial origin of the latter. On the contrary, our data support the natural origin of the COVID-19 virus, likely derived from bats, possibly transferred to pangolins, before spreading to man. CONCLUSIONS Speculations about the artificial origin of SARS-CoV-2 are most likely unfounded. On the contrary, when carefully handled, engineered organisms provide a unique opportunity to study biological systems in a controlled fashion. Biotechnology is a powerful tool to advance medical research and should not be abandoned because of irrational fears.", "title": "Bioinformatic analysis indicates that SARS-CoV-2 is unrelated to known artificial coronaviruses.", "pid": "deajwhx0", "bm25_score": 215.8368377685547}, {"text": "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a positive-sense single stranded RNA virus with high human transmissibility. This study generated Whole Genome data to determine the origin and pattern of transmission of SARS-CoV-2 from the first six cases tested in The Gambia. Total RNA from SARS-CoV-2 was extracted from inactivated nasopharyngeal-oropharyngeal swabs of six cases and converted to cDNA following the ARTIC COVID-19 sequencing protocol. Libraries were constructed with the NEBNext ultra II DNA library prep kit for Illumina and Oxford Nanopore Ligation sequencing kit and sequenced on Illumina MiSeq and Nanopore GridION, respectively. Sequencing reads were mapped to the Wuhan reference genome and compared to eleven other SARS-CoV-2 strains of Asian, European and American origins. A phylogenetic tree was constructed with the consensus genomes for local and non-African strains. Three of the Gambian strains had a European origin (UK and Spain), two strains were of Asian origin (Japan). In The Gambia, Nanopore and Illumina sequencers were successfully used to identify the sources of SARS-CoV-2 infection in COVID-19 cases.", "title": "Origin of imported SARS-CoV-2 strains in The Gambia identified from Whole Genome Sequences", "pid": "z14rf85c", "bm25_score": 215.82704162597656}, {"text": "BACKGROUND COVID-19 in China was first reported to the World Health Organization on December 31st 2019. The first cases were officially identified around December 8th 2019. The origin of COVID-19 is not confirmed, but half the early cases were linked to a seafood market in Wuhan. The first two documented cases did not attend the seafood market. News reports, social media and informal sources may contain information about outbreaks prior to formal notification. OBJECTIVE To identify early signals of pneumonia and/or severe acute respiratory illness (SARI) in China, prior to official recognition of the COVID 19 outbreak in December 2019, using open source data. METHODS In order to capture early reports we searched an open source epidemic observatory, Epiwatch from 1st October2019 in China, for severe acute respiratory illness (SARI) or pneumonia related illnesses. Google and Chinese search engine Baidu were used. RESULTS There was an increase in reports following the official notification of COVID 19 to WHO on December 31 2019, and a retracted report on December 26th 2019. A report of severe pneumonia was identified on November 22 2019 in Xiangyang, Index patient was retrospectively identified on 17 November. CONCLUSIONS The lack of reports of a SARI outbreaks prior to December 31st, with a retracted report on December 26th suggests media censorship, given formal reports that cases began on December 8th. However, the findings also support relatively recent origin of COVID-19 in November 2019. The case reported on November 22nd was transferred to Wuhan approximately 1 incubation period before the first reported cases on December 8th, and should be further investigated, as only half of the early cases had exposure to the seafood market. It has since been reported that another case of COVID 19 has been retrospectively identified in Hubei on November 17th, confirming that the infection was present prior to December. CLINICALTRIAL", "title": "Using open-source intelligence to detect early signals of COVID-19 in China, Descriptive study.", "pid": "w9yibx5o", "bm25_score": 215.8240966796875}, {"text": "Covid­19 origin and transmission to humans. Covid­19 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid­19 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS­CoV­2 transmission. However, the source(s) and transmission routine(s) of SARS­CoV­2 remain elusive' (1).", "title": "[Editorial] Possibility of transmission through dogs being a contributing factor to the extreme Covid­19 outbreak in North Italy", "pid": "jwxt4ygt", "bm25_score": 215.76580810546875}, {"text": "OBJECTIVE: SARS-CoV-2 is responsible for the present coronavirus pandemic and some suggestions were made about its possible artificial origin. We, therefore, compared SARS-CoV-2 with such known viruses that were prepared in the laboratory and other relevant natural strains to estimate their genetic relatedness. MATERIALS AND METHODS: BLAST and clustalW were used to identify and align viral sequences of SARS-CoV-2 to other animal coronaviruses (human, bat, mouse, pangolin) and related artificial constructs. Phylogenetics trees were then prepared using iTOL. RESULTS: Our study supports the notion that known artificial coronaviruses, including the chimeric SL-SHC014-MA15 synthesized in 2015, differ too much from SARS-CoV-2 to hypothesize an artificial origin of the latter. On the contrary, our data support the natural origin of the COVID-19 virus, likely derived from bats, possibly transferred to pangolins, before spreading to man. CONCLUSIONS: Speculations about the artificial origin of SARS-CoV-2 are most likely unfounded. On the contrary, when carefully handled, engineered organisms provide a unique opportunity to study biological systems in a controlled fashion. Biotechnology is a powerful tool to advance medical research and should not be abandoned because of irrational fears.", "title": "Bioinformatic analysis indicates that SARS-CoV-2 is unrelated to known artificial coronaviruses", "pid": "icwvm7jp", "bm25_score": 215.68423461914062}, {"text": "The novel coronavirus, SARS-CoV-2, causes the unfathomable pandemic in the history of humankind. Bangladesh is also a victim of this critical situation. To investigate the genomic features of the pathogen, the first complete genome of the virus has very recently been published. Therefore, the long awaiting questions regarding the possible origin and typing of the strain(s) can now be answered. Here, we endeavor to mainly discuss the published reports or online-accessed data (results) regarding those issues and presented a comprehensive picture of the typing of the virus alongside the probable origin of the sub-clade containing Bangladeshi strain. Our observation suggested that this strain might have originated from the United Kingdom (UK) or other European countries epidemiologically linked to the UK. According to different genotyping classification schemes, this strain belongs to A2a clade under G major clade, is of B and/or L type, and is a SARS-CoV-2a sub-strain. In the forwarding days, randomized genome data will certainly voluminate in Bangladesh, however because of globalization and immigrant movements, we urgently need a mass regional sequencing approach targeting the partial or complete genome that can link the epidemiological data and may help in further clinical interventions. This article is protected by copyright. All rights reserved.", "title": "Understanding the possible origin and genotyping of first Bangladeshi SARS-CoV-2 strain", "pid": "3dm9duoz", "bm25_score": 215.67665100097656}, {"text": "Coronavirus has emerged as a global health treat due to its accelerated geographic spread over the last two decades. This article reviews the current state of knowledge concerning the origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19). Historically, it has caused two pandemics: severe acute respiratory syndrome and Middle East respiratory syndrome followed by the present COVID-19 that emerged from China. The virus is believed to be acquired from zoonotic source and spreads through direct and contact transmission. The symptomatic phase manifests with fever, cough and myalgia to severe respiratory failure. The diagnosis is confirmed using reverse transcriptase PCR. Management of COVID-19 is mainly by supportive therapy along with mechanical ventilation in severe cases. Preventive strategies form the major role in reducing the public spread of virus along with successful disease isolation and community containment. Development of a vaccine to eliminate the virus from the host still remains an ongoing challenge.", "title": "Origin, transmission, diagnosis and management of coronavirus disease 2019 (COVID-19).", "pid": "e6h1qvdk", "bm25_score": 215.63787841796875}, {"text": "The initial cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) occurred in Wuhan, China, in December 2019 and swept the world by 23 June 2020 with 8,993,659 active cases, 469,587 deaths across 216 countries, areas or territories. This strongly implies global transmission occurred before the lockdown of China. However, the initial source's transmission routes of SARS-CoV-2 remain obscure and controversial. Research data suggest bat (RaTG13) and pangolin carried CoV were the proximal source of SARS-CoV-2. In this study, we used systematic phylogenetic analysis of Coronavirinae subfamily along with wild type human SARS-CoV, MERS-CoV, and SARS-CoV-2 strains. The key residues of the receptor-binding domain (RBD) and O-linked glycan were compared. SARS-CoV-2 strains were clustered with RaTG13 (97.41% identity), Pangolin-CoV (92.22% identity) and Bat-SL-CoV (80.36% identity), forms a new clade-2 in lineage B of beta-CoV. The alignments of RBD contact residues to ACE2 justified? Those SARS-CoV-2 strains sequences were 100% identical by each other, significantly varied in RaTG13 and pangolin-CoV. SARS-CoV-2 has a polybasic cleavage site with an inserted sequence of PRRA compared to RaTG13 and only PRR to pangolin. Only serine (Ser) in pangolin and both threonine (Thr) and serine (Ser) O-linked glycans were seen in RaTG13, suggesting that a detailed study needed in Pangolin (Manis javanica) and bat (Rhinolophus affinis) related CoV. This article is protected by copyright. All rights reserved.", "title": "An update on origin of SARS-CoV-2: Despite closest identity, bat (RaTG13) and Pangolin derived Coronaviruses varied in the critical binding site and O-linked glycan residues", "pid": "r25aqii5", "bm25_score": 215.61192321777344}, {"text": "Covid‑19 origin and transmission to humans. Covid‑19 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid‑19 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS‑CoV‑2 transmission. However, the source(s) and transmission routine(s) of SARS‑CoV‑2 remain elusive' (1).", "title": "Possibility of transmission through dogs being a contributing factor to the extreme Covid-19 outbreak in North Italy", "pid": "k9lcpjyo", "bm25_score": 215.58595275878906}, {"text": "A group of 27 prominent public health scientists from outside China is pushing back against a steady stream of stories and even a scientific paper suggesting a laboratory in Wuhan, China, may be the origin of the outbreak of COVID-19 “The rapid, open, and transparent sharing of data on this outbreak is now being threatened by rumours and misinformation around its origins,” the scientists, from nine countries, write in a statement published online by The Lancet yesterday", "title": "Scientists ‘strongly condemn’ rumors and conspiracy theories about origin of coronavirus outbreak ;Science ;AAAS", "pid": "ec8lpgl3", "bm25_score": 215.54827880859375}, {"text": "", "title": "Is SARS-CoV-2 originated from laboratory? A rebuttal to the claim of formation via laboratory recombination", "pid": "q30e792q", "bm25_score": 215.5255584716797}, {"text": "", "title": "Origins of MERS-CoV, and lessons for 2019-nCoV", "pid": "gyj5213f", "bm25_score": 215.4848175048828}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the coronavirus disease of 2019 (COVID-19). First identified in Wuhan (Hubei, China) in December of 2019, it has since been declared a pandemic by the World Health Organization in March of 2020. In this study, we will provide a brief review of viral origin, identification, symptoms, transmission, diagnosis, and potential treatment strategies for the newly identified SARS-CoV-2 strain.", "title": "Brief Review on COVID-19: The 2020 Pandemic Caused by SARS-CoV-2", "pid": "v8i97mbx", "bm25_score": 215.4571533203125}, {"text": "", "title": "Probable Pangolin Origin of SARS-CoV-2 Associated with the COVID-19 Outbreak", "pid": "4ilpph77", "bm25_score": 215.44448852539062}, {"text": "In late December 2019, some cases of atypical pneumonia, at that time of unknown origin, were reported in Wuhan, China. Days later, the etiologic agent was identified as a new coronavirus. This new coronavirus was called SARS-CoV-2 and the disease it produces was named COVID-19. The origin of this new virus is presumed zoonotic, with bats being its probable vector. Due to the rapid number of infections and deaths that occurred first in China and later around the world, the infection of this virus quickly went from being an isolated outbreak in a Chinese region to becoming a health emergency of international concern and later, a pandemic. The purpose of this review is to study the most relevant and current information on the pathogen, as well as epidemiology, pathology, clinical features, transmission, prevention, and treatment of the disease.", "title": "Pandemia COVID-19, la nueva emergencia sanitaria de preocupación internacional: una revisión./ [Pandemic COVID-19, the new health emergency of international concern: a review]", "pid": "x3sb1o4u", "bm25_score": 215.43963623046875}, {"text": "The coronavirus disease 19 (COVID-19) is a highly transmittable and pathogenic viral infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which emerged in Wuhan, China and spread around the world. Genomic analysis revealed that SARS-CoV-2 is phylogenetically related to severe acute respiratory syndrome-like (SARS-like) bat viruses, therefore bats could be the possible primary reservoir. The intermediate source of origin and transfer to humans is not known, however, the rapid human to human transfer has been confirmed widely. There is no clinically approved antiviral drug or vaccine available to be used against COVID-19. However, few broad-spectrum antiviral drugs have been evaluated against COVID-19 in clinical trials, resulted in clinical recovery. In the current review, we summarize and comparatively analyze the emergence and pathogenicity of COVID-19 infection and previous human coronaviruses severe acute respiratory syndrome coronavirus (SARS-CoV) and middle east respiratory syndrome coronavirus (MERS-CoV). We also discuss the approaches for developing effective vaccines and therapeutic combinations to cope with this viral outbreak.", "title": "COVID-19 infection: Origin, transmission, and characteristics of human coronaviruses", "pid": "1mjaycee", "bm25_score": 215.43365478515625}, {"text": "", "title": "Origine de SARS-CoV-2 : le probable et le possible", "pid": "4xlonqd0", "bm25_score": 215.41368103027344}, {"text": "Bats are presumed reservoirs of diverse coronaviruses (CoVs) including progenitors of Severe Acute Respiratory Syndrome (SARS)-CoV and SARS-CoV-2, the causative agent of COVID-19. However, the evolution and diversification of these coronaviruses remains poorly understood. We used a Bayesian statistical framework and sequence data from all known bat-CoVs (including 630 novel CoV sequences) to study their macroevolution, cross-species transmission, and dispersal in China. We find that host-switching was more frequent and across more distantly related host taxa in alpha-than beta-CoVs, and more highly constrained by phylogenetic distance for beta-CoVs. We show that inter-family and -genus switching is most common in Rhinolophidae and the genus Rhinolophus. Our analyses identify the host taxa and geographic regions that define hotspots of CoV evolutionary diversity in China that could help target bat-CoV discovery for proactive zoonotic disease surveillance. Finally, we present a phylogenetic analysis suggesting a likely origin for SARS-CoV-2 in Rhinolophus spp. bats.", "title": "Origin and cross-species transmission of bat coronaviruses in China", "pid": "8arwlhf0", "bm25_score": 215.400634765625}, {"text": "To investigate the genetic diversity, time origin, and evolutionary history of the 2019-nCoV outbreak in China and Thailand, a total of 12 genome sequences of the virus with known sampling date (24 December 2019 and 13 January 2020) and geographic location (primarily Wuhan city, Hubei Province, China, but also Bangkok, Thailand) were analyzed. Phylogenetic and likelihood-mapping analyses of these genome sequences were performed. On the basis of our results, the star-like signal and topology of 2019-nCoV may be indicative of potentially large \"first generation\" human-to-human virus transmission. We estimated that 2019-nCoV likely originated in Wuhan on 9 November 2019 (95% credible interval: 25 September 2019 and 19 December 2019), and that Wuhan is the major hub for the spread of the 2019-nCoV outbreak in China and elsewhere. Our results could be useful for designing effective prevention strategies for 2019-nCoV in China and beyond.", "title": "Potential of large \"first generation\" human-to-human transmission of 2019-nCoV", "pid": "50xzptr1", "bm25_score": 215.36521911621094}, {"text": "BACKGROUND: COVID-19 in China was first reported to the World Health Organization on December 31st 2019. The first cases were officially identified around December 8th 2019. The origin of COVID-19 is not confirmed, but half the early cases were linked to a seafood market in Wuhan. The first two documented cases did not attend the seafood market. News reports, social media and informal sources may contain information about outbreaks prior to formal notification. OBJECTIVE: To identify early signals of pneumonia and/or severe acute respiratory illness (SARI) in China, prior to official recognition of the COVID 19 outbreak in December 2019, using open source data. METHODS: In order to capture early reports we searched an open source epidemic observatory, Epiwatch from 1st October2019 in China, for severe acute respiratory illness (SARI) or pneumonia related illnesses. Google and Chinese search engine Baidu were used. RESULTS: There was an increase in reports following the official notification of COVID 19 to WHO on December 31 2019, and a retracted report on December 26th 2019. A report of severe pneumonia was identified on November 22 2019 in Xiangyang, Index patient was retrospectively identified on 17 November. CONCLUSIONS: The lack of reports of a SARI outbreaks prior to December 31st, with a retracted report on December 26th suggests media censorship, given formal reports that cases began on December 8th. However, the findings also support relatively recent origin of COVID-19 in November 2019. The case reported on November 22nd was transferred to Wuhan approximately 1 incubation period before the first reported cases on December 8th, and should be further investigated, as only half of the early cases had exposure to the seafood market. It has since been reported that another case of COVID 19 has been retrospectively identified in Hubei on November 17th, confirming that the infection was present prior to December.", "title": "Using open-source intelligence to detect early signals of COVID-19 in China, Descriptive study", "pid": "m4ctyt7p", "bm25_score": 215.30352783203125}, {"text": "In December 2019, an outbreak of pneumonia of unknown origin was reported in Wuhan, Hubei Province, China. Pneumonia cases were epidemiologically linked to the Huanan Seafood Wholesale Market. Inoculation of respiratory samples into human airway epithelial cells, Vero E6 and Huh7 cell lines, led to the isolation of a novel respiratory virus whose genome analysis showed it to be a novel coronavirus related to SARS-CoV, and therefore named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus belonging to the subgenus Sarbecovirus. The global spread of SARS-CoV-2 and the thousands of deaths caused by coronavirus disease (COVID-19) led the World Health Organization to declare a pandemic on 12 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. In this review, we provide information regarding the epidemiology, serological and molecular diagnosis, origin of SARS-CoV-2 and its ability to infect human cells, and safety issues. Then we focus on the available therapies to fight COVID-19, the development of vaccines, the role of artificial intelligence in the management of the pandemic and limiting the spread of the virus, the impact of the COVID-19 epidemic on our lifestyle, and preparation for a possible second wave.", "title": "The COVID-19 pandemic", "pid": "2tyt8255", "bm25_score": 215.29495239257812}, {"text": "COVID-19 is a new type of coronavirus disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It originated in China in the month of December 2019 and quickly started to spread within the country. On 31st December 2019, it was first reported to country office of World Health Organization (WHO) in China. Since then, it has spread to most of the countries around the globe. However, there has been a recent rise in trend in believing that it would go away during summer days, which has not yet been properly investigated. In this paper, relationship of daily number of confirmed cases of COVID-19 with three environmental factors, viz. maximum relative humidity (RH_max), maximum temperature (T_max) and highest wind speed (WS_max), considering the incubation period, have been investigated statistically, for four of the most affected places of China, viz. Beijing, Chongqing, Shanghai, Wuhan and five of the most affected places of Italy, viz. Bergamo, Cremona, Lodi, Milano. It has been found that the relationship with maximum relative humidity and highest wind is mostly negligible, whereas relationship with maximum temperature is ranging between negligible to moderate.", "title": "Statistical investigation of relationship between spread of coronavirus disease (COVID-19) and environmental factors based on study of four mostly affected places of China and five mostly affected places of Italy", "pid": "4ay3hsi7", "bm25_score": 215.2569580078125}, {"text": "The fast-growing outbreak of the 2019 novel coronavirus (2019-nCoV), which originated from Wuhan locating in central China at the end of 2019, spread to multiple cities in merely a month. Although the mortality of this disease was lower than that of SARS, the incredible contagiousness was much higher than SRAS-CoV. Because of the tremendous clout of 2019-nCoV, it is essential to hold more details about it and monitor its future evolution. This mini review consequently summarizes the key elements of epidemiology features, providing updated relevant findings and novel insights related to 2019-nCoV.", "title": "Epidemiological Features of the 2019 Novel Coronavirus Outbreak in China.", "pid": "okmpsv47", "bm25_score": 215.2347412109375}, {"text": "There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.", "title": "The SARS-CoV-2 outbreak: What we know", "pid": "950x4b9a", "bm25_score": 215.23350524902344}, {"text": "BACKGROUND: SARS-CoV-2 began spreading in December 2019 and has since become a pandemic that has impacted many aspects of human society. Several issues concerning the origin, time of introduction to humans, evolutionary patterns, and underlying force driving the SARS-CoV-2 outbreak remain unclear. METHOD: Genetic variation in 137 SARS-CoV-2 genomes and related coronaviruses as of 2/23/2020 was analyzed. RESULT: After correcting for mutational bias, the excess of low frequency mutations on both synonymous and nonsynonymous sites was revealed which is consistent with the recent outbreak of the virus. In contrast to adaptive evolution previously reported for SARS-CoV during its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation. The sequence similarity in the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression that occurred approximately 40 years ago. The current outbreak of SARS-CoV-2 was estimated to have originated on 12/11/2019 (95% HPD 11/13/2019-12/23/2019). The effective population size of the virus showed an approximately 20-fold increase from the onset of the outbreak to the lockdown of Wuhan (1/23/2020) and ceased to increase afterwards, demonstrating the effectiveness of social distancing in preventing its spread. Two mutations, 84S in orf8 protein and 251 V in orf3 protein, occurred coincidentally with human intervention. The former first appeared on 1/5/2020 and plateaued around 1/23/2020. The latter rapidly increased in frequency after 1/23/2020. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China is two times higher than those derived from the rest of the world. A network analysis found that haplotypes collected from Wuhan were interior and had more mutational connections, both of which are consistent with the observation that the SARS-CoV-2 outbreak originated in China. CONCLUSION: SARS-CoV-2 might have cryptically circulated within humans for years before being discovered. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and determine the critical steps required for effective spreading.", "title": "The origin and underlying driving forces of the SARS-CoV-2 outbreak", "pid": "vahud6o5", "bm25_score": 215.22607421875}, {"text": "Mutation and adaptation have driven the co-evolution of coronaviruses (CoVs) and their hosts, including human beings, for thousands of years. Before 2003, two human CoVs (HCoVs) were known to cause mild illness, such as common cold. The outbreaks of severe acute respiratory syndrome (SARS) and the Middle East respiratory syndrome (MERS) have flipped the coin to reveal how devastating and life-threatening an HCoV infection could be. The emergence of SARS-CoV-2 in central China at the end of 2019 has thrusted CoVs into the spotlight again and surprised us with its high transmissibility but reduced pathogenicity compared to its sister SARS-CoV. HCoV infection is a zoonosis and understanding the zoonotic origins of HCoVs would serve us well. Most HCoVs originated from bats where they are non-pathogenic. The intermediate reservoir hosts of some HCoVs are also known. Identifying the animal hosts has direct implications in the prevention of human diseases. Investigating CoV-host interactions in animals might also derive important insight on CoV pathogenesis in humans. In this review, we present an overview of the existing knowledge about the seven HCoVs, with a focus on the history of their discovery as well as their zoonotic origins and interspecies transmission. Importantly, we compare and contrast the different HCoVs from a perspective of virus evolution and genome recombination. The current CoV disease 2019 (COVID-19) epidemic is discussed in this context. In addition, the requirements for successful host switches and the implications of virus evolution on disease severity are also highlighted.", "title": "Zoonotic origins of human coronaviruses", "pid": "dnla56uh", "bm25_score": 215.19422912597656}, {"text": "In December 2019, an outbreak of pneumonia of unknown origin was reported in Wuhan, Hubei Province, China. Pneumonia cases were epidemiologically linked to the Huanan Seafood Wholesale Market. Inoculation of respiratory samples into human airway epithelial cells, Vero E6 and Huh7 cell lines, led to the isolation of a novel respiratory virus whose genome analysis showed it to be a novel coronavirus related to SARS-CoV, and therefore named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus belonging to the subgenus Sarbecovirus. The global spread of SARS-CoV-2 and the thousands of deaths caused by coronavirus disease (COVID-19) led the World Health Organization to declare a pandemic on 12 March 2020. To date, the world has paid a high toll in this pandemic in terms of human lives lost, economic repercussions and increased poverty. In this review, we provide information regarding the epidemiology, serological and molecular diagnosis, origin of SARS-CoV-2 and its ability to infect human cells, and safety issues. Then we focus on the available therapies to fight COVID-19, the development of vaccines, the role of artificial intelligence in the management of the pandemic and limiting the spread of the virus, the impact of the COVID-19 epidemic on our lifestyle, and preparation for a possible second wave.", "title": "The COVID-19 pandemic.", "pid": "ft4rbcxf", "bm25_score": 215.19395446777344}, {"text": "BACKGROUND: SARS-CoV-2 began spreading in December 2019 and has since become a pandemic that has impacted many aspects of human society. Several issues concerning the origin, time of introduction to humans, evolutionary patterns, and underlying force driving the SARS-CoV-2 outbreak remain unclear. METHOD: Genetic variation in 137 SARS-CoV-2 genomes and related coronaviruses as of 2/23/2020 was analyzed. RESULT: After correcting for mutational bias, the excess of low frequency mutations on both synonymous and nonsynonymous sites was revealed which is consistent with the recent outbreak of the virus. In contrast to adaptive evolution previously reported for SARS-CoV during its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation. The sequence similarity in the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression that occurred approximately 40 years ago. The current outbreak of SARS-CoV-2 was estimated to have originated on 12/11/2019 (95% HPD 11/13/2019–12/23/2019). The effective population size of the virus showed an approximately 20-fold increase from the onset of the outbreak to the lockdown of Wuhan (1/23/2020) and ceased to increase afterwards, demonstrating the effectiveness of social distancing in preventing its spread. Two mutations, 84S in orf8 protein and 251 V in orf3 protein, occurred coincidentally with human intervention. The former first appeared on 1/5/2020 and plateaued around 1/23/2020. The latter rapidly increased in frequency after 1/23/2020. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China is two times higher than those derived from the rest of the world. A network analysis found that haplotypes collected from Wuhan were interior and had more mutational connections, both of which are consistent with the observation that the SARS-CoV-2 outbreak originated in China. CONCLUSION: SARS-CoV-2 might have cryptically circulated within humans for years before being discovered. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and determine the critical steps required for effective spreading.", "title": "The origin and underlying driving forces of the SARS-CoV-2 outbreak", "pid": "59492sjb", "bm25_score": 215.144775390625}, {"text": "", "title": "Where did SARS-CoV-2 come from?", "pid": "vc78113o", "bm25_score": 215.12838745117188}, {"text": "Abstract The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country’s earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world’s COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada’s first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.", "title": "Tracking the origin of early COVID-19 cases in Canada", "pid": "wmfcey6f", "bm25_score": 215.10675048828125}, {"text": "The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country's earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world's COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada's first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.", "title": "Tracking the origin of early COVID-19 cases in Canada", "pid": "kgifmjvb", "bm25_score": 215.0982208251953}, {"text": "Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade’s first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as ‘Public Health Emergency of International Concern’ on January 30(th), 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.", "title": "Emerging novel coronavirus (2019-nCoV)—current scenario, evolutionary perspective based on genome analysis and recent developments", "pid": "1qkwsh6a", "bm25_score": 215.0980682373047}, {"text": "Since the early 2000s, three novel zooanthroponous coronaviruses (Betacoronavirus) have emerged. The first outbreak of infection (SARS) caused by SARS-CoV virus occurred in the fall of 2002 in China (Guangdong Province). A second outbreak (MERS) associated with the new MERS-CoV virus appeared in Saudi Arabia in autumn 2012. The third epidemic, which turned into a COVID-19 pandemic caused by SARS-CoV-2 virus, emerged in China (Hubei Province) in the autumn 2019. This review focuses on ecological and genetic aspects that lead to the emergence of new human zoanthroponous coronaviruses. The main mechanism of adaptation of zoonotic betacoronaviruses to humans is to changes in the receptor-binding domain of surface protein (S), as a result of which it gains the ability to bind human cellular receptors of epithelial cells in respiratory and gastrointestinal tract. This process is caused by the high genetic diversity and variability combined with frequent recombination, during virus circulation in their natural reservoir - bats (Microchiroptera, Chiroptera). Appearance of SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus), and MERS (subgenus Merbecovirus) viruses is a result of evolutionary events occurring in bat populations with further transfer of viruses to the human directly or through the intermediate vertebrate hosts, ecologically connected with bats. This review is based on the report at the meeting «Coronavirus - a global challenge to science» of the Scientific Council «Life Science» of the Russian Academy of Science: Lvov D.K., Alkhovsky S.V., Burtseva E.I. COVID-19 pandemic sources: origin, biology and genetics of coronaviruses of SARS-CoV, SARS-CoV-2, MERS-CoV (Conference hall of Presidium of RAS, 14 Leninsky Prospect, Moscow, Russia. April 16, 2020).", "title": "[Source of the COVID-19 pandemic: ecology and genetics of coronaviruses (Betacoronavirus: Coronaviridae) SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus), and MERS-CoV (subgenus Merbecovirus).]", "pid": "66xk0qqq", "bm25_score": 215.093505859375}, {"text": "Reanalysis of the epidemic curve from the initial cluster of cases with novel coronavirus (2019-nCoV) in December 2019 indicates substantial human-to-human transmission. It is possible that the common exposure history at a seafood market in Wuhan originated from the human-to-human transmission events within the market, and the early, strong emphasis that market exposure indicated animal-to-human transmission was potentially the result of observer bias. To support the hypothesis of zoonotic origin of 2019-nCoV stemming from the Huanan seafood market, the index case should have had exposure history related to the market and the virus should have been identified from animals sold at the market. As these requirements remain unmet, zoonotic spillover at the market must not be overemphasized.", "title": "Initial Cluster of Novel Coronavirus (2019-nCoV) Infections in Wuhan, China Is Consistent with Substantial Human-to-Human Transmission", "pid": "z9dolxky", "bm25_score": 215.08511352539062}, {"text": "Abstract There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.", "title": "The SARS-CoV-2 outbreak: What we know", "pid": "5fg87lvu", "bm25_score": 215.0510711669922}, {"text": "The novel coronavirus, SARS‐CoV‐2, causes the unfathomable pandemic in the history of humankind. Bangladesh is also a victim of this critical situation. To investigate the genomic features of the pathogen, the first complete genome of the virus has very recently been published. Therefore, the long awaiting questions regarding the possible origin and typing of the strain(s) can now be answered. Here, we endeavor to mainly discuss the published reports or online‐accessed data (results) regarding those issues and presented a comprehensive picture of the typing of the virus alongside the probable origin of the sub‐clade containing Bangladeshi strain. Our observation suggested that this strain might have originated from the United Kingdom (UK) or other European countries epidemiologically linked to the UK. According to different genotyping classification schemes, this strain belongs to A2a clade under G major clade, is of B and/or L type, and is a SARS‐CoV‐2a sub‐strain. In the forwarding days, randomized genome data will certainly voluminate in Bangladesh, however because of globalization and immigrant movements, we urgently need a mass regional sequencing approach targeting the partial or complete genome that can link the epidemiological data and may help in further clinical interventions. This article is protected by copyright. All rights reserved.", "title": "Understanding the possible origin and genotyping of first Bangladeshi SARS‐CoV‐2 strain", "pid": "68g8noys", "bm25_score": 215.04324340820312}, {"text": "", "title": "Origin of SARS remains a mystery", "pid": "a7w6lael", "bm25_score": 215.0318145751953}, {"text": "One cannot spend more than 5 minutes on social media at the moment without finding a link to some conspiracy theory or other regarding the origin of SARS-CoV2, the coronavirus responsible for the COVID-19 pandemic. From the virus being deliberately released as a bioweapon, to pharmaceutical companies blocking the trials of natural remedies to boost their dangerous drugs and vaccines, the internet is rife with far-fetched rumour. And predictably, now that the first immunization trials have started, the anti-vaccine lobby have latched on to most of them. In the last week the trailer for a new 'bombshell documentary' Plandemic has been doing the rounds, gaining notoriety for being repeatedly removed from YouTube and Facebook. We usually wouldn't pay much heed to such things, but for retrovirologists like us the name associated with these claims is unfortunately too familiar: Dr Judy Mikovits.", "title": "FAKE SCIENCE: XMRV, COVID-19 AND THE TOXIC LEGACY OF DR JUDY MIKOVITS.", "pid": "pvrp8u8n", "bm25_score": 215.029541015625}, {"text": "The initial cases of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) occurred in Wuhan, China, in December 2019 and swept the world by 23 June 2020 with 8 993 659 active cases, 469 587 deaths across 216 countries, areas or territories. This strongly implies global transmission occurred before the lockdown of China. However, the initial source's transmission routes of SARS‐CoV‐2 remain obscure and controversial. Research data suggest bat (RaTG13) and pangolin carried CoV were the proximal source of SARS‐CoV‐2. In this study, we used systematic phylogenetic analysis of Coronavirinae subfamily along with wild type human SARS‐CoV, MERS‐CoV, and SARS‐CoV‐2 strains. The key residues of the receptor‐binding domain (RBD) and O‐linked glycan were compared. SARS‐CoV‐2 strains were clustered with RaTG13 (97.41% identity), Pangolin‐CoV (92.22% identity) and Bat‐SL‐CoV (80.36% identity), forms a new clade‐2 in lineage B of beta‐CoV. The alignments of RBD contact residues to ACE2 justified? Those SARS‐CoV‐2 strains sequences were 100% identical by each other, significantly varied in RaTG13 and pangolin‐CoV. SARS‐CoV‐2 has a polybasic cleavage site with an inserted sequence of PRRA compared to RaTG13 and only PRR to pangolin. Only serine (Ser) in pangolin and both threonine (Thr) and serine (Ser) O‐linked glycans were seen in RaTG13, suggesting that a detailed study needed in pangolin (Manis javanica) and bat (Rhinolophus affinis) related CoV.", "title": "An update on the origin of SARS‐CoV‐2: Despite closest identity, bat (RaTG13) and pangolin derived coronaviruses varied in the critical binding site and O‐linked glycan residues", "pid": "ip38x8bu", "bm25_score": 215.02748107910156}, {"text": "Since the early 2000s, three novel zooanthroponous coronaviruses (Betacoronavirus) have emerged. The first outbreak of infection (SARS) caused by SARS-CoV virus occurred in the fall of 2002 in China (Guangdong Province). A second outbreak (MERS) associated with the new MERS-CoV virus appeared in Saudi Arabia in autumn 2012. The third epidemic, which turned into a COVID-19 pandemic caused by SARS-CoV-2 virus, emerged in China (Hubei Province) in the autumn 2019. This review focuses on ecological and genetic aspects that lead to the emergence of new human zoanthroponous coronaviruses. The main mechanism of adaptation of zoonotic betacoronaviruses to humans is to changes in the receptor-binding domain of surface protein (S), as a result of which it gains the ability to bind human cellular receptors of epithelial cells in respiratory and gastrointestinal tract. This process is caused by the high genetic diversity and variability combined with frequent recombination, during virus circulation in their natural reservoir - bats (Microchiroptera, Chiroptera). Appearance of SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus), and MERS (subgenus Merbecovirus) viruses is a result of evolutionary events occurring in bat populations with further transfer of viruses to the human directly or through the intermediate vertebrate hosts, ecologically connected with bats. This review is based on the report at the meeting «Coronavirus - a global challenge to science¼ of the Scientific Council «Life Science¼ of the Russian Academy of Science: Lvov D.K., Alkhovsky S.V., Burtseva E.I. COVID-19 pandemic sources: origin, biology and genetics of coronaviruses of SARS-CoV, SARS-CoV-2, MERS-CoV (Conference hall of Presidium of RAS, 14 Leninsky Prospect, Moscow, Russia. April 16, 2020).", "title": "[Source of the COVID-19 pandemic: ecology and genetics of coronaviruses (Betacoronavirus: Coronaviridae) SARS-CoV, SARS-CoV-2 (subgenus Sarbecovirus), and MERS-CoV (subgenus Merbecovirus).]", "pid": "6y1gwszn", "bm25_score": 215.00811767578125}, {"text": "Bats have been recognized as the natural reservoirs of a large variety of viruses. Special attention has been paid to bat coronaviruses as the two emerging coronaviruses which have caused unexpected human disease outbreaks in the 21st century, Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV), are suggested to be originated from bats. Various species of horseshoe bats in China have been found to harbor genetically diverse SARS-like coronaviruses. Some strains are highly similar to SARS-CoV even in the spike protein and are able to use the same receptor as SARS-CoV for cell entry. On the other hand, diverse coronaviruses phylogenetically related to MERS-CoV have been discovered worldwide in a wide range of bat species, some of which can be classified to the same coronavirus species as MERS-CoV. Coronaviruses genetically related to human coronavirus 229E and NL63 have been detected in bats as well. Moreover, intermediate hosts are believed to play an important role in the transmission and emergence of these coronaviruses from bats to humans. Understanding the bat origin of human coronaviruses is helpful for the prediction and prevention of another pandemic emergence in the future.", "title": "Bat origin of human coronaviruses", "pid": "d2knbzhl", "bm25_score": 214.99285888671875}, {"text": "OBJECTIVE: COVID-19 has recently become a pandemic affecting many countries worldwide. This study aims to evaluate the current status of COVID-19 in Taiwan and analyze the source of infection. METHODS: National data regarding SARS-CoV-2 infection were obtained from Taiwan. CDC at the end of April 2020. These data were subjected to analysis of the current status and correlation between indigenous and imported COVID-19 cases. A phylogenetic tree was created to analyze the phylogeny of Taiwanese SARS-CoV-2 isolates. RESULTS: The first case of SARS-CoV-2 infection in Taiwan was detected on January 21, 2020. Epidemiological data indicate that by April 30, there were a total of 429 COVID-19 confirmed cases with the death rate of 1.3%. Most cases were identified as imported (79.9%; 343/429), with the majority originating from the United States of America (22.1%) and the United Kingdom (17.6%). Results from phylogenetic tree analyses indicate that the Taiwanese SARS-CoV-2 isolates were clustered with the SARS-CoV-2 isolates from other countries (bootstrap value 98%) and sub-clustered with bat SARS-like coronaviruses (bootstrap value 99%). CONCLUSION: This study suggests that the importation of SARS-CoV-2 infection was the primary risk-factor resulting in the COVID-19 epidemic in Taiwan.", "title": "Importation of SARS-CoV-2 infection leads to major COVID-19 epidemic in Taiwan", "pid": "giu9j0k1", "bm25_score": 214.99252319335938}, {"text": "SARS-CoV-2, a new coronavirus strain responsible for COVID-19 has emerged in Wuhan City, China and still continuing its worldwide pandemic nature. Considering the severity of the disease, a number of studies are underway, and full genomic sequences have already been released in the last few weeks to enable the understanding of the evolutionary origin and molecular characteristics of this virus. Bioinformatics analysis, satellite derived imaging data and epidemiological attributes were employed to investigate origin, immunogenic resemblance and global threat of newly pandemic SARS-CoV-2 including Bangladesh perspective. Based on currently available genomic information, a phylogeny study was employed focusing four types of representative viral proteins (spike, membrane, envelope and nucleoprotein) of SARS-CoV-2, HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HKU1, MERS-CoV, HKU4, HKU5 and BufCoV-HKU26. The findings clearly demonstrated that SARS-CoV-2 exhibited evolutionary convergent relation with previously reported SARS-CoV. It was also found that SARS-CoV-2 proteins were highly similar and identical to SARS-CoV proteins, though proteins from other coronaviruses showed lower level of similarity and identical patterns. The cross-checked conservancy analysis of SARS-CoV-2 antigenic epitopes showed significant conservancy with antigenic epitopes derived from SARS-CoV. The study also prioritized the temperature comparison through satellite imaging alongside compiling and analyzing the epidemiological outbreak information on the 2019 novel coronavirus based on several open datasets on COVID-19 (SARS-CoV-2) and discussed possible threats to Bangladesh.", "title": "Ancestral origin, antigenic resemblance and epidemiological insights of novel coronavirus (SARS-CoV-2): Global burden and Bangladesh perspective", "pid": "a4jn6gpk", "bm25_score": 214.97804260253906}, {"text": "The fast-growing outbreak of the 2019 novel coronavirus (2019-nCoV), which originated from Wuhan locating in central China at the end of 2019, spread to multiple cities in merely a month. Although the mortality of this disease was lower than that of SARS, the incredible contagiousness was much higher than SRAS-CoV. Because of the tremendous clout of 2019-nCoV, it is essential to hold more details about it and monitor its future evolution. This mini review consequently summarizes the key elements of epidemiology features, providing updated relevant findings and novel insights related to 2019-nCoV.", "title": "Epidemiological Features of the 2019 Novel Coronavirus Outbreak in China", "pid": "uv3djven", "bm25_score": 214.97674560546875}, {"text": "Results of analysis of phylogenetic, virological, epidemiological, ecological, clinical data of COVID-19 outbreaks in Wuhan, China (PRC) in comparison with SARS-2002 and MERS-2012 outbreaks allow to conclude: - the etiological agent of COVID-19 is coronavirus (2019-CoV), phylogenetically close to the SARS-CoV, isolated from human, and SARS-related viruses isolated from bats (SARS-related bat CoV viruses). These viruses belong to the Sarbecovirus subgenus, Betacoronavirus genus, Orthocoronavirinae subfamily, Coronaviridae family (Cornidovirinea: Nidovirales). COVID-19 is a variant of SARS-2002 and is different from MERS-2012 outbreak, which were caused by coronavirus belonged to the subgenus Merbecovirus of the same genus; - according to the results of phylogenetic analysis of 35 different betacoronaviruses, isolated from human and from wild animals in 2002-2019, the natural source of COVID-19 and SARS-CoV (2002) is bats of Rhinolophus genus (Rhinolophidae) and, probably, some species of other genera. An additional reservoir of the virus could be an intermediate animal species (snakes, civet, hedgehogs, badgers, etc.) that are infected by eating of infected bats. SARS-like coronaviruses circulated in bats in the interepidemic period (2003-2019); - seasonal coronaviruses (subgenus Duvinacovirus, Alphacoronavirus) are currently circulating (November 2019 - January 2020) in the European part of Russia, Urals, Siberia and the Far East of Russia, along with the influenza viruses A(H1N1)pdm09, A(H3N2), and В, as well as six other respiratory viruses (HPIV, HAdV, HRSV, HRV, HBoV, and HMPV).", "title": "[Etiology of epidemic outbreaks COVID-19 on Wuhan, Hubei province, Chinese People Republic associated with 2019-nCoV (Nidovirales, Coronaviridae, Coronavirinae, Betacoronavirus, Subgenus Sarbecovirus): lessons of SARS-CoV outbreak.]", "pid": "vcfljekt", "bm25_score": 214.9559326171875}, {"text": "The COVID-19 global pandemic is not even over yet but it has already taught us a lot of lessons - the hard way. The vast majority of the global community has blamed the Chinese Illegal wildlife markets for the origin of this pandemic. Through careful scientific analysis, I have explained in this article that we don't need such wildlife markets for these kinds of outbreaks to occur in the future. I have also explained how India which is the second-most populous country in the world, could be the origin of the next outbreak, even though such wildlife markets are either very rare or do not exist at all in India.", "title": "Could India be the origin of next COVID-19 like epidemic?", "pid": "cniyembt", "bm25_score": 214.9527130126953}, {"text": "The positive-strand RNA viruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and recently emerged COVID-19 epidemics, demonstrated the transmission capability of the coronaviruses by crossing the species barrier and emergence in humans. The source of coronavirus disease 2019 (COVID-19) is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), firstly reported in December 2019 at Wuhan, China. COVID-19 is a kind of viral pneumonia. The outbreak of SARS-CoV-2 (COVID-19) has been reported as the introduction of the third highly pathogenic coronavirus which crossed the species barrier and spread into the human population. Severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) were the first two epidemic viruses, respectively, in the twenty-first century. Introduction of the 2019 novel coronaviruses (2019-nCoV) in human population is a worldwide concern, and this might have generated via RNA recombination among the previous reported coronaviruses. The COVID-19 is spreading in an alarming rate, and till date no vaccine or specific medicines are available in the market. The newly emerged coronavirus COVID-19 is strongly related to SARS-CoV except little dissimilarity. In this chapter, we will discuss about the alterations and variations in antigenicity, structural changes, and RNA recombination which might be responsible for the COVID-19 emergence.", "title": "Emergence and Reemergence of Severe Acute Respiratory Syndrome (SARS) Coronaviruses", "pid": "jqexwnq2", "bm25_score": 214.9496307373047}, {"text": "A novel coronavirus, probably of bat origin, has caused an outbreak of severe respiratory infection in humans in Wuhan, China and has been dispersed globally by travelers. The WHO has declared the spread of the infection a Public Health Emergency of International Concern.", "title": "Travellers give wings to novel coronavirus (2019-nCoV)", "pid": "qyf59ghf", "bm25_score": 214.94955444335938}, {"text": "Results of analysis of phylogenetic, virological, epidemiological, ecological, clinical data of COVID-19 outbreaks in Wuhan, China (PRC) in comparison with SARS-2002 and MERS-2012 outbreaks allow to conclude: - the etiological agent of COVID-19 is coronavirus (2019-CoV), phylogenetically close to the SARS-CoV, isolated from human, and SARS-related viruses isolated from bats (SARS-related bat CoV viruses). These viruses belong to the Sarbecovirus subgenus, Betacoronavirus genus, Orthocoronavirinae subfamily, Coronaviridae family (Cornidovirinea: Nidovirales). COVID-19 is a variant of SARS-2002 and is different from MERS-2012 outbreak, which were caused by coronavirus belonged to the subgenus Merbecovirus of the same genus; - according to the results of phylogenetic analysis of 35 different betacoronaviruses, isolated from human and from wild animals in 2002-2019, the natural source of COVID-19 and SARS-CoV (2002) is bats of Rhinolophus genus (Rhinolophidae) and, probably, some species of other genera. An additional reservoir of the virus could be an intermediate animal species (snakes, civet, hedgehogs, badgers, etc.) that are infected by eating of infected bats. SARS-like coronaviruses circulated in bats in the interepidemic period (2003-2019); - seasonal coronaviruses (subgenus Duvinacovirus, Alphacoronavirus) are currently circulating (November 2019 - January 2020) in the European part of Russia, Urals, Siberia and the Far East of Russia, along with the influenza viruses A(H1N1)pdm09, A(H3N2), and В, as well as six other respiratory viruses (HPIV, HAdV, HRSV, HRV, HBoV, and HMPV).", "title": "[Etiology of epidemic outbreaks COVID-19 on Wuhan, Hubei province, Chinese People Republic associated with 2019-nCoV (Nidovirales, Coronaviridae, Coronavirinae, Betacoronavirus, Subgenus Sarbecovirus): lessons of SARS-CoV outbreak.]", "pid": "wt9j5mvd", "bm25_score": 214.93930053710938}, {"text": "In December 2019 a new human coronavirus emerged in Wuhan, China, which is known as SARS-CoV‑2. The clinical course of the disease known as coronavirus disease 2019 (COVID-19) ranges from mild respiratory symptoms to severe lung failure. The virus is currently rapidly spreading around the world and pushing health systems to the limits of their capacity due to the exponential increase in the number of cases. The origin of SARS-CoV‑2 lies in the bat coronavirus pool and has now emerged in the human population due to interspecies transmission. Molecular diagnostic methods have been established in a very short time and a number of clinical studies on the effectiveness of different antiviral drugs are ongoing. The development of a vaccine using different approaches is also under investigation. Considering the high number of cases and mortality rates of up to 9% there is an urgent need for action. This article summarizes the current state of knowledge on human coronaviruses with a strong focus on the current data on SARS-CoV‑2. Due to the daily changing level of knowledge, the article reflects the status up to 21 March 2020.", "title": "Coronaviren: von der banalen Erkältung zum schweren Lungenversagen: Chronologie einer Pandemie", "pid": "awtiqxx5", "bm25_score": 214.93426513671875}, {"text": "Abstract Objective COVID-19 has recently become a pandemic affecting many countries worldwide. This study aims to evaluate current status of COVID-19 in Taiwan and analyze the source of infection. Methods National data regarding SARS-CoV-2 infection were obtained from Taiwan CDC at the end of April, 2020. These data were subjected for analysis of the current status and correlation between indigenous and imported COVID-19 cases. Phylogenetic tree was performed to analyze the phylogeny of Taiwanese SARS-CoV-2 isolates. Results The initial case of SARS-CoV-2 infection in Taiwan was detected on January 21, 2020. Epidemiological data indicate that by April 30, there were a total of 429 COVID-19 confirmed cases with the death rate of 1.3%. Most of cases were identified as imported (79.9%; 343/429) with majority transmitted from United States of America (22.1%) and United Kingdom (17.6%). Results from phylogenetic tree analyses indicate that the Taiwanese SARS-CoV-2 isolates were clustered with the SARS-CoV-2 isolates from other countries (bootstrap value 98%) and sub-clustered with bat SARS-like coronaviruses (bootstrap value 99%). Conclusion This study suggests that importation of SARS-CoV-2 infection was the primary risk-factor resulting in the COVID-19 epidemic in Taiwan.", "title": "Importation of SARS-CoV-2 infection leads to major COVID-19 epidemic in Taiwan", "pid": "yzyixucr", "bm25_score": 214.9240264892578}, {"text": "One cannot spend >5 min on social media at the moment without finding a link to some conspiracy theory or other regarding the origin of SARS-CoV2, the coronavirus responsible for the COVID-19 pandemic. From the virus being deliberately released as a bioweapon to pharmaceutical companies blocking the trials of natural remedies to boost their dangerous drugs and vaccines, the Internet is rife with far-fetched rumors. And predictably, now that the first immunization trials have started, the antivaccine lobby has latched on to most of them. In the last week, the trailer for a new \"bombshell documentary\" Plandemic has been doing the rounds, gaining notoriety for being repeatedly removed from YouTube and Facebook. We usually would not pay much heed to such things, but for retrovirologists like us, the name associated with these claims is unfortunately too familiar: Dr. Judy Mikovits.", "title": "Fake Science: XMRV, COVID-19, and the Toxic Legacy of Dr. Judy Mikovits", "pid": "1aj04b74", "bm25_score": 214.8891143798828}, {"text": "Middle East respiratory syndrome (MERS) is an emerging infectious disease, caused by Middle East respiratory syndrome coronavirus (MERS-CoV) and is considered to be a zoonosis. However, the natural reservoirs of MERS-CoV remain obscure, with bats and camels as the most suspected sources. In this article, we review the evidence supporting a bat/camel origin of human MERS-CoV infection and current knowledge on the modes of camel-to-human transmission of MERS-CoV.", "title": "Evidence for zoonotic origins of Middle East respiratory syndrome coronavirus", "pid": "0194oljo", "bm25_score": 214.86761474609375}, {"text": "The ongoing Coronavirus Disease 2019 (COVID-19) outbreak, originated in the end of 2019 in Wuhan, China, has claimed more than 2200 lives and posed a huge threat to global public health. The Chinese government has implemented control measures including setting up special hospitals and travel restriction to mitigate the spread. We propose conceptual models for the outbreak in Wuhan with the consideration of individual behavioural reaction and governmental actions, e.g., holiday extension, travel restriction, hospitalisation and quarantine. We employed the estimates of these two key components from the 1918 influenza pandemic in London, United Kingdom, incorporated zoonotic introductions and the emigration, then computed future trends and the reporting ratio. The model is concise in structure, and it successfully captures the course of the COVID-19 outbreak, and thus sheds light on understanding the trends of the outbreak.", "title": "A conceptual model for the outbreak of Coronavirus disease 2019 (COVID-19) in Wuhan, China with individual reaction and governmental action", "pid": "zq2h0avw", "bm25_score": 214.85562133789062}, {"text": "", "title": "Ideas and the origin of evidence during the COVID-19 pandemic.", "pid": "kvb7moqt", "bm25_score": 214.83079528808594}, {"text": "The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the 21st century. We analyzed >4,700 SARS-CoV-2 genomes and associated meta-data retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and >160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a uniform mutation occurrence along branches that could complicate the design of future vaccines. The root of SARS-CoV-2 genomes locates at the Chinese haplogroup B1, with a TMRCA dating to 12 November 2019 - thus matching epidemiological records. Sub-haplogroup A2a originates in China and represents the major non-Asian outbreak. Multiple founder effect episodes, most likely associated with super-spreader hosts, explain COVID-19 pandemic to a large extent.", "title": "The impact of super-spreaders in COVID-19: mapping genome variation worldwide", "pid": "qw05apnf", "bm25_score": 214.82205200195312}, {"text": "Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.", "title": "Origin and evolution of pathogenic coronaviruses", "pid": "ne5r4d4b", "bm25_score": 214.79953002929688}, {"text": "A newly emerged coronavirus, SARS-CoV-2, caused severe outbreaks of pneumonia in China in December 2019 and has since spread to various countries around the world. To probe the origin and transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences of viruses available in the GISAID platform as of March 05, 2020. A substantial number of earliest sequences reported in Wuhan in December 2019, including those of viruses recovered from the Huanan Seafood Market (HNSM), the site of the initial outbreak, were genetically diverse, suggesting that viruses of multiple sources were involved in the original outbreak. The viruses were subsequently disseminated to different parts of China and other countries, with diverse mutational profiles being recorded in strains recovered subsequently. Interestingly, four genetic clusters defined as Super-transmitters (STs) were found to become dominant and were responsible for the major outbreaks in various countries. Among the four clusters, ST1 is widely disseminated in Asia and the US and mainly responsible for outbreaks in the states of Washington and California in the US as well as those in South Korea at the end of February and early March, whereas ST4 contributed to the pandemic in Europe. Each ST cluster carried a signature mutation profile which allowed us to trace the origin and transmission patterns of specific viruses in different parts of the world. Using the signature mutations as markers of STs, we further analysed 1539 genome sequences reported after February 29, 2020. We found that around 90% of these genomes belonged to STs with ST4 being the dominant one and their contribution to pandemic in different continents were also depicted. The identification of these super-transmitters provides insight into the control of further transmission of SARS-CoV-2.", "title": "Identification of super-transmitters of SARS-CoV-2", "pid": "tnfgbl05", "bm25_score": 214.7983856201172}, {"text": "Since December 2019, coronavirus disease 2019 (COVID-19) emerged in Wuhan, Central China and rapidly spread throughout China. Up to March 3, 2020, SARS-CoV-2 has infected more than 89,000 people in China and other 66 countries across six continents. In this study, we used 10 new sequenced genomes of SARS-CoV-2 and combined 136 genomes from GISAID database to investigate the genetic variation and population demography through different analysis approaches (e.g. Network, EBSP, Mismatch, and neutrality tests). The results showed that 80 haplotypes had 183 substitution sites, including 27 parsimony-informative and 156 singletons. Sliding window analyses of genetic diversity suggested a certain mutations abundance in the genomes of SARS-CoV-2, which may be explaining the existing widespread and high adaptation of the deadly virus. Phylogenetic analysis showed that the view, pangolin acted as an intermediate host, may be controversial. The network indicated that, in the original haplotype (H14), one patient sample lived near the Huanan seafood market (approximate 2 km), indicating high possibility of the patient having a history of unconscious contact with this market. However, based on this clue, we cannot accurately concluded that whether this market was the origin center of SARS-CoV-2. Additionally, 16 genomes, collected from this market, assigned to 10 haplotypes, indicated a circulating infection within the market in a short term and then leading to the outbreak of SARS-CoV-2 in Wuhan and other areas. The EBSP results showed that the first estimated expansion date of SARS-CoV-2 began from 7 December 2019, which may indicated that the transmission could have begun from person to person in mid to late November.", "title": "Genome-wide data inferring the evolution and population demography of the novel pneumonia coronavirus (SARS-CoV-2)", "pid": "fnj57b0l", "bm25_score": 214.79725646972656}, {"text": "Coronaviruses are the well-known cause of severe respiratory, enteric and systemic infections in a wide range of hosts including man, mammals, fish, and avian. The scientific interest on coronaviruses increased after the emergence of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) outbreaks in 2002-2003 followed by Middle East Respiratory Syndrome CoV (MERS-CoV). This decade's first CoV, named 2019-nCoV, emerged from Wuhan, China, and declared as 'Public Health Emergency of International Concern' on January 30th, 2020 by the World Health Organization (WHO). As on February 4, 2020, 425 deaths reported in China only and one death outside China (Philippines). In a short span of time, the virus spread has been noted in 24 countries. The zoonotic transmission (animal-to-human) is suspected as the route of disease origin. The genetic analyses predict bats as the most probable source of 2019-nCoV though further investigations needed to confirm the origin of the novel virus. The ongoing nCoV outbreak highlights the hidden wild animal reservoir of the deadly viruses and possible threat of spillover zoonoses as well. The successful virus isolation attempts have made doors open for developing better diagnostics and effective vaccines helping in combating the spread of the virus to newer areas.", "title": "Emerging novel coronavirus (2019-nCoV)-current scenario, evolutionary perspective based on genome analysis and recent developments", "pid": "22fc1qly", "bm25_score": 214.79559326171875}, {"text": "The Coronavirus pandemic (COVID-19) is one of the most devastating in this century. It originated in China in December 2019 caused by the SARS-Cov-2 virus, and in less than a month it had been classified as an \"International Public Health Emergency\". To date there are nearly 3 million people infected and more than 250,000 deaths caused by the disease worldwide. Initially it affects the respiratory tract with atypical pneumonia and in severe cases it produces systemic inflammation with cytokine storm that can cause rapid deterioration with circulatory and respiratory failure, coagulopathy and a lethality rate of approximately 7%. In Mexico, the first case was detected in February 2020, and to date there are 26,616 confirmed cases and 2,961 deaths throughout the country. The low number of diagnostic tests conducted in our country clearly underestimates the real incidence and impact of the disease. The most affected groups are those with risk factors such as age over 60, presence of hypertension, diabetes or cardiovascular disease. Of the confirmed cases, 15% are healthcare workers. There is no specific treatment or vaccine yet, so it is important to have hygiene, social isolation and personal protection measures. Health, social and economic consequences could have great impact in the near future.", "title": "The SARS-CoV-2 (COVID-19) coronavirus pandemic: current situation and implications for Mexico.", "pid": "flamivec", "bm25_score": 214.7857666015625}, {"text": "", "title": "Ideas and the origin of evidence during the COVID-19 pandemic", "pid": "4977dzxz", "bm25_score": 214.7743682861328}, {"text": "This communication aims to advocate a more coordinate activity mainly between medical and environmental scientists to clarify some confusing information related to airborne diffusion mechanisms of COVID-19. In this frame it is suggested that parameters other than environmental pollution (accounting for pollution-to-human transmission mechanisms), as for example parameters involving commercial exchanges (accounting for human-to-human transmission mechanisms), should be considered to better justify the difference in the initial diffusion of virus in Italy.", "title": "Commercial exchanges instead of air pollution as possible origin of COVID-19 initial diffusion phase in Italy: More efforts are necessary to address interdisciplinary research", "pid": "99s7lzdh", "bm25_score": 214.75674438476562}, {"text": "There are outstanding evolutionary questions on the recent emergence of coronavirus SARS-CoV-2/hCoV-19 in Hubei province that caused the COVID-19 pandemic, including (1) the relationship of the new virus to the SARS-related coronaviruses, (2) the role of bats as a reservoir species, (3) the potential role of other mammals in the emergence event, and (4) the role of recombination in viral emergence. Here, we address these questions and find that the sarbecoviruses – the viral subgenus responsible for the emergence of SARS-CoV and SARS-CoV-2 – exhibit frequent recombination, but the SARS-CoV-2 lineage itself is not a recombinant of any viruses detected to date. In order to employ phylogenetic methods to date the divergence events between SARS-CoV-2 and the bat sarbecovirus reservoir, recombinant regions of a 68-genome sarbecovirus alignment were removed with three independent methods. Bayesian evolutionary rate and divergence date estimates were consistent for all three recombination-free alignments and robust to two different prior specifications based on HCoV-OC43 and MERS-CoV evolutionary rates. Divergence dates between SARS-CoV-2 and the bat sarbecovirus reservoir were estimated as 1948 (95% HPD: 1879-1999), 1969 (95% HPD: 1930-2000), and 1982 (95% HPD: 1948-2009). Despite intensified characterization of sarbecoviruses since SARS, the lineage giving rise to SARS-CoV-2 has been circulating unnoticed for decades in bats and been transmitted to other hosts such as pangolins. The occurrence of a third significant coronavirus emergence in 17 years together with the high prevalence and virus diversity in bats implies that these viruses are likely to cross species boundaries again. In Brief The Betacoronavirus SARS-CoV-2 is a member of the sarbecovirus subgenus which shows frequent recombination in its evolutionary history. We characterize the extent of this genetic exchange and identify non-recombining regions of the sarbecovirus genome using three independent methods to remove the effects of recombination. Using these non-recombining genome regions and prior information on coronavirus evolutionary rates, we obtain estimates from three approaches that the most likely divergence date of SARS-CoV-2 from its most closely related available bat sequences ranges from 1948 to 1982. Key Points RaTG13 is the closest available bat virus to SARS-CoV-2; a sub-lineage of these bat viruses is able to infect humans. Two sister lineages of the RaTG13/SARS-CoV-2 lineage infect Malayan pangolins. The sarbecoviruses show a pattern of deep recombination events, indicating that there are high levels of co-infection in horseshoe bats and that the viral pool can generate novel allele combinations and substantial genetic diversity; the sarbecoviruses are efficient ‘explorers’ of phenotype space. The SARS-CoV-2 lineage is not a recent recombinant, at least not involving any of the bat or pangolin viruses sampled to date. Non-recombinant regions of the sarbecoviruses can be identified, allowing for phylogenetic inference and dating to be performed. We constructed three such regions using different methods. We estimate that RaTG13 and SARS-CoV-2 diverged 40 to 70 years ago. There is a diverse unsampled reservoir of generalist viruses established in horseshoe bats. While an intermediate host responsible for the zoonotic event cannot be ruled out, the relevant evolution for spillover to humans very likely occurred in horseshoe bats.", "title": "Evolutionary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic", "pid": "h2uc7ria", "bm25_score": 214.74668884277344}, {"text": "The spread of SARS-CoV-2 since December 2019 has become a pandemic and impacted many aspects of human society. Here, we analyzed genetic variation of SARS-CoV-2 and its related coronavirus and found the evidence of intergenomic recombination. After correction for mutational bias, analysis of 137 SARS-CoV-2 genomes as of 2/23/2020 revealed the excess of low frequency mutations on both synonymous and nonsynonymous sites which is consistent with recent origin of the virus. In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China was two time higher than those derived from the rest of the world. In addition, in network analysis, haplotypes collected from Wuhan city were at interior and have more mutational connections, both of which are consistent with the observation that the outbreak of cov-19 was originated from China. SUMMARY In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated.", "title": "The origin and underlying driving forces of the SARS-CoV-2 outbreak", "pid": "bawgldfi", "bm25_score": 214.74447631835938}, {"text": "The ongoing pandemic of a new human coronavirus, SARS-CoV-2, has generated enormous global concern. We and others in China were involved in the initial genome sequencing of the virus. Herein, we describe what genomic data reveal about the emergence SARS-CoV-2 and discuss the gaps in our understanding of its origins.", "title": "A Genomic Perspective on the Origin and Emergence of SARS-CoV-2", "pid": "5hio4lgc", "bm25_score": 214.74200439453125}, {"text": "In early December 2019, the 2019 novel coronavirus (COVID-19) was identified as the agent responsible for the first pneumonia cases of unknown origin in Wuhan, the capital of the Hubei region in China. The virus has been identified as a novel enveloped RNA betacoronavirus2 , that has been promptly named SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). The World Health Organization (WHO), on January 12, 2020 declared the COVID-19 a public health emergency of international concern. On March 11, the WHO made the assessment that COVID-19 can be characterized as a pandemic.", "title": "Papa Giovanni XXIII Bergamo Hospital at the time of the COVID-19 outbreak: letter from the warfront.", "pid": "d11cj86k", "bm25_score": 214.73272705078125}, {"text": "In December, 2019, an infection outbreak occurred in Wuhan of unknown cause, which attracts intense attention. Shortly after the virus was identified with the name of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), the epidemic of coronavirus disease 2019 (COVID-19) broke out and an information storm occurred. At that time, two important aspects: the stage and the links of epidemic, were unclear. Answers to the questions, what are the sources, how do infections occur, and who will be affected should be clarified as the outbreak continues to evolve. Furthermore, the epidemic process and the stage of epidemic should be explored and discussed. Based on information of SARS, middle east respiratory syndrome(MERS) and COVID-19, the links of epidemic (the sources, the routes of infection, and the susceptible population) will be discussed as well as the role of the natural and the social factors. Epidemiology characteristics of patients will be traced based on current information.", "title": "Epidemiology of coronavirus disease 2019(COVID-19) caused by SARS-CoV-2.", "pid": "mxvbbkc4", "bm25_score": 214.7311248779297}, {"text": "According to what was published by the WHO (World Health Organization), a first case of acute respiratory infection, of unknown origin, appeared in the province of HUBEI, CHINA, in the city of WUHAN, (December 2019). After having ruled out other etiological agents, the isolation of a new coronavirus (7-01-2020) was achieved, which was called new coronavirus (nCOV, COVID-19), currently named SARS-CoV-2. Coronaviruses, being important pathogens, can infect the respiratory, gastrointestinal, hepatic, and nervous systems of humans and birds, livestock, bats, mice, and other wild animals. Since the outbreaks of SARS (Severe Acute Respiratory Syndrome) in 2002 and MERS (Middle East Respiratory Syndrome) in 2012, the transmission of these viruses between humans and animals has been demonstrated.", "title": "Coronavirus-2019. General considerations/ Coronavirus-2019. Consideraciones Generales", "pid": "n6jgr1kx", "bm25_score": 214.71815490722656}, {"text": "", "title": "Exploring the presence of animal origin in the causation of corona virus disease 2019 outbreak and strategies to prevent acquisition of the infection", "pid": "pf7oon65", "bm25_score": 214.71519470214844}, {"text": "", "title": "Exploring the Presence of Animal Origin in the Causation of Corona Virus Disease 2019 Outbreak and Strategies to Prevent Acquisition of the Infection", "pid": "fxrbzfht", "bm25_score": 214.71519470214844}, {"text": "A novel Coronavirus, 2019-nCoV, has been identified as the causal pathogen of an ongoing epidemic, with the first cases reported in Wuhan, China, last December 2019, and has since spread to other countries worldwide, included Europe and very recently Italy. In this short report, phylogenetic reconstruction was used to better understand the transmission dynamics of the virus from its first introduction in China focusing on the more recent evidence of infection in a couple of Chinese tourists arrived in Italy on 23rd January 2020 and labeled as Coronavirus Italian cases. A maximum clade credibility tree has been built using a dataset of 54 genome sequences of 2019-nCoV plus two closely related bat strains (SARS-like CoV) available in GenBank. Bayesian time-scaled phylogenetic analysis was implemented in BEAST 1.10.4. The Bayesian phylogenetic reconstruction showed that 2019-2020 nCoV firstly introduced in Wuhan on 25 November 2019, started epidemic transmission reaching many countries worldwide, including Europe and Italy where the two strains isolated dated back 19 January 2020, the same that the Chinese tourists arrived in Italy. Strains isolated outside China were intermixed with strains isolated in China as evidence of likely imported cases in Rome, Italy, and Europe, as well. In conclusion, this report suggests that further spread of 2019-nCoV epidemic was supported by human mobility and that quarantine of suspected or diagnosed cases is useful to prevent further transmission. Viral genome phylogenetic analysis represents a useful tool for the evaluation of transmission dynamics and preventive action.", "title": "The first two cases of 2019-nCoV in Italy: Where they come from?", "pid": "2cvp8wch", "bm25_score": 214.7003173828125}, {"text": "This communication aims to advocate a more coordinate activity mainly between medical and environmental scientists to clarify some confusing information related to airborne diffusion mechanisms of COVID-19. In this frame it is suggested that parameters other than environmental pollution (accounting for pollution-to human transmission mechanisms), as for example parameters involving commercial exchanges (accounting for human-to human transmission mechanisms), should be considered to better justify the difference in the initial diffusion of virus in Italy.", "title": "Commercial exchanges instead of air pollution as possible origin of COVID-19 initial diffusion phase in Italy: more efforts are necessary to address interdisciplinary research", "pid": "edc509xr", "bm25_score": 214.6981201171875}, {"text": "A novel coronavirus (nCoV-2019) was the cause of an outbreak of respiratory illness detected in Wuhan, Hubei Province, China in December of 2019. Genomic analyses of nCoV-2019 determined a 96% resemblance with a coronavirus isolated from a bat in 2013 (RaTG13); however, the receptor binding motif (RBM) of these two genomes share low sequence similarity. This divergence suggests a possible alternative source for the RBM coding sequence in nCoV-2019. We identified high sequence similarity in the RBM between nCoV-2019 and a coronavirus genome reconstructed from a viral metagenomic dataset from pangolins possibly indicating a more complex origin for nCoV-2019.", "title": "Evidence of recombination in coronaviruses implicating pangolin origins of nCoV-2019", "pid": "dnxhtbxn", "bm25_score": 214.68907165527344}, {"text": "Research efforts of the ongoing SARS-CoV-2 pandemic have focused on viral genome sequence analysis to understand how the virus spread across the globe. Here, we assess three recently identified SARS-CoV-2 genomes in Beijing from June 2020 and attempt to determine the origin of these genomes, made available in the GISAID database. The database contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Including the three new samples and excluding samples with missing annotations, we analyzed 7, 643 SARS-CoV-2 genomes. Using principal component analysis computed on a similarity matrix that compares all pairs of the SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index, we find that the newly discovered virus genomes from Beijing are in a genetic cluster that consists mostly of cases from Europe and South(east) Asia. The sequences of the new cases are most related to virus genomes from a small number of cases from China (March 2020), cases from Europe (February to early May 2020), and cases from South(east) Asia (May to June 2020). These findings could suggest that the original cases of this genetic cluster originated from China in March 2020 and were re-introduced to China by transmissions from samples from South(east) Asia between April and June 2020.", "title": "Unsupervised cluster analysis of SARS-CoV-2 genomes indicates that recent (June 2020) cases in Beijing are from a genetic subgroup that consists of mostly European and South(east) Asian samples, of which the latter are the most recent", "pid": "4oa0gsos", "bm25_score": 214.6857147216797}, {"text": "Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats(1–4). Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans(5–7). Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.", "title": "A pneumonia outbreak associated with a new coronavirus of probable bat origin", "pid": "o877uul1", "bm25_score": 214.6567840576172}, {"text": "The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) reached over two million confirmed cases worldwide, and numbers are still growing at a fast rate. The majority of new infections are now being reported outside of China, where the outbreak officially originated in December 2019 in Wuhan. Despite the wide outbreak of the infection, a remarkable asymmetry is observed in the number of cases and in the distribution of the severity of the COVID-19 symptoms in patients with respect to the countries/regions. In the early stages of a new pathogen outbreak, it is critical to understand the dynamics of the infection transmission, in order to follow contagion over time and project the epidemiological situation in the near future. While it is possible to reason that observed variation in the number and severity of cases stem from the initial number of infected individuals, the difference in the testing policies and social aspects of community transmissions, the factors that could explain high discrepancy in areas with a similar level of healthcare still remain unknown. Here we introduce a binary classifier based on an artificial neural network that can help in explaining those differences and that can be used to support the design of containment policies. We propose that air pollutants, and specifically particulate matter (PM) 2.5 and ozone, are oppositely related with the SARS-CoV-2 infection frequency and could serve as surrogate markers to complement the infection outbreak anticipation.", "title": "Spatial-temporal variations of atmospheric factors contribute to SARS-CoV-2 outbreak", "pid": "4omocd8q", "bm25_score": 214.6517333984375}, {"text": "Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1-4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.", "title": "A pneumonia outbreak associated with a new coronavirus of probable bat origin", "pid": "d5yt2fih", "bm25_score": 214.647705078125}, {"text": "2019 novel coronavirus (SARS-CoV-2), which originated in Wuhan, China, has attracted the world's attention over the last month. The Chinese government has taken emergency measures to control the outbreak and has undertaken initial steps in the diagnosis and treatment of 2019 novel coronavirus infection disease (COVID-19). However, SARS-CoV-2 possesses powerful pathogenicity as well as transmissibility and still holds many mysteries that are yet to be solved, such as whether the virus can be transmitted by asymptomatic patients or by mothers to their infants. Our research presents selected available cases of COVID-19 in China to better understand the transmission and diagnosis regarding this infectious disease.", "title": "The transmission and diagnosis of 2019 novel coronavirus infection disease (COVID-19): A Chinese perspective", "pid": "jb6o4v6p", "bm25_score": 214.63934326171875}, {"text": "Since the identification of the first cases of the coronavirus in December 2019 in Wuhan, China, there has been a significant amount of confusion regarding the origin and spread of the so-called 'coronavirus', officially named SARS-CoV-2, and the cause of the disease COVID-19 Conflicting messages from the media and officials across different countries and organizations, the abundance of disparate sources of information, unfounded conspiracy theories on the origins of the newly emerging virus and the inconsistent public health measures across different countries, have all served to increase the level of anxiety in the population Where did the virus come from? How is it transmitted? How does it cause disease? Is it like flu? What is a pandemic? What can we do to stop its spread? Written by a leading expert, this concise and accessible introduction provides answers to the most common questions surrounding coronavirus for a general audience", "title": "Understanding Coronavirus", "pid": "hmvo5b0q", "bm25_score": 214.6367645263672}, {"text": "In December, 2019, an infection outbreak occurred in Wuhan of unknown cause, which attracts intense attention. Shortly after the virus was identified with the name of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), the epidemic of coronavirus disease 2019 (COVID-19) broke out and an information storm occurred. At that time, two important aspects: the stage and the links of epidemic, were unclear. Answers to the questions, what are the sources, how do infections occur, and who will be affected should be clarified as the outbreak continues to evolve. Furthermore, the epidemic process and the stage of epidemic should be explored and discussed. Based on information of SARS, middle east respiratory syndrome(MERS) and COVID-19, the links of epidemic (the sources, the routes of infection, and the susceptible population) will be discussed as well as the role of the natural and the social factors. Epidemiology characteristics of patients will be traced based on current information.", "title": "Epidemiology of coronavirus disease 2019(COVID-19) caused by SARS-CoV-2", "pid": "89qmvo9a", "bm25_score": 214.62869262695312}, {"text": "The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan city, China in December 2019 and thereafter its spillover across the world has created a global pandemic and public health crisis. Today, it appears as a threat to human civilization. Scientists and medical practitioners across the world are involved to trace out the origin and evolution of SARS-CoV-2 (also called 2019 novel coronavirus and referred as 2019-nCoV), its transmission route, cause of pathogenicity, and possible remedial action. In this work, we aim to find out the origin, evolutionary patternthat led to its pathogenicity and possible transmission pathway of 2019-nCoV. To achieve the aims we conducted a large-scale deep phylogenetic analysis on the 162 complete Orthocoronavirinae genomes consisting of four genera namely Alphacoronavirus, Betacoronavirus, Deltacoronavirus and Gammacoronavirus, their gene trees analysis and subsequently genome and gene recombination analyses. Our analyses revealed that i) bat, pangolin and anteater are the natural hosts of 2019-nCoV, ii) outbreak of 2019-nCoV took place via inter-intra species transmission mode, iii) host-specific adaptive mutation made 2019-nCoV more virulent, and the presence of widespread recombination events led to the evolution of new 2019-nCoV strain and/or could be determinant of its pathogenicity. Highlights Orthocoronavirinae genome phylogeny revealed that bat, pangolin and anteater are natural reservoir hosts of novel coronavirus (2019-nCoV/SARS-CoV-2). Host-specific adaptive mutation occurred among the coronaviruses. Transmission of 2019-nCoV to human took place by inter-intra species mode of transmission. Presence of widespread recombination events led to the evolution of new 2019-nCoV strain and/or could be determinant of its pathogenicity.", "title": "Deep phylogenetic analysis of Orthocoronavirinae genomes traces the origin, evolution and transmission route of 2019 novel coronavirus", "pid": "fs07zdu6", "bm25_score": 214.62457275390625}, {"text": "Before the severe acute respiratory syndrome outbreak in 2003, coronaviruses (CoVs) were not considered to be highly pathogenic to humans. However, it was this epidemic that highlighted this group of viruses and included them among the causative agents of emerging epidemic diseases. In addition, in 2012, another new CoV responsible for the Middle East respiratory syndrome was identified. Both infections were considered a threat to global health security. At present, the third epidemic caused by a CoV is being faced. This new CoV, called 2019-nCoV, was originated in the city of Wuhan, China, and has been linked to severe respiratory infections in humans. Thanks to the collaboration of experts worldwide, more information about this virus and its infection is reported each day, which allows modifying the recommendations for its prevention and treatment, without forgetting that the ultimate goal is to control this epidemic. In this review, the important aspects of this new coronavirus, 2019-nCoV, and its disease, COVID-19, have been summarized with the information available up to February 2020.", "title": "COVID-19: The outbreak caused by a new coronavirus.", "pid": "r6a6ro7w", "bm25_score": 214.6201934814453}, {"text": "The emergence of an unusual Corona virus (COVID-19) flu pandemic starting in China in December 2019, spreading all around the globe is a major threat to public health The investigations have shown this virus originated from a seafood market in Wuhan However, the unavailability of medicines for the new disease is a big challenge all around An attempt has been made in the present article to familiarise about the morphology of the virus The study of effect of pH, temperature and relative humidity is also depicted Various preventive measures have also been discussed The natural dietary measures suggested in the paper would be very beneficial to improve and boost the immunity of the mankind", "title": "Study of Morphological Nature of Coronavirus: Causes and Prevention", "pid": "6i4b5ydo", "bm25_score": 214.61581420898438}, {"text": "To investigate the genetic diversity, time origin, and evolutionary history of the 2019‐nCoV outbreak in China and Thailand, a total of 12 genome sequences of the virus with known sampling date (24 December 2019 and 13 January 2020) and geographic location (primarily Wuhan city, Hubei Province, China, but also Bangkok, Thailand) were analyzed. Phylogenetic and likelihood‐mapping analyses of these genome sequences were performed. On the basis of our results, the star‐like signal and topology of 2019‐nCoV may be indicative of potentially large “first generation” human‐to‐human virus transmission. We estimated that 2019‐nCoV likely originated in Wuhan on 9 November 2019 (95% credible interval: 25 September 2019 and 19 December 2019), and that Wuhan is the major hub for the spread of the 2019‐nCoV outbreak in China and elsewhere. Our results could be useful for designing effective prevention strategies for 2019‐nCoV in China and beyond.", "title": "Potential of large “first generation” human‐to‐human transmission of 2019‐nCoV", "pid": "475nei28", "bm25_score": 214.614501953125}]}
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"zx28gr34": 0, "zxvim4t8": 0, "zxx7tikz": 2, "zytu7wue": 0}, "bm25_results": [{"text": "We don't know if changing seasons will help stem the outbreak, says Michael Le Page", "title": "Will heat kill the coronavirus?", "pid": "0pujch9v", "bm25_score": 216.47994995117188}, {"text": "BACKGROUND: There is sufficient epidemiological and biological evidence of increased human susceptibility to viral pathogens such as Middle East respiratory syndrome coronavirus, respiratory syncytial virus, human metapneumovirus and influenza virus, in cold weather. The pattern of outbreak of the coronavirus disease 2019 (COVID-19) in China during the flu season is further proof that meteorological conditions may potentially influence the susceptibility of human populations to coronaviruses, a situation that may become increasingly evident as the current global pandemic of COVID-19 unfolds. MAIN BODY: A very rapid spread and high mortality rates have characterized the COVID-19 pandemic in countries north of the equator where air temperatures have been seasonally low. It is unclear if the currently high rates of COVID-19 infections in countries of the northern hemisphere will wane during the summer months, or if fewer people overall will become infected with COVID-19 in countries south of the equator where warmer weather conditions prevail through most of the year. However, apart from the influence of seasons, evidence based on the structural biology and biochemical properties of many enveloped viruses similar to the novel severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 (aetiology of COVID-19), support the higher likelihood of the latter of the two outcomes. Other factors that may potentially impact the rate of virus spread include the effectiveness of infection control practices, individual and herd immunity, and emergency preparedness levels of countries. CONCLUSION: This report highlights the potential influence of weather conditions, seasons and non-climatological factors on the geographical spread of cases of COVID-19 across the globe.", "title": "A close look at the biology of SARS-CoV-2, and the potential influence of weather conditions and seasons on COVID-19 case spread", "pid": "eiek6olk", "bm25_score": 215.67767333984375}, {"text": "Objective: To investigate the meteorological condition for incidence and spread of 2019-nCoV infection, to predict the epidemiology of the infectious disease, and to provide a scientific basis for prevention and control measures against the new disease. Methods: The meteorological factors during the outbreak period of the novel coronavirus pneumonia in Wuhan in 2019 were collected and analyzed, and were confirmed with those of Severe Acute Respiratory Syndrome (SARS) in China in 2003. Data of patients infected with 2019-nCoV and SARS coronavirus were collected from WHO website and other public sources. Results: This study found that the suitable temperature range for 2019-nCoV coronavirus survival is (13-24 degree Celsius), among which 19 degree Celsius lasting about 60 days is conducive to the spread between the vector and humans; the humidity range is 50%-80%, of which about 75% humidity is conducive to the survival of the coronavirus; the suitable precipitation range is below 30 mm/ month. Cold air and continuous low temperature over one week are helpful for the elimination of the virus. The prediction results show that with the approach of spring, the temperature in north China gradually rises, and the coronavirus spreads to middle and high latitudes along the temperature line of 13-18 degree Celsius. The population of new coronavirus infections is concentrated in Beijing, Tianjin, Hebei, Jiangsu, Zhejiang, Shanghai and other urban agglomerations. Starting from May 2020, the Beijing-Tianjin-Hebei urban agglomeration, the Central China Zhengzhou-Wuhan urban agglomeration, the eastern Jiangsu-Zhejiang-Shanghai urban agglomeration, and the southern Pearl River Delta urban agglomeration are all under a high temperature above 24 degree Celsius, which is not conducive to the survival and reproduction of coronaviruses, so the epidemic is expected to end. Conclusions: A wide range of continuous warm and dry weather is conducive to the survival of 2019-nCoV. The coming of spring, in addition to the original Wuhan-Zhengzhou urban agglomeration in central China, means that the prevention and control measures in big cities located in mid-latitude should be strengthened, especially the monitoring of transportation hubs. The Pearl River Delta urban agglomeration is a concentrated area of population in south China, with a faster temperature rise than those in mid-high latitudes, and thus the prevention in this area should be prioritized. From a global perspective, cities with a mean temperature below 24 degree Celsius are all high-risk cities for 2019-nCoV transmission before June.", "title": "Analysis of meteorological conditions and prediction of epidemic trend of 2019-nCoV infection in 2020", "pid": "60qmiwjm", "bm25_score": 215.61927795410156}, {"text": "", "title": "Do Humidity and Temperature Impact the Spread of the Novel Coronavirus?", "pid": "3dgd54xr", "bm25_score": 215.575927734375}, {"text": "Predicting COVID-19 epidemic development in the upcoming warm season has attracted much attention in the hope of providing helps to fight the epidemic. It requires weather (environmental) factors to be included in prediction models, but there are few models to achieve it successfully. In this study, we proposed a new concept of environmental infection rate (RE), based on floating time of respiratory droplets in the air and inactivation rate of virus to solve the problem. More than half of the particles in the droplets can float in the atmosphere for 1-2 hours. The prediction results showed that high RE values (>3.5) are scattered around 30N in winter (Dec.-Feb.). As the weather warms, its distribution area expands and extends to higher latitudes of northern hemisphere, reaching its maximum in April, and then shrinking northward. These indicated that the spread of COVID-19 in most parts of the northern hemisphere is expected to decline after Apr., but the risks in high latitudes will remain high in May. In the south of southern hemisphere, the RE values tend to subside from Apr. to July. The high modeled RE values up to July, however, suggested that warmer weather will not stop COVID-19 from spreading. Public health intervention is needed to overcome the outbreak.", "title": "Warmer weather and global trends in the coronavirus COVID-19", "pid": "fj3a2y1o", "bm25_score": 215.5178985595703}, {"text": "(1) Background: The virulence of coronavirus diseases due to viruses like SARS-CoV or MERS-CoV decreases in humid and hot weather. The putative temperature dependence of infectivity by the new coronavirus SARS-CoV-2 or covid-19 has a high predictive medical interest. (2) Methods: External temperature and new covid-19 cases in 21 countries and in the French administrative regions were collected from public data. Associations between epidemiological parameters of the new case dynamics and temperature were examined using an ARIMA model. (3) Results: We show that, in the first stages of the epidemic, the velocity of contagion decreases with country- or region-wise temperature. (4) Conclusions: Results indicate that high temperatures diminish initial contagion rates, but seasonal temperature effects at later stages of the epidemy remain questionable. Confinement policies and other eviction rules should account for climatological heterogeneities, in order to adapt the public health decisions to possible geographic or seasonal gradients.", "title": "Temperature Decreases Spread Parameters of the New Covid-19 Case Dynamics", "pid": "03s9spbi", "bm25_score": 215.38629150390625}, {"text": "Coronavirus spread is more serious in urban metropolitan cities compared to rural areas. It is observed from the data on the infection rate available in the various sources that the cold and dry conditions accelerate the spread of coronavirus. In the present work, the existing theory of respiratory droplet drying is used to propose the mechanism of virus spread under various climates and the indoor environment conditions which plays a greater role in the virus spread. This concept is assessed using four major parameters such as population density, climate severity, the volume of indoor spaces, and air-conditioning usage which affect the infection spread and mortality using the data available for various states of India. Further, it is analysed using the data from various states in India along with the respective climatic conditions. It is found that under some indoor scenarios, the coronaviruses present in the respiratory droplets become active due to size reduction that occurs both in sessile and airborne droplet nuclei causing an increase in the spread. Understanding this mechanism will be very useful to take the necessary steps to reduce the rate of transmission by initiating corrective measures and maintaining the required conditions in the indoor built environment.", "title": "The contribution of dry indoor built environment on the spread of Coronavirus: Data from various Indian states", "pid": "poh1y6o7", "bm25_score": 215.3821258544922}, {"text": "Pandemic enveloped RNA Novel Corona Virus' 2019 (SARS-CoV-2) appears as a beating reed which induce overwhelming outbreak all over the world since November 2019 to till date. Inherent Immunity developed by traditional food habit, exposure to various antigens and vitamin D induced sunlight exposure. Meteorological parameters are the important factors which influencing the severe acute respiratory syndrome (SARS) like infectious disease. Aim of this review to enhance our knowledge and explore the association among build up immunity, weather parameters and Corona virus disease (COVID-19) death. In this review we emphasize role of meteorological factor included degree of sun exposure and effect of temperature on enveloped lipid bi-layer structure of Novel corona virus. These meteorological factors and inherent immunity may have impact on SARS-CoV-2 incidence among South East Asian including Bangladeshi. In summary, this study suggests that temperature-humidity variation, inherent immunity and lower life expectancy of South East Asia may be important.", "title": "Sub-continental Atmosphere and Inherent Immune System may have Impact on Novel Corona Virus' 2019 (nCovid-19) Prevalence in South East Asia.", "pid": "ww1rgcds", "bm25_score": 215.32032775878906}, {"text": "The new coronavirus, called 2019-nCoV, is a new type of virus that was first identified in Wuhan, China, in December 2019. Environmental conditions necessary for survival and spread of 2019-nCoV are somewhat transparent but unlike animal coronaviruses. We are poorly aware of their survival in environment and precise factors of their transmission. Countries located in east and west of globe did not have a significant impact on prevalence of disease among communities, and on the other hand, north and south have provided a model for relative prediction of disease outbreaks. The 2019-nCoV can survive for up to 9 days at 25 °C, and if this temperature rises to 30 °C, its lifespan will be shorter. The 2019-nCoV is sensitive to humidity, and lifespan of viruses in 50% humidity is longer than that of 30%. Also, temperature and humidity are important factors influencing the COVID-19 mortality rate and may facilitate 2019-nCoV transmission. Thus, considering the available and recent evidence, it seems that low temperatures, as well as dry and unventilated air, may affect stability and transmissibility of 2019-nCoV.", "title": "Environmental concern regarding the effect of humidity and temperature on 2019-nCoV survival: fact or fiction", "pid": "zqsfw75p", "bm25_score": 215.3003387451172}, {"text": "The COVID-19 pandemic has affected most countries of the world. As corona viruses are highly prevalent in the cold season, the question remains whether or not the pandemic will improve with increasing temperatures in the Northern hemisphere. We use data from a primary care registry of almost 15,000 patients over 20 years to retrieve information on viral respiratory infection outbreaks. Our analysis suggests that the severity of the pandemic will be softened by the seasonal change to summer.", "title": "Will the COVID-19 pandemic slow down in the Northern hemisphere by the onset of summer? An epidemiological hypothesis", "pid": "iztm1z6g", "bm25_score": 215.2655029296875}, {"text": "The undefendable outbreak of novel coronavirus (SARS-COV-2) lead to a global health emergency due to its higher transmission rate and longer symptomatic duration, created a health surge in a short time. Since Nov 2019 the outbreak in China, the virus is spreading exponentially everywhere. The current study focuses on the relationship between environmental parameters and the growth rate of COVID-19. The statistical analysis suggests that the temperature changes retarded the growth rate and found that -6.28{degrees}C and +14.51{degrees}C temperature is the favorable range for COVID-19 growth. Gutenberg- Richter's relationship is used to estimate the mean daily rate of exceedance of confirmed cases concerning the change in temperature. Temperature is the most influential parameter that reduces the growth at the rate of 13-16 cases/day with a 1{degrees}C rise in temperature.", "title": "Does weather affect the growth rate of COVID-19, a study to comprehend transmission dynamics on human health", "pid": "r1yjphnn", "bm25_score": 215.25189208984375}, {"text": "", "title": "Coronavirus, Climate Change, and a Bit of Hope", "pid": "zibyhw7e", "bm25_score": 215.19451904296875}, {"text": "Objective: many potential factors contribute to the outbreak of COVID-19.It aims to explore the effects of various meteorological factors on the incidence of COVID-19. Methods: Taking Hubei province of China as an example, where COVID-19 was first reported and there were the most cases, we collected 53 days of confirmed cases (total 67773 cases) and ten meteorological parameters up to March 10. Correlation analysis and linear regression were used to judge the relationship of meteorological factors and increment of COVID-19 confirmed cases. Results: Under 95% CI, the increment of confirmed cases in Hubei were correlated with four meteorological parameters of average pressure, average temperature, minimum temperature and average water vapor pressure (equivalent to absolute humidity).The average pressure was positively correlated with the increment (r=+0.358).The negative correlations included average temperature (r=-0.306), minimum temperature (r=-0.347), and average water vapor pressure (r=-0.326). The linear regression results show if minimum temperature increases by 1℃, the incremental confirmed cases in Hubei decreases by 72.470 units on average. Conclusion: Statistically, the incidence of COVID-19 was correlated with average pressure, average temperature, minimum temperature and average water vapor pressure. It is positively correlated with the average pressure and negatively correlated with the other three parameters. Compared with relative humidity, 2019-nCov is more sensitive to water vapor pressure. The reason why the epidemic situation in Hubei expanded rapidly is significantly related to the climate characteristics of low temperature and dryness of Hubei in winter.", "title": "Meteorological factors correlate with transmission of 2019-nCoV: Proof of incidence of novel coronavirus pneumonia in Hubei Province, China", "pid": "lmjaldcs", "bm25_score": 215.1695098876953}, {"text": "Assessment of the risks posed by severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) on surfaces requires data on survival of this virus on environmental surfaces and on how survival is affected by environmental variables, such as air temperature (AT) and relative humidity (RH). The use of surrogate viruses has the potential to overcome the challenges of working with SARS-CoV and to increase the available data on coronavirus survival on surfaces. Two potential surrogates were evaluated in this study; transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) were used to determine effects of AT and RH on the survival of coronaviruses on stainless steel. At 4 degrees C, infectious virus persisted for as long as 28 days, and the lowest level of inactivation occurred at 20% RH. Inactivation was more rapid at 20 degrees C than at 4 degrees C at all humidity levels; the viruses persisted for 5 to 28 days, and the slowest inactivation occurred at low RH. Both viruses were inactivated more rapidly at 40 degrees C than at 20 degrees C. The relationship between inactivation and RH was not monotonic, and there was greater survival or a greater protective effect at low RH (20%) and high RH (80%) than at moderate RH (50%). There was also evidence of an interaction between AT and RH. The results show that when high numbers of viruses are deposited, TGEV and MHV may survive for days on surfaces at ATs and RHs typical of indoor environments. TGEV and MHV could serve as conservative surrogates for modeling exposure, the risk of transmission, and control measures for pathogenic enveloped viruses, such as SARS-CoV and influenza virus, on health care surfaces.", "title": "Effects of air temperature and relative humidity on coronavirus survival on surfaces.", "pid": "tjplc5j6", "bm25_score": 215.14866638183594}, {"text": "The seasonality of influenza viruses and endemic human coronaviruses was tracked over an 8-year period to assess key epidemiologic reduction points in disease incidence for an urban area in the northeast United States. Patients admitted to a pediatric hospital with worsening respiratory symptoms were tested using a multiplex PCR assay from nasopharyngeal swabs. The additive seasonal effects of outdoor temperatures and indoor relative humidity (RH) were evaluated. The 8-year average peak activity of human coronaviruses occurred in the first week of January, when droplet and contact transmission was enabled by the low indoor RH of 20-30%. Previous studies have shown that an increase in RH to 50% has been associated with markedly reduced viability and transmission of influenza virus and animal coronaviruses. As disease incidence was reduced by 50% in early March, to 75% in early April, to greater than 99% at the end of April, a relationship was observed from colder temperatures in January with a low indoor RH to a gradual increase in outdoor temperatures in April with an indoor RH of 45-50%. As a lipid-bound, enveloped virus with similar size characteristics to endemic human coronaviruses, SARS-CoV-2 should be subject to the same dynamics of reduced viability and transmission with increased humidity. In addition to the major role of social distancing, the transition from lower to higher indoor RH with increasing outdoor temperatures could have an additive effect on the decrease in SARS-CoV-2 cases in May. Over the 8-year period of this study, human coronavirus activity was either zero or >99% reduction in the months of June through September, and the implication would be that SARS-Cov-2 may follow a similar pattern.", "title": "The Seasonal End of Human Coronavirus Hospital Admissions with Implications for SARS-CoV-2", "pid": "3xw4qjoy", "bm25_score": 215.14376831054688}, {"text": "Abstract The undefendable outbreak of novel coronavirus (SARS-COV-2) lead to a global health emergency due to its higher transmission rate and longer symptomatic duration, created a health surge in a short time. Since Nov 2019 the outbreak in China, the virus is spreading exponentially everywhere. The current study focuses on the relationship between environmental parameters and the growth rate of COVID-19. The statistical analysis suggests that the temperature changes retarded the growth rate and found that -6.28°C and +14.51°C temperature is the favorable range for COVID-19 growth. Gutenberg- Richter's relationship is used to estimate the mean daily rate of exceedance of confirmed cases concerning the change in temperature. Indeed, temperature is the most influential parameter that reduces the growth at the rate of 13-17 cases/day with a 1°C rise in temperature.", "title": "Does weather affect the growth rate of COVID-19, a study to comprehend transmission dynamics on human health", "pid": "w7ycc07b", "bm25_score": 215.14126586914062}, {"text": "It is well-known that atmospheric pollution, first and foremost the particulate matter (PM), causes serious diseases in humans China’s metropolises and Italy’s Po Valley have in fact achieved a concerning degree of notoriety thanks to runaway air pollution problems The spread of viral respiratory diseases is facilitated in polluted environments, an example of which is the respiratory syncytial virus bronchiolitis In this opinion paper, we consider the possible relationship between air pollution, primarily airborne PM10–2 5, and the spread of the novel coronavirus in Northern Italy If it is true that the novel coronavirus remains active from some hours to several days on various surfaces, it is logical to postulate that the same can occur when it is adsorbed or absorbed by the atmospheric particulate matter, which may also help carry the virus into the human respiratory system As the Earth presents us with a very high bill to pay, governments and other authorities need to take prompt action to counter excessive pollution levels, both in Italy and in other countries", "title": "Novel Coronavirus: How Atmospheric Particulate Affects Our Environment and Health", "pid": "lnwc8mfg", "bm25_score": 215.07809448242188}, {"text": "Pandemic enveloped RNA Novel Corona Virus' 2019 (SARS-CoV-2) appears as a beating reed which induce overwhelming outbreak all over the world since November 2019 to till date. Inherent Immunity developed by traditional food habit, exposure to various antigens and vitamin D induced sunlight exposure. Meteorological parameters are the important factors which influencing the severe acute respiratory syndrome (SARS) like infectious disease. Aim of this review to enhance our knowledge and explore the association among build up immunity, weather parameters and Corona virus disease (COVID-19) death. In this review we emphasize role of meteorological factor included degree of sun exposure and effect of temperature on enveloped lipid bi-layer structure of Novel corona virus. These meteorological factors and inherent immunity may have impact on SARS-CoV-2 incidence among South East Asian including Bangladeshi. In summary, this study suggests that temperature-humidity variation, inherent immunity and lower life expectancy of South East Asia may be important.", "title": "Sub-continental Atmosphere and Inherent Immune System may have Impact on Novel Corona Virus' 2019 (nCovid-19) Prevalence in South East Asia", "pid": "p8p6e72k", "bm25_score": 215.06341552734375}, {"text": "Scientists and doctors have observed for thousands of years that some diseases, such as polio and influenza, rise and fall with the seasons But why? Ongoing research in animals and humans suggests a variety of causes, including changes in the environment (like pH, temperature, and humidity) and even seasonal and daily changes to our own immune systems Figuring out those answers could one day make all the difference in minimizing the impact of infectious disease outbreaks—such as coronavirus disease 2019", "title": "How diseases rise and fall with the seasons—and what it could mean for coronavirus", "pid": "zespmk29", "bm25_score": 215.05918884277344}, {"text": "UV (ultraviolet) light is an important factor should be considered to predict coronavirus epidemic growth pace. UV is different from weather temperature since UV is electromagnetic wavelength from 10 nm to 400 nm in size, shorter than of visible lights. For some people, UV light can lead to cancer from unprotected sun exposure, however, for tropical people, which have been used to live in such condition, have resisted from negative effect high UV index. Moreover, UV has the capability to inactivate virus. This conclusion has been discussed deeply with biological experts. Although UV light has the ability to inactivate viruses, it may be meaningless in areas with high air pollution where UV light turns into heat.", "title": "UV light influences covid-19 activity through big data: trade offs between northern subtropical, tropical, and southern subtropical countries", "pid": "odbi4yvz", "bm25_score": 215.0515899658203}, {"text": "Recent literature has suggested that climate conditions have considerably significant influences on the transmission of coronavirus COVID-19. However, there is a lack of comprehensive study that investigates the relationships between multiple weather factors and the development of COVID-19 pandemic while excluding the impact of social factors. In this paper, we study the relationships between six main weather factors and the infection statistics of COVID-19 on 250 cities in Mainland China. Our correlation analysis using weather and infection statistics indicates that all the studied weather factors are correlated with the spread of COVID-19, where precipitation shows the strongest correlation. We also build a weather-aware predictive model that forecasts the number of infected cases should there be a second wave of the outbreak in Mainland China. Our predicted results show that cities located in different geographical areas are likely to be challenged with the second wave of COVID-19 at very different time periods and the severity of the outbreak varies to a large degree, in correspondence with the varying weather conditions.", "title": "The Weather Impacts the Outbreak of COVID-19 in Mainland China", "pid": "akb96git", "bm25_score": 215.04112243652344}, {"text": "Using a model developed for estimating solar inactivation of viruses of biodefense concerns, we calculated the expected inactivation of SARS‐CoV‐2 virus, cause of COVID‐19 pandemic, by artificial UVC and by solar ultraviolet radiation in several cities of the world during different times of the year. The UV sensitivity estimated here for SARS‐CoV‐2 is compared with those reported for other ssRNA viruses, including influenza A virus. The results indicate that SARS‐CoV‐2 aerosolized from infected patients and deposited on surfaces could remain infectious outdoors for considerable time during the winter in many temperate‐zone cities, with continued risk for re‐aerosolization and human infection. Conversely, the presented data indicate that SARS‐CoV‐2 should be inactivated relatively fast (faster than influenza A) during summer in many populous cities of the world, indicating that sunlight should have a role in the occurrence, spread rate, and duration of coronavirus pandemics.", "title": "Estimated Inactivation of Coronaviruses by Solar Radiation With Special Reference to COVID‐19", "pid": "az7f7zgr", "bm25_score": 215.0030975341797}, {"text": "Preliminary evidence suggests that climate may modulate the transmission of SARS-CoV-2. Yet it remains unclear whether seasonal and geographic variations in climate can substantially alter the pandemic trajectory, given high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic probing different scenarios based on known coronavirus biology. We find that while variations in weather may be important for endemic infections, during the pandemic stage of an emerging pathogen the climate drives only modest changes to pandemic size. A preliminary analysis of non-pharmaceutical control measures indicates that they may moderate the pandemic-climate interaction via susceptible depletion. Our findings suggest, without effective control measures, strong outbreaks are likely in more humid climates and summer weather will not substantially limit pandemic growth.", "title": "Susceptible supply limits the role of climate in the early SARS-CoV-2 pandemic", "pid": "aiwxlxzt", "bm25_score": 214.98995971679688}, {"text": "Environmental factors, including seasonal climatic variability, can strongly impact on spatio-temporal patterns of infectious disease outbreaks, but relationships between Covid-19 dynamics and climate remain controversial. We assessed the impact of temperature and humidity on the global patterns of Covid-19 early outbreak dynamics during January-March 2020. Here we show that Covid-19 growth rates peaked in temperate regions of the Northern Hemisphere with mean temperature of ~5 C, and specific humidity of 4-6 g/m3 during the outbreak period, while they were lower both in warmer/wetter and colder/dryer regions. Relationships between Covid-19 and climate were robust to the potential confounding effects of air pollution and socio-economic variables, including population size, density and health expenditure. The strong relationship between local climate and Covid-19 growth rates suggests the possibility of seasonal variation in the spatial pattern of outbreaks, with temperate regions of the Southern Hemisphere becoming at particular risk of severe outbreaks during the austral autumn-winter.", "title": "Climate affects global patterns of COVID-19 early outbreak dynamics", "pid": "fcaeoyxd", "bm25_score": 214.9573516845703}, {"text": "Since the World Health Organization has declared the current outbreak of the novel coronavirus (COVID-19) a global pandemic, some have been anticipating that the mitigation could happen in the summer like seasonal influenza, while medical solutions are still in a slow progress. Experimental studies have revealed a few evidences that coronavirus decayed quickly under the exposure of heat and humidity. This study aims to carry out an epidemiological investigation to establish the association between meteorological factors and COVID-19 in high risk areas of the United States (U.S.). We analyzed daily new confirmed cases of COVID-19 and seven meteorological measures in top 50 U.S. counties with the most accumulative confirmed cases from March 22, 2020 to April 22, 2020. Our analyses indicate that each meteorological factor and COVID-19 more likely have a nonlinear association rather than a linear association over the wide ranges of temperature, relative humidity, and precipitation observed. Average temperature, minimum relative humidity, and precipitation were better predictors to address the meteorological impact on COVID-19. By including all the three meteorological factors in the same model with their lagged effects up to 3 days, the overall impact of the average temperature on COVID-19 was found to peak at 68.45 °F and decrease at higher degrees, though the overall relative risk percentage (RR %) reduction did not become significantly negative up to 85 °F. There was a generally downward trend of RR % with the increase of minimum relative humidity; nonetheless, the trend reversed when the minimum relative humidity exceeded 91.42%. The overall RR % of COVID-19 climbed to the highest level of 232.07% (95% confidence interval = 199.77, 267.85) with 1.60 inches of precipitation, and then started to decrease. When precipitation exceeded 1.85 inches, its impact on COVID-19 became significantly negative. Our findings alert people to better have self-protection during the pandemic rather than expecting that the natural environment can curb coronavirus for human beings.", "title": "Meteorological impacts on the incidence of COVID-19 in the U.S.", "pid": "miyvn7vd", "bm25_score": 214.93124389648438}, {"text": "As the number of confirmed cases of Coronavirus disease 2019 (COVID-19) continues to increase, there has been a rising concern regarding the effect of weather conditions, especially over the upcoming summer, on the transmission of this disease. In this study, we assess the transmission of COVID-19 under different weather conditions by investigating the propagation of infectious respiratory droplets. A comprehensive mathematical model is established to explore their evaporation, heat transfer and kinematics under different temperature, humidity and ventilation conditions. The transmitting pathway of COVID-19 through respiratory droplets is divided into short-range droplet contacts and long-range aerosol exposure. We show that the effect of weather conditions is not monotonic: low temperature and high humidity facilitate droplet contact transmission, while high temperature and low humidity promote the formation of aerosol particles and accumulation of particles with a diameter of 2.5 m or less (PM2.5). Our model suggests that the 6 ft of social distance recommended by the Center for Disease Control and Prevention (CDC) may be insufficient in certain environmental conditions, as the droplet spreading distance can be as long as 6 m (19.7 ft) in cold and humid weather. The results of this study suggest that the current pandemic may not ebb in the summer of the northern hemisphere without proper intervention, as there is an increasing chance of aerosol transmission. We also emphasize that the meticulous design of building ventilation systems is critical in containing both the droplet contact infections and aerosol exposures.", "title": "COVID-19: Effects of weather conditions on the propagation of respiratory droplets", "pid": "tyhtdawb", "bm25_score": 214.87806701660156}, {"text": "Coronavirus disease 2019 (COVID19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV2), it was first identified in 2019 in Wuhan, China and has resulted in the 2019-20 coronavirus pandemic. As of March 1, 2020, 79,968 patients in China and 7169 outside of China had tested positive for COVID19 and a mortality rate of 3.6% has been observed amongst Chinese patients. Its primary mode of transmission is via respiratory droplets from coughs and sneezes. The virus can remain viable for up to three days on plastic and stainless steel or in aerosols for upto 3 hours and is relatively more stable than the known human coronaviruses. It is stable in faeces at room temperature for at least 1-2 days and can be stable in infected patients for up to 4 days. Heat at 56 degree Celsius kills the SARS coronavirus at around 10000 units per 15 minutes. Thus, temperature is an important factor in survival of COVID19 virus and this article focuses on understanding the relationship between temperature and COVID19 transmission from the data available between January-March 2020.", "title": "Effects of temperature on COVID-19 transmission", "pid": "ycrrsr5c", "bm25_score": 214.87744140625}, {"text": "On February 1, 2020, China announced a novel coronavirus CoVID-19 outbreak to the public. CoVID-19 was classified as an epidemic by the World Health Organization (WHO). Although the disease was discovered and concentrated in Hubei Province, China, it was exported to all of the other Chinese provinces and spread globally. As of this writing, all plans have failed to contain the novel coronavirus disease, and it has continued to spread to the rest of the world. This study aimed to explore and interpret the effect of environmental and metrological variables on the spread of coronavirus disease in 30 provinces in China, as well as to investigate the impact of new China regulations and plans to mitigate further spread of infections. This article forecasts the size of the disease spreading based on time series forecasting. The growing size of CoVID-19 in China for the next 210 days is estimated by predicting the expected confirmed and recovered cases. The results revealed that weather conditions largely influence the spread of coronavirus in most of the Chinese provinces. This study has determined that increasing temperature and short-wave radiation would positively increase the number of confirmed cases, mortality rate, and recovered cases. The findings of this study agree with the results of our previous study.", "title": "The correlation between the spread of COVID-19 infections and weather variables in 30 Chinese provinces and the impact of Chinese government mitigation plans", "pid": "al7gffw2", "bm25_score": 214.84439086914062}, {"text": "The novel coronavirus (SARS-CoV-2/ 2019-nCoV) identified in Wuhan, China, in December 2019 has caused great damage to public health and economy worldwide with over 140,000 infected cases up to date. Previous research has suggested an involvement of meteorological conditions in the spread of droplet-mediated viral diseases, such as influenza. However, as for the recent novel coronavirus, few studies have discussed systematically about the role of daily weather in the epidemic transmission of the virus. Here, we examine the relationships of meteorological variables with the severity of the outbreak on a worldwide scale. The confirmed case counts, which indicates the severity of COVID-19 spread, and four meteorological variables, i.e., air temperature, relative humidity, wind speed, and visibility, were collected daily between January 20 and March 11 (52 days) for 430 cities and districts all over China, 21 cities/ provinces in Italy, 21 cities/ provinces in Japan, and 51 other countries around the world. Four different time delays of weather (on the day, 3 days ago, 7 days ago, and 14 days ago) as to the epidemic situation were taken for modeling and we finally chose the weather two weeks ago to model against the daily epidemic situation as its correlated with the outbreak best. Taken Chinese cities as a discovery dataset, it was suggested that temperature, wind speed, and relative humidity combined together could best predict the epidemic situation. The meteorological model could well predict the outbreak around the world with a high correlation (r2>0.6) with the real data. Using this model, we further predicted the possible epidemic situation in the future 12 days in several high-latitude cities with potential outbreak. This model could provide more information for government's future decisions on COVID-19 outbreak control.", "title": "Roles of meteorological conditions in COVID-19 transmission on a worldwide scale", "pid": "3svnvozz", "bm25_score": 214.84127807617188}, {"text": "As new cases of COVID-19 are being confirmed pressure is mounting to increase understanding of the factors underlying the spread the disease. Using data on local transmissions until the 23rd of March 2020, we develop an ensemble of 200 ecological niche models to project monthly variation in climate suitability for spread of SARS-CoV-2 throughout a typical climatological year. Although cases of COVID-19 are reported all over the world, most outbreaks display a pattern of clustering in relatively cool and dry areas. The predecessor SARS-CoV-1 was linked to similar climate conditions. Should the spread of SARS CoV-2 continue to follow current trends, asynchronous seasonal global outbreaks could be expected. According to the models, temperate warm and cold climates are more favorable to spread of the virus, whereas arid and tropical climates are less favorable. However, model uncertainties are still high across much of sub- Saharan Africa, Latin America and South East Asia. While models of epidemic spread utilize human demography and mobility as predictors, climate can also help constrain the virus. This is because the environment can mediate human-to-human transmission of SARS-CoV-2, and unsuitable climates can cause the virus to destabilize quickly, hence reducing its capacity to become epidemic.", "title": "Spread of SARS-CoV-2 Coronavirus likely to be constrained by climate", "pid": "jjdtuofy", "bm25_score": 214.79954528808594}, {"text": "Several studies have confirmed the impact of weather conditions on the evolution of the Covid-19 pandemic. We wanted to verify this phenomenon in the city of Oran in Algeria, which experienced its first case of Covid19 on March 19, 2020. The data studied are the new Covid19 cases, the average, minimum and maximum temperatures, as well as the relative humidity rate. A first analysis of the data with a Spearman rank correlation test did not yield significant results. Taking into account the average incubation period to adjust the data made it possible, during a second analysis, to show that the minimum temperature is significantly correlated with the new cases of Covid19 in Oran. This study can help establish prevention policies against Covid19, especially during fall in temperatures in autumn and winter.", "title": "Impact of meteorological parameters on the Covid-19 incidence. The case of the city of Oran, Algeria.", "pid": "zvvwwc0r", "bm25_score": 214.79330444335938}, {"text": "We test the hypothesis of COVID-19 contagion being influenced by meteorological parameters such as temperature or humidity. We analysed data at high spatial resolution (regions in Italy and counties in the USA) and found that while at low resolution this might seem the case, at higher resolution no correlation is found. Our results are consistent with a poor outdoors transmission of the disease. However, a possible indirect correlation between good weather and a decrease in disease spread may occur, as people spend longer time outdoors.", "title": "Weather variables impact on COVID-19 incidence", "pid": "hadnxjeo", "bm25_score": 214.79324340820312}, {"text": "Adaptation of species to new environments is governed by natural selection that discriminates among genetic variations and favors survival of the fittest. Here, we propose climate plays an important role in the evolution of SARS CoV-2 and the spread of COVID-19 all over the world which was previously not known. To understand the climatic factors responsible for shaping the molecular determinants of the novel coronavirus, genotyping SARS CoV-2 across different latitudes and Koppen’s climate is imperative. It seems this virus follows inverse latitudinal biodiversity gradient due to its preference towards Koppen’s temperate (C) and cold climate (D). Our molecular phylogenetic analysis revealed division of 176 SARS CoV-2 strains into two variant groups, G1 and G2, well defined by four mutations. Initially, SARS CoV-2 was restricted to a “humid-subtropical” (Cfa) climate of southeast China, which soon spread all over the world having C climate. Genomic information superimposed on global Koppen’s climate map elucidates that the gradation “humid-subtropical” (Cfa) and “marine-temperate” (Cfb) to “humid-continental” (Dfa-Dfb) climate drives the evolution of G1 into G2 variant group. It seems an early infection in Europe and USA is due to the dominance of C climate. Russia and North America were infected through linkage of C to D climate and South America from C to A climate. Our study elucidates viruses are sensitive to climate and combined genomic and climatic studies provide crucial information about the pathogenesis and natural spreading pathways during a pandemic which will enable us to take pre-emptive precautionary measures in such outbreaks. Graphical Abstract In Brief The authors elucidate adaptation of SARS CoV-2 to different climates by studying phylogenetics and the distribution of strains on Koppen’s climate map. Highlights SARS CoV-2 follows inverse latitudinal gradient. Phylogenetic network divides SARS CoV-2 strains into two variant groups, G1 and G2. G1 strains is restricted to Koppen’s “temperate” climate (mainly Cfa-Cfb). G2 strains has evolved from G1 to sustain in “humid-continental” (Dfa-Dfb) and “tropical-savannah” (Aw) climate.", "title": "Climatic-niche evolution of SARS CoV-2", "pid": "niq3hosc", "bm25_score": 214.7913818359375}, {"text": "The virus causing COVID-19 has spread rapidly worldwide and threatens millions of lives. It remains unknown if summer weather will reduce its continued spread, thereby alleviating strains on hospitals and providing time for vaccine development. Early insights from laboratory studies of related coronaviruses predicted that COVID-19 would decline at higher temperatures, humidity, and ultraviolet light. Using current, fine-scaled weather data and global reports of infection we developed a model that explained 36% of variation in early growth rates before intervention, with 17% based on weather or demography and 19% based on country-specific effects. We found that ultraviolet light was most strongly associated with lower COVID-19 growth rates. Projections suggest that, in the absence of intervention, COVID-19 will decrease temporarily during summer, rebound by autumn, and peak next winter. However, uncertainty remains high and the probability of a weekly doubling rate remained >20% throughout the summer in the absence of control. Consequently, aggressive policy interventions will likely be needed in spite of seasonal trends.", "title": "Seasonality and uncertainty in COVID-19 growth rates", "pid": "0vlzwksu", "bm25_score": 214.718017578125}, {"text": "Similar to other viruses, coronavirus infection triggers cellular stress responses in infected host cells. The close association of coronavirus replication with the endoplasmic reticulum (ER) results in the ER stress responses, which impose a challenge to the viruses. Viruses, in turn, have come up with various mechanisms to block or subvert these responses. One of the ER stress responses is inhibition of the global protein synthesis to reduce the amount of unfolded proteins inside the ER lumen. Viruses have evolved the capacity to overcome the protein translation shutoff to ensure viral protein production. Here, we review the strategies exploited by coronavirus to modulate cellular stress response pathways. The involvement of coronavirus-induced stress responses and translational control in viral pathogenesis will also be briefly discussed.", "title": "Regulation of Stress Responses and Translational Control by Coronavirus", "pid": "vj3wk150", "bm25_score": 214.70480346679688}, {"text": "The COVID-19 pandemic has led to six million confirmed cases by May 31, 2020. Impacts of regional weather and climate on epidemics have been investigated but need further study with new methods. We combined the number of monthly confirmed new cases and death with month, latitude, temperature, humidity, rainfall, and sunshine ultraviolet (UV) to explore the climate impact on epidemics in 116 countries and territories with at least 1000 confirmed cases. Correlation and regression analyses were performed with Stata. Humid subtropical climate regions had the most confirmed COVID-19 cases (24.4%). The case mortality in temperate marine regions was the highest (11.6%). Case-weighted means of the latitude, monthly maximum temperature, relative humidity, rainfall, and sunshine UV were 36.7 degrees, 20.5, 63%, 63mm, and 53.5, respectively. The case mortality was 7.44% in cold regions but only 4.68% in hot regions, 7.14% in rainy regions but only 3.86% in rainless regions, and 7.40% in cloudy regions but only 4.64% in sunny regions. Monthly confirmed cases increase as the temperature, rainfall, and sunshine UV rise in cold regions (r=0.34, 0.26, 0.26, respectively), but no correlation in hot regions. Every 1 increase in monthly maximum temperature leads to an increase in the natural logarithm of monthly confirmed new cases by 2.4% in cold regions. Monthly confirmed cases increase as the temperature, rainfall, and sunshine UV rise in arid regions (r=0.29, 0.28, 0.26, respectively), but no correlation in humid regions. Monthly confirmed new cases increase as the temperature and sunshine UV rise in rainy regions (r=0.30, 0.29), but no correlation in rainless regions. Monthly confirmed new deaths increase as the temperature and sunshine UV rise in cloudy regions (r=0.30, 0.30), but no correlation in sunny regions. It is wise to escape from an epicenter full of miasma to a hot sunny place in dry season without pollution. As peaking in the spring depends on the climate, the peak will go in the summer.", "title": "Impacts of regional climate on the COVID-19 pandemic", "pid": "k1l16pmm", "bm25_score": 214.70294189453125}, {"text": "Abstract Background The relation between weather conditions, viral transmission and seasonal activity of respiratory viruses is not fully understood. Objectives To investigate the impact of outdoor weather in a temperate climate setting on the seasonal epidemiology of viruses causing respiratory tract infections, particularly influenza A (IFA). Study design In total, 20,062 clinical nasopharyngeal swab samples referred for detection of respiratory pathogens using a multiplex PCR panel, between October 2010 and July 2013, were included. Results of PCR detection were compared with local meteorological data for the same period. Results Low temperature and vapor pressure (VP) were associated with weekly incidence of IFA, respiratory syncytial virus, metapneumovirus, bocavirus and adenovirus but no association with relative humidity was found. The incidence of human rhinovirus and enterovirus was independent of temperature. During seasonal IFA outbreaks, the weekly drop of average temperature (compared with the week before) was strongly associated with the IFA incidence recorded the following week. Conclusion A sudden drop in outdoor temperature might activate the annual influenza epidemic in a temperate climate by facilitating aerosol spread in dry air. These conditions also seem to affect the incidence of other respiratory pathogens but not human rhino- or enterovirus, suggesting that routes of infection other than aerosol may be relevant for these agents.", "title": "A four year seasonal survey of the relationship between outdoor climate and epidemiology of viral respiratory tract infections in a temperate climate", "pid": "buhu5c41", "bm25_score": 214.70223999023438}, {"text": "The present study examines the impact of weather indicators on the COVID-19 outbreak in the majorly affected states of India. In this study, we hypothesize that the weather indicators could significantly influence the impact of the corona virus. The Kendall and Spearman rank correlation tests were chosen to conduct the statistical analysis. In this regard, we compiled a daily dataset including confirmed case counts, Recovered case counts, Deceased cases, Average Temperature, Maximum Relative Humidity, Maximum Wind Speed for six most affected states of India during the period of March 25, 2020 to April 24, 2020. We investigated that the average Humidity and Average Temperature seven days ago play a significant role in the recovery of coronavirus cases. The rise in average temperature will improve the recovery rate in the days to come. The cities with very high humidity levels or dry weather conditions have high probabilities of recovery from COVID-19. The findings of this research will help the policymakers to identify risky geographic areas and enforce timely preventive measures.", "title": "Impact of weather indicators on the COVID-19 outbreak: A multi-state study in India", "pid": "yi57n8nc", "bm25_score": 214.69248962402344}, {"text": "The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID-19 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle-income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time-based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short- and long-term interventions to manage outbreaks at the international, national, and subnational levels in the region.", "title": "Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare, and respond to COVID-19", "pid": "w5kjmw88", "bm25_score": 214.6332244873047}, {"text": "Using a model developed for estimating solar inactivation of viruses of biodefense concerns, we calculated the expected inactivation of SARS-CoV-2 virus, cause of COVID-19 pandemic, by artificial UVC and by solar ultraviolet radiation in several cities of the world during different times of the year. The UV sensitivity estimated here for SARS-CoV-2 is compared with those reported for other ssRNA viruses, including influenza A virus. The results indicate that SARS-CoV-2 aerosolized from infected patients and deposited on surfaces could remain infectious outdoors for considerable time during the winter in many temperate-zone cities, with continued risk for re-aerosolization and human infection. Conversely, the presented data indicate that SARS-CoV-2 should be inactivated relatively fast (faster than influenza A) during summer in many populous cities of the world, indicating that sunlight should have a role in the occurrence, spread rate, and duration of coronavirus pandemics.", "title": "Estimated Inactivation of Coronaviruses by Solar Radiation With Special Reference to COVID-19", "pid": "7emv2bao", "bm25_score": 214.6331787109375}, {"text": "Using a model developed for estimating solar inactivation of viruses of biodefense concerns, we calculated the expected inactivation of SARS-CoV-2 virus, cause of COVID-19 pandemic, by artificial UVC and by solar ultraviolet radiation in several cities of the world during different times of the year. The UV sensitivity estimated here for SARS-CoV-2 is compared with those reported for other ssRNA viruses, including influenza A virus. The results indicate that SARS-CoV-2 aerosolized from infected patients and deposited on surfaces could remain infectious outdoors for considerable time during the winter in many temperate-zone cities, with continued risk for re-aerosolization and human infection. Conversely, the presented data indicate that SARS-CoV-2 should be inactivated relatively fast (faster than influenza A) during summer in many populous cities of the world, indicating that sunlight should have a role in the occurrence, spread rate and duration of coronavirus pandemics.", "title": "Estimated Inactivation of Coronaviruses by Solar Radiation With Special Reference to COVID-19", "pid": "4xijeti6", "bm25_score": 214.6228790283203}, {"text": "Results from two studies involving challenge with respiratory syncytial viruses showed that volunteers who developed colds were more sensitive to a visually distracting pattern presented prior to virus challenge than were volunteers who did not get a cold. Volunteers with sub-clinical infections reported more illusions after virus challenge than they had done before, whereas uninfected volunteers and those with colds tended to report fewer illusions on the second test. These effects did not occur when volunteers were challenged with either a coronavirus or rhinovirus. Overall, the results confirm that behavioural measures may be related to susceptibility to subsequent illness, and that viral infections may influence visual perception. They also show that the effects vary according to the nature of the infecting agent, which agrees with results from studies looking at other aspects of behaviour.", "title": "The common cold, pattern sensitivity and contrast sensitivity.", "pid": "7d9umzl2", "bm25_score": 214.61514282226562}, {"text": "", "title": "Coronavirus and Malta: weathering the storm", "pid": "5s3en8g5", "bm25_score": 214.60775756835938}, {"text": "Abstract Background Our understanding of climate factors and their links to the Middle East Respiratory Syndrome Coronavirus (MERS-CoV) outbreaks is incomplete. This study aimed to estimate the monthly incidence of MERS-CoV cases and to investigate their correlation to climate factors. Methods The study used aggregated monthly MERS-CoV cases that reported to the Saudi Center for Disease Prevention and Control from the Riyadh Region between November 1, 2012 and December 31, 2018. Data on the meteorological situation throughout the study period was calculated based on Google reports on the Riyadh Region (24.7136°N, 46.6753°E). The Poisson regression was used to estimate the incidence rate ratio (IRR) and its 95% confidence intervals (CI) for each climate factor. Results A total of 712 MERS-CoV cases were included in the analysis (mean age 54.2±9.9 years), and more than half (404) (56.1%) MERS-CoV cases were diagnosed during a five-month period from April to August. The highest peak timing positioned in August 2015, followed by April 2014, June 2017, March 2015, and June 2016. High temperatures (IRR=1.054, 95% CI: 1.043–1.065) and a high ultraviolet index (IRR=1.401, 95% CI: 1.331–1.475) were correlated with a higher incidence of MERS-CoV cases. However, low relative humidity (IRR=0.956, 95% CI: 0.948–0.964) and low wind speed (IRR=0.945, 95% CI: 0.912–0.979) were correlated with a lower incidence of MERS-CoV cases. Conclusion The novel coronavirus, MERS-CoV, is influenced by climate conditions with increasing incidence between April and August. High temperature, high ultraviolet index, low wind speed, and low relative humidity are contributors to increased MERS-CoV cases. The climate factors must be evaluated in hospitals and community settings and integrated into guidelines to serve as source of control measures to prevent and eliminate the risk of infection.", "title": "Climate factors and incidence of Middle East respiratory syndrome coronavirus", "pid": "5czqwdwl", "bm25_score": 214.5916748046875}, {"text": "Twenty-four adult volunteers were inoculated with nasal drops containing a coronavirus of 229E serotype to determine the differences in the clinical and physiological reactions which occur between clinically infected, sub-clinically infected and non-infected individuals. Thirteen volunteers were clinically infected, 8 had sub-clinical infections and 3 were uninfected. Nasal airway resistance and the temperature of the nasal mucosa increased in all infected subjects both with and without symptoms: the core temperature increased also but to a lesser extent. Mucosal blood flow and nasal secretion increased only in those with symptoms. The albumin content of the nasal secretion increased in the clinically infected, suggesting that it was derived, partially at least, from the circulation. The nasal cycle of variation in airway resistance between the two sides of the nose was observed in all three groups but increased only in those clinically infected.", "title": "Changes in human nasal mucosa during experimental coronavirus common colds.", "pid": "hvkwlgbk", "bm25_score": 214.55819702148438}, {"text": "The main route of transmission of SARS CoV infection is presumed to be respiratory droplets. However the virus is also detectable in other body fluids and excreta. The stability of the virus at different temperatures and relative humidity on smooth surfaces were studied. The dried virus on smooth surfaces retained its viability for over 5 days at temperatures of 22–25°C and relative humidity of 40–50%, that is, typical air-conditioned environments. However, virus viability was rapidly lost (>3 log(10)) at higher temperatures and higher relative humidity (e.g., 38°C, and relative humidity of >95%). The better stability of SARS coronavirus at low temperature and low humidity environment may facilitate its transmission in community in subtropical area (such as Hong Kong) during the spring and in air-conditioned environments. It may also explain why some Asian countries in tropical area (such as Malaysia, Indonesia or Thailand) with high temperature and high relative humidity environment did not have major community outbreaks of SARS.", "title": "The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus", "pid": "x3b6j5d0", "bm25_score": 214.5545196533203}, {"text": "OBJECTIVE The causal agent for SARS is considered as a novel coronavirus that has never been described both in human and animals previously. The stability of SARS coronavirus in human specimens and in environments was studied. METHODS Using a SARS coronavirus strain CoV-P9, which was isolated from pharyngeal swab of a probable SARS case in Beijing, its stability in mimic human specimens and in mimic environment including surfaces of commonly used materials or in household conditions, as well as its resistance to temperature and UV irradiation were analyzed. A total of 10(6) TCID50 viruses were placed in each tested condition, and changes of the viral infectivity in samples after treatments were measured by evaluating cytopathic effect (CPE) in cell line Vero-E6 at 48 h after infection. RESULTS The results showed that SARS coronavirus in the testing condition could survive in serum, 1:20 diluted sputum and feces for at least 96 h, whereas it could remain alive in urine for at least 72 h with a low level of infectivity. The survival abilities on the surfaces of eight different materials and in water were quite comparable, revealing reduction of infectivity after 72 to 96 h exposure. Viruses stayed stable at 4 degrees C, at room temperature (20 degrees C) and at 37 degrees C for at least 2 h without remarkable change in the infectious ability in cells, but were converted to be non-infectious after 90-, 60- and 30-min exposure at 56 degrees C, at 67 degrees C and at 75 degrees C, respectively. Irradiation of UV for 60 min on the virus in culture medium resulted in the destruction of viral infectivity at an undetectable level. CONCLUSION The survival ability of SARS coronavirus in human specimens and in environments seems to be relatively strong. Heating and UV irradiation can efficiently eliminate the viral infectivity.", "title": "Stability of SARS coronavirus in human specimens and environment and its sensitivity to heating and UV irradiation.", "pid": "gp3ib74q", "bm25_score": 214.5529022216797}, {"text": "It is shown that the evaporation rate of a liquid sample containing the culture of coronavirus affects its survival on a substrate. Possible mechanisms of such influence can be due to the appearance of large, about 140 bar, non comprehensive capillary pressures and the associated dynamic forces during the movement of the evaporation front in a sample with the virus. A simulation of isothermal evaporation of a thin liquid sample based on the Stefan problem was performed. The comparison of simulation data and recent experiments on the coronavirus survival on various surfaces showed that the rate of isothermal evaporation of aqueous samples, which is higher for heat-conducting materials, correlates well with the lifetime of the coronavirus on these surfaces.", "title": "Isothermal evaporation rate of deposited liquid aerosols and the SARS-CoV-2 coronavirus survival", "pid": "80ev0j5a", "bm25_score": 214.5486297607422}, {"text": "The rapid global spread of the novel, pathogenic, SARS-CoV-2 causing the severe acute respiratory disease COVID-19, becomes a major health problem worldwide and pose the need for international predictive programs. Given the lack of both specific drugs and an efficient preventive vaccine, the expectation that SARS-CoV-2 transmission rate might decrease in temperate regions during summer, dominated the social scene. Here, we attempted a prediction of the worldwide spread of the infections based on climatic data, expressed by 19 bioclimatic variables. The calculated probability maps shown that potential areas of infection follow a shift from the Tropical to Temperate and Mediterranean Bioclimatic regions, and back to the Tropics again. Maps show an increased probability of infections in Europe, followed by an expansion covering areas of the Middle East and Northern Africa, as well as Eastern coastal areas of North America, South-Eastern coastal areas of Latin America and two areas of Southern Australia, and later return to areas of Southeastern Asia, in a manner similar to that of influenza strains (H3N2). Our approach may therefore be of value for the worldwide spread of SARS-CoV-2, suggesting an optimistic scenario of asynchronous seasonal global outbreaks, like other viral respiratory diseases. Consequently, we suggest the incorporation of a climatic impact in the design and implementation of public health policies. Maps of our model are available (constantly updated up to the saturation of the model) at: https://navaak.shinyapps.io/CVRisk/.", "title": "Climatic influences on the worldwide spread of SARS-CoV-2", "pid": "czh7xqph", "bm25_score": 214.54852294921875}, {"text": "Temperature and relative humidity are major factors determining virus inactivation in the environment. This article reviews inactivation data of coronaviruses on surfaces and in liquids from published studies and develops secondary models to predict coronaviruses inactivation as a function of temperature and relative humidity. A total of 102 D-values (time to obtain a log10 reduction of virus infectivity), including values for SARS-CoV-2, were collected from 26 published studies. The values obtained from the different coronaviruses and studies were found to be generally consistent. Five different models were fitted to the global dataset of D-values. The most appropriate model considered temperature and relative humidity. A spreadsheet predicting the inactivation of coronaviruses and the associated uncertainty is presented and can be used to predict virus inactivation for untested temperatures, time points or new coronavirus strains.", "title": "Modelling the thermal inactivation of viruses from the Coronaviridae family in suspensions or on surfaces with various relative humidities.", "pid": "4hbwg18z", "bm25_score": 214.53907775878906}, {"text": "The Coronaviridae family, an enveloped RNA virus family, and, more particularly, human coronaviruses (HCoV), were historically known to be responsible for a large portion of common colds and other upper respiratory tract infections. HCoV are now known to be involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates, elderly people and immunosuppressed patients. They have also been involved in nosocomial viral infections. In 2002–2003, the outbreak of severe acute respiratory syndrome (SARS), due to a newly discovered coronavirus, the SARS-associated coronavirus (SARS-CoV); led to a new awareness of the medical importance of the Coronaviridae family. This pathogen, responsible for an emerging disease in humans, with high risk of fatal outcome; underline the pressing need for new approaches to the management of the infection, and primarily to its prevention. Another interesting feature of coronaviruses is their potential environmental resistance, despite the accepted fragility of enveloped viruses. Indeed, several studies have described the ability of HCoVs (i.e. HCoV 229E, HCoV OC43 (also known as betacoronavirus 1), NL63, HKU1 or SARS-CoV) to survive in different environmental conditions (e.g. temperature and humidity), on different supports found in hospital settings such as aluminum, sterile sponges or latex surgical gloves or in biological fluids. Finally, taking into account the persisting lack of specific antiviral treatments (there is, in fact, no specific treatment available to fight coronaviruses infections), the Coronaviridae specificities (i.e. pathogenicity, potential environmental resistance) make them a challenging model for the development of efficient means of prevention, as an adapted antisepsis-disinfection, to prevent the environmental spread of such infective agents. This review will summarize current knowledge on the capacity of human coronaviruses to survive in the environment and the efficacy of well-known antiseptic-disinfectants against them, with particular focus on the development of new methodologies to evaluate the activity of new antiseptic-disinfectants on viruses.", "title": "Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies", "pid": "bp6st31f", "bm25_score": 214.52426147460938}, {"text": "The 2020 coronavirus pandemic is developing at different paces throughout the world. Some areas, like the Caribbean Basin, have yet to see the virus strike at full force. When it does, there is reasonable evidence to suggest the consequent COVID‐19 outbreaks will overwhelm healthcare systems and economies. This is particularly concerning in the Caribbean as pandemics can have disproportionately higher mortality impacts on lower and middle income countries. Preliminary observations from our team and others suggest that temperature and climatological factors could influence the spread of this novel coronavirus, making spatiotemporal predictions of its infectiousness possible. This review studies geographic and time‐based distribution of known respiratory viruses in the Caribbean Basin in an attempt to foresee how the pandemic will develop in this region. This review is meant to aid in planning short‐ and long‐term interventions to manage outbreaks at the international, national and sub‐national levels in the region. This article is protected by copyright. All rights reserved.", "title": "Weathering the pandemic: How the Caribbean Basin can use viral and environmental patterns to predict, prepare and respond to COVID‐19", "pid": "gan10za0", "bm25_score": 214.49588012695312}, {"text": "On February 1, 2020, China announced a novel coronavirus CoVID-19 outbreak to the public. CoVID-19 was classified as an epidemic by the World Health Organization (WHO). Although the disease was discovered and concentrated in Hubei Province, China, it was exported to all of the other Chinese provinces and spread globally. As of this writing, all plans have failed to contain the novel coronavirus disease, and it has continued to spread to the rest of the world. This study aimed to explore and interpret the effect of environmental and metrological variables on the spread of coronavirus disease in 30 provinces in China, as well as to investigate the impact of new China regulations and plans to mitigate further spread of infections. This article forecasts the size of the disease spreading based on time series forecasting. The growing size of CoVID-19 in China for the next 210 days is estimated by predicting the expected confirmed and recovered cases. The results revealed that weather conditions largely influence the spread of coronavirus in most of the Chinese provinces. This study has determined that increasing temperature and short-wave radiation would positively increase the number of confirmed cases, mortality rate, and recovered cases. The findings of this study agree with the results of our previous study.", "title": "The correlation between the spread of COVID-19 infections and weather variables in 30 Chinese provinces and the impact of Chinese government mitigation plans.", "pid": "6a9to2w9", "bm25_score": 214.48739624023438}, {"text": "Recently, anovel coronavirus virus disease (COVID-19) has become a serious concern for global public health hazards. Infectious disease outbreaks such as COVID-19can also significantly affect the sustainable development of urban areas. Several factors such as population density and climatology parameters could potentially affect the spread of the COVID-19. In this study, a combination of the virus optimization algorithm (VOA) and adaptive network-based fuzzy inference system (ANFIS) to investigate the effects of various climate-related factors and population density on the spread of the COVID-19. For this purpose, data on the climate-related factors and the confirmed infected cases by the COVID-19across the U.S counties was used.The results show that the variable defined for the population density had the most significant impact on the performance of the developed models, which is an indication of the importance social distancing in reducing the infection rate and spread rate of the COVID-19. Among the climatology parameters, an increase in the maximum temperature was found to reduce the infection rate. Average temperature, minimum temperature, precipitation, and average wind speed were not found to significantly affect the spread of the COVID-19 while an increase in the relative humidity was found to slightly increase the infection rate. The findings of this research show that it could be expected to have reduced infection rate over the summer season. However, it should be noted that the models developed in this study were based on limited one-month data. Future investigation can benefit from using more comprehensive data covering a wider range for the input variables.", "title": "Determinants of the infection rate of the COVID-19 in the U.S. using ANFIS and virus optimization algorithm (VOA)", "pid": "w8gjfomz", "bm25_score": 214.4838409423828}, {"text": "The COVID-19 pandemic has outspread obstreperously in India. As of June 04, 2020, more than 2 lakh cases have been confirmed with a death rate of 2.81%. It has been noticed that, out of each 1000 tests, 53 result positively infected. In order to investigate the impact of weather conditions on daily transmission occurring in India, daily data of Maximum (TMax), Minimum (TMin), Mean (TMean) and Dew Point Temperature (TDew), Diurnal Temperature range (TRange), Average Relative Humidity, Range in Relative Humidity, and Wind Speed (WS) over 9 most affected cities are analysed in several time frames: weather of that day, 7, 10, 12, 14, 16 days before transmission. Spearman rank correlation (r) shows significant but low correlation with most of the weather parameters, however, comparatively better association exists on 14 days lag. Diurnal range in Temperature and Relative Humidity shows non-significant correlation. Analysis shows, COVID-19 cases likely to be increased with increasing air temperature, however role of humidity is not clear. Among weather parameters, Minimum Temperature was relatively better correlate than other. 80% of the total confirmed cases were registered when TMax, TMean, TMin, TRange, TDew, and WS on 12-16 days ago vary within a range of 33.6-41.3 deg C, 29.8-36.5 deg C, 24.8-30.4 deg C, 7.5-15.2 deg C, 18.7-23.6 deg C, and 4.2-5.75 m/s respectively, hence, it gives an idea of susceptible weather conditions for such transmission in India. Using Support Vector Machine based regression, the daily cases are profoundly estimated with more than 80% accuracy, which indicate that coronavirus transmission cannot be well linearly correlated with any single weather parameters, rather multivariate non-linear approach must be employed. Accounting lag of 12-16 days, the association found to be excellent, thus depict that there is an incubation period of 12-16 days for coronavirus transmission in Indian scenario.", "title": "Impact of Daily Weather on COVID-19 outbreak in India", "pid": "uj8a09t3", "bm25_score": 214.4822235107422}, {"text": "BACKGROUND: Previous reports have suggested that transmission of SARS-CoV-2 is reduced by higher temperatures and higher humidity. We analyzed case-data from the United States to investigate effects of temperature, precipitation, and UV Light on community transmission of SARS-CoV-2. METHODS: Daily reported cases of SARS-CoV-2 across the United States from 01/22/2020 to 04/03/2020 were analyzed. We used negative binomial regression modelling to investigate whether daily maximum temperature, precipitation, UV Index and the incidence 5 days later were related. We performed sensitivity analyses at 3 days, 7 days and 9 days to assess transmission lags. RESULTS: A maximum temperature greater than 52°F on a given day was associated with a lower rate of new cases at 5 days[IRR: 0.85(0.76,0.96)p=0.009]. Among observations with daily temperatures below 52°F, there was a significant inverse association between the maximum daily temperature and the rate of cases at 5 days [IRR 0.98(0.97,0.99)p=0.001]. The rate of new cases was predicted to be lower for theoretical states that maintained a stable maximum daily temperature above 52°F with a predicted 23-fewer cases per-million per-day by 25 days of the epidemic. A 1-unit higher UV index was associated with a lower rate at 5 days [IRR 0.97(0.95,0.99)p=0.004]. Precipitation was not associated with a greater rate of cases at 5 days [IRR 0.98(0.89,1.08)p=0.65]. CONCLUSION: The incidence of disease declines with increasing temperature up until 52°F and is lower at warmer versus cooler temperatures. However, the association between temperature and transmission is small and transmission is likely to remain high at warmer temperatures.", "title": "Maximum Daily Temperature, Precipitation, Ultra-Violet Light and Rates of Transmission of SARS-Cov-2 in the United States", "pid": "7vwjcp53", "bm25_score": 214.48109436035156}, {"text": "Quantifying the role of temperature and humidity on the transmission of SARS-CoV-2 has been confounded by a lack of controlled experiments, the sudden rise in detection rates, and changing weather patterns. In this paper we focus our analysis on data from Colombia, which presents unique economic, demographic and geological characteristics that favor the study of temperature and humidity upon SARS-CoV-2 transmission: the weather varies dramatically across five natural regions (from the Caribbean coast and the Amazon rainforest to the Andean mountains), there are no pronounced seasons, there is a central port of entry, the use of public transportation dominates inter- and intracity travel, and indoor climate control is rare. While only controlled experiments can precisely quantify the role of temperature and humidity upon SARS-CoV-2 transmission, we observe significant attenuation of transmission in climates with sustained daily maximum temperatures above 30 degrees Celsius and simultaneous mean relative humidity below 78%. We hypothesize that temperature and relative humidity comodulate the infectivity of SARS-CoV-2 within respiratory droplets.", "title": "The transmission of SARS-CoV-2 is likely comodulated by temperature and by relative humidity", "pid": "jlop0lui", "bm25_score": 214.4716339111328}, {"text": "The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health.", "title": "Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials", "pid": "4d4l6mzl", "bm25_score": 214.46884155273438}, {"text": "Coronaviruses (CoV) are a large family of viruses causing a spectrum of disease ranging from the common cold to more severe diseases as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). The recent outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency worldwide. SARS-CoV-2, the virus responsible for COVID-19, is spread by human-to-human transmission via droplets or direct contact. However, since SARS-CoV-2 (as well as other coronaviruses) has been found in the fecal samples and anal swabs of some patients, the possibility of fecal-oral (including waterborne) transmission need to be investigated and clarified. This scoping review was conducted to summarize research data on CoV in water environments. A literature survey was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded more than 3000 records, but only 12 met the criteria and were included and discussed in this review. In detail, the review captured relevant studies investigating three main areas: 1) CoV persistence/survival in waters; 2) CoV occurrence in water environments; 3) methods for recovery of CoV from waters. The data available suggest that: i) CoV seems to have a low stability in the environment and is very sensitive to oxidants, like chlorine; ii) CoV appears to be inactivated significantly faster in water than non-enveloped human enteric viruses with known waterborne transmission; iii) temperature is an important factor influencing viral survival (the titer of infectious virus declines more rapidly at 23°C-25 °C than at 4 °C); iv) there is no current evidence that human coronaviruses are present in surface or ground waters or are transmitted through contaminated drinking-water; v) further research is needed to adapt to enveloped viruses the methods commonly used for sampling and concentration of enteric, non enveloped viruses from water environments. The evidence-based knowledge reported in this paper is useful to support risk analysis processes within the drinking and wastewater chain (i.e., water and sanitation safety planning) to protect human health from exposure to coronavirus through water.", "title": "Coronavirus in water environments: Occurrence, persistence and concentration methods - A scoping review", "pid": "hn9fj8h8", "bm25_score": 214.46194458007812}, {"text": "Due to the close relationship between the incidence of infectious diseases by epidemics and environmental conditions, this research explores the temperature, evaporation, precipitation and regional climate effects on the local transmission of coronavirus SARS-CoV-2 inside 31 states and capital of Mexico since February 29 (national onset) to March 31, 2020. Statistical analysis was conducted to explore the association between the daily local COVID-19 confirmed positive cases (LCPC) and both climate characteristics and the daily weather reported by the regional meteorological stations. In this work, the local transmission ratio (LTR) was calculated with the regional LCPC divided by the number of the effective contagion days since regional onset in each state. The results showed a negative association between temperature (mean, max and min) and climate classification with both LCPC and LTR variables. The precipitation associated positively with LCPC and LTR. The associations between the climate classification with LCPC and LTR are statistically significant. The tropical climate (mean temperature around 25.95 °C and mean precipitation around 8.74 mm) delayed the regional onset. However, the regional onset in dry climates emerged earlier as consequence of the lower temperatures and higher precipitations (20.57 °C and 20.87 mm respectively) than the observed in the tropical climate. The fastest regional onsets were observed in tempered climates in states where the lowest temperatures and lowest precipitations were registered (19.65 °C and 8.48 mm respectively). Meteorological factors influenced the trend on the regional outbreaks in Mexican's states likely by the host predisposition and susceptibility during the cold winter season. In Mexico, the climate characteristics played a crucial role on the local infection during the phase 1 being the tempered regions (as Michoacán, Jalisco, Puebla, etc.) more vulnerable than the dry (as Chihuahua, Durango or Zacatecas, etc.) or tropical areas (as Colima, Campeche, Morelos etc.).", "title": "The temperature and regional climate effects on communitarian COVID-19 contagion in Mexico throughout phase 1", "pid": "uzx4rpjd", "bm25_score": 214.4618682861328}, {"text": "This paper investigates whether the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic could have been favored by specific weather conditions and other factors. It is found that the 2020 winter weather in the region of Wuhan (Hubei, Central China)-where the virus first broke out in December and spread widely from January to February 2020-was strikingly similar to that of the Northern Italian provinces of Milan, Brescia and Bergamo, where the pandemic broke out from February to March. The statistical analysis was extended to cover the United States of America, which overtook Italy and China as the country with the highest number of confirmed COronaVIrus Disease 19 (COVID-19) cases, and then to the entire world. The found correlation patterns suggest that the COVID-19 lethality significantly worsens (4 times on average) under weather temperatures between 4 &#8728; C and 12 &#8728; C and relative humidity between 60% and 80%. Possible co-factors such as median population age and air pollution were also investigated suggesting an important influence of the former but not of the latter, at least, on a synoptic scale. Based on these results, specific isotherm world maps were generated to locate, month by month, the world regions that share similar temperature ranges. From February to March, the 4-12 &#8728; C isotherm zone extended mostly from Central China toward Iran, Turkey, West-Mediterranean Europe (Italy, Spain and France) up to the United State of America, optimally coinciding with the geographic regions most affected by the pandemic from February to March. It is predicted that in the spring, as the weather gets warm, the pandemic will likely worsen in northern regions (United Kingdom, Germany, East Europe, Russia and North America) while the situation will likely improve in the southern regions (Italy and Spain). However, in autumn, the pandemic could come back and affect the same regions again. The Tropical Zone and the entire Southern Hemisphere, but in restricted colder southern regions, could avoid a strong pandemic because of the sufficiently warm weather during the entire year and because of the lower median age of their population. Google-Earth-Pro interactive-maps covering the entire world are provided as supplementary files.", "title": "Distribution of the SARS-CoV-2 Pandemic and Its Monthly Forecast Based on Seasonal Climate Patterns", "pid": "04rbtmmi", "bm25_score": 214.45852661132812}, {"text": "Previous research has identified a relationship between climate and occurrence of SARS‐CoV and MERS‐CoV cases, information that can be used to reduce the risk of infection. Using COVID‐19 notification and postcode data from New South Wales, Australia during the exponential phase of the epidemic in 2020, we used time series analysis to investigate the relationship between 749 cases of locally acquired COVID‐19 and daily rainfall, 9 a.m. and 3 p.m. temperature, and 9 a.m. and 3 p.m. relative humidity. Lower 9 a.m. relative humidity (but not rainfall or temperature) was associated with increased case occurrence; a reduction in relative humidity of 1% was predicted to be associated with an increase of COVID‐19 cases by 6.11%. During periods of low relative humidity, the public health system should anticipate an increased number of COVID‐19 cases.", "title": "The role of climate during the COVID‐19 epidemic in New South Wales, Australia", "pid": "380s4j70", "bm25_score": 214.4576416015625}, {"text": "Preliminary evidence suggests that climate may modulate the transmission of SARS-CoV-2. Yet it remains unclear whether seasonal and geographic variations in climate can substantially alter the pandemic trajectory, given high susceptibility is a core driver. Here, we use a climate-dependent epidemic model to simulate the SARS-CoV-2 pandemic probing different scenarios of climate-dependence based on known coronavirus biology. We find that while variations in humidity may be important for endemic infections, during the pandemic stage of an emerging pathogen such as SARS-CoV-2 climate may drive only modest changes to pandemic size and duration. Our results suggest that, in the absence of effective control measures, significant cases in the coming months are likely to occur in more humid (warmer) climates, irrespective of the climate-dependence of transmission and that summer temperatures will not substantially limit pandemic growth.", "title": "Susceptible supply limits the role of climate in the COVID-19 pandemic", "pid": "zxx7tikz", "bm25_score": 214.45361328125}, {"text": "A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 100,000 confirmed infections and 4000 fatalities (as of 10 March 2020). The outbreak has been declared a pandemic by the WHO on Mar 11, 2020. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterise our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures, and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.", "title": "Potential impact of seasonal forcing on a SARS-CoV-2 pandemic.", "pid": "28sgnyh1", "bm25_score": 214.45164489746094}, {"text": "A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 100,000 confirmed infections and 4000 fatalities (as of 10 March 2020). The outbreak has been declared a pandemic by the WHO on Mar 11, 2020. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterise our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures, and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.", "title": "Potential impact of seasonal forcing on a SARS-CoV-2 pandemic", "pid": "ac0whd9v", "bm25_score": 214.44113159179688}, {"text": "The COVID-19 disease, a respiratory disease transmitted by a new betacoronavirus SARS-CoV-2. As for other viral respiratory agents, SARS-CoV-2 spreads by person to person through respiratory droplets and direct contact and potentially by indirect contact through fomites. The goal of the current study is to evaluate whether the increase of temperature can influence the environmental endurance of SARS-CoV-2.We tested SARS-CoV-2 environmental stability in parallel at room temperature (RT, 20-25 Celsius degrees) and at average maximum temperature of June (JT) estimated at 28 Celsius degrees in Italy. The virus inoculated on plastic surface was harvested at predefined time-points and tested to evaluate viral titres on Vero cells by TCID50. Our results confirm that fomite transmission of the emerging SARS-CoV2 is possible, since the virus remains viable on surfaces up to 84 hours at both RT and JT. Moreover, a remarkable difference between the two temperatures exists, suggesting that virus vitality can be influenced by the environmental temperature. Our results support the hypothesis that in the hot season the increase of temperature could influence the environmental endurance of SARS-CoV2 and reduce Covid-19 transmission probability.", "title": "SARS-CoV-2 infection: the environmental endurance of the virus can be influenced by the increase of temperature", "pid": "h81b4imf", "bm25_score": 214.42955017089844}, {"text": "The present work describes spreading of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) at the tropical and temperate zones which are explained based on insolation energy, Particulate Matter (PM(2.5)), latitude, temperature, humidity, Population Density (PD), Human Development Index (HDI) and Global Health Security Index (GHSI) parameters. In order to analyze the spreading of SARS-CoV-2 by statistical data based on the confirmed positive cases which are collected between December 31, 2019 to April 25, 2020. The present analysis reveals that the outbreak of SARS-CoV-2 in the major countries lie on the Equator is 78,509 cases, the countries lie on the Tropic of Cancer is 62,930 cases (excluding China) and the countries lie on the Tropic of Capricorn is 22,842 cases. The tropical countries, which comes between the Tropic of Cancer and Tropic of Capricorn is reported to be 1,77,877 cases. The temperate zone countries, which are above and below the tropical countries are reported to be 25, 66,171 cases so, the pandemic analysis describes the correlation between latitude, temperate zones, PM(2.5) and local environmental factors. Hence, the temperature plays a pivotal role in the spreading of coronavirus at below 20 °C. The spreading of SARS-CoV-2 cases in Northern and Southern Hemispheres has inverse order against absorption of insolated energy. In temperate zone countries, the concentration of PM(2.5) at below 20 μg/m(3) has higher spreading rate of SARS-CoV-2 cases. The effect of insolation energy and PM(2.5), it is confirmed that the spreading of SARS-CoV-2 is explained by dumb-bell model and solid/liquid interface formation mechanism. The present meta-analysis also focuses on the impact of GHSI, HDI, PD and PM(2.5) on spreading of SARS-CoV-2 cases.", "title": "The effect of latitude and PM(2.5) on spreading of SARS-CoV-2 in tropical and temperate zone countries()", "pid": "0y62eqdx", "bm25_score": 214.41937255859375}, {"text": "Cell surface receptor engagement is a critical aspect of viral infection. This paper compares the dynamics of virus-receptor interactions for SARS-CoV (CoV1) and CoV2. At low (endosomal) pH, the binding free energy landscape of CoV1 and CoV2 interactions with the angiotensin-converting enzyme 2 (ACE2) receptor is almost the same. However, at neutral pH the landscape is different due to the loss of a pH-switch (His445Lys) in the receptor binding domain (RBD) of CoV2 relative to CoV1. Namely, CoV1 stabilizes a transition state above the bound state. In situations where small external strains are applied by, say, shear flow in the respiratory system, the off rate of the viral particle is enhanced. As a result, CoV1 virions are expected to detach from cell surfaces in time scales that are much faster than the time needed for other receptors to reach out and stabilize virus attachment. On the other hand, the loss of this pH-switch, which sequence alignments show is unique to CoV2, eliminates the transition state and allows the virus to stay bound to the ACE2 receptor for time scales compatible with the recruitment of additional ACE2 receptors diffusing in the cell membrane. This has important implications for viral infection and its pathology. CoV1 does not trigger high infectivity in the nasal area because it either rapidly drifts down the respiratory tract or is exhaled. By contrast, this novel mutation in CoV2 should not only retain the infection in the nasal cavity until ACE2-rich cells are sufficiently depleted, but also require fewer particles for infection. This mechanism explains observed longer incubation times, extended period of viral shedding, and higher rate of transmission. These considerations governing viral entry suggest that number of ACE2-rich cells in human nasal mucosa, which should be significantly smaller for children (and females relative to males), should also correlate with onset of viral load that could be a determinant of higher virus susceptibility. Critical implications for the development of new vaccines to combat current and future pandemics that, like SARS-CoV2, export evolutionarily successful strains via higher transmission rates by viral retention in nasal epithelium are also discussed.", "title": "Loss of pH switch unique to SARS-CoV2 supports unfamiliar virus pathology", "pid": "2dfiwo65", "bm25_score": 214.3911590576172}, {"text": "The spatial distribution of the COVID-19 infection in China cannot be explained solely by geographical distance and regulatory stringency. In this research we investigate how meteorological conditions and air pollution, as concurring factors, impact COVID-19 transmission, using data on new confirmed cases from 219 prefecture cities from January 24 to February 29, 2020. Results revealed a kind of nonlinear dose-response relationship between temperature and coronavirus transmission. We also found that air pollution indicators are positively correlated with new confirmed cases, and the coronavirus further spreads by 5-7% as the AQI increases by 10 units. Further analysis based on regional divisions revealed that in northern China the negative effects of rising temperature on COVID-19 is counteracted by aggravated air pollution. In the southern cities, the ambient temperature and air pollution have a negative interactive effect on COVID-19 transmission, implying that rising temperature restrains the facilitating effects of air pollution and that they jointly lead to a decrease in new confirmed cases. These results provide implications for the control and prevention of this disease and for the anticipation of another possible pandemic.", "title": "Effects of meteorological conditions and air pollution on COVID-19 transmission: Evidence from 219 Chinese cities.", "pid": "o6q2rkv7", "bm25_score": 214.3822021484375}, {"text": "Abstract The coronavirus pandemic, which has numerous global implications, has led people to believe that nothing will be the same as before. The present day is dominated by studies on determining the factors that affect, taking preventive actions, and trying to find an effective treatment on top priority. Meteorological parameters are among the crucial factors affecting infectious diseases. The present study examines the correlation between weather and coronavirus disease 2019 (COVID-19) by considering nine cities in Turkey. In this regard, temperature (°C), dew point (°C), humidity (%), and wind speed (mph) are considered as parameters of weather. Research states that the incubation period of COVID-19 varies from 1 day to 14 days. Therefore, the effects of each parameter within 1, 3, 7, and 14 days are examined. In addition, the population is included as an effective parameter for evaluation. The analyses are conducted based on Spearman's correlation coefficients. The results showed that the highest correlations were observed for population, wind speed 14 days ago, and temperature on the day, respectively. The study results may guide authorities and decision-makers on taking specific measures for the cities.", "title": "Impact of weather on COVID-19 pandemic in Turkey", "pid": "jxa9h27b", "bm25_score": 214.37391662597656}, {"text": "The novel coronavirus (COVID-19) has already spread to almost every country in the world and has infected over 3 million people. To understand the transmission mechanism of this highly contagious virus, it is necessary to study the potential factors, including meteorological conditions. Here, we present a machine learning approach to study the effect of temperature, humidity and wind speed on the number of infected people in the three most populous autonomous communities in Spain. We find that there is a moderate inverse correlation between temperature and the daily number of infections. This correlation manifests for temperatures recorded up to 6 days before the onset, which corresponds well to the known mean incubation period of COVID-19. We also show that the correlation for humidity and wind speed is not significant.", "title": "Effect of Temperature on the Transmission of COVID-19: A Machine Learning Case Study in Spain", "pid": "r9yrr45q", "bm25_score": 214.3709716796875}, {"text": "A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 80,000 confirmed infections and 2,700 fatalities (as of Feb 27, 2020). Imported cases and transmission clusters of various sizes have been reported globally suggesting a pandemic is likely. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterize our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.", "title": "Potential impact of seasonal forcing on a SARS-CoV-2 pandemic", "pid": "3p2dl8yf", "bm25_score": 214.37039184570312}, {"text": "Abstract Coronaviruses (CoV) are a large family of viruses causing a spectrum of disease ranging from the common cold to more severe diseases as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). The recent outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency worldwide. SARS-CoV-2, the virus responsible for COVID-19, is spread by human-to-human transmission via droplets or direct contact. However, since SARS-CoV-2 (as well as other coronaviruses) has been found in the fecal samples and anal swabs of some patients, the possibility of fecal-oral (including waterborne) transmission need to be investigated and clarified. This scoping review was conducted to summarize research data on CoV in water environments. A literature survey was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded more than 3000 records, but only 12 met the criteria and were included and discussed in this review. In detail, the review captured relevant studies investigating three main areas: 1) CoV persistence/survival in waters; 2) CoV occurrence in water environments; 3) methods for recovery of CoV from waters. The data available suggest that: i) CoV seems to have a low stability in the environment and is very sensitive to oxidants, like chlorine; ii) CoV appears to be inactivated significantly faster in water than non-enveloped human enteric viruses with known waterborne transmission; iii) temperature is an important factor influencing viral survival (the titer of infectious virus declines more rapidly at 23°C–25 °C than at 4 °C); iv) there is no current evidence that human coronaviruses are present in surface or ground waters or are transmitted through contaminated drinking-water; v) further research is needed to adapt to enveloped viruses the methods commonly used for sampling and concentration of enteric, non enveloped viruses from water environments. The evidence-based knowledge reported in this paper is useful to support risk analysis processes within the drinking and wastewater chain (i.e., water and sanitation safety planning) to protect human health from exposure to coronavirus through water.", "title": "Coronavirus in water environments: Occurrence, persistence and concentration methods - A scoping review", "pid": "eyf2dogw", "bm25_score": 214.36647033691406}, {"text": "Background: Most people raise a similar concern during this tough time of the COVID-19 pandemic caused by SARS-CoV-2 infection regarding when this outbreak will come to end. A recent thorough-general study on the success of China dealing with COVID-19 outbreak has concluded to recommend the need for a multi-sectoral approach to prevent future outbreaks of emerging infectious diseases including for the still-occurring COVID-19 outbreak with the initiative for the highest interest of the health of mankind Discussion: The prevalence of SARS-CoV as the predecessor of SARS-CoV-2 has been concluded to be more suitable in spring than autumn and winter, with nothing prevalence in summer. No coincidence that SARS-CoV-2 infection has outbreak around the world from January 2020 to the present, April 2020, as ever predicted to reoccur based on its predecessor, SARS-CoV, that have prevalence been high since January, February, March, April, until early May 2003. As opposed to other seasons, summer has low atmospheric pressure as its exemption that provenly causes virus inactivation. Conclusions: The denotative nature of SARS-CoV-2 seems to reflect its predecessor, SARS-CoV, which begins nearing the end of the year and reaches its optimum hence in spring, thereafter, finally ends in summer. Low atmospheric pressure in the summer impresses that it is the potential cause of ending the outbreak by deactivating SARS-CoV-2, apart from the hot temperature of weather. The knowledge to be gained here is further closely correlated to the fact that coronavirus is able to have genetic recombination that may bring about new genotypes and, consequently, outbreaks later occurring.", "title": "Any contribution of the season change to the spread of covid-19 caused by sars-cov-2?", "pid": "q3tc522t", "bm25_score": 214.36434936523438}, {"text": "This paper investigates the correlation between the high level of coronavirus SARS-CoV-2 infection accelerated transmission and lethality, and surface air pollution in Milan metropolitan area, Lombardy region in Italy. For January-April 2020 period, time series of daily average inhalable gaseous pollutants ozone (O3) and nitrogen dioxide (NO2), together climate variables (air temperature, relative humidity, wind speed, precipitation rate, atmospheric pressure field and Planetary Boundary Layer) were analyzed. In spite of being considered primarily transmitted by indoor bioaerosols droplets and infected surfaces or direct human-to-human personal contacts, it seems that high levels of urban air pollution, and climate conditions have a significant impact on SARS-CoV-2 diffusion. Exhibited positive correlations of ambient ozone levels and negative correlations of NO2 with the increased rates of COVID-19 infections (Total number, Daily New positive and Total Deaths cases), can be attributed to airborne bioaerosols distribution. The results show positive correlation of daily averaged O3 with air temperature and inversely correlations with relative humidity and precipitation rates. Viral genome contains distinctive features, including a unique N-terminal fragment within the spike protein, which allows coronavirus attachment on ambient air pollutants. At this moment it is not clear if through airborne diffusion, in the presence of outdoor and indoor aerosols, this protein \"spike\" of the new COVID-19 is involved in the infectious agent transmission from a reservoir to a susceptible host during the highest nosocomial outbreak in some agglomerated industrialized urban areas like Milan is. Also, in spite of collected data for cold season (winter-early spring) period, when usually ozone levels have lower values than in summer, the findings of this study support possibility as O3 can acts as a COVID-19 virus incubator. Being a novel pandemic coronavirus version, it might be ongoing during summer conditions associated with higher air temperatures, low relative humidity and precipitation levels.", "title": "Assessing the relationship between ground levels of ozone (O3) and nitrogen dioxide (NO2) with coronavirus (COVID-19) in Milan, Italy", "pid": "ksu2gjyb", "bm25_score": 214.3619384765625}, {"text": "The stability of human coronavirus 229E infectivity was maximum at pH 6.0 when incubated at either 4 or 33 degrees C. However, the influence of pH was more pronounced at 33 degrees C. Viral infectivity was completely lost after a 14-day incubation period at 22, 33, or 37 degrees C but remained relatively constant at 4 degrees C for the same length of time. Finally, the infectious titer did not show any significant reduction when subjected to 25 cycles of thawing and freezing. These studies will contribute to optimize virus growth and storage conditions, which will facilitate the molecular characterization of this important pathogen.", "title": "Effect of pH and temperature on the infectivity of human coronavirus 229E.", "pid": "jpw8f2op", "bm25_score": 214.3494873046875}, {"text": "Meteorological parameters are the critical factors affecting the transmission of infectious diseases such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and influenza. Consequently, infectious disease incidence rates are likely to be influenced by the weather change. This study investigates the role of Singapore's hot tropical weather in COVID-19 transmission by exploring the association between meteorological parameters and the COVID-19 pandemic cases in Singapore. This study uses the secondary data of COVID-19 daily cases from the webpage of Ministry of Health (MOH), Singapore. Spearman and Kendall rank correlation tests were used to investigate the correlation between COVID-19 and meteorological parameters. Temperature, dew point, relative humidity, absolute humidity, and water vapor showed positive significant correlation with COVID-19 pandemic. These results will help the epidemiologists to understand the behavior of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus against meteorological variables. This study finding would be also a useful supplement to help the local healthcare policymakers, Center for Disease Control (CDC), and the World Health Organization (WHO) in the process of strategy making to combat COVID-19 in Singapore.", "title": "Association of COVID-19 pandemic with meteorological parameters over Singapore", "pid": "pwul6lco", "bm25_score": 214.34127807617188}, {"text": "", "title": "Shedding ultraviolet light on coronavirus", "pid": "hat7u1bu", "bm25_score": 214.33795166015625}, {"text": "Previous research has identified a relationship between climate and occurrence of SARS-CoV and MERS-CoV cases, information that can be used to reduce the risk of infection. Using COVID-19 notification and postcode data from New South Wales, Australia during the exponential phase of the epidemic in 2020, we used time series analysis to investigate the relationship between 749 cases of locally acquired COVID-19 and daily rainfall, 9 a.m. and 3 p.m. temperature, and 9 a.m. and 3 p.m. relative humidity. Lower 9 a.m. relative humidity (but not rainfall or temperature) was associated with increased case occurrence; a reduction in relative humidity of 1% was predicted to be associated with an increase of COVID-19 cases by 6.11%. During periods of low relative humidity, the public health system should anticipate an increased number of COVID-19 cases.", "title": "The role of climate during the COVID-19 epidemic in New South Wales, Australia", "pid": "zbxo87y9", "bm25_score": 214.3370361328125}, {"text": "The spatial distribution of the COVID-19 infection in China cannot be explained solely by geographical distance and regulatory stringency. In this research we investigate how meteorological conditions and air pollution, as concurring factors, impact COVID-19 transmission, using data on new confirmed cases from 219 prefecture cities from January 24 to February 29, 2020. Results revealed a kind of nonlinear dose-response relationship between temperature and coronavirus transmission. We also found that air pollution indicators are positively correlated with new confirmed cases, and the coronavirus further spreads by 5-7% as the AQI increases by 10 units. Further analysis based on regional divisions revealed that in northern China the negative effects of rising temperature on COVID-19 is counteracted by aggravated air pollution. In the southern cities, the ambient temperature and air pollution have a negative interactive effect on COVID-19 transmission, implying that rising temperature restrains the facilitating effects of air pollution and that they jointly lead to a decrease in new confirmed cases. These results provide implications for the control and prevention of this disease and for the anticipation of another possible pandemic.", "title": "Effects of meteorological conditions and air pollution on COVID-19 transmission: Evidence from 219 Chinese cities", "pid": "4j47etsu", "bm25_score": 214.28305053710938}, {"text": "The pandemic of the COVID-19 disease extended from China across the north-temperate zone, and more recently to the tropics and southern hemisphere. We find no evidence that spread rates decline with temperatures above 20 oC, suggesting that the COVID-19 disease is unlikely to behave as a seasonal respiratory virus.", "title": "No Evidence for Temperature-Dependence of the COVID-19 Epidemic", "pid": "bnrmh1qs", "bm25_score": 214.28134155273438}, {"text": "This paper investigates whether the Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) pandemic could have been favored by specific weather conditions and other factors. It is found that the 2020 winter weather in the region of Wuhan (Hubei, Central China)—where the virus first broke out in December and spread widely from January to February 2020—was strikingly similar to that of the Northern Italian provinces of Milan, Brescia and Bergamo, where the pandemic broke out from February to March. The statistical analysis was extended to cover the United States of America, which overtook Italy and China as the country with the highest number of confirmed COronaVIrus Disease 19 (COVID-19) cases, and then to the entire world. The found correlation patterns suggest that the COVID-19 lethality significantly worsens (4 times on average) under weather temperatures between 4 °C and 12 °C and relative humidity between 60% and 80%. Possible co-factors such as median population age and air pollution were also investigated suggesting an important influence of the former but not of the latter, at least, on a synoptic scale. Based on these results, specific isotherm world maps were generated to locate, month by month, the world regions that share similar temperature ranges. From February to March, the 4–12 °C isotherm zone extended mostly from Central China toward Iran, Turkey, West-Mediterranean Europe (Italy, Spain and France) up to the United State of America, optimally coinciding with the geographic regions most affected by the pandemic from February to March. It is predicted that in the spring, as the weather gets warm, the pandemic will likely worsen in northern regions (United Kingdom, Germany, East Europe, Russia and North America) while the situation will likely improve in the southern regions (Italy and Spain). However, in autumn, the pandemic could come back and affect the same regions again. The Tropical Zone and the entire Southern Hemisphere, but in restricted colder southern regions, could avoid a strong pandemic because of the sufficiently warm weather during the entire year and because of the lower median age of their population. Google-Earth-Pro interactive-maps covering the entire world are provided as supplementary files.", "title": "Distribution of the SARS-CoV-2 Pandemic and Its Monthly Forecast Based on Seasonal Climate Patterns", "pid": "26gf4q1v", "bm25_score": 214.2738494873047}, {"text": "The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "title": "Coronaviruses widespread on nonliving surfaces: important questions and promising answers", "pid": "fxx5vrg0", "bm25_score": 214.26246643066406}, {"text": "COVID-19 is having a great impact on public health, mortality and economy worldwide, in spite of the efforts to prevent its epidemy. The SARS-CoV-2 genome is different from that of MERS-CoV and SARS-CoV, although also expected to spread differently according to meteorological conditions. Our main goal is to investigate the role of some meteorological variables on the expansion of this outbreak. In this study, an exponential model relating the number of accumulated confirmed cases and time was considered. The rate of COVID-19 spread, using as criterion the doubling time of the number of confirmed cases, was used as dependent variable in a linear model that took four independent meteorological variables: temperature, humidity, precipitation and wind speed. Only China cases were considered, to control both cultural aspects and containment policies. Confirmed cases and the 4 meteorological variables were gathered between January 23 and March 1 (39 days) for the 31 provinces of Mainland China. Several periods of time were sampled for each province, obtaining more than one value for the rate of disease progression. Two different periods of time were tested, of 12 and 15 days, along with 3 and 5 different starting points in time, randomly chosen. The median value for each meteorological variable was computed, using the same time period; models with adjusted R square above 0.75 were selected. The rate of progression and doubling time were computed and used to fit a linear regression model. Models were evaluated using alpha=0.05. Results indicate that the doubling time correlates positively with temperature and inversely with humidity, suggesting that a decrease in the rate of progression of COVID-19 with the arrival of spring and summer in the north hemisphere. A 20oC increase is expected to delay the doubling time in 1.8 days. Those variables explain 18% of the variation in disease doubling time; the remaining 82% may be related to containment measures, general health policies, population density, transportation or cultural aspects.", "title": "Role of temperature and humidity in the modulation of the doubling time of COVID-19 cases", "pid": "qz2joxys", "bm25_score": 214.25994873046875}, {"text": "Abstract Meteorological parameters are the critical factors affecting the transmission of infectious diseases such as Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome (SARS), and influenza. Consequently, infectious disease incidence rates are likely to be influenced by the weather change. This study investigates the role of Singapore's hot tropical weather in COVID-19 transmission by exploring the association between meteorological parameters and the COVID-19 pandemic cases in Singapore. This study uses the secondary data of COVID-19 daily cases from the webpage of Ministry of Health (MOH), Singapore. Spearman and Kendall rank correlation tests were used to investigate the correlation between COVID-19 and meteorological parameters. Temperature, dew point, relative humidity, absolute humidity, and water vapor showed positive significant correlation with COVID-19 pandemic. These results will help the epidemiologists to understand the behavior of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) virus against meteorological variables. This study finding would be also a useful supplement to help the local healthcare policymakers, Center for Disease Control (CDC), and the World Health Organization (WHO) in the process of strategy making to combat COVID-19 in Singapore.", "title": "Association of COVID-19 pandemic with meteorological parameters over Singapore", "pid": "1bxt21za", "bm25_score": 214.24964904785156}, {"text": "The present study presents a view on exploring the relationship pattern between COVID 19 daily cases with weather parameters and air pollutants in mainland India. We consider mean temperature, relative humidity, solar radiation, rainfall, wind speed, PM2.5, PM10, SO2, NO2 and CO as independent variable and daily COVID 19 cases as dependent variable for 18 states during 18th march to 30th April, 2020.After dividing the dataset for 0 to 10 day, 10 to 25 days and 0 to 44 days, the current study applied Akaike s Information Criteria (AIC) and Generalized Additive Model (GAM) to examine the kind of relationship between independent variables with COVID 19 cases. Initially GAM model result shows variables like temperature and solar radiation has positive relation (p<0.05) in 0 to 10 days study with daily cases. In 25 days dataset it significantly shows that temperature has positive relation above 23 degree centigrade, SO2 has a negative relationship and relative humidity has negative (between 30% to 45% and > 60%) and a positive relationship (45% to 60%) with COVID 19 cases (p=0.05). 44 days dataset has six parameters includes temperature as positive, relative humidity as negative (between 0 to 45%) and then positive (after >45%), NO2 as Positive (0 to 35 microgram/m3) followed by negative trend (after > 40 microgram/m3), SO2 and rainfall as negative relation. After sensitive analysis, it is found that weather variables like relative humidity, solar radiation and rainfall are more sensitive than temperature and wind speed. Whereas pollutants like NO2, PM2.5, PM10 and CO are more sensitive variables than SO2 in this study. In summary this study finds temperature, relative humidity, solar radiation, wind speed, SO2, PM2.5, and CO may be important factors associated with COVID 19 pandemic. Keywords: Weather parameter, Air pollutants, Daily COVID 19 cases, Akaike s Information Criteria (AIC), Generalized Additive Model (GAM) and Sensitive analysis.", "title": "Examine the impact of weather and ambient air pollutant parameters on daily case of COVID-19 in India.", "pid": "trf6zyd1", "bm25_score": 214.2420196533203}, {"text": "", "title": "Potential Impact of Climate on Novel Corona Virus (COVID-19) Epidemic", "pid": "hnbnr731", "bm25_score": 214.2362060546875}, {"text": "COVID-19 is a new type of coronavirus disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It originated in China in the month of December 2019 and quickly started to spread within the country. On 31st December 2019, it was first reported to country office of World Health Organization (WHO) in China. Since then, it has spread to most of the countries around the globe. However, there has been a recent rise in trend in believing that it would go away during summer days, which has not yet been properly investigated. In this paper, relationship of daily number of confirmed cases of COVID-19 with three environmental factors, viz. maximum relative humidity (RH_max), maximum temperature (T_max) and highest wind speed (WS_max), considering the incubation period, have been investigated statistically, for four of the most affected places of China, viz. Beijing, Chongqing, Shanghai, Wuhan and five of the most affected places of Italy, viz. Bergamo, Cremona, Lodi, Milano. It has been found that the relationship with maximum relative humidity and highest wind is mostly negligible, whereas relationship with maximum temperature is ranging between negligible to moderate.", "title": "Statistical investigation of relationship between spread of coronavirus disease (COVID-19) and environmental factors based on study of four mostly affected places of China and five mostly affected places of Italy", "pid": "4ay3hsi7", "bm25_score": 214.22988891601562}, {"text": "The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "title": "Coronaviruses widespread on nonliving surfaces: important questions and promising answers.", "pid": "9xv9t5ba", "bm25_score": 214.22573852539062}, {"text": "The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "title": "Seasonality of Respiratory Viral Infections.", "pid": "1npav6m4", "bm25_score": 214.220458984375}, {"text": "This study aimed to evaluate the relationship between weather factors (temperature, humidity, solar radiation, wind speed, and rainfall) and COVID-19 infection in the State of Rio de Janeiro, Brazil. Solar radiation showed a strong (-0.609, p < 0.01) negative correlation with the incidence of novel coronavirus (SARS-CoV-2). Temperature (maximum and average) and wind speed showed negative correlation (p < 0.01). Therefore, in this studied tropical state, high solar radiation can be indicated as the main climatic factor that suppress the spread of COVID-19. High temperatures, and wind speed also are potential factors. Therefore, the findings of this study show the ability to improve the organizational system of strategies to combat the pandemic in the State of Rio de Janeiro, Brazil, and other tropical countries around the word.", "title": "Relationship between COVID-19 and weather: Case study in a tropical country", "pid": "bhq4t850", "bm25_score": 214.21673583984375}, {"text": "Abstract This paper investigates the correlation between the high level of coronavirus SARS-CoV-2 infection accelerated transmission and lethality, and surface air pollution in Milan metropolitan area, Lombardy region in Italy. For January–April 2020 period, time series of daily average inhalable gaseous pollutants ozone (O3) and nitrogen dioxide (NO2), together climate variables (air temperature, relative humidity, wind speed, precipitation rate, atmospheric pressure field and Planetary Boundary Layer) were analyzed. In spite of being considered primarily transmitted by indoor bioaerosols droplets and infected surfaces or direct human-to-human personal contacts, it seems that high levels of urban air pollution, and climate conditions have a significant impact on SARS-CoV-2 diffusion. Exhibited positive correlations of ambient ozone levels and negative correlations of NO2 with the increased rates of COVID-19 infections (Total number, Daily New positive and Total Deaths cases), can be attributed to airborne bioaerosols distribution. The results show positive correlation of daily averaged O3 with air temperature and inversely correlations with relative humidity and precipitation rates. Viral genome contains distinctive features, including a unique N-terminal fragment within the spike protein, which allows coronavirus attachment on ambient air pollutants. At this moment it is not clear if through airborne diffusion, in the presence of outdoor and indoor aerosols, this protein “spike” of the new COVID-19 is involved in the infectious agent transmission from a reservoir to a susceptible host during the highest nosocomial outbreak in some agglomerated industrialized urban areas like Milan is. Also, in spite of collected data for cold season (winter-early spring) period, when usually ozone levels have lower values than in summer, the findings of this study support possibility as O3 can acts as a COVID-19 virus incubator. Being a novel pandemic coronavirus version, it might be ongoing during summer conditions associated with higher air temperatures, low relative humidity and precipitation levels.", "title": "Assessing the relationship between ground levels of ozone (O3) and nitrogen dioxide (NO2) with coronavirus (COVID-19) in Milan, Italy", "pid": "owgs9n9z", "bm25_score": 214.21249389648438}, {"text": "Host shifts - where a pathogen jumps between different host species - are an important source of emerging infectious disease. With ongoing climate change there is an increasing need to understand the effect changes in temperature may have on emerging infectious disease. We investigated whether species’ susceptibilities change with temperature and ask if susceptibility is greatest at different temperatures in different species. We infected 45 species of Drosophilidae with an RNA virus and measured how viral load changes with temperature. We found the host phylogeny explained a large proportion of the variation in viral load at each temperature, with strong phylogenetic correlations between viral loads across temperature. The variance in viral load increased with temperature, whilst the mean viral load did not, such that as temperature increased the most susceptible species become more susceptible, and the least susceptible less so. We found no significant relationship between a species’ susceptibility across temperatures and proxies for thermal optima; critical thermal maximum and minimum or basal metabolic rate. These results suggest that whilst the rank order of species susceptibilities can remain the same with changes in temperature, the likelihood of host shifts into a given species may increase or decrease. Author Summary Emerging infectious diseases are often the result of a host shift, where a pathogen jumps from one host species into another. Understanding the factors underlying host shifts is a major goal for infectious disease researchers. This effort has been further complicated by the fact that host-parasite interactions are now taking place in a period of unprecedented global climatic warming. Here, we ask how host shifts are affected by temperature by carrying out experimental infections using an RNA virus across a wide range of related species, at three different temperatures. We find that as temperature increases the most susceptible species become more susceptible, and the least susceptible less so. This has important consequences for our understanding of host shift events in a changing climate, and suggests that temperature changes may affect the likelihood of a host shift into certain species.", "title": "Changes in temperature alter susceptibility to a virus following a host shift", "pid": "7tulgjhy", "bm25_score": 214.21002197265625}, {"text": "BACKGROUND The outbreak of the new coronavirus infection in Wuhan City, Hubei Province in December 2019, poses a huge threat to China and even global public health security. Respiratory droplets and contact transmission are the main routes of transmission of new coronaviruses. Compared with SARS and Ebola viruses, new coronavirus infections are infectious during the incubation period. Traditional SEIR (susceptibility-exposure-infection-Removal) There are some differences in conditions for the prediction of the epidemic trend of new coronavirus infection. The outbreak of the new coronavirus infection coincided with the Spring Festival before and after the Chinese Spring Festival.It is necessary to make appropriate optimization and amendments to the traditional model to meet the actual evolution of the epidemic situation. METHODS The traditional SEIR model assumes that the virus-infected person is not infectious during the incubation period and that the infected person did not take isolation measures during the illness. The transmission of the new coronavirus no longer meets the basic assumptions of the classical kinetic system. Therefore, this article first establishes a modified SEIR model. Predict and analyze the changing trend of the epidemic situation, then estimate the parameters involved in the infection dynamics model, and then use Matlab to simulate the established dynamic equations based on public data and analyze the results. Recommendations for universal prevention and control of infectious diseases. RESULTS The first case of new coronavirus infection was confirmed in Wuhan on December 8, 2019. When Wuhan City took no action, assuming the average daily number of contacts per infected person k = 5, the number of infected persons will reach about 2,384,803 people; If wuhan adopts the measures of sealing the city on January 22, 2020, under the premise of k=2, the number of infected people decreases by 19,773 compared with that on January 23, and there is no significant change in the time when the number of infected people reaches the peak. Under the premise of k = 1, the number of infected persons was reduced by 14,330 compared with the closure on January 23, and the time to reach the peak of the number of infected persons was reduced by 2 days. If Wuhan City is closed for one day, the number of infected persons will increase from 106,145 to 130,626 under the premise of k = 2; the number of infected persons will increase from 74,369 to 92,010 under the premise of k = 1. CONCLUSIONS Comparing the number of confirmed diagnoses actually notified by the department with the number of infected people obtained from the simulation of the model, it can be seen that the city closure measures adopted by the Wuhan Municipal Government on January 23 and the first-level response measures adopted by the country are effective for the epidemic Prevention and control play a vital role. Wearing a mask when going out and avoiding close contact with people can effectively reduce the infection rate.", "title": "Prediction of New Coronavirus Infection Based on a Modified SEIR Model", "pid": "1mu1z4xd", "bm25_score": 214.20973205566406}, {"text": "The coronavirus pandemic, which has numerous global implications, has led people to believe that nothing will be the same as before. The present day is dominated by studies on determining the factors that affect, taking preventive actions, and trying to find an effective treatment on top priority. Meteorological parameters are among the crucial factors affecting infectious diseases. The present study examines the correlation between weather and coronavirus disease 2019 (COVID-19) by considering nine cities in Turkey. In this regard, temperature (°C), dew point (°C), humidity (%), and wind speed (mph) are considered as parameters of weather. Research states that the incubation period of COVID-19 varies from 1 day to 14 days. Therefore, the effects of each parameter within 1, 3, 7, and 14 days are examined. In addition, the population is included as an effective parameter for evaluation. The analyses are conducted based on Spearman's correlation coefficients. The results showed that the highest correlations were observed for population, wind speed 14 days ago, and temperature on the day, respectively. The study results may guide authorities and decision-makers on taking specific measures for the cities.", "title": "Impact of weather on COVID-19 pandemic in Turkey", "pid": "ds3nmssp", "bm25_score": 214.1909942626953}, {"text": "Global warming and the associated climate changes are predictable. They are enhanced by burning of fossil fuels and the emission of huge amounts of CO(2) gas which resulted in greenhouse effect. It is expected that the average global temperature will increase with 2–5 °C in the next decades. As a result, the earth will exhibit marked climatic changes characterized by extremer weather events in the coming decades, such as the increase in temperature, rainfall, summertime, droughts, more frequent and stronger tornadoes and hurricanes. Epidemiological disease cycle includes host, pathogen and in certain cases intermediate host/vector. A complex mixture of various environmental conditions (e.g. temperature and humidity) determines the suitable habitat/ecological niche for every vector host. The availability of suitable vectors is a precondition for the emergence of vector-borne pathogens. Climate changes and global warming will have catastrophic effects on human, animal and environmental ecosystems. Pathogens, especially neglected tropical disease agents, are expected to emerge and re-emerge in several countries including Europe and North America. The lives of millions of people especially in developing countries will be at risk in direct and indirect ways. In the present review, the role of climate changes in the spread of infectious agents and their vectors is discussed. Examples of the major emerging viral, bacterial and parasitic diseases are also summarized.", "title": "Climatic changes and their role in emergence and re-emergence of diseases", "pid": "kcvtvki1", "bm25_score": 214.1823272705078}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus that may be sensitive to heat. We assessed whether the spread of coronavirus disease 2019 (COVID-19) correlates with air temperature. We also studied whether additional climate, geographical, and population variables were correlated. The total number of confirmed COVID-19 cases and mortality rates reported in each country between 1st Jan and 31st Mar 2020 were compared with the country's three-month average atmospheric air temperature, precipitation and latitude. Spearman's correlation coefficient (rs) was used to identify significant correlations. Our analysis included a total of 748,555 confirmed COVID-19 cases worldwide. The total number of patients with COVID-19 decreased with increasing atmospheric air temperature (rs = -0.54, 95%CI: [-0.64, -0.42]; P <0.001) and increased with an increasing latitude (rs =0.60, 95%CI: [0.48, 0.70]; P <0.001). Our findings justify further studies to examine the effect of air temperature on infectivity of SAR-CoV-2.", "title": "Correlation of the global spread of coronavirus disease-19 with atmospheric air temperature", "pid": "foha7ozb", "bm25_score": 214.1821746826172}, {"text": "Abstract Due to the close relationship between the incidence of infectious diseases by epidemics and environmental conditions, this research explores the temperature, evaporation, precipitation and regional climate effects on the local transmission of coronavirus SARS-CoV-2 inside 31 states and capital of Mexico since February 29 (national onset) to March 31, 2020. Statistical analysis was conducted to explore the association between the daily local COVID-19 confirmed positive cases (LCPC) and both climate characteristics and the daily weather reported by the regional meteorological stations. In this work, the local transmission ratio (LTR) was calculated with the regional LCPC divided by the number of the effective contagion days since regional onset in each state. The results showed a negative association between temperature (mean, max and min) and climate classification with both LCPC and LTR variables. The precipitation associated positively with LCPC and LTR. The associations between the climate classification with LCPC and LTR are statistically significant. The tropical climate (mean temperature around 25.95 °C and mean precipitation around 8.74 mm) delayed the regional onset. However, the regional onset in dry climates emerged earlier as consequence of the lower temperatures and higher precipitations (20.57 °C and 20.87 mm respectively) than the observed in the tropical climate. The fastest regional onsets were observed in tempered climates in states where the lowest temperatures and lowest precipitations were registered (19.65 °C and 8.48 mm respectively). Meteorological factors influenced the trend on the regional outbreaks in Mexican's states likely by the host predisposition and susceptibility during the cold winter season. In Mexico, the climate characteristics played a crucial role on the local infection during the phase 1 being the tempered regions (as Michoacán, Jalisco, Puebla, etc.) more vulnerable than the dry (as Chihuahua, Durango or Zacatecas, etc.) or tropical areas (as Colima, Campeche, Morelos etc.).", "title": "The temperature and regional climate effects on communitarian COVID-19 contagion in Mexico throughout phase 1", "pid": "ehyuesvf", "bm25_score": 214.1640625}, {"text": "OBJECTIVE To understand the association between the SARS outbreak and the environmental temperature, and to provide a scientific basis for prevention and control measures against it. METHODS The daily numbers of the probable SARS patients and the daily meteorological factors during the SARS outbreak period in Hong Kong, Guangzhou, Beijing, and Taiyuan were used in the data analysis. Ecological analysis was conducted to explore the association between the daily numbers of probable SARS patients and the environmental temperature and its variations. RESULTS There was a significant correlation between the SARS cases and the environmental temperature seven days before the onset and the seven day time lag corresponds well with the known incubation period for SARS. The optimum environmental temperature associated with the SARS cases was between 16 degrees C to 28 degrees C, which may encourage virus growth. A sharp rise or decrease in the environmental temperature related to the cold spell led to an increase of the SARS cases because of the possible influence of the weather on the human immune system. This study provided some evidence that there is a higher possibility for SARS to reoccur in spring than that in autumn and winter. CONCLUSION Current knowledge based on case studies of the SARS outbreak in the four cities suggested that the SARS outbreaks were significantly associated with the temperature and its variations. However, because the fallacy and the uncontrolled confounding effects might have biased the results, the possibility of other meteorological factors having an affect on the SARS outbreaks deserves further investigation.", "title": "An initial investigation of the association between the SARS outbreak and weather: with the view of the environmental temperature and its variation.", "pid": "r69dnsdm", "bm25_score": 214.1546630859375}, {"text": "The outbreak of coronavirus disease 2019 (COVID-19), caused by the virus SARS-CoV-2, has been rapidly increasing in the United States. Boroughs of New York City, including Queens county, turn out to be the epicenters of this infection. According to the data provided by the New York State Department of Health, most of the cases of new COVID-19 infections in New York City have been found in the Queens county where 42,023 people have tested positive, and 3221 people have died as of 20 April 2020. Person-to-person transmission and travels were implicated in the initial spread of the outbreaks, but factors related to the late phase of rapidly spreading outbreaks in March and April are still uncertain. A few previous studies have explored the links between air pollution and COVID-19 infections, but more data is needed to understand the effects of short-term exposures of air pollutants and meteorological factors on the spread of COVID-19 infections, particularly in the U.S. disease epicenters. In this study, we have focused on ozone and PM2.5, two major air pollutants in New York City, which were previously found to be associated with respiratory viral infections. The aim of our regression modeling was to explore the associations among ozone, PM2.5, daily meteorological variables (wind speed, temperature, relative humidity, absolute humidity, cloud percentages, and precipitation levels), and COVID-19 confirmed new cases and new deaths in Queens county, New York during March and April 2020. The results from these analyses showed that daily average temperature, daily maximum eight-hour ozone concentration, average relative humidity, and cloud percentages were significantly and positively associated with new confirmed cases related to COVID-19; none of these variables showed significant associations with new deaths related to COVID-19. The findings indicate that short-term exposures to ozone and other meteorological factors can influence COVID-19 transmission and initiation of the disease, but disease aggravation and mortality depend on other factors.", "title": "Short-Term Effects of Ambient Ozone, PM2.5, and Meteorological Factors on COVID-19 Confirmed Cases and Deaths in Queens, New York", "pid": "g6i86tdj", "bm25_score": 214.15097045898438}]}
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"zzp6cj76": 0}, "bm25_results": [{"text": "In contrast with adults, children infected by severe acute respiratory syndrome-corona virus (SARS-CoV) develop milder clinical symptoms. Because of this, it is speculated that children vaccinated with various childhood vaccines might develop cross immunity against SARS-CoV. Antisera and T cells from mice immunised with various vaccines were used to determine whether they developed cross reactivity against SARS-CoV. The results showed no marked cross reactivity against SARS-CoV, which implies that the reduced symptoms among children infected by SARS-CoV may be caused by other factors.", "title": "Children's vaccines do not induce cross reactivity against SARS-CoV.", "pid": "eo4ehcjv", "bm25_score": 219.03091430664062}, {"text": "An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.", "title": "SARS-CoV-2 infection protects against rechallenge in rhesus macaques", "pid": "car394ou", "bm25_score": 218.92611694335938}, {"text": "An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.", "title": "SARS-CoV-2 infection protects against rechallenge in rhesus macaques", "pid": "t3sjv4hv", "bm25_score": 218.82278442382812}, {"text": "Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9-17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.", "title": "Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2", "pid": "buwz6lu3", "bm25_score": 218.53619384765625}, {"text": "The emergence of SARS-CoV-2 and its inordinately rapid spread is posing severe challenges to the wellbeing of millions of people worldwide, health care systems and the global economy. While many younger people experience no or mild symptoms on infection, older adults are highly susceptible to life-threatening respiratory and systemic conditions which demand a full understanding and leveraging of knowledge of the differences between immunity in young and old people. Consequently, we welcome papers addressing any issues relevant to immunity and ageing in the context of SARS-CoV-2, and will endeavour to fast-track peer-review. We aim to provide a platform exclusively for discussions of individual and age differences in susceptibility and immune responses to COVID caused by SARS-CoV-2 infection and how to prevent or reduce severity of disease in older adults.", "title": "Can an effective SARS-CoV-2 vaccine be developed for the older population?", "pid": "fi1ldwe8", "bm25_score": 218.44512939453125}, {"text": "Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9–17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.", "title": "Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2", "pid": "8i1u1a9t", "bm25_score": 218.3339385986328}, {"text": "Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.", "title": "Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques", "pid": "tdorhy8x", "bm25_score": 218.29006958007812}, {"text": "Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.", "title": "Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques.", "pid": "5dbuxvc4", "bm25_score": 218.237060546875}, {"text": "Trained immunity is a type of non-specific memory-like immune response induced by some pathogens and vaccines, such as BCG, which can confer antigen-independent protection against a wide variety of pathogens. The BCG vaccine has been extensively used to protect against tuberculosis for almost a 100 years. Interestingly, this vaccine reduces children's mortality caused by infections unrelated to Mycobacterium tuberculosis infection, a phenomenon thought to be due to the induction of trained immunity. The SARS-CoV-2 pandemic has infected, as of April 22, 2020, 2,623,231 people globally, causing a major public health problem worldwide. Currently, no vaccine or treatment is available to control this pandemic. We analyzed the number of positive cases and deaths in different countries and correlated them with the inclusion of BCG vaccination at birth in their national vaccination programs. Interestingly, those countries where BCG vaccination is given at birth have shown a lower contagion rate and fewer COVID-19-related deaths, suggesting that this vaccine may induce trained immunity that could confer some protection for SARS-CoV-2.", "title": "Could BCG Vaccination Induce Protective Trained Immunity for SARS-CoV-2?", "pid": "8earvduw", "bm25_score": 218.1869354248047}, {"text": "The WHO has declared SARS-CoV-2 outbreak a public health emergency of international concern. However, to date, there was hardly any study in characterizing the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. In this study, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and analyzed their SARS-CoV-2-specific antibody and T cell responses. We observed SARS-CoV-2-specific humoral and cellular immunity in the patients. Both were detected in newly discharged patients, suggesting both participate in immune-mediated protection to viral infection. However, follow-up patients (2 weeks post discharge) exhibited high titers of IgG antibodies, but with low levels of virus-specific T cells, suggesting that they may enter a quiescent state. Our work has thus provided a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in designing an effective vaccine to protect and treat SARS-CoV-2 infection.", "title": "Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2", "pid": "dptgg05n", "bm25_score": 217.79611206054688}, {"text": "Abstract SARS-CoV-2 infection is mild in the majority of individuals, but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed ‘trained immunity’, by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections, through epigenetic, transcriptional and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole microorganism vaccines may represent an important tool for reducing susceptibility and severity to SARS-CoV-2.", "title": "Trained immunity: a tool for reducing susceptibility and severity of SARS-CoV-2 infection", "pid": "dqs21e0q", "bm25_score": 217.78895568847656}, {"text": "Abstract Over 12 years have elapsed since severe acute respiratory syndrome (SARS) triggered the first global alert for coronavirus infections. Virus transmission in humans was quickly halted by public health measures and human infections of SARS coronavirus (SARS-CoV) have not been observed since. However, other coronaviruses still pose a continuous threat to human health, as exemplified by the recent emergence of Middle East respiratory syndrome (MERS) in humans. The work on SARS-CoV widens our knowledge on the epidemiology, pathophysiology and immunology of coronaviruses and may shed light on MERS coronavirus (MERS-CoV). It has been confirmed that T-cell immunity plays an important role in recovery from SARS-CoV infection. Herein, we summarize T-cell immunological studies of SARS-CoV and discuss the potential cross-reactivity of the SARS-CoV-specific immunity against MERS-CoV, which may provide useful recommendations for the development of broad-spectrum vaccines against coronavirus infections.", "title": "T-cell immunity of SARS-CoV: Implications for vaccine development against MERS-CoV", "pid": "wh9vvgv2", "bm25_score": 217.7643585205078}, {"text": "Abstract Although the recent SARS coronavirus (SARS-CoV) that appeared in 2002 has now been contained, the possibility of re-emergence of SARS-CoV remains. Due to the threat of re-emergence, the overall fatality rate of ∼10%, and the rapid dispersion of the virus via international travel, viable vaccine candidates providing protection from SARS are clearly needed. We developed an attenuated VSV recombinant (VSV-S) expressing the SARS coronavirus (SARS-CoV) spike (S) protein. In cells infected with this recombinant, S protein was synthesized, glycosylated at approximately 17 Asn residues, and transported via the Golgi to the cell surface. Mice vaccinated with VSV-S developed SARS-neutralizing antibody and were able to control a challenge with SARS-CoV performed at 1 month or 4 months after a single vaccination. We also demonstrated, by passive antibody transfer, that the antibody response induced by the vaccine was sufficient for controlling SARS-CoV infection. A VSV-vectored SARS vaccine could have significant advantages over other SARS vaccine candidates described to date.", "title": "Long-term protection from SARS coronavirus infection conferred by a single immunization with an attenuated VSV-based vaccine", "pid": "w9rqnz9h", "bm25_score": 217.74378967285156}, {"text": "Motivated by historical and present clinical observations, we discuss the possible unfavorable evolution of the immunity (similar to documented antibody-dependent enhancement scenarios) after a first infection with COVID-19. More precisely we ask the question of how the epidemic outcomes are affected if the initial infection does not provide immunity but rather sensitization to future challenges. We first provide background comparison with the 2003 SARS epidemic. Then we use a compartmental epidemic model structured by immunity level (taken here as age classes) that we fit on available data; this allows to derive quantitative insights into the future number of severe cases and deaths.", "title": "Immunity after COVID-19: protection or sensitization ?", "pid": "g6g34uvh", "bm25_score": 217.73362731933594}, {"text": "SARS-CoV-2 infection is mild in the majority of individuals but progresses into severe pneumonia in a small proportion of patients. The increased susceptibility to severe disease in the elderly and individuals with co-morbidities argues for an initial defect in anti-viral host defense mechanisms. Long-term boosting of innate immune responses, also termed \"trained immunity,\" by certain live vaccines (BCG, oral polio vaccine, measles) induces heterologous protection against infections through epigenetic, transcriptional, and functional reprogramming of innate immune cells. We propose that induction of trained immunity by whole-microorganism vaccines may represent an important tool for reducing susceptibility to and severity of SARS-CoV-2.", "title": "Trained Immunity: a Tool for Reducing Susceptibility to and the Severity of SARS-CoV-2 Infection", "pid": "g5ovvjc6", "bm25_score": 217.7247772216797}, {"text": "Abstract A key goal to controlling COVID-19 is developing an effective vaccine. Development of a vaccine requires knowledge of what constitutes a protective immune response and also features that might be pathogenic. Protective and pathogenic aspects of the response to SARS-CoV-2 are not well understood, partly because the virus has infected humans for only 6 months. However, insight into coronavirus immunity can be informed by previous studies of immune responses to non-human coronaviruses, to common cold coronaviruses, and to SARS-CoV and MERS-CoV. Here we review the literature describing these responses and discuss their relevance to the SARS-CoV-2 immune response.", "title": "Lessons for COVID-19 immunity from other coronavirus infections", "pid": "s6v4bgev", "bm25_score": 217.67410278320312}, {"text": "", "title": "Pre-existing immunity to SARS-CoV-2: the knowns and unknowns", "pid": "vqnkdskx", "bm25_score": 217.6226043701172}, {"text": "Abstract SARS-coronavirus (SARS-CoV) has recently been identified as the causative agent of SARS. We constructed a series of recombinant DIs (rDIs), a highly attenuated vaccinia strain, expressing a gene encoding four structural proteins (E, M, N and S) of SARS-CoV individually or simultaneously. These rDIs elicited SARS-CoV-specific serum IgG antibody and T-cell responses in vaccinated mice following intranasal or subcutaneous administration. Mice that were subcutaneously vaccinated with rDIs expressing S protein with or without other structural proteins induced a high level of serum neutralizing IgG antibodies and demonstrated marked protective immunity against SARS-CoV challenge in the absence of a mucosal IgA response. These results indicate that the potent immune response elicited by subcutaneous injection of rDIs containing S is able to control mucosal infection by SARS-CoV. Thus, replication-deficient DIs constructs hold promise for the development of a safe and potent SARS vaccine.", "title": "Induction of protective immunity against severe acute respiratory syndrome coronavirus (SARS-CoV) infection using highly attenuated recombinant vaccinia virus DIs", "pid": "n1pkj68j", "bm25_score": 217.60411071777344}, {"text": "Effective herd immunity against SARS-CoV-2 will be determined on many factors: the percentage of the immune population, the length and effectiveness of the immune response and the stability of the viral epitopes. The required percentage of immune individuals has been estimated to be 50-66% of the population which, given the current infection rates, will take long to be achieved. Furthermore, data from SARS-CoV suggest that the duration of immunity may not be sufficiently significant, while the immunity response against SARS-CoV-2 may not be efficiently effective in all patients, as relapses have already been reported. In addition, the development of mutant strains, which has already been documented, can cause the reemergence of the epidemic. In conclusion, the development of an effective vaccine is an urgent necessity, as long-term natural immunity to SARS-CoV-2 may not be sufficient for the control of the current and future outbreaks.", "title": "Long-term and herd immunity against SARS-CoV-2: implications from current and past knowledge", "pid": "pcyscqux", "bm25_score": 217.60153198242188}, {"text": "Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.", "title": "Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV", "pid": "dtwstwbe", "bm25_score": 217.59854125976562}, {"text": "The current COVID-19 pandemic, caused by a novel coronavirus SARS-CoV-2, poses serious threats to public health and social stability, calling for urgent need for vaccines and therapeutics. SARS-CoV-2 is genetically close to SARS-CoV, thus it is important to define the between antigenic cross-reactivity and neutralization. In this study, we firstly analyzed 20 convalescent serum samples collected from SARS-CoV infected individuals during the 2003 SARS outbreak. All patient sera reacted strongly with the S1 subunit and receptor-binding domain (RBD) of SARS-CoV, cross-reacted with the S ectodomain, S1, RBD, and S2 proteins of SARS-CoV-2, and neutralized both SARS-CoV and SARS-CoV-2 S protein-driven infections. Multiple panels of antisera from mice and rabbits immunized with a full-length S and RBD immunogens of SARS-CoV were also characterized, verifying the cross-reactive neutralization against SARS-CoV-2. Interestingly, we found that a palm civet SARS-CoV-derived RBD elicited more potent cross-neutralizing responses in immunized animals than the RBD from a human SARS-CoV strain, informing a strategy to develop a universe vaccine against emerging CoVs. Summary Serum antibodies from SARS-CoV infected patients and immunized animals cross-neutralize SARS-CoV-2 suggests strategies for universe vaccines against emerging CoVs.", "title": "Cross-reactive neutralization of SARS-CoV-2 by serum antibodies from recovered SARS patients and immunized animals", "pid": "7jwhypgs", "bm25_score": 217.55789184570312}, {"text": "The World Health Organization has declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, a pandemic. There is currently a lack of knowledge about the antibody response elicited from SARS-CoV-2 infection. One major immunological question concerns antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by analyzing plasma from patients infected by SARS-CoV-2 or SARS-CoV and from infected or immunized mice. Our results show that, although cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses may be rare, indicating the presence of a non-neutralizing antibody response to conserved epitopes in the spike. Whether such low or non-neutralizing antibody response leads to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding antigenicity differences between SARS-CoV-2 and SARS-CoV but also has implications for immunogen design and vaccine development.", "title": "Cross-reactive Antibody Response between SARS-CoV-2 and SARS-CoV Infections", "pid": "72fokkad", "bm25_score": 217.4899139404297}, {"text": "Severe acute respiratory syndrome (SARS) is a serious and fatal infectious disease caused by SARS coronavirus (SARS-Cov), a novel human coronavirus. SARS-Cov infection stimulates cytokines (e.g., IL-10, IFN-gamma, IL-1, etc.) expression dramatically, and T lymphocytes and their subsets CD4(+) and CD8(+) T cells are decreased after onset of the disease. SARS-specific IgG antibody is generated in the second week and persists for a long time, whereas IgM is expressed transiently. The spike protein and neucleocapsid protein are most abundant in SARS-Cov and contribute dominantly to the antibody production during the course of disease. Spike protein, especially the ACE-2 binding region (318-510aa) is capable of producing neutralizing antibody to SARS-Cov. Neucleocapsid protein induces protective specific CTL to SARS-Cov. Therefore, applications with spike subunit, neucleocapsid subunit as well as inactivated SARS-Cov are three prospective vaccination strategies for SARS.", "title": "SARS Immunity and Vaccination.", "pid": "xi73bzud", "bm25_score": 217.4658660888672}, {"text": "While individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory of related pathogens can influence the disease outcome. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated a map of public and private predicted CD8+ T cell epitopes between coronaviruses. Moreover, to assess the potential risk of self-reactivity and/or diminished T cell response for peptides identical or highly similar to the host, we identified predicted epitopes with high sequence similarity with human proteome. Lastly, we compared predicted epitopes from coronaviruses with epitopes from influenza virus deposited in IEDB to support vaccine development against different virus strains. We believe the comprehensive in silico profile of private and public predicted epitopes across coronaviruses and influenza viruses will facilitate design of vaccines capable of protecting against various viral infections.", "title": "CD8+ T cell cross-reactivity against SARS-CoV-2 conferred by other coronavirus strains and influenza virus", "pid": "x8asawcv", "bm25_score": 217.46575927734375}, {"text": "Summary The World Health Organization has declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge about the antibody response elicited from SARS-CoV-2 infection. One major immunological question concerns antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by analyzing plasma from patients infected by SARS-CoV-2 or SARS-CoV, and from infected or immunized mice. Our results show that, while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses may be rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether such low or non-neutralizing antibody response leads to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has implications for immunogen design and vaccine development.", "title": "Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections", "pid": "mxafg0t9", "bm25_score": 217.44003295898438}, {"text": "Effective herd immunity against SARS-CoV-2 will be determined on many factors: the percentage of the immune population, the length and effectiveness of the immune response and the stability of the viral epitopes. The required percentage of immune individuals has been estimated to be 50–66% of the population which, given the current infection rates, will take long to be achieved. Furthermore, data from SARS-CoV suggest that the duration of immunity may not be sufficiently significant, while the immunity response against SARS-CoV-2 may not be efficiently effective in all patients, as relapses have already been reported. In addition, the development of mutant strains, which has already been documented, can cause the reemergence of the epidemic. In conclusion, the development of an effective vaccine is an urgent necessity, as long-term natural immunity to SARS-CoV-2 may not be sufficient for the control of the current and future outbreaks.", "title": "Long-term and herd immunity against SARS-CoV-2: implications from current and past knowledge", "pid": "6jr3z9wx", "bm25_score": 217.4114227294922}, {"text": "In order to properly understand the spread of SARS-CoV-2 infection and development of humoral immunity, researchers have evaluated the presence of serum antibodies of people worldwide experiencing the pandemic. These studies rely on the use of recombinant proteins from the viral genome in order to identify serum antibodies that recognize SARS-CoV-2 epitopes. Here, we discuss the cross-reactivity potential of SARS-CoV-2 antibodies with the full spike proteins of four other Betacoronaviruses that cause disease in humans, MERS-CoV, SARS-CoV, HCoV-OC43, and HCoV-HKU1. Using enzyme-linked immunosorbent assays (ELISAs), we detected the potential cross-reactivity of antibodies against SARS-CoV-2 towards the four other coronaviruses, with the strongest cross-recognition between SARS-CoV-2 and SARS /MERS-CoV antibodies, as expected based on sequence homology of their respective spike proteins. Further analysis of cross-reactivity could provide informative data that could lead to intelligently designed pan-coronavirus therapeutics or vaccines.", "title": "Serologic cross-reactivity of SARS-CoV-2 with endemic and seasonal Betacoronaviruses", "pid": "yigj0u3n", "bm25_score": 217.39028930664062}, {"text": "In the current SARS-CoV-2 pandemic a key unsolved question is the quality and duration of acquired immunity in recovered individuals. This is crucial to solve, however SARS-CoV-2 has circulated for under five months, precluding a direct study. We therefore monitored 10 subjects over a time span of 35 years (1985-2020), providing a total of 2473 follow up person-months, and determined a) their antibody levels following infection by any of the four seasonal human coronaviruses, and b) the time period after which reinfections by the same virus can occur. An alarmingly short duration of protective immunity to coronaviruses was found by both analyses. We saw frequent reinfections at 12 months post-infection and a substantial reduction in antibody levels as soon as 6 months post-infection.", "title": "Human coronavirus reinfection dynamics: lessons for SARS-CoV-2", "pid": "u5nxm9tu", "bm25_score": 217.34432983398438}, {"text": "Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed \"original antigenic sin.\" The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.", "title": "Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS", "pid": "nacxjt2f", "bm25_score": 217.3130340576172}, {"text": "Summary The World Health Organization has declared SARS-CoV-2 virus outbreak a world-wide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in 8 newly discharged patients. Follow-up analysis on another cohort of 6 patients 2 weeks post discharge also revealed high titers of IgG antibodies. In all 14 patients tested, 13 displayed serum neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in developing an effective vaccine to SARS-CoV-2 infection.", "title": "Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals", "pid": "0tn06al2", "bm25_score": 217.28038024902344}, {"text": "Human coronavirus (HCoV) is one of the most common causes of respiratory tract infections throughout the world. Two phenomena observed so far in the development of the SARS-CoV-2 pandemic deserve further attention. First, the relative absence of clinical signs of infections in children, second, the early appearance of IgG in certain patients. From the point of view of immune system physiology, such an early rise of specific IgG is expected in secondary immune responses when memory to a cross-reactive antigen is present, usually from an earlier infection with a coronavirus. It is actually typical for the immune system to respond, to what it already knows, a phenomenon that has been observed in many infections with closely related viruses and has been termed “original antigenic sin.” The question then arises whether such cross-reactive antibodies are protective or not against the new virus. The worst scenario would be when such cross-reactive memory antibodies to related coronaviruses would not only be non-protective but even enhance infection and the clinical course. Such a phenomenon of antibody dependent enhancement (ADE) has already been described in several viral infections. Thus, the development of IgG against SARS-CoV-2 in the course of COVID-19 might not be a simple sign of viral clearance and developing protection against the virus. On the contrary, due to cross-reaction to related coronavirus strains from earlier infections, in certain patients IgG might enhance clinical progression due to ADE. The patient's viral history of coronavirus infection might be crucial to the development of the current infection with SARS-CoV-2. Furthermore, it poses a note of caution when treating COVID-19 patients with convalescent sera.", "title": "Antibody Dependent Enhancement Due to Original Antigenic Sin and the Development of SARS", "pid": "7k24r3p5", "bm25_score": 217.2799530029297}, {"text": "The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It also has implications in developing an effective vaccine to SARS-CoV-2 infection.", "title": "Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals", "pid": "53j3ly3v", "bm25_score": 217.2261505126953}, {"text": "The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.", "title": "A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease", "pid": "yzffm05r", "bm25_score": 217.21839904785156}, {"text": "A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection. One Sentence Summary Neutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days.", "title": "Lack of Reinfection in Rhesus Macaques Infected with SARS-CoV-2", "pid": "q4m2uj6r", "bm25_score": 217.21551513671875}, {"text": "The World Health Organization has recently declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 infection. One major immunological question is concerning the antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by using plasma from patients infected by SARS-CoV-2 or SARS-CoV, and plasma obtained from infected or immunized mice. Our results show that while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses is rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding the antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine", "title": "Cross-reactive antibody response between SARS-CoV-2 and SARS-CoV infections", "pid": "ukz73rp2", "bm25_score": 217.21145629882812}, {"text": "The current pandemic is caused by the SARS-CoV-2 virus and large progress in understanding the pathology of the virus has been made since its emergence in late 2019. Several reports indicate short lasting immunity against endemic coronaviruses, which contrasts repeated reports that biobanked venous blood contains SARS-CoV-2 reactive T cells even before the outbreak in Wuhan. This suggests there exists a preformed T cell memory in individuals not exposed to the pandemic virus. Given the similarity of SARS-CoV-2 to other members of the Coronaviridae family, the endemic coronaviruses appear likely candidates to generate this T cell memory. However, given the apparent poor immunological memory created by the endemic coronaviruses, other immunity against other common pathogens might offer an alternative explanation. Here, we utilize a combination of epitope prediction and similarity to common human pathogens to identify potential sources of the SARS-CoV-2 T cell memory. We find that no common human virus, other than beta-coronaviruses, can explain the pre-existing SARS-CoV-2 reactive T cells in uninfected individuals. Our study suggests OC43 and HKU1 are the most likely pathogens giving rise to SARS-CoV-2 preformed immunity.", "title": "SARS-CoV-2 reactive T cells in uninfected individuals are likely expanded by beta-coronaviruses", "pid": "guzohu7y", "bm25_score": 217.19430541992188}, {"text": "Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.", "title": "Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV", "pid": "dqour5jr", "bm25_score": 217.17222595214844}, {"text": "A double-inactivated, candidate whole virus vaccine against severe acute respiratory syndrome associated coronavirus (SARS-CoV) was developed and manufactured at large scale using fermenter cultures of serum protein free Vero cells. A two step inactivation procedure involving sequential formaldehyde and U.V. inactivation was utilised in order to ensure an extremely high safety margin with respect to residual infectivity. The immunogenicity of this double-inactivated vaccine was characterised in the mouse model. Mice that were immunised twice with the candidate SARS-CoV vaccine developed high antibody titres against the SARS-CoV spike protein and high levels of neutralising antibodies. The use of the adjuvant Al(OH)(3) had only a minor effect on the immunogenicity of the vaccine. In addition, cell mediated immunity as measured by interferon-γ and interleukin-4 stimulation, was elicited by vaccination. Moreover, the vaccine confers protective immunity as demonstrated by prevention of SARS-CoV replication in the respiratory tract of mice after intranasal challenge with SARS-CoV. Protection of mice was correlated to antibody titre against the SARS-CoV S protein and neutralising antibody titre.", "title": "A double-inactivated whole virus candidate SARS coronavirus vaccine stimulates neutralising and protective antibody responses", "pid": "ogb83fgc", "bm25_score": 217.15780639648438}, {"text": "Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "title": "Protective immunity after COVID-19 has been questioned: what can we do without SARS-CoV-2-IgG detection?", "pid": "rsz7ch2a", "bm25_score": 217.15737915039062}, {"text": "The current practice for diagnosis of SARS-CoV-2 infection relies on PCR testing of nasopharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk. This testing strategy likely underestimates the true prevalence of infection, creating the need for serologic methods to detect infections missed by the limited testing to date. Here, we describe the development of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A preliminary study of human sera collected prior to the SARS-CoV-2 pandemic demonstrates overall high IgG reactivity to common human coronaviruses and low IgG reactivity to epidemic coronaviruses including SARS-CoV-2, with some cross-reactivity of conserved antigenic domains including S2 domain of spike protein and nucleocapsid protein. This array can be used to answer outstanding questions regarding SARS-CoV-2 infection, including whether baseline serology for other coronaviruses impacts disease course, how the antibody response to infection develops over time, and what antigens would be optimal for vaccine development.", "title": "Analysis of Serologic Cross-Reactivity Between Common Human Coronaviruses and SARS-CoV-2 Using Coronavirus Antigen Microarray", "pid": "lw12h047", "bm25_score": 217.14654541015625}, {"text": "T cell reactivity against SARS-CoV-2 was observed in unexposed people; however, the source and clinical relevance of the reactivity remains unknown. It is speculated that this reflects T cell memory to circulating ‘common cold’ coronaviruses. It will be important to define specificities of these T cells and assess their association with COVID-19 disease severity and vaccine responses.", "title": "Pre-existing immunity to SARS-CoV-2: the knowns and unknowns", "pid": "bw6a5gmy", "bm25_score": 217.1261749267578}, {"text": "CD4 T follicular helper (Tfh) cells are important for the generation of long-lasting and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center response is an important question as we investigate vaccine options for the current pandemic. Here we report that, following infection with SARS-CoV-2, adult rhesus macaques exhibited transient accumulation of activated, proliferating Tfh cells in their peripheral blood on a transitory basis. The CD4 helper cell responses were skewed predominantly toward a Th1 response in blood, lung, and lymph nodes, reflective of the interferon-rich cytokine environment following infection. We also observed the generation of germinal center Tfh cells specific for the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, and a corresponding early appearance of antiviral serum IgG antibodies but delayed or absent IgA antibodies. Our data suggest that a vaccine promoting Th1-type Tfh responses that target the S protein may lead to protective immunity.", "title": "SARS-CoV-2 infection induces germinal center responses with robust stimulation of CD4 T follicular helper cells in rhesus macaques", "pid": "l7lqn4js", "bm25_score": 217.092041015625}, {"text": "Abstract Five years after the first severe acute respiratory syndrome (SARS) outbreak, several candidate SARS-coronavirus (CoV) vaccines are at various stages of preclinical and clinical development. Based on the observation that SARSCoV infection is efficiently controlled upon passive transfer of antibodies directed against the spike (S) protein of SARS-CoV, vaccines containing the S protein have been formulated. Animals immunized with inactivated whole virus vaccines or live-recombinant vaccines expressing the SARS-CoV S protein (e.g., using rabies virus, vesicular stomatitis virus, bovine parainfluenza virus type 3, adenovirus, or attenuated vaccinia virus MVA as a vector), as well as mice immunized with DNA vaccines expressing the S protein gene all developed neutralizing antibodies to SARS-CoV and were protected against SARS-CoV challenge. Although much effort has been focused on developing a SARS vaccine, the commercial viability of such a vaccine for SARS-CoV will ultimately depend on whether the virus re-emerges in the near future. This vaccine should induce highly cross-reactive neutralizing antibodies to protect against newly emerging viruses related to SARS-CoV and protect both the gastrointestinal and respiratory tract in the absence of significant side effects. Given the fact that in the previous outbreak mainly the elderly succumbed to the infection, special attention should be given to vaccines that are able to efficiently protect aged individuals.", "title": "Chapter 36 SARS", "pid": "87g7g5au", "bm25_score": 217.06100463867188}, {"text": "Of the seven coronaviruses associated with disease in humans, SARS-CoV, MERS-CoV and SARS-CoV-2 cause considerable mortality but also share significant sequence homology, and potentially antigenic epitopes capable of inducing an immune response. The degree of similarity is such that perhaps prior exposure to one virus could confer partial immunity to another. Indeed, data suggests a considerable amount of cross-reactivity and recognition by the hosts immune response between different coronavirus infections. While the ongoing COVID-19 outbreak rapidly overwhelmed medical facilities of particularly Europe and North America, accounting for 78% of global deaths, only 8% of deaths have occurred in Asia where the outbreak originated. Interestingly, Asia and the Middle East have previously experienced multiple rounds of coronavirus infections, perhaps suggesting buildup of acquired immunity to the causative SARS-CoV-2 that underlies COVID-19. This article hypothesizes that a causative factor underlying such low morbidity in these regions is perhaps (at least in part) due to acquired immunity from multiple rounds of coronavirus infections and discusses the mechanisms and recent evidence to support such assertions. Further investigations of such phenomenon would allow us to examine strategies to confer protective immunity, perhaps aiding vaccine development.", "title": "Cross-immunity between respiratory coronaviruses may limit COVID-19 fatalities", "pid": "01q4pu9k", "bm25_score": 217.05807495117188}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "title": "Protective immunity after COVID-19 has been questioned: What can we do without SARS-CoV-2-IgG detection?", "pid": "rs79r7kc", "bm25_score": 217.04168701171875}, {"text": "Background. In the background of the current COVID-19 pandemic, serological tests are being used to assess past infection and immunity against SARS-CoV-2. This knowledge is paramount to determine the transmission dynamics of SARS-CoV-2 through the post pandemic period. Several individuals belonging to households with an index COVID-19 patient, reported symptoms of COVID-19 but discrepant serology results. Methods. Here we investigated the humoral and cellular immune responses against SARS-CoV-2 in seven families, including nine index patients and eight contacts, who had evidence of serological discordances within the households. Ten unexposed healthy donors were enrolled as controls. Results. All index patients recovered from a mild COVID-19. They all developed anti-SARS-CoV-2 antibodies and a significant T cell response detectable up to 69 days after symptom onset. Six of the eight contacts reported COVID-19 symptoms within 1 to 7 days after the index patients but all were SARS-CoV-2 seronegative. Six out of eight contacts developed a SARS-CoV-2-specific T cell response against structural and/or accessory proteins that lasts up to 80 days post symptom onset suggesting a past SARS-CoV-2 infection. Conclusion. Exposure to SARS-CoV-2 can induce virus-specific T cell responses without seroconversion. T cell responses may be more sensitive indicators of SARS-Co-V-2 exposure than antibodies. Our results indicate that epidemiological data relying only on the detection of SARS-CoV-2 antibodies may lead to a substantial underestimation of prior exposure to the virus", "title": "Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion", "pid": "eml8uilb", "bm25_score": 216.99473571777344}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging human coronavirus responsible for coronavirus disease 2019 (COVID-19), a predominantly respiratory disease that has become a global pandemic. Millions of people worldwide are suffering from COVID-19, and hundreds of thousands of those infected have died. Nevertheless, many more people who have been infected with SARS-CoV-2 are asymptomatic or suffer a mild disease characterized by dry cough and mild fever. This new pandemic poses a threat to public health on a global scale, and an intervention to prevent continued spread of SARS-CoV-2 virus is of the utmost importance. To assess preventive and therapeutic strategies, it is imperative to understand the pathogenesis and immune response against SARS-CoV-2. In this review, we concentrate on the protective adaptive immune response elicited by this novel coronavirus as well as requirements for a successful vaccine inducing optimal protection.", "title": "Protective Adaptive Immunity Against Severe Acute Respiratory Syndrome Coronaviruses 2 (SARS-CoV-2) and Implications for Vaccines", "pid": "bcqdm2b1", "bm25_score": 216.95962524414062}, {"text": "To date, understanding whether acquired immunity and presence of anti SARS‐Cov2 antibodies protects against reinfection is one the most important focus of the scientific community [1‐2]. Several studies suggest that acquired immunity may protect upon further exposure to SARS‐COV2 [3‐6]. Contrary to this picture, we describe a case of a patient recovered from COVID‐19 pneumonia with positive serology, followed up by 6 negative nasopharyngeal swab‐PCR tests performed along 1 month, who later on, after exposure to the virus, presented another positive RT‐PCR test and a second IgM seroconversion. This report opens up several possible interpretations. This article is protected by copyright. All rights reserved.", "title": "New IgM seroconversion and positive RT‐PCR test after exposure to the virus in recovered COVID‐19 patient", "pid": "38mhmxvd", "bm25_score": 216.9420928955078}, {"text": "The outbreak of the 2019 Novel Coronavirus (SARS-CoV-2) rapidly spread from Wuhan, China to more than 150 countries, areas or territories, causing staggering number of infections and deaths. A systematic profiling of the immune vulnerability landscape of SARS-CoV-2, which can bring critical insights into the immune clearance mechanism, peptide vaccine development, and antiviral antibody development, is lacking. In this study, we investigated the potential of the SARS-CoV-2 viral proteins to induce class I and II MHC presentation and to form linear antibody epitopes. We created an online database to broadly share the predictions as a resource for the research community. Using this resource, we showed that genetic variations in SARS- CoV-2, though still few for the moment, already follow the pattern of mutations in related coronaviruses, and could alter the immune vulnerability landscape of this virus. Importantly, we discovered evidence that SARS-CoV-2, along with related coronaviruses, used mutations to evade attack from the human immune system. Overall, we present an immunological resource for SARS-CoV-2 that could promote both therapeutic development and mechanistic research.", "title": "The immune vulnerability landscape of the 2019 Novel Coronavirus, SARS-CoV-2", "pid": "xetzg7gp", "bm25_score": 216.9195556640625}, {"text": "Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of human infections. One limitation to the evaluation of potential therapies and vaccines to inhibit SARS-CoV-2 infection and ameliorate disease is the lack of susceptible small animals in large numbers. Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss. Passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss. The development of an accessible mouse model of SARS-CoV-2 infection and pathogenesis will expedite the testing and deployment of therapeutics and vaccines.", "title": "A SARS-CoV-2 infection model in mice demonstrates protection by neutralizing antibodies", "pid": "0slywdik", "bm25_score": 216.9159393310547}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.", "title": "Development of an inactivated vaccine candidate for SARS-CoV-2", "pid": "5bftuzw5", "bm25_score": 216.89683532714844}, {"text": "Uncertain rates of asymptomatic infections have raised concerns about potentially high rates of thus far undiagnosed SARS-CoV-2 infections. Serological testing for SARS-CoV-2 specific IgG can be helpful in identification of asymptomatic infections. We report baseline results of the CVOID-19 Contact (CoCo) Study, which follows 217 frontline healthcare workers at a university hospital and performs weekly SARS-CoV-2 specific serology (IgA/IgG). The majority of participants had direct contact to patients with infectious respiratory diseases. Study participants estimated their personal likelihood of having had a SARS-CoV-2 infection with a mean of 20.9% (range 0 to 90%). In contrast, anti-SARS-CoV-2-IgG prevalence was in the range of 1-2% among health care workers. The CoCo Study is not fully representative for other hospitals and the sensitivity of anti-SARS-CoV-2 serology in low prevalence conditions may require further improvement. Taken together, low rates of SARS-CoV-2 specific IgG in healthcare workers in Northern Germany are in sharp contrast to the high personal risk perception. Regular anti-SARS-CoV-2 IgG testing of health-care workers may aid in monitoring the pandemic, assessing the quality of immune responses, directing resources for protective measures, and assuring CVID-19 care in the long run.", "title": "Perceived versus proven SARS-CoV-2 specific immune responses in health care workers", "pid": "x5g3qjs2", "bm25_score": 216.87008666992188}, {"text": "Vaccine-induced antibodies can prevent or, in the case of feline infectious peritonitis virus, aggravate infections by coronaviruses. We investigated whether a recombinant native full-length S-protein trimer (triSpike) of severe acute respiratory syndrome coronavirus (SARS-CoV) was able to elicit a neutralizing and protective immune response in animals and analyzed the capacity of anti-S antibodies to mediate antibody-dependent enhancement (ADE) of virus entry in vitro and enhancement of replication in vivo. SARS-CoV-specific serum and mucosal immunoglobulins were readily detected in immunized animals. Serum IgG blocked binding of the S-protein to the ACE2 receptor and neutralized SARS-CoV infection in vitro. Entry into human B cell lines occurred in a FcγRII-dependent and ACE2-independent fashion indicating that ADE of virus entry is a novel cell entry mechanism of SARS-CoV. Vaccinated animals showed no signs of enhanced lung pathology or hepatitis and viral load was undetectable or greatly reduced in lungs following challenge with SARS-CoV. Altogether our results indicate that a recombinant trimeric S protein was able to elicit an efficacious protective immune response in vivo and warrant concern in the safety evaluation of a human vaccine against SARS-CoV.", "title": "Antibodies against trimeric S glycoprotein protect hamsters against SARS-CoV challenge despite their capacity to mediate FcγRII-dependent entry into B cells in vitro", "pid": "mqnz9gts", "bm25_score": 216.8597869873047}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are currently no SARS-CoV-2-specific treatments or vaccines available due to the novelty of the virus. Hence, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans.", "title": "Development of an inactivated vaccine candidate for SARS-CoV-2", "pid": "f5s0ntps", "bm25_score": 216.83966064453125}, {"text": "Abstract A secreted, glycosylated polypeptide containing amino acids 14 to 762 of the SARS coronavirus (SARS-CoV) spike protein and a polyhistidine tag was expressed in recombinant baculovirus-infected insect cells. Mice received the affinity-purified protein with either a saponin (QS21) or a Ribi (MPL + TDM) adjuvant subcutaneously and were challenged intranasally with SARS-CoV. Both regimens induced binding and neutralizing antibodies and protection against SARS-CoV intranasal infection. However, the best results were obtained with QS21 and protein, which provided the highest antibody as well as complete protection of the upper and lower respiratory tract.", "title": "Neutralizing antibody and protective immunity to SARS coronavirus infection of mice induced by a soluble recombinant polypeptide containing an N-terminal segment of the spike glycoprotein", "pid": "rwxjlhid", "bm25_score": 216.8259735107422}, {"text": "Background It is to be determined whether people infected with SARS-CoV-2 will develop long-term immunity against SARS-CoV-2 and retain long-lasting protective antibodies after the infection is resolved. This study was to explore to explore the outcomes of IgG antibodies to SARS-CoV-2 in four groups of individuals in Wuhan, China. Methods We included the following four groups of individuals who received both COVID-19 IgM/IgG tests and RT-PCR tests for SARS-CoV-2 from February 29, 2020 to April 29, 2020: 1470 hospitalized patients with COVID-19 from Leishenshan Hospital, Zhongnan Hospital of Wuhan University, and Wuhan No. 7 Hospital, 3832 healthcare providers without COVID-19 diagnosis, 19555 general workers, and 1616 other patients to be admitted to the hospital (N=26473). COVID-19 patients who received IgM/IgG tests <21 days after symptom onset were excluded. Results IgG prevalence was 89.8% (95% CI 88.2-91.3%) in COVID-19 patients, 4.0% (95% CI 3.4-4.7%) in healthcare providers, 4.6 (95% CI 4.3-4.9 %) in general workers, and 1.0% in other patients (p all <0.001 for comparisons with COVID-19 patients). IgG prevalence increased significantly by age among healthcare workers and general workers. Prevalence of IgM antibodies to SARS-CoV-2 was 31.4% in COVID-19 patients, 1.5% in healthcare providers, 1.3% in general workers, and 0.2% in other patients. Conclusions Very few healthcare providers had IgG antibodies to SARS-CoV-2, though a significant proportion of them had been infected with the virus. After SARS-CoV-2 infection, people are unlikely to produce long-lasting protective antibodies against this virus.", "title": "Prevalence of IgG antibodies to SARS-CoV-2 in Wuhan -implications for the ability to produce long-lasting protective antibodies against SARS-CoV-2", "pid": "066rysjh", "bm25_score": 216.81407165527344}, {"text": "To assess the current coronavirus pandemic, there is a pressing need to determine the exposure and seroconversion to SARS-CoV-2 on a local and global level. Here, we demonstrate a sensitive and specific S-protein based assay that is well suited for detection of weak SARS- CoV-2-directed IgG responses, and that could identify exposed individuals with asymptomatic infection without the requirement of PCR diagnostics. Our results raise the possibility that on- going population-based studies using less sensitive state-of-the-art serological assays may significantly underestimate the frequency of exposure and seroconversion to SARS-CoV-2.", "title": "Detection of asymptomatic SARS-CoV-2 exposed individuals by a sensitive S-based ELISA.", "pid": "frwte0tp", "bm25_score": 216.80596923828125}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging coronavirus that belongs to the ß-genus, causing the outbreak of coronavirus disease 19 (COVID-19). SARS-CoV-2 infection can stimulate a pronounced immune response in the host, which embodies in the decrease of lymphocytes and aberrant increase of cytokines in COVID-19 patients. SARS-CoV-2 RNA and proteins interact with various pattern recognition receptors that switch on antiviral immune responses to regulate viral replication and spreading within the host in vivo. However, overactive and impaired immune responses also cause immune damage and subsequent tissue inflammation. This article focuses on the dual roles of immune system during SARS-CoV-2 infection, providing a theoretical basic for identifying therapeutic targets in a situation with an unfavourable immune reaction.", "title": "SARS-CoV-2 infection-induced immune responses: Friends or foes?", "pid": "e1mw9lx1", "bm25_score": 216.79942321777344}, {"text": "The COVID-19 pandemic caused by SARS-CoV-2 has brought about an unprecedented crisis, taking a heavy toll on human health, lives as well as the global economy. There are no SARS-CoV-2-specific treatments or vaccines available due to the novelty of this virus. Hence, rapid development of effective vaccines against SARS-CoV-2 is urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies potently neutralized 10 representative SARS-CoV-2 strains, indicative of a possible broader neutralizing ability against SARS-CoV-2 strains circulating worldwide. Immunization with two different doses (3μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without any antibody-dependent enhancement of infection. Systematic evaluation of PiCoVacc via monitoring clinical signs, hematological and biochemical index, and histophathological analysis in macaques suggests that it is safe. These data support the rapid clinical development of SARS-CoV-2 vaccines for humans. One Sentence Summary A purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) confers complete protection in non-human primates against SARS-CoV-2 strains circulating worldwide by eliciting potent humoral responses devoid of immunopathology", "title": "Rapid development of an inactivated vaccine for SARS-CoV-2", "pid": "m1bvurwi", "bm25_score": 216.79212951660156}, {"text": "The SARS-CoV­2 causes a disease spectrum that includes asymptomatic and mildly symptomatic infections with subclinical manifestations but which can nevertheless still be potentially contagious. Evidence from SARS-CoV­2 infected macaque monkeys and from studies with seasonal coronaviruses suggests that the infection is likely to produce an immunity that is protective for a certain period of time. Available test methods enable a high degree of reliability, e.g. if high-quality serological methods are combined. Although individual test results have to be interpreted with caution, serosurveillance in a tertiary eye care center and large eye research institute can reduce anxiety and provide clarity regarding the actual number of (unreported) SARS-CoV­2 infections.", "title": "Seroprävalenz und SARS-CoV-2-Testung in Gesundheitsberufen./ [Seroprevalence and SARS-CoV-2 testing in healthcare occupations]", "pid": "rlpe6tpm", "bm25_score": 216.7650604248047}, {"text": "The SARS-CoV-2 virus is responsible for the current worldwide coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. The Spike glycoprotein of SARS-CoV-2 mediates viral entry and is the main target for neutralizing antibodies. Understanding the antibody response directed against SARS-CoV-2 is crucial for the development of vaccine, therapeutic and public health interventions. Here we performed a cross-sectional study on 98 SARS-CoV-2-infected individuals to evaluate humoral responses against the SARS-CoV-2 Spike. The vast majority of infected individuals elicited anti-Spike antibodies within 2 weeks after the onset of symptoms. The levels of receptor-binding domain (RBD)-specific IgG persisted overtime, while the levels of anti-RBD IgM decreased after symptoms resolution. Some of the elicited antibodies cross-reacted with other human coronaviruses in a genus-restrictive manner. While most of individuals developed neutralizing antibodies within the first two weeks of infection, the level of neutralizing activity was significantly decreased over time. Our results highlight the importance of studying the persistence of neutralizing activity upon natural SARS-CoV-2 infection.", "title": "Cross-sectional evaluation of humoral responses against SARS-CoV-2 Spike", "pid": "xzl23c52", "bm25_score": 216.74940490722656}, {"text": "The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.", "title": "DNA vaccine protection against SARS-CoV-2 in rhesus macaques", "pid": "w9zyshzb", "bm25_score": 216.74786376953125}, {"text": "The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.", "title": "DNA vaccine protection against SARS-CoV-2 in rhesus macaques", "pid": "pfjq2m42", "bm25_score": 216.74354553222656}, {"text": "COVID 19 is disease caused by novel corona virus, SARS-CoV2 originated in China most probably of Bat origin. Till date, no specific vaccine or drug has been discovered to tackle the infections caused by SARS-CoV2. In response to this pandemic, we utilized bioinformatics knowledge to develop efficient vaccine candidate against SARS-CoV2. Designed vaccine was rich in effective BCR and TCR epitopes screened from the sequence of S-protein of SARS-CoV2. Predicted BCR and TCR epitopes were antigenic in nature non-toxic and probably non-allergen. Modelled and refined tertiary structure was predicted as valid for further use. Protein-Protein interaction prediction of TLR2/4 and designed vaccine indicates promising binding. Designed multiepitope vaccine has induced cell mediated and humoral immunity along with increased interferon gamma response. Macrophages and dendritic cells were also found increased over the vaccine exposure. In silico codon optimization and cloning in expression vector indicates that vaccine can be efficiently expressed in E. coli. In conclusion, predicted vaccine is a good antigen, probable no allergen and has potential to induce cellular and humoral immunity.", "title": "In Silico design and characterization of multi-epitopes vaccine for SARS-CoV2 from its spike proteins", "pid": "7dw32xby", "bm25_score": 216.74205017089844}, {"text": "The world has given an outbreak alarm in the last two decades, with different members of the coronavirus family infecting people at different times. The spread of the SARS-CoV-2 virus, which last appeared in December 2019 in China and spread rapidly to all over the world, has led the scientific world to studies on these viruses. While scientists are trying to develop vaccines or drugs against the virus, the body's immune response to the virus is emerged the biggest guide. In this review, we aimed to provide a good view on immune strategies by comparing immunological responses to SARS-CoV-2 disease among other members of the family, SARS-CoV and MERS-CoV. In the near future, it may contribute to vaccine or drug studies to be developed on immune intervention.", "title": "Immune Responses to SARS-CoV, MERS-CoV and SARS-CoV-2", "pid": "chaa3swx", "bm25_score": 216.7413787841797}, {"text": "The world has given an outbreak alarm in the last two decades, with different members of the coronavirus family infecting people at different times. The spread of the SARS-CoV-2 virus, which last appeared in December 2019 in China and spread rapidly to all over the world, has led the scientific world to studies on these viruses. While scientists are trying to develop vaccines or drugs against the virus, the body's immune response to the virus is emerged the biggest guide. In this review, we aimed to provide a good view on immune strategies by comparing immunological responses to SARS-CoV-2 disease among other members of the family, SARS-CoV and MERS-CoV. In the near future, it may contribute to vaccine or drug studies to be developed on immune intervention.", "title": "Immune Responses to SARS-CoV, MERS-CoV and SARS-CoV-2.", "pid": "v155jl20", "bm25_score": 216.7405242919922}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of human infections. One limitation to the evaluation of potential therapies and vaccines to inhibit SARS-CoV-2 infection and ameliorate disease is the lack of susceptible small animals in large numbers. Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss. Passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss. The development of an accessible mouse model of SARS-CoV-2 infection and pathogenesis will expedite the testing and deployment of therapeutics and vaccines.", "title": "A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies", "pid": "amsmd809", "bm25_score": 216.73638916015625}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 6 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic, the question emerges whether human-to-animal transmission is possible and if so, which animal species are most at risk. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.", "title": "Insights on cross-species transmission of SARS-CoV-2 from structural modeling", "pid": "mtq6yh25", "bm25_score": 216.73507690429688}, {"text": "The global fight against coronavirus disease 2019 (COVID-19) is largely based on strategies to boost immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent its severe course and complications. The human defence may include antibodies which interact with SARS-CoV-2 and neutralize its aggressive actions on multiple organ systems. Protective cross-reactivity of antibodies against measles and other known viral infections has been postulated, primarily as a result of the initial observations of asymptomatic and mild COVID-19 in children. Uncontrolled case series have demonstrated virus-neutralizing effect of convalescent plasma, supporting its efficiency at early stages of contracting SARS-CoV-2. Given the variability of the virus structure, the utility of convalescent plasma is limited to the geographic area of its preparation, and for a short period of time. Intravenous immunoglobulin may also be protective in view of its nonspecific antiviral and immunomodulatory effects. Finally, human monoclonal antibodies may interact with some SARS-CoV-2 proteins, inhibiting the virus-receptor interaction and prevent tissue injury. The improved understanding of the host antiviral responses may help develop safe and effective immunotherapeutic strategies against COVID-19 in the foreseeable future.", "title": "Perspectives of Immune Therapy in Coronavirus Disease 2019", "pid": "0l86swz1", "bm25_score": 216.73287963867188}, {"text": "Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.", "title": "A serological assay to detect SARS-CoV-2 seroconversion in humans.", "pid": "u79trvqf", "bm25_score": 216.70347595214844}, {"text": "There have been concerns about high rates of thus far undiagnosed SARS-CoV-2 infections in the health-care system. The COVID-19 Contact (CoCo) Study follows 217 frontline health-care professionals at a university hospital with weekly SARS-CoV-2-specific serology (IgA/IgG). Study participants estimated their personal likelihood of having had a SARS-CoV-2 infection with a mean of 21% [median 15%, interquartile range (IQR) 5-30%]. In contrast, anti-SARS-CoV-2 IgG prevalence was about 1-2% at baseline. Regular anti-SARS-CoV-2 IgG testing of health-care professionals may aid in directing resources for protective measures and care of COVID-19 patients in the long run.", "title": "Perceived versus proven SARS-CoV-2-specific immune responses in health-care professionals", "pid": "kp661rmo", "bm25_score": 216.7027587890625}, {"text": "Background: Children have a lower rate of COVID-19, potentially related to cross-protective immunity conferred by seasonal coronaviruses (HCoVs). We tested if prior infections with seasonal coronaviruses impacted SARS-CoV-2 infections and related Multisystem Inflammatory Syndrome (MIS). Methods: This cross-sectional observational study in Paris hospitals enrolled 739 pauci or asymptomatic children (HOS group) plus 36 children with suspected MIS (MIS group). Prevalence, antigen specificity and neutralizing capability of SARS-CoV-2 antibodies were tested. Antibody frequency and titres against Nucleocapsid (N) and Spike (S) of the four seasonal coronaviruses (NL63, HKU1, 229E, OC43) were measured in a subset of seropositive patients (54 SARS-CoV-2 (HOS-P subgroup) and 15 MIS (MIS-P subgroup)), and in 118 matched SARS-CoV-2 seronegative patients (CTL subgroup). Findings: SARS-CoV-2 mean prevalence rate in HOSP children was 11.7% from April 1 to June 1. Neutralizing antibodies were found in 55.6% of seropositive children, and their relative frequency increased with time (up to 100 % by mid-May). A majority of MIS children (25/36) were SARS-CoV-2 seropositive, of which all tested (n=15) had neutralizing antibodies. On average, seropositive MIS children had higher N and S1 SARS-CoV-2 titres as compared to HOS children. Patients from HOS-P, MIS-P, and CTL subgroups had a similar prevalence of antibodies against the four seasonal HCoVs (66.9 -100%). The level of anti-SARS-CoV-2 antibodies was not significantly different in children who had prior seasonal coronavirus infection. Interpretation: Prior infection with HCoVs does not prevent SARS-CoV-2 infection and related MIS in children. Children develop neutralizing antibodies after SARS-CoV-2 infection.", "title": "Prior infection by seasonal coronaviruses does not prevent SARS-CoV-2 infection and associated Multisystem Inflammatory Syndrome in children", "pid": "49q2xxkw", "bm25_score": 216.68521118164062}, {"text": "Since the outbreak of a SARS epidemic last year, significant advances have been made on our understanding of the mechanisms of interaction between the SARS coronavirus (CoV) and the immune system. Strong humoral responses have been found in most patients following SARS-CoV infection, with high titers of neutralizing Abs present in their convalescent sera. The nucleocapsid (N) and spike (S) proteins of SARS-CoV appear to be the dominant antigens recognized by serum Abs. CD4+ T cell responses against the N protein have been observed in SARS patients and an HLA-A2-restricted cytotoxic T lymphocyte epitope in the S protein has been identified. It is likely that the immune responses induced by SARS-CoV infection could also cause pathological damage to the host, especially in the case of proinflammatory cytokines. There is also evidence suggesting that SARS-CoV might be able to directly invade cells of the immune system. Our understanding on the interaction between SARS-CoV, the immune system and local tissues is essential to future diagnosis, control and treatment of this very contagious disease.", "title": "Immunological responses against SARS-coronavirus infection in humans.", "pid": "7ro1up5b", "bm25_score": 216.68511962890625}, {"text": "The population of 168 countries all over the world is struggling with the outbreak of COVID-19. The outbreak is declared as pandemic and public health emergency of international concern declared by WHO. SARS-CoV-2 responsible for the present health emergency exhibited close resemblance with SARS-CoV. Both the viruses are zoonotic and belong to a large family of viruses Coronaviridae. The complete virus particle is made up of four major structural proteins, namely spikes (S), nucleocapsid (N), membrane (M), and envelope (E) encoded by virus genome. The S protein of virus shows similarity to S protein of SARS-CoV. COVID-19 spreads from person to person, and this makes it more vulnerable for causing infection. Several efforts are taken to find prevention strategies for COVID-19. Researchers across the globe are working to find effective vaccination for SARS-CoV-2. There is no vaccine or medication available till date for COVID-19. Preventive measures such as social distancing, awareness, maintenance of hygiene, isolation, and movement restrictions can help in control of COVID-19 spread. Proper sanitization and cleaned and sanitized public transport can be effective in inhibiting the spread of the virus. In the present situation of medical emergency, cooperation and support by following advices from the WHO and government only facilitate everyone to come over.", "title": "Prevention and Control Strategies for SARS-CoV-2 Infection", "pid": "x1u70y1x", "bm25_score": 216.6477813720703}, {"text": "The lower than expected number of SARS-CoV-2 cases in countries with fragile health systems is puzzling. Herein, we hypothesize that BCG vaccination policies and vaccine strain preferences adopted by different countries might influence the SARS-CoV-2 transmission patterns and/or COVID-19 associated morbidity and mortality. We also postulate that until a specific vaccine is developed, SARS-CoV-2 vulnerable populations could be immunized with BCG vaccines to attain heterologous nonspecific protection from the new coronavirus. In the lights of our investigations the most resistant countries appear to be the ones using Group I BCG strain. Within these countries, however, those who employs Russian strain is even more protected against COVID-19 infection.", "title": "Could individuals from countries using bcg vaccination be resistant to sars-cov-2 induced infections?/ Verem aşısı uygulayan ülkelerin bireyleri sars-cov-2 virüsünün yol açtığı enfeksiyona karşı daha dirençli olabilir mi?", "pid": "ogj0c3u9", "bm25_score": 216.63034057617188}, {"text": "Serological assays can detect anti-SARS-CoV-2 (SARS2) antibodies, but their sensitivity often comes at the expense of specificity. Here we used a Ternary Automated Blood Im-munoassay (TRABI) to assess the IgG response against SARS2 in 3,815 prepandemic plasma samples and 126 virologically and/or clinically confirmed COVID-19 samples. Posterior probabilities were calculated from 3x8 measurements of logarithmically diluted samples against the ectodomain and the receptor-binding domain of the spike protein and the nucleoprotein. We then performed 429,624 assays on 17,901 blood samples from patients of the University Hospital Zurich and from healthy blood donors. We found se-ropositivity in 44 of 8,591 patients and in 26 of 5,388 blood donors from December 2019 to May 2020. Western blotting confirmed seropositivity in COVID samples but in none of the prepandemic samples. Solution-equilibrium measurements revealed immunodominant antibodies with nanomolar affinity in COVID samples, whereas prepandemic plasma showed lower affinities despite similar titers for individual SARS2 antigens. Hence, TRABI identifies seropositive individuals in large unselected cohorts, discriminates be-tween SARS2 immunity and low-affinity crossreactivity, and is therefore suitable for large-scale nationwide screening campaigns.", "title": "Population-wide evolution of SARS-CoV-2 immunity tracked by a ternary immunoassay", "pid": "wgc6ch47", "bm25_score": 216.59690856933594}, {"text": "Expectations are high on serological tests for SARS-CoV-2. Further knowledge of the immunity is needed, but also evaluation of the reliability of the tests. Important for the latter is for which purpose the test is conducted and how common the outcome to be identified is (antibodies). For the determination of immunity at the individual level, the specificity of the test must be very high, preferably 100%. Even tests where the specificity is perceived as high, e.g. 95% or 99%, can lead to a large proportion of false positives, if the proportion of the population actually infected is small.", "title": "[Serological tests should be related to the aim of the testing, as well as the population].", "pid": "mz29ek4z", "bm25_score": 216.59352111816406}, {"text": "Here, we describe a serological enzyme-linked immunosorbent assay for the screening and identification of human SARS-CoV-2 seroconverters. This assay does not require the handling of infectious virus, can be adjusted to detect different antibody types in serum and plasma and is amenable to scaling. Serological assays are of critical importance to help define previous exposure to SARS-CoV-2 in populations, identify highly reactive human donors for convalescent plasma therapy and investigate correlates of protection.", "title": "A serological assay to detect SARS-CoV-2 seroconversion in humans", "pid": "1vd4zcad", "bm25_score": 216.58218383789062}, {"text": "The rapid spread of the corona virus pandemic is an existential problem for many people in numerous countries. So far, there is no effective vaccine protection or proven therapy available against the SARS-CoV-2 virus. In this review, we describe the role of passive immunization in times of the corona virus. Passive immunization could be a bridging technology to improve the immune defense of critically ill patients until better approaches with effective medications are available.", "title": "The role of passive immunization in the age of SARS-CoV-2: an update", "pid": "sqa44tkr", "bm25_score": 216.57821655273438}, {"text": "Broadly protective vaccines against known and pre-emergent human coronaviruses (HCoVs) are urgently needed. To gain a deeper understanding of cross-neutralizing antibody responses, we mined the memory B cell repertoire of a convalescent SARS donor and identified 200 SARS-CoV-2 binding antibodies that target multiple conserved sites on the spike (S) protein. A large proportion of the non-neutralizing antibodies display high levels of somatic hypermutation and cross-react with circulating HCoVs, suggesting recall of pre-existing memory B cells (MBCs) elicited by prior HCoV infections. Several antibodies potently cross-neutralize SARS-CoV, SARS-CoV-2, and the bat SARS-like virus WIV1 by blocking receptor attachment and inducing S1 shedding. These antibodies represent promising candidates for therapeutic intervention and reveal a target for the rational design of pan-sarbecovirus vaccines.", "title": "Broad neutralization of SARS-related viruses by human monoclonal antibodies", "pid": "egj0aym6", "bm25_score": 216.57261657714844}, {"text": "The continued explosive spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) despite aggressive public health measures has triggered an unprecedented international vaccine effort. However, correlates of protection, which can help guide intelligent vaccine design, are not known for SARS-CoV-2. Research on influenza immunity and vaccine development may provide valuable lessons for coronavirus efforts, especially considering similarities in rapid evolutionary potential. The apparent inevitability of future novel coronavirus outbreaks must prompt work on a universal coronavirus vaccine.", "title": "Universal coronavirus vaccines: the time to start is now", "pid": "yrrz7oef", "bm25_score": 216.56373596191406}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS-CoV-2 infection needs to be determined. Here, 26 cases of COVID-19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms, and no case of severe symptoms was found among these patients. Strikingly, a subset of these patients had SARS-CoV-2 and virus-specific IgG coexist for an unexpectedly long time, with two cases for up to 50 days. One COVID-19 patient who did not produce any SARS-CoV-2-bound IgG successfully cleared SARS-CoV-2 after 46 days of illness, revealing that without antibody-mediated adaptive immunity, innate immunity alone may still be powerful enough to eliminate SARS-CoV-2. This report may provide a basis for further analysis of both innate and adaptive immunity in SARS-CoV-2 clearance, especially in nonsevere cases.", "title": "Long-term coexistence of SARS-CoV-2 with antibody response in COVID-19 patients", "pid": "x1k6ao9h", "bm25_score": 216.55929565429688}, {"text": "There have been concerns about high rates of thus far undiagnosed SARS-CoV-2 infections in the health-care system. The COVID-19 Contact (CoCo) Study follows 217 frontline health-care professionals at a university hospital with weekly SARS-CoV-2-specific serology (IgA/IgG). Study participants estimated their personal likelihood of having had a SARS-CoV-2 infection with a mean of 21% [median 15%, interquartile range (IQR) 5–30%]. In contrast, anti-SARS-CoV-2 IgG prevalence was about 1–2% at baseline. Regular anti-SARS-CoV-2 IgG testing of health-care professionals may aid in directing resources for protective measures and care of COVID-19 patients in the long run.", "title": "Perceived versus proven SARS-CoV-2-specific immune responses in health-care professionals", "pid": "t07xxyov", "bm25_score": 216.55624389648438}, {"text": "Since December 2019, COVID-19, the clinical syndrome associated with SARS-CoV-2 infection, has infected more than 6.2 million people and brought the function of the global community to a halt. As the number of patients recovered from COVID-19 rises and the world transitions toward reopening, the question of acquired immunity versus the possibility of reinfection are critical to anticipating future viral spread. Here, we present a case of a patient previously recovered from COVID-19 who re-presents with new respiratory, radiographical, laboratory, and RT-PCR findings concerning for re-infection. We review this case in the context of the evolving discussion and theories surrounding dynamic RT-PCR results, prolonged viral shedding, and the possibility of developed immunity.", "title": "A case report of possible novel coronavirus 2019 reinfection", "pid": "aed6psww", "bm25_score": 216.55259704589844}, {"text": "", "title": "SARS-CoV-2, “common cold” coronaviruses’ cross-reactivity and “herd immunity”: The razor of Ockham (1285-1347)?", "pid": "uzhj4i1q", "bm25_score": 216.51593017578125}, {"text": "SARS-CoV-2 is a novel coronavirus that is the causative agent of coronavirus infectious disease 2019 (COVID-19). As of 17 April 2020, it has infected 2 114 269 people, resulting in 145 144 deaths. The timing, magnitude and longevity of humoral immunity is not yet understood for SARS-CoV-2. Nevertheless, understanding this is urgently required to inform the likely future dynamics of the pandemic, to guide strategies to allow relaxation of social distancing measures and to understand how to deploy limiting vaccine doses when they become available to achieve maximum impact. SARS-CoV-2 is the seventh human coronavirus to be described. Four human coronaviruses circulate seasonally and cause common colds. Two other coronaviruses, SARS and MERS, have crossed from animal sources into humans but have not become endemic. Here we review what is known about the human humoral immune response to epidemic SARS CoV and MERS CoV and to the seasonal, endemic coronaviruses. Then we summarize recent, mostly non-peer reviewed, studies into SARS-CoV-2 serology and reinfection in humans and non-human primates and summarize current pressing research needs.", "title": "The dynamics of humoral immune responses following SARS-CoV-2 infection and the potential for reinfection", "pid": "fzdmcahf", "bm25_score": 216.50921630859375}, {"text": "The S2 domain of the severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein is responsible for fusion between virus and target cell membranes, and is expected to be immungenic. In this study, we investigated the immune responses against the S2 subunit in BALB/c mice, which were vaccinated either with plasmid DNA encoding the S2 domain (residues 681-1120), the recombinant S2 fragment (residues 681-980) in incomplete Freund's adjuvant, or with inactivated SARS-CoV. The increased number of specific cytotoxic cells (CTLs) and the high titer of specific antibody showed stimulation of both arms of the immune system in these groups. The shift in cytokines suggested that Th1-polarized immune response was induced by plasmid pCoVS2, meanwhile the Th2-dominant response was induced by recombinant S2 fragment and inactivated vaccine. However, the titer of neutralizing antibodies was only detectable in mice immunized with inactivated virus, but not with pCoVS2 plasmid. Taken together, the S2 domain could induce specific cellular immune response and a high level of total IgG but little neutralizing antibodies against infection by SARSCoV.", "title": "Elicitation of immunity in mice after immunization with the S2 subunit of the severe acute respiratory syndrome coronavirus.", "pid": "4sxnbrd5", "bm25_score": 216.50570678710938}, {"text": "Viruses can generate molecular mimicry phenomena within their hosts. Why shouldsevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) not be considered one of these?Information in this short review suggests that it might be so and, thus, encourages research aimingat testing this possibility. We propose, as a working hypothesis, that the virus induces antibodiesand that some of them crossreact with host's antigens, thus eliciting autoimmune phenomena withdevasting consequences in various tissues and organs. If confirmed, by in vitro and in vivo tests,this could drive researchers to find effective treatments against the virus.", "title": "Does SARS-CoV-2 Trigger Stress-InducedAutoimmunity by Molecular Mimicry? A Hypothesis.", "pid": "di8lljoi", "bm25_score": 216.50091552734375}, {"text": "Novel SARS coronavirus (SARS-CoV-2) has caused a pandemic condition world-wide and has been declared as public health emergency of International concern by WHO in a very short span of time. The community transmission of this highly infectious virus has severely affected various parts of China, Italy, Spain and USA among others. The prophylactic solution against SARS-CoV-2 infection is challenging due to the high mutation rate of its RNA genome. Herein, we exploited a next generation vaccinology approach to construct a multi-epitope vaccine candidate against SARS-CoV-2 with high antigenicity, safety and efficacy to combat this deadly infectious agent. The whole proteome was scrutinized for the screening of highly conserved, antigenic, non-allergen and non-toxic epitopes having high population coverage that can elicit both humoral and cellular mediated immune response against COVID-19 infection. These epitopes along with four different adjuvants were utilized to construct a multi-epitope vaccine candidate that can generate strong immunological memory response having high efficacy in humans. Various physiochemical analyses revealed the formation of a stable vaccine product having a high propensity to form a protective solution against the detrimental SARS-CoV-2 strain with high efficacy. The vaccine candidate interacted with immunological receptor TLR3 with high affinity depicting the generation of innate immunity. Further, the codon optimization and in silico expression show the plausibility of the high expression and easy purification of the vaccine product. Thus, this present study provides an initial platform of the rapid generation of an efficacious protective vaccine for combating COVID-19.", "title": "Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes", "pid": "lmstdmyb", "bm25_score": 216.49658203125}, {"text": "Severe acute respiratory syndrome coronavirus 2 infection causing coronavirus disease 2019 has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS-CoV-2 infection needs to be determined. Here, 26 cases of COVID-19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms and no cases of severe symptoms were found among these patients. A striking feature of some patients is that SARS-CoV-2 could exist in patients who have virus-specific IgG antibodies for a very long period, with one case for up to 36 days. One COVID-19 patient who did not produce any SARS-CoV-2-bound IgG successfully cleared SARS-CoV-2 after 46 days of illness, revealing that without antibody-mediated adaptive immunity, innate immunity may still be powerful enough to eliminate SARS-CoV-2. Overall, this report may provide a basis for further analysis of both innate and adaptive immunity in SARS-CoV-2 clearance, especially in non-severe cases. This study also has implications for understanding the pathogenesis and treatment of SARS-CoV-2.", "title": "Long-term Co-existence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) with Antibody Response in Non-severe Coronavirus Disease 2019 (COVID-19) Patients", "pid": "12edypl7", "bm25_score": 216.49554443359375}, {"text": "SARS-CoV-2 is the coronavirus agent of the COVID-19 pandemic causing high mortalities. In contrast, the widely spread human coronaviruses OC43, HKU1, 229E, and NL63 tend to cause only mild symptoms. The present study shows, by in silico analysis, that these common human viruses are expected to induce immune memory against SARS-CoV-2 by sharing protein fragments (antigen epitopes) for presentation to the immune system by MHC class I. A list of such epitopes is provided. The number of these epitopes and the prevalence of the common coronaviruses suggest that a large part of the world population has some degree of specific immunity against SARS-CoV-2 already, even without having been infected by that virus. For inducing protection, booster vaccinations enhancing existing immunity are less demanding than primary vaccinations against new antigens. Therefore, for the discussion on vaccination strategies against COVID-19, the available immune memory against related viruses should be part of the consideration.", "title": "Expected immune recognition of COVID-19 virus by memory from earlier infections with common coronaviruses in a large part of the world population", "pid": "majelie8", "bm25_score": 216.49087524414062}, {"text": "", "title": "How to train health personnel to protect themselves from SARS-CoV-2 (novel coronavirus) infection when caring for a patient or suspected case", "pid": "50xhia4r", "bm25_score": 216.485595703125}, {"text": "We have investigated novel vaccine strategies against severe acute respiratory syndrome (SARS) CoV using cDNA constructs encoding the structural antigens: (S), (M), (E), or (N) protein, derived from SARS CoV. PBL from healthy human volunteers were administered i.p. into IL-2 receptor γ-chain disrupted SCID mice, and SCID-PBL/hu mice were constructed. These mice can be used to analyze the human immune response in vivo. SARS M DNA vaccine and N DNA vaccine induced human CTL specific for SARS CoV antigens. Alternatively, SARS M DNA vaccines inducing human neutralizing antibodies and human monoclonal antibodies against SARS CoV are now being developed. These results show that these vaccines can induce virus-specific immune responses and should provide a useful tool for development of protective and therapeutic vaccines.", "title": "Development of vaccines and passive immunotherapy against SARS corona virus using SCID-PBL/hu mouse models", "pid": "bdse9o26", "bm25_score": 216.45315551757812}, {"text": "The outbreak of SARS coronavirus 2 (SARS-CoV-2), which occurred in Wuhan, China in December 2019, has caused a worldwide pandemic of coronavirus disease 2019 (COVID-19). However, there is a lack of epidemiological tools to guide effective public policy development. Here we present epidemiological evidence that SARS-CoV-2 S type exited Wuhan or other epicenters in China earlier than L type and conferred partial resistance to the virus on infected populations. Analysis of regional disparities in incidence has revealed that a sharp decline in influenza epidemics is a useful surrogate indicator for the undocumented spread of SARS-CoV-2. The biggest concern in the world is knowing when herd immunity has been achieved and scheduling a time to regain the living activities of each country. This study provides a useful tool to guide the development of local policies to contain the virus.", "title": "Epidemiological Tools that Predict Partial Herd Immunity to SARS Coronavirus 2", "pid": "7onenxg7", "bm25_score": 216.4418182373047}, {"text": "", "title": "Children are protected against SARS-CoV-2 infection", "pid": "2u8rxzgb", "bm25_score": 216.4387664794922}, {"text": "The causative agent of severe acute respiratory syndrome (SARS) has been identified as a new type of coronavirus. Here, we have investigated the ability of adenoviral delivery of codon-optimised SARS-CoV strain Urbani structural antigens spike protein S1 fragment, membrane protein, and nucleocapsid protein to induce virus-specific broad immunity in rhesus macaques. We immunised rhesus macaques intramuscularly with a combination of the three Ad5-SARS-CoV vectors or a control vector and gave a booster vaccination on day 28. The vaccinated animals all had antibody responses against spike protein S1 fragment and T-cell responses against the nucleocapsid protein. All vaccinated animals showed strong neutralising antibody responses to SARS-CoV infection in vitro. These results show that an adenoviral-based vaccine can induce strong SARS-CoV-specific immune responses in the monkey, and hold promise for development of a protective vaccine against the SARS causal agent.", "title": "Effects of a SARS-associated coronavirus vaccine in monkeys", "pid": "vduk4asq", "bm25_score": 216.4336395263672}, {"text": "As the current SARS-CoV-2 pandemic continues, serological assays are urgently needed for rapid diagnosis, contact tracing and for epidemiological studies. So far, there is little data on how commercially available tests perform with real patient samples and if detected IgG antibodies provide protective immunity. Focusing on IgG antibodies, we demonstrate the performance of two ELISA assays (Euroimmun SARS-CoV-2 IgG & Vircell COVID-19 ELISA IgG) in comparison to one lateral flow assay ((LFA) FaStep COVID-19 IgG/IgM Rapid Test Device) and two in-house developed assays (immunofluorescence assay (IFA) and plaque reduction neutralization test (PRNT)). We tested follow up serum/plasma samples of individuals PCR-diagnosed with COVID-19. Most of the SARS-CoV-2 samples were from individuals with moderate to severe clinical course, who required an in-patient hospital stay. For all examined assays, the sensitivity ranged from 58.8 to 76.5% for the early phase of infection (days 5-9) and from 93.8 to 100% for the later period (days 10-18) after PCR-diagnosed with COVID-19. With exception of one sample, all positive tested samples in the analysed cohort, using the commercially available assays examined (including the in-house developed IFA), demonstrated neutralizing (protective) properties in the PRNT, indicating a potential protective immunity to SARS-CoV-2. Regarding specificity, there was evidence that samples of endemic coronavirus (HCoV-OC43, HCoV-229E) and Epstein Barr virus (EBV) infected individuals cross-reacted in the ELISA assays and IFA, in one case generating a false positive result (may giving a false sense of security). This need to be further investigated.", "title": "Clinical performance of SARS-CoV-2 IgG antibody tests and potential protective immunity", "pid": "bah2ege0", "bm25_score": 216.4309844970703}, {"text": "SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this outbreak, specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS-CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. Universal Immune System Simulator (UISS) in silico platform is potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2.", "title": "In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform", "pid": "48knj0tm", "bm25_score": 216.42185974121094}, {"text": "In many parts of the United States, SARS-CoV-2 cases have reached peak infection rates, prompting administrators to create protocols to resume elective cases. As elective procedures and surgeries get scheduled, ASCs must implement some form of widespread testing in order to ensure the safety of both the ASC staff as well as the patients being seen. The CDC recently announced the approval of new serological testing for SARS-CoV-2, a test that can indicate the presence of IgM and IgG antibodies in the serum against viral particles. However, the possibility for reinfection raises questions about the utility of this new serological test, as the presence of IgG may not correspond to long-term immunity. The coronavirus has been known to form escape mutations, which may correspond to reduction in immunoglobulin binding capacity. Patients who develop more robust immune responses with formation of memory CD8+ T-cells and helper CD4+ T-cells will be the most equipped if exposed to the virus, but unfortunately the serology test will not help us in distinguishing those individuals. Given the inherent disadvantages of serological testing, antibody testing alone should not be used when deciding patient care and should be combined with PCR testing.", "title": "Efficacy of Serology Testing in Predicting Reinfection in Patients with SARS-CoV-2.", "pid": "g1dij8ty", "bm25_score": 216.42042541503906}, {"text": "", "title": "Development of passive immunity against SARS-CoV-2 for management of immunodeficient patients - a perspective", "pid": "rirftuu9", "bm25_score": 216.41696166992188}]}
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"zl2url8z": 1, "zljb9bok": 0, "zn9ljvub": 0, "zndtddty": 0, "zpc9r4cl": 1, "zrnczve3": 0, "zs7i07k3": 0, "zs86lyxq": 1, "zso922ae": 1, "v0v0ahjh": 1, "ff04vt1d": 1, "zwaxie0c": 0, "zwtqc774": 0, "lf88bwh2": 2, "zy9lb7d9": 2, "zyumxab4": 0}, "bm25_results": [{"text": "The new coronavirus SARS-CoV-2, first identified in Wuhan, China in December, 2019, can cause Severe Acute Respiratory Syndrome (SARS) with massive alveolar damage and progressive respiratory failure. We present the relevant autopsy findings of the first patient known to have died from COVID19 pneumonia in Spain, carried out on the 14th of February, 2020, in our hospital (Hospital Arnau de Vilanova-Lliria, Valencia). Histological examination revealed typical changes of diffuse alveolar damage (DAD) in both the exudative and proliferative phase of acute lung injury. Intra-alveolar multinucleated giant cells, smudge cells and vascular thrombosis were present. The diagnosis was confirmed by reverse real-time PCR assay on a throat swab sample taken during the patient's admission. The positive result was reported fifteen days subsequent to autopsy.", "title": "Autopsy findings from the first known death from Severe Acute Respiratory Syndrome SARS-CoV-2 in Spain", "pid": "y4t38b69", "bm25_score": 215.1083984375}, {"text": "Infection by the new corona virus strain SARS-CoV-2 and its related syndrome COVID-19 has caused several hundreds of thousands of deaths worldwide. Patients of higher age and with preexisting chronic health conditions are at an increased risk of fatal disease outcome. However, detailed information on causes of death and the contribution of comorbidities to death yet is missing. Here, we report autopsy findings on causes of death and comorbidities of 26 decedents that had clinically presented with severe COVID-19. We found that septic shock and multi organ failure was the most common immediate cause of death, often due to suppurative pulmonary infection. Respiratory failure due to diffuse alveolar damage presented as the most immediate cause of death in fewer cases. Several comorbidities, such as hypertension, ischemic heart disease, and obesity were present in the vast majority of patients. Our findings reveal that causes of death were directly related to COVID-19 in the majority of decedents, while they appear not to be an immediate result of preexisting health conditions and comorbidities. We therefore suggest that the majority of patients had died of COVID-19 with only contributory implications of preexisting health conditions to the mechanism of death.", "title": "Causes of Death and Comorbidities in Patients with COVID-19", "pid": "9yb9a9vz", "bm25_score": 215.0832061767578}, {"text": "The mortality rate of coronavirus disease-19 (COVID-19) has been reported as 1-6% in most studies. The cause of most deaths has been acute pneumonia. Nevertheless, it has been noted that cardiovascular failure can also lead to death. Three COVID-19 patients were diagnosed based on reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab test and radiological examinations in our hospital. The patients received medications at the discretion of the treating physician. In this case series, chest computed tomography scans and electrocardiograms, along with other diagnostic tests were used to evaluate these individuals. Sudden cardiac death in COVID-19 patients is not common, but it is a major concern. So, it is recommended to monitor cardiac condition in selected patients with COVID-19.", "title": "Sudden cardiac death in COVID-19 patients, a report of three cases", "pid": "u9omhsgu", "bm25_score": 214.6771240234375}, {"text": "The mortality rate of coronavirus disease-19 (COVID-19) has been reported as 1–6% in most studies. The cause of most deaths has been acute pneumonia. Nevertheless, it has been noted that cardiovascular failure can also lead to death. Three COVID-19 patients were diagnosed based on reverse transcriptase-polymerase chain reaction of a nasopharyngeal swab test and radiological examinations in our hospital. The patients received medications at the discretion of the treating physician. In this case series, chest computed tomography scans and electrocardiograms, along with other diagnostic tests were used to evaluate these individuals. Sudden cardiac death in COVID-19 patients is not common, but it is a major concern. So, it is recommended to monitor cardiac condition in selected patients with COVID-19.", "title": "Sudden cardiac death in COVID-19 patients, a report of three cases", "pid": "378cfb23", "bm25_score": 214.67129516601562}, {"text": "As of April 2020, the coronavirus 2019 (COVID-19) pandemic has resulted in more than 210,000 deaths globally. The most common cause of death from COVID-19 is acute respiratory failure. We report the case of a 78-year-old female with a history of hypertension, cerebrovascular accident (CVA), type 2 diabetes mellitus, and sarcoidosis, who presented to the emergency department with one day of dyspnea. The patient experienced a rapid decline in respiratory function and was intubated in the intensive care unit (ICU), meeting the Berlin criteria for severe acute respiratory distress syndrome (ARDS). Chest radiography revealed diffuse bilateral coalescent opacities, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA swab test was positive for COVID-19. The patient experienced acute kidney injury with uptrending creatinine levels and remained lethargic and unresponsive throughout her ICU stay, suggestive of potential hypoxic brain injury. In light of the patient’s poor clinical status, age, and significant comorbidities, prognosis was conveyed about medical futility and patient’s family agreed to terminal extubation and the patient expired peacefully, exactly one week from hospital admission. This case report highlights the speed at which severe ARDS can present and contribute to end-organ dysfunction in COVID-19 patients.", "title": "A Case Report of Rapidly Lethal Acute Respiratory Distress Syndrome Secondary to Coronavirus Disease 2019 Viral Pneumonia", "pid": "q6wp6c08", "bm25_score": 214.57766723632812}, {"text": "A recently developed pneumonia caused by SARS-CoV-2 bursting in Wuhan, China, has quickly spread across the world. We report the clinical characteristics of 82 cases of death from COVID-19 in a single center. Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital's electronic medical records according to previously designed standardized data collection forms. All patients were local residents of Wuhan, and a large proportion of them were diagnosed with severe illness when admitted. Due to the overwhelming of our system, a total of 14 patients (17.1%) were treated in the ICU, 83% of deaths never received Critical Care Support, only 40% had mechanical ventilation support despite 100% needing oxygen and the leading cause of death being pulmonary. Most of the patients who died were male (65.9%). More than half of the patients who died were older than 60 years (80.5%), and the median age was 72.5 years. The bulk of the patients who died had comorbidities (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), followed by sepsis/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhagic, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), and increased C-reactive protein (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%) levels. A high level of IL-6 (>10 pg/ml) was observed in all detected patients. The median time from initial symptoms to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p = 0.002), alanine aminotransferase (p = 0.037) and time from initial symptoms to death was remarkably observed. Older males with comorbidities are more likely to develop severe disease and even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but the virus itself and cytokine release syndrome-mediated damage to other organs, including cardiac, renal, hepatic, and hemorrhagic damage, should be taken seriously as well.", "title": "Clinical characteristics of 82 cases of death from COVID-19.", "pid": "ls0x41h1", "bm25_score": 214.5353546142578}, {"text": "COVID-19 is an acute respiratory tract infection caused by a coronavirus known as SARS-CoV-2. The common signs of infection include respiratory symptoms such as shortness of breath, breathing difficulties, dry cough, fever, and in some patients, severe acute respiratory syndrome, kidney failure, and death. 312,009 deaths from COVID-19 has been reported as of today. While respiratory symptoms are commonly caused by the infection, the use of mechanical ventilation is required for some patients. The following is intended to review the development and testing of a 3D printed and open-source mechanical ventilation device that is capable of adjusting breathing rate, volume, and pressure simultaneously and was designed according to the latest clinical observations of the current pandemic. The intuitive design of this device along with the use of primarily 3D printed or readily available components allow the rapid manufacturing and transportation of this ventilation device to the impacted regions.", "title": "Open source 3D printed Ventilation Device", "pid": "ivbf4kuq", "bm25_score": 214.52049255371094}, {"text": "Background: COVID-19 was the leading cause of death in the United States over the three-month period March through May 2020. Another perspective is COVID-19s toll in terms of years of life lost. We calculated years of life lost for COVID-19 and other leading causes of death over those three months in the US. We also predicted years of life lost for COVID-19 and ischemic heart diseases (which includes heart attacks) for March through August 2020. Methods: Years of life lost are the sum of differences between life expectancy at age of death and age at death. Average years of life lost, years of life lost divided by the number of deaths, were also calculated. We used the COVID-19 Projections Using Machine Learning model to predict years of life lost from COVID-19 through the end of August 2020. Results: COVID-19 caused 12,035 more deaths than ischemic heart diseases during March through May 2020 but ischemic heart diseases years of life lost were 1.5% greater than those for COVID-19. Average years of life lost were 10.8 and 12.4 for COVID-19 and ischemic heart diseases, respectively. At the end of August, COVID-19 may overtake ischemic heart diseases as the leading cause of deaths and years of life lost in the US. Conclusion: Each COVID-19 death causes more than a decade of lost life in the US. We are reminded of a Danish Proverb that states \"Prediction is difficult, especially when dealing with the future.\" We suggest that while dying is bad, losing life is even worse.", "title": "COVID-19: Dying is Bad--Losing Life is Worse", "pid": "gtp01rna", "bm25_score": 214.48741149902344}, {"text": "", "title": "Risk factors for death from COVID-19", "pid": "97pdrvvt", "bm25_score": 214.43394470214844}, {"text": "In the last few weeks Italy first, and then several other countries across the world, have been swept up by the deadly wave of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes the illness named COVID-19, from the acronym CO (corona) VI (virus) D (disease) and 19 (year of the virus identification). The medical community is working day and night to assist affected people and experts in communicable diseases are striving in multiple ways to understand the progression of events leading to the lethal respiratory syndrome.", "title": "COVID‐19: what if the brain had a role in causing the deaths?", "pid": "6t3jrmr7", "bm25_score": 214.4226837158203}, {"text": "Abstract Background. Today humanity is facing another infectious threat: a newly emerging virus SARS-CoV-2 causing COVID-19. It was already described that COVID-19 mortality among elderly people and people with such underlying conditions as obesity, cardiovascular diseases, cancer, chronic respiratory diseases, and diabetes s increased. Dysregulation of the immune responses vital for antiviral defense, which are typical for chronic inflammation, led us to a hypothesis that chronic inflammation is the main risk factor for increased susceptibility and mortality from COVID-19. Method. Based on the available information for 126 countries, statistical analysis to find out whether the difference in incidence and mortality within countries can be explained by the existing chronic inflammation among the countries population, was conducted. Results. A positive correlation between the percentage of people dying from chronic noncommunicable diseases and COVID-19 incidence (p<0.001) and mortality (p<0.001) within countries. Conclusion. The problem of COVID-19-caused high mortality rate may be a consequence of the high number of people having chronic low-grade inflammation as a precondition, and thus, one of the potential ways to reduce risk of morbidity and mortality is to focus on this widespread health problem, mainly occurring in developed countries and to take corresponding diagnostic, preventative, and treatment measures.", "title": "COVID-19 Pandemic: Is Chronic Inflammation a Major Cause of Death?", "pid": "bmvdwa68", "bm25_score": 214.39820861816406}, {"text": "In this case report, a 50-year-old man who had no medical history, presented with multiple cardiac arrests following a week with progressing symptoms of pneumonia. After achieving return of spontaneous circulation he presented with respiratory failure with severe hypoxia, septic shock, and multiple organ failure. A chest X-ray showed signs of acute respiratory distress syndrome. Despite aggressive intensive care management, the patient died 7.5 hours after admission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was later confirmed, and the presumed cause of death was SARS-CoV-2 pneumonia. In conclusion: coronavirus disease 2019 (COVID-19) can lead to a fatal outcome in younger healthy residents, who are not treated timely in case of severe symptoms like dyspnoea.", "title": "[Fatal outcome of coronavirus disease 2019 in a previously healthy 50-year-old man].", "pid": "oirh39hs", "bm25_score": 214.37631225585938}, {"text": "A recently developed pneumonia caused by SARS-CoV-2 bursting in Wuhan, China, has quickly spread across the world. We report the clinical characteristics of 82 cases of death from COVID-19 in a single center. Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital's electronic medical records according to previously designed standardized data collection forms. All patients were local residents of Wuhan, and a large proportion of them were diagnosed with severe illness when admitted. Due to the overwhelming of our system, a total of 14 patients (17.1%) were treated in the ICU, 83% of deaths never received Critical Care Support, only 40% had mechanical ventilation support despite 100% needing oxygen and the leading cause of death being pulmonary. Most of the patients who died were male (65.9%). More than half of the patients who died were older than 60 years (80.5%), and the median age was 72.5 years. The bulk of the patients who died had comorbidities (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), followed by sepsis/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhagic, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), and increased C-reactive protein (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%) levels. A high level of IL-6 (>10 pg/ml) was observed in all detected patients. The median time from initial symptoms to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p = 0.002), alanine aminotransferase (p = 0.037) and time from initial symptoms to death was remarkably observed. Older males with comorbidities are more likely to develop severe disease and even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but the virus itself and cytokine release syndrome-mediated damage to other organs, including cardiac, renal, hepatic, and hemorrhagic damage, should be taken seriously as well.", "title": "Clinical characteristics of 82 cases of death from COVID-19", "pid": "jq0x08mw", "bm25_score": 214.32431030273438}, {"text": "The spread of pandemic COVID-19 has created unprecedented need for information. The pandemic is the cause of significant mortality and with this the need for rapidly disseminated information for palliative care professionals regarding the prevalence of symptoms, their intensity, their resistance or susceptibility to symptom control and the mode of death for patients. METHODS: We undertook a systematic review of published evidence for symptoms in patients with COVID-19 (with a specific emphasis on symptoms at end of life) and on modes of death. Inclusion: prospective or retrospective studies detailing symptom presence and/or cause or mode of death from COVID-19. RESULTS: 12 papers met the inclusion criteria and gave details of symptom burden: four of these specifically in the dying and two detailed the cause or mode of death. Cough, breathlessness, fatigue and myalgia are significant symptoms in people hospitalised with COVID-19. Dyspnoea is the most significant symptom in the dying. The mode of death was described in two papers and is predominantly through respiratory or heart failure. CONCLUSIONS: There remains a dearth of information regarding symptom burden and mode of death to inform decisions regarding end-of-life care in patients dying with COVID-19. Rapid data gathering on the mode of death and the profile of symptoms in the dying and their prevalence and severity in areas where COVID-19 is prevalent will provide important intelligence for clinicians. This should be done urgently, within ethical norms and the practicalities of a public health, clinical and logistical emergency.", "title": "Symptom burden and clinical profile of COVID-19 deaths: a rapid systematic review and evidence summary", "pid": "ndke01xy", "bm25_score": 214.29434204101562}, {"text": "COVID-19 is not deadly early in life, but mortality increases exponentially with age, which is the strongest predictor of mortality. Mortality is higher in men than in women, because men age faster, and it is especially high in patients with age-related diseases, such as diabetes and hypertension, because these diseases are manifestations of aging and a measure of biological age. At its deepest level, aging (a program-like continuation of developmental growth) is driven by inappropriately high cellular functioning. The hyperfunction theory of quasi-programmed aging explains why COVID-19 vulnerability (lethality) is an age-dependent syndrome, linking it to other age-related diseases. It also explains inflammaging and immunosenescence, hyperinflammation, hyperthrombosis, and cytokine storms, all of which are associated with COVID-19 vulnerability. Anti-aging interventions, such as rapamycin, may slow aging and age-related diseases, potentially decreasing COVID-19 vulnerability.", "title": "From causes of aging to death from COVID-19", "pid": "joigb8qm", "bm25_score": 214.25611877441406}, {"text": "Abstract Purpose: Currently, COVID-19 is causing a large number of deaths globally. However, few researches focused on the clinical features of death patients. This study conducted a retrospective analysis of clinical characteristics and mortal causes in Chinese COVID-19 death patients. Patients and methods: The clinical characteristics of death patients were collected from publicized by local health authorities in China. Expressions of virus targets in human organs were obtained from GTEx database. Results: 159 patients from 24 provinces in China were recruited in our study, including 26 young patients under 60 and 133 aged 60 or older. The median age was 71 years, which indicated that most death patients were elderly. More male patients died of COVID-19 than females (1.65 fold). Hypertension was the most common coexisting disorder and respiratory failure was the most common direct cause of death. Fever (71.19%) and cough (55.08%) were the predominant presenting symptoms. There was one asymptomatic patient. In addition, by comparing young and old patients, heart disease was identified as an important risk factor for death in the aged patients. ACE2 and TMPRSS2 were the targets of SARS-CoV-2, we analyzed their expression in different organs. TMPRSS2 and ACE2 had a high expression in the organs which had corresponding clinical features in death patients. Conclusion: Male, age and heart disease were the main risk factors of death. Beside, asymptomatic patients with serious coexisting disorders may also die of SARS-CoV-2. Thus, more attention should be paid to the old patients with heart disease and asymptomatic patients in the treatment . Keywords: COVID-19, SARS-Cov-2, death, coexisting disorder, cause of death", "title": "The clinical characteristics and mortal causes analysis of COVID-19 death patients", "pid": "dtlwjndn", "bm25_score": 214.25311279296875}, {"text": "The spread of pandemic COVID-19 has created unprecedented need for information. The pandemic is the cause of significant mortality and with this the need for rapidly disseminated information for palliative care professionals regarding the prevalence of symptoms, their intensity, their resistance or susceptibility to symptom control and the mode of death for patients. METHODS We undertook a systematic review of published evidence for symptoms in patients with COVID-19 (with a specific emphasis on symptoms at end of life) and on modes of death. Inclusion: prospective or retrospective studies detailing symptom presence and/or cause or mode of death from COVID-19. RESULTS 12 papers met the inclusion criteria and gave details of symptom burden: four of these specifically in the dying and two detailed the cause or mode of death. Cough, breathlessness, fatigue and myalgia are significant symptoms in people hospitalised with COVID-19. Dyspnoea is the most significant symptom in the dying. The mode of death was described in two papers and is predominantly through respiratory or heart failure. CONCLUSIONS There remains a dearth of information regarding symptom burden and mode of death to inform decisions regarding end-of-life care in patients dying with COVID-19. Rapid data gathering on the mode of death and the profile of symptoms in the dying and their prevalence and severity in areas where COVID-19 is prevalent will provide important intelligence for clinicians. This should be done urgently, within ethical norms and the practicalities of a public health, clinical and logistical emergency.", "title": "Symptom burden and clinical profile of COVID-19 deaths: a rapid systematic review and evidence summary.", "pid": "7ksh8c5v", "bm25_score": 214.2217254638672}, {"text": "The pandemia of coronavirus disease 2019 (COVID-19) has caused more than 355,000 confirmed deaths worldwide. However, publications on postmortem findings are scarce. We present the pulmonary findings in four cases of fatal COVID-19 with a spectrum of lung pathology reflecting disease course and duration, invasive therapies, and laboratory features. Early disease is characterized by neutrophilic, exudative capillaritis with microthrombosis and high levels of IL-1beta and IL-6. Later stages are associated with diffuse alveolar damage and ongoing intravascular thrombosis in small to medium-sized pulmonary vessels, occasionally with areas of infarction equivalents, accompanied by laboratory features of disseminated intravascular coagulation. In late stages, organizing pneumonia with extensive intra-alveolar proliferation of fibroblasts and marked metaplasia of alveolar epithelium can be observed. Viral RNA is encountered in the lung, with virus particles in endothelial cells and pneumocytes. In many patients, multi-organ failure with severe liver damage sets in finally, possibly as consequence of an early-onset pro-inflammatory cytokine storm and/or thrombotic microangiopathy.", "title": "The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation", "pid": "vx5cszxg", "bm25_score": 214.19752502441406}, {"text": "Here, we report the pathological findings of nine complete autopsies of individuals who died in community settings in the UK, three of which were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), three tested negative for SARS-CoV-2 but are likely false negatives, and three died of other respiratory infections. Autopsy revealed firm, consolidated lungs or lobar pneumonia. Histology of the lungs showed changes of diffuse alveolar damage with fibrin membrane formation, thickened alveolar walls and interstitium with lymphocytic infiltrate, and type 2 pneumocyte hyperplasia with shedding into the alveolar space. This series is the first in the world to describe autopsy findings in individuals dying suddenly in the community, not previously known to have COVID-19 infection, and the first autopsy series in the UK. During a time when testing in the UK is currently primarily offered to patients in hospital or symptomatic key workers, with limited testing available in community settings, it highlights the importance of testing for COVID-19 at autopsy. Two deaths occurred in care homes where a diagnosis of COVID-19 allowed the health protection team to provide support in that 'closed setting' to reduce the risks of onward transmission. This work highlights the need for frequent COVID-19 testing in the management of patients in community settings. Comprehensive virology and microbiology assessment is pivotal to correctly identify the cause of death, including those due to COVID-19 infection, and to derive accurate death statistics.", "title": "COVID-19 autopsy in people who died in community settings: the first series.", "pid": "fnv2moum", "bm25_score": 214.1963348388672}, {"text": "Covid-19 death has a different relationship with age than is the case for other severe respiratory pathogens. The Covid-19 death rate increases exponentially with age, and the main risk factors are age itself, as well as having underlying conditions such as hypertension, diabetes, cardiovascular disease, severe chronic respiratory disease and cancer. Furthermore, the almost complete lack of deaths in children suggests that infection alone is not sufficient to cause death; rather, one must have gone through a number of changes, either as a result of undefined aspects of aging, or as a result of chronic disease. These characteristics of Covid-19 death are consistent with the multistep model of disease, a model which has primarily been used for cancer, and more recently for amyotrophic lateral sclerosis (ALS). We applied the multi-step model to data on Covid-19 case fatality rates (CFRs) from China, South Korea, Italy, Spain and Japan. In all countries we found that a plot of ln (CFR) against ln (age) was approximately linear with a slope of about 5. As a comparison, we also conducted similar analyses for selected other respiratory diseases. SARS showed a similar log-log age-pattern to that of Covid-19, albeit with a lower slope, whereas seasonal and pandemic influenza showed quite different age-patterns. Thus, death from Covid-19 and SARS appears to follow a distinct age-pattern, consistent with a multistep model of disease that in the case of Covid-19 is probably defined by comorbidities and age producing immune-related susceptibility. Identification of these steps would be potentially important for prevention and therapy for SARS-COV-2 infection.", "title": "Is death from Covid-19 a multistep process?", "pid": "zl2url8z", "bm25_score": 214.1848907470703}, {"text": "", "title": "Excess out-of-hospital deaths during COVID-19 outbreak: evidence of pulmonary embolism as a main determinant", "pid": "nx00gawo", "bm25_score": 214.1739044189453}, {"text": "BACKGROUND: COVID-19 can cause a fatal outcome in elderly patients, as this case report illustrates. CASE PRESENTATION: An active male in his nineties with a high level of function, despite several severe chronic diseases, was admitted to Oslo University Hospital after two days of fatigue, fever, dyspnoea and dry cough. He scored qSOFA 1 of 3 points due to high respiratory rate, and SIRS 2 of 4 points due to high respiratory rate and fever of 39.4º C. PCR for influenza virus was negative and he received benzylpenicillin for pneumonia. The chest X-ray taken initially showed no lung affection. On day 5 after symptom debut he was tested for COVID-19 which was positive. He had not been travelling to high-risk areas or been exposed to any known confirmed COVID-19 patients. On the same day, a chest CT scan was performed that showed ground-glass opacities. In subsequent days the patient's health rapidly deteriorated. He developed irreversible respiratory failure with hypoxia without hypercapnia despite substantial oxygen support. Chest X-ray taken on disease day 7 showed progression of consolidations. The patient died 9 days after symptom debut. INTERPRETATION: This case illustrates a severe course of COVID-19 with fatal outcome. The patient was also one of the earliest admitted with COVID-19 in a Norwegian hospital and marked a new phase of the epidemic, as he had not been travelling to high-risk areas or been exposed to any confirmed COVID-19 patients.", "title": "En mann i 90-årene med feber og tørrhoste./ En mann i 90-årene med feber og tørrhoste./ A man in his nineties with fever and dry cough", "pid": "ofuk5k9f", "bm25_score": 214.16163635253906}, {"text": "“Severe acute respiratory syndrome” (SARS) due to coronavirus (SARS-CoV-2) infection is a well-known cause of death. Sometimes, demise can occur unexpectedly in apparently previous healthy individual after a brief period of trivial flu-like symptoms. In these doubtful cases, the forensic pathologist could be requested to define the cause of death occurred outside the hospital. In this report, the authors describe two autopsied cases of SARS-CoV-2-related deaths which occurred suddenly at home and were not preceded by hospitalization, highlighting associated histopathologic patterns and correlating them to pathophysiology of viral infection.", "title": "SARS-CoV-2-related deaths in routine forensic autopsy practice: histopathological patterns", "pid": "3m7243ty", "bm25_score": 214.15603637695312}, {"text": "Here, we report the pathological findings of nine complete autopsies of individuals who died in community settings in the UK, three of which were positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), three tested negative for SARS-CoV-2 but are likely false negatives, and three died of other respiratory infections. Autopsy revealed firm, consolidated lungs or lobar pneumonia. Histology of the lungs showed changes of diffuse alveolar damage with fibrin membrane formation, thickened alveolar walls and interstitium with lymphocytic infiltrate, and type 2 pneumocyte hyperplasia with shedding into the alveolar space. This series is the first in the world to describe autopsy findings in individuals dying suddenly in the community, not previously known to have COVID-19 infection, and the first autopsy series in the UK. During a time when testing in the UK is currently primarily offered to patients in hospital or symptomatic key workers, with limited testing available in community settings, it highlights the importance of testing for COVID-19 at autopsy. Two deaths occurred in care homes where a diagnosis of COVID-19 allowed the health protection team to provide support in that 'closed setting' to reduce the risks of onward transmission. This work highlights the need for frequent COVID-19 testing in the management of patients in community settings. Comprehensive virology and microbiology assessment is pivotal to correctly identify the cause of death, including those due to COVID-19 infection, and to derive accurate death statistics.", "title": "COVID-19 autopsy in people who died in community settings: the first series", "pid": "85npeznw", "bm25_score": 214.15585327148438}, {"text": "Abstract Objectives This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. Methods The clinical records, laboratory findings and radiological assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. Results The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-dimer, LDH and lactate levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts. Conclusions The clinical characteristics of 25 death cases with COVID-19 we summarized, which would be helpful to identify critically ill patients of COVID-19 early and reduce their mortality.", "title": "Clinical characteristics of 25 death cases with COVID-19: a retrospective review of medical records in a single medical center, Wuhan, China", "pid": "qvhwypjt", "bm25_score": 214.1547393798828}, {"text": "Background. Coronavirus disease 2019 (COVID-19) triggered by infection with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been widely pandemic all over the world. The aim of this study was to analyze the influence factors of death risk among 200 COVID-19 patients. Methods. Two hundred patients with confirmed SARS-CoV-2 infection were recruited. Demographic data and clinical characteristics were collected from electronic medical records. Biochemical indexes on admission were measured and patient's prognosis was tracked. The association of demographic data, clinical characteristics and biochemical indexes with death risk was analyzed. Results. Of 200 COVID-19 patients, 163 (81.5%) had at least one of comorbidities, including diabetes, hypertension, hepatic disease, cardiac disease, chronic pulmonary disease and others. Among all patients, critical cases, defined as oxygenation index lower than 200, accounted for 26.2%. Severe cases, oxygenation index from 200 to 300, were 29.7%. Besides, common cases, oxygenation index higher than 300, accounted for 44.1%. At the end of follow-up, 34 (17%) were died on mean 10.9 day after hospitalization. Stratified analysis revealed that older ages, lower oxygenation index and comorbidities elevated death risk of COVID-19 patients. On admission, 85.5% COVID-19 patients were with at least one of extrapulmonary organ injuries. Univariable logistic regression showed that ALT and TBIL, two indexes of hepatic injury, AST, myoglobin and LDH, AST/ALT ratio, several markers of myocardial injury, creatinine, urea nitrogen and uric acid, three indexes of renal injury, were positively associated with death risk of COVID-19 patients. Multivariable logistic regression revealed that AST/ALT ratio, urea nitrogen, TBIL and LDH on admission were positively correlated with death risk of COVID-19 patients. Conclusion. Older age, lower oxygenation index and comorbidities on admission elevate death risk of COVID-19 patients. AST/ALT ratio, urea nitrogen, TBIL and LDH on admission may be potential prognostic indicators. Early hospitalization is of great significance to prevent multiple organ damage and improve the survival of COVID-19 patients.", "title": "Influence factors of death risk among COVID-19 patients in Wuhan, China: a hospital-based case-cohort study", "pid": "igfur3l9", "bm25_score": 214.14695739746094}, {"text": "In December 2019 a novel disease [coronavirus disease 19 (COVID-19) emerged in the Wuhan province of the People's Republic of China. COVID-19 is caused by a novel coronavirus (SARS-CoV-2) thought to have jumped species, from another mammal to humans. A pandemic caused by this virus is running rampant throughout the world. Thousands of cases of COVID-19 are reported in England and over 10,000 patients have died. Whilst there has been progress in managing this disease, it is not clear which factors, besides age, affect the severity and mortality of COVID-19. A recent analysis of COVID-19 in Italy identified links between air pollution and death rates. Here, we explored the correlation between three major air pollutants linked to fossil fuels and SARS-CoV-2 lethality in England. We compare up-to-date, real-time SARS-CoV-2 cases and death measurements from public databases to air pollution data monitored across over 120 sites in different regions. We found that the levels of some markers of poor air quality, nitrogen oxides and ozone, are associated with COVID-19 lethality in different English regions. We conclude that the levels of some air pollutants are linked to COVID-19 cases and morbidity. We suggest that our study provides a useful framework to guide health policy in countries affected by this pandemic.", "title": "Links between air pollution and COVID-19 in England", "pid": "lfl7mnd8", "bm25_score": 214.14413452148438}, {"text": "Coronavirus disease 2019 (COVID-19) is an infectious disease that primarily affects the respiratory system, but it may cause cardiovascular complications such as thromboembolism. Rarely, pulmonary embolism may be encountered in patients with severe COVID-19 infection, especially in intensive care units. An asymptomatic young case of COVID-19 presenting with sudden death due to acute massive pulmonary embolism has not been previously described. We report a 41-year-old woman presented to emergency department with sudden death during physical activity. She had only history of diabetes mellitus and she was asymptomatic until sudden death. CT pulmonary angiography and chest CT scans revealed acute massive embolism and typical imaging findings of COVID-19 pneumonia, respectively. Interestingly, the patient had no symptoms or signs of infection and also had no risk factors for thromboembolism. COVID-19 infection appears to induce venous thromboembolism, especially pulmonary embolism. The case is remarkable in terms of showing how insidious and life-threatening COVID-19 infection can be.", "title": "Sudden death due to acute pulmonary embolism in a young woman with COVID-19", "pid": "qsamn8bk", "bm25_score": 214.14022827148438}, {"text": "The COVID-19 virus has infected millions of people and resulted in hundreds of thousands of deaths worldwide. By using the logistic regression model, we identified novel critical factors associated with COVID19 cases, death, and case fatality rates in 154 countries and in the 50 U.S. states. Among numerous factors associated with COVID-19 risk, we found that the unitary state system was counter-intuitively positively associated with increased COVID-19 cases and deaths. Blood type B was a protective factor for COVID-19 risk, while blood type A was a risk factor. The prevalence of HIV, influenza and pneumonia, and chronic lower respiratory diseases was associated with reduced COVID-19 risk. Obesity and the condition of unimproved water sources were associated with increased COVID-19 risk. Other factors included temperature, humidity, social distancing, smoking, and vitamin D intake. Our comprehensive identification of the factors affecting COVID-19 transmission and fatality may provide new insights into the COVID-19 pandemic and advise effective strategies for preventing and migrating COVID-19 spread.", "title": "Identifying novel factors associated with COVID-19 transmission and fatality using the machine learning approach", "pid": "yl7m77fo", "bm25_score": 214.13589477539062}, {"text": "A novel coronavirus, SARS-CoV-2, emerged in December 2019, leading within a few months to a global pandemic. COVID-19, the disease caused by this highly contagious virus, can have serious health consequences, though risks of complications are highly age-dependent. Rates of hospitalization and death are less than 0.1% in children, but increase to 10% or more in older people. Moreover, at all ages, men are more likely than women to suffer serious consequences from COVID-19. These patterns are familiar to the geroscience community. The effects of age and sex on mortality rates from COVID-19 mirror the effects of aging on almost all major causes of mortality. These similarities are explored here, and underscore the need to consider the role of basic biological mechanisms of aging on potential treatment and outcomes of COVID-19.", "title": "A geroscience perspective on COVID-19 mortality", "pid": "mcrf27ew", "bm25_score": 214.11807250976562}, {"text": "\"Severe acute respiratory syndrome\" (SARS) due to coronavirus (SARS-CoV-2) infection is a well-known cause of death. Sometimes, demise can occur unexpectedly in apparently previous healthy individual after a brief period of trivial flu-like symptoms. In these doubtful cases, the forensic pathologist could be requested to define the cause of death occurred outside the hospital. In this report, the authors describe two autopsied cases of SARS-CoV-2-related deaths which occurred suddenly at home and were not preceded by hospitalization, highlighting associated histopathologic patterns and correlating them to pathophysiology of viral infection.", "title": "SARS-CoV-2-related deaths in routine forensic autopsy practice: histopathological patterns", "pid": "myhgm3eq", "bm25_score": 214.11199951171875}, {"text": "The spreading of Coronavirus (SARS-CoV-2) pandemic, known as COVID-19, has caused a great number of fatalities all around the World. Up to date (2020 May 6) in Italy we had more than 28,000 deaths, while there were more than 205.000 infected. The majority of patients affected by COVID-19 complained only slight symptoms: fatigue, myalgia or cough, but more than 15% of Chinese patients progressed into severe complications, with acute respiratory distress syndrome (ARDS), needing intensive treatment. We tried to summarize data reported in the last months from several Countries, highlighting that COVID-19 was characterized by cytokine storm (CS) and endothelial dysfunction in severely ill patients, where the progression of the disease was fast and fatal. Endothelial dysfunction was the fundamental mechanism triggering a pro-coagulant state, finally evolving into intravascular disseminated coagulation, causing embolization of several organs and consequent multiorgan failure (MOF). The Italian Society of Clinical Hemorheology and Microcirculation was aimed to highlight the role of microcirculatory dysfunction in the pathogenetic mechanisms of COVID-19 during the spreading of the biggest challenges to the World Health.", "title": "COVID-19 Sepsis and Microcirculation Dysfunction", "pid": "dklpifdj", "bm25_score": 214.1042938232422}, {"text": "", "title": "Covid-19: risk factors for severe disease and death.", "pid": "jtui5j90", "bm25_score": 214.08680725097656}, {"text": "Summary Background The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2) is a highly infectious disease, which was occurred in Wuhan, Hubei Province, China in December 2019. As of February 13, 2020, a total of 59883 cases of COVID-19 in China have been confirmed and 1368 patients have died from the disease. However, the clinical characteristics of the dyed patients were still not clearly clarified. This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. Methods The clinical records, laboratory findings and radiologic assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. Findings The mean age of the dead was 71.48 years, the average course of the disease was 10.56 days, all patients eventually died of respiratory failure. All of those who died had underlying diseases, the most common of which was hypertension (16/25, 64%), followed by diabetes (10/25, 40%), heart diseases (8/25, 32%), kidney diseases (5/25, 20%), cerebral infarction (4/25, 16%), chronic obstructive pulmonary disease (COPD, 2/25, 8%), malignant tumors (2/25, 8%) and acute pancreatitis (1/25, 4%). The most common organ damage outside the lungs was the heart, followed by kidney and liver. In the patients' last examination before death, white blood cell and neutrophil counts were elevated in 17 patients (17/25, 68%) and 18 patients (18/25, 72%), lymphocyte counts were decreased in 22 patients (22/25, 88%). Most patients' PCT, CRP and SAA levels were elevated, the percentages were 90.5% (19/21), 85% (19/20) and 100% (21/21) respectively. The levels of the last test of neutrophils (15/16, 93.8%), PCT (11/11, 100%), CRP (11/13, 84.6%), cTnI (8/9, 88.9%), D-Dimer (11/12, 91.6%) and LDH (9/9, 100%) were increased as compared to the first test, while the levels of lymphocytes were decreased (14/16, 87.5%). Interpretation The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-Dimer and LDH levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts.", "title": "Clinical characteristics of 25 death cases infected with COVID-19 pneumonia: a retrospective review of medical records in a single medical center, Wuhan, China", "pid": "qg2o0ug4", "bm25_score": 214.0808868408203}, {"text": "", "title": "COVID-19: what if the brain had a role in causing the deaths?", "pid": "nay6x9y1", "bm25_score": 214.075439453125}, {"text": "OBJECTIVES: This study aims to summarize the clinical characteristics of death cases with COVID-19 and to identify critically ill patients of COVID-19 early and reduce their mortality. METHODS: The clinical records, laboratory findings and radiological assessments included chest X-ray or computed tomography were extracted from electronic medical records of 25 died patients with COVID-19 in Renmin Hospital of Wuhan University from Jan 14 to Feb 13, 2020. Two experienced clinicians reviewed and abstracted the data. RESULTS: The age and underlying diseases (hypertension, diabetes, etc.) were the most important risk factors for death of COVID-19 pneumonia. Bacterial infections may play an important role in promoting the death of patients. Malnutrition was common to severe patients. Multiple organ dysfunction can be observed, the most common organ damage was lung, followed by heart, kidney and liver. The rising of neutrophils, SAA, PCT, CRP, cTnI, D-dimer, LDH and lactate levels can be used as indicators of disease progression, as well as the decline of lymphocytes counts. CONCLUSIONS: The clinical characteristics of 25 death cases with COVID-19 we summarized, which would be helpful to identify critically ill patients of COVID-19 early and reduce their mortality.", "title": "Clinical characteristics of 25 death cases with COVID-19: A retrospective review of medical records in a single medical center, Wuhan, China", "pid": "8om7z5cc", "bm25_score": 214.05947875976562}, {"text": "The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020. Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died. Univariate and multivariate logistic regression analysis revealed that age &#8805;65†years (OR 3.765, 95% CI 1.146‒17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755‒8.044; p=0.007), CD3+CD8+ T-cells &#8804;75†cells·µL-1 (OR 3.982, 95% CI 1.132‒14.006; p<0.001) and cardiac troponin I &#8805;0.05†ng·mL-1 (OR 4.077, 95% CI 1.166‒14.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia. In a sex-, age- and comorbid illness-matched case-control study, CD3+CD8+ T-cells &#8804;75†cells·µL-1 and cardiac troponin I &#8805;0.05†ng·mL-1 remained as predictors for high mortality from COVID-19 pneumonia.We identified four risk factors: age &#8805;65†years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells &#8804;75†cells·µL-1 and cardiac troponin I &#8805;0.05†ng·mL-1 The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.", "title": "Predictors of mortality for patients with COVID-19 pneumonia caused by SARS-CoV-2: a prospective cohort study", "pid": "5wazfkey", "bm25_score": 214.04888916015625}, {"text": "Coronavirus Disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has infected more than 3.0 million people worldwide and killed more than 200,000 as of April 27, 2020, making it the most lethal pandemic since the Spanish flu of 1918.1, 2 COVID-19 may preferentially infect individuals with cardiovascular conditions, is more severe in subjects with cardiovascular comorbidities, may directly or indirectly affect the heart and may interact with cardiovascular medications.3 In addition, the widespread effects of the pandemic on the global healthcare system affects the routine and emergency cardiac care for patients who are, may be, or are not infected with COVID-19.", "title": "Current perspectives on Coronavirus 2019 (COVID-19) and cardiovascular disease: A white paper by the JAHA editors.", "pid": "tr5whji0", "bm25_score": 214.03558349609375}, {"text": "COVID-19 is an ongoing pandemic caused by the SARS-CoV-2 coronavirus that poses one of the greatest challenges to public health in recent years. SARS-CoV-2 is highly contagious and often leads to severe viral pneumonia with respiratory failure and death in the elderly and subjects with pre-existing conditions, but the reason for this age dependence is unclear. Here, we found that the case fatality rate for COVID-19 grows exponentially with age in Italy, Spain, South Korea, and China, with the doubling time approaching that of all-cause human mortality. In addition, men and those with multiple age-related diseases are characterized by increased mortality. Moreover, similar mortality patterns were found for all-cause pneumonia. We further report that the gene expression of ACE2, the SARS-CoV-2 receptor, grows in the lung with age, except for subjects on a ventilator. Together, our findings establish COVID-19 as an emergent disease of aging, and age and age-related diseases as its major risk factors. In turn, this suggests that COVID-19, and deadly respiratory diseases in general, may be targeted, in addition to therapeutic approaches that affect specific pathways, by approaches that target the aging process.", "title": "COVID-19 is an emergent disease of aging", "pid": "uatnaro4", "bm25_score": 214.01324462890625}, {"text": "This study described the epidemiologic and clinical characteristics of patients who died from SARS-CoV-2 infection, and pointed out the potential risk factors associated with fatal outcomes. Retrospective data from 42 death cases due to SARS-CoV-2 infection at Tongji Hospital Affiliated to Huazhong University of Science and Technology, Wuhan, China was analyzed. Demographics, clinical detection, laboratory findings, and treatments of the deceased were collected and analyzed. The average time between onset of symptoms and admission to the hospitals was 11 ± 5 days of hospitalization. Among the deceased, 60% were with co-morbidities. All of them were having fever and bilateral pneumonia on computed tomography, abnormal infection-related biomarkers, and renal impairment. Abnormal blood coagulation parameters that appeared in more than half of them, were consistent with disseminated intravascular coagulation. All of the patients were treated in the ICU. Based on the fact that SARS-CoV-2 infection carries a risk of mortality, we may infer a few older male patients with underlying comorbidities are likely to have the increased risk. Impaired consciousness level, markers of renal impairment and coagulation abnormalities may be poor prognostic factors.", "title": "Epidemiologic and clinical characteristics of 42 deaths caused by SARS-CoV-2 infection in Wuhan, China: A retrospective study", "pid": "jzz250o1", "bm25_score": 214.00328063964844}, {"text": "Objective To provide Covid-19 fatality rate, correlations with comorbidities and sensitivity of nasopharingeal swab. Design Prospective cohort study performed between February 21th and March 19rd, 2020 Setting Hospital-based study Participants Of 2,217 admitted, 766 consecutive individuals either reporting or presenting with fever, cough or dyspnea, and suspected to carry Covid-19 infection were examined. Intervention All individuals underwent body temperature and pulse oximetry recording, hematological screening, chest X-ray and/or computed tomography (CT) and SARS-COV-2 assay on nasopharyngeal swab. Onset symptoms, course, comorbidities, number of drugs, use of angiotensin converting enzyme inhibitors and angiotensin-II-receptor antagonists, and follow-up swab, clinical, hematological, and radiological exams, treatments, non-invasive respiratory support, ICU admission, and deaths were recorded. Main outcome measures Primary outcomes were non-invasive respiratory support, intensive care unit (ICU) admission, and death. Results Median age of 411 Covid-19 patients was 70.5 years (range 1-99; 66.6% males). CT was positive in 74% and negative in 3.2%. Six patients died within 72 hours; another 66 during hospitalization. Fatality rate was 17.5% (74% males). No death occurred below 60 years. Mortality was 6.6% in 60-69 decade, 21.1% in 70-79, 38.8% in 80-89, and 83.3% above 90 years. Non-invasive respiratory support rate was 27.2%; ICU admission 6.8%. Older age, cough and dyspnea at onset, hypertension, cardiovascular diseases, diabetes, renal insufficiency, >7 drugs intake and positive X-ray at admission were significantly associated with death. Low lymphocyte count, high C-reactive protein, aspartate aminotransferase and lactate dehydrogenase, and low PO2 partial pressure with high lactate at arterial blood gas analysis at admission were also significantly associated with death. Of 32 swab negative patients, 40.6% turned positive at follow-up. Using CT as reference, nasopharyngeal swab had 80% sensitivity. Comorbidity network analysis revealed homogenous distribution of deceased and 60-80 aged patients across diseases. Conclusions Covid-19 caused high mortality among patients older than 70 years and correlated by pre-existing multiorgan impairment irrespective of the age.", "title": "SARS-COV-2 comorbidity network and outcome in hospitalized patients in Crema, Italy", "pid": "qb28o1jl", "bm25_score": 213.9981231689453}, {"text": "The current outbreak of COVID-19 severe respiratory disease, which started in Wuhan, China, is an ongoing challenge, and a major threat to public health that requires surveillance, prompt diagnosis, and research efforts to understand this emergent pathogen and to develop an effective response. Due to the scientific community's efforts, there is an increasing body of published studies describing the virus' biology, its transmission and diagnosis, its clinical features, its radiological findings, and the development of candidate therapeutics and vaccines. Despite the decline in postmortem examination rate, autopsy remains the gold standard to determine why and how death happens. Defining the pathophysiology of death is not only limited to forensic considerations; it may also provide useful clinical and epidemiologic insights. Selective approaches to postmortem diagnosis, such as limited postmortem sampling over full autopsy, can also be useful in the control of disease outbreaks and provide valuable knowledge for managing appropriate control measures. In this scenario, we strongly recommend performing full autopsies on patients who died with suspected or confirmed COVID-19 infection, particularly in the presence of several comorbidities. Only by working with a complete set of histological samples obtained through autopsy can one ascertain the exact cause(s) of death, optimize clinical management, and assist clinicians in pointing out a timely and effective treatment to reduce mortality. Death can teach us not only about the disease, it might also help with its prevention and, above all, treatment.", "title": "COVID-19 Deaths: Are We Sure It Is Pneumonia? Please, Autopsy, Autopsy, Autopsy!", "pid": "ic3tp5d0", "bm25_score": 213.99063110351562}, {"text": "In this case report, a 50-year-old man who had no medical history, presented with multiple cardiac arrests following a week with progressing symptoms of pneumonia After achieving return of spontaneous circulation he presented with respiratory failure with severe hypoxia, septic shock, and multiple organ failure A chest X-ray showed signs of acute respiratory distress syndrome Despite aggressive intensive care management, the patient died 7 5 hours after admission Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was later confirmed, and the presumed cause of death was SARS-CoV-2 pneumonia In conclusion: coronavirus disease 2019 (COVID-19) can lead to a fatal outcome in younger healthy residents, who are not treated timely in case of severe symptoms like dyspnoea", "title": "[Fatal outcome of coronavirus disease 2019 in a previously healthy 50-year-old man]", "pid": "oqalb61j", "bm25_score": 213.98553466796875}, {"text": "As of early June, 2020, approximately 7 million COVID-19 cases and 400,000 deaths have been reported. This paper examines four demographic and clinical factors (age, time to hospital, presence of chronic disease, and sex) and utilizes Shapley values from coalitional game theory and machine learning to evaluate their relative importance in predicting COVID-19 mortality. The analyses suggest that out of the 4 factors studied, age is the most important in predicting COVID-19 mortality, followed by time to hospital. Sex and presence of chronic disease were both found to be relatively unimportant, and the two global interpretation techniques differed in ranking them. Additionally, this paper creates partial dependence plots to determine and visualize the marginal effect of each factor on COVID-19 mortality and demonstrates how local interpretation of COVID-19 mortality prediction can be applicable in a clinical setting. Lastly, this paper derives clinically applicable decision rules about mortality probabilities through a parsimonious 3-split surrogate tree, demonstrating that high-accuracy COVID-19 mortality prediction can be achieved with simple, interpretable models.", "title": "Who dies from COVID-19? Post-hoc explanations of mortality prediction models using coalitional game theory, surrogate trees, and partial dependence plots", "pid": "xkcs8ove", "bm25_score": 213.97268676757812}, {"text": "Nitrogen dioxide (NO2) is an ambient trace-gas result of both natural and anthropogenic processes. Long-term exposure to NO2 may cause a wide spectrum of severe health problems such as hypertension, diabetes, heart and cardiovascular diseases and even death. The objective of this study is to examine the relationship between long-term exposure to NO2 and coronavirus fatality. The Sentinel-5P is used for mapping the tropospheric NO2 distribution and the NCEP/NCAR reanalysis for evaluating the atmospheric capability to disperse the pollution. The spatial analysis has been conducted on a regional scale and combined with the number of death cases taken from 66 administrative regions in Italy, Spain, France and Germany. Results show that out of the 4443 fatality cases, 3487 (78%) were in five regions located in north Italy and central Spain. Additionally, the same five regions show the highest NO2 concentrations combined with downwards airflow which prevent an efficient dispersion of air pollution. These results indicate that the long-term exposure to this pollutant may be one of the most important contributors to fatality caused by the COVID-19 virus in these regions and maybe across the whole world.", "title": "Assessing nitrogen dioxide (NO2) levels as a contributing factor to coronavirus (COVID-19) fatality", "pid": "wuuijty9", "bm25_score": 213.96722412109375}, {"text": "Forensic investigations generally contain extensive morphological examinations to accurately diagnose the cause of death. Thus, the appearance of a new disease often creates emerging challenges in morphological examinations due to the lack of available data from autopsy- or biopsy-based research. Since late December 2019, an outbreak of a novel seventh coronavirus disease has been reported in China caused by \"severe acute respiratory syndrome coronavirus 2\" (SARS-CoV-2). On March 11, 2020, the new clinical condition COVID-19 (Corona-Virus-Disease-19) was declared a pandemic by the World Health Organization (WHO). Patients with COVID-19 mainly have a mild disease course, but severe disease onset might result in death due to proceeded lung injury with massive alveolar damage and progressive respiratory failure. However, the detailed mechanisms that cause organ injury still remain unclear. We investigated the morphological findings of a COVID-19 patient who died during self-isolation. Pathologic examination revealed massive bilateral alveolar damage, indicating early-phase \"acute respiratory distress syndrome\" (ARDS). This case emphasizes the possibility of a rapid severe disease onset in previously mild clinical condition and highlights the necessity of a complete autopsy to gain a better understanding of the pathophysiological changes in SARS-CoV-2 infections.", "title": "Gross and histopathological pulmonary findings in a COVID-19 associated death during self-isolation", "pid": "b26j2sm4", "bm25_score": 213.96043395996094}, {"text": "", "title": "Covid-19: Known risk factors fail to explain the increased risk of death among people from ethnic minorities.", "pid": "cureysw2", "bm25_score": 213.95826721191406}, {"text": "", "title": "Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China: Wu C, Chen X, Cai Y, et al. JAMA Intern Med. doi:10.1001/jamainternmed.2020.0994.", "pid": "jjjr3ymt", "bm25_score": 213.95443725585938}, {"text": "BACKGROUND: Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. METHODS: In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. FINDINGS: 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. INTERPRETATION: The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.", "title": "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study", "pid": "k36rymkv", "bm25_score": 213.95361328125}, {"text": "", "title": "Mortality and survival of COVID-19", "pid": "zxjlzyxq", "bm25_score": 213.94793701171875}, {"text": "BACKGROUND: Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. METHODS: In this retrospective, multicentre cohort study, we included all adult inpatients (&#8805;18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. FINDINGS: 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 µg/mL (18·42, 2·64-128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. INTERPRETATION: The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 µg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. FUNDING: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.", "title": "Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study", "pid": "9819n3zf", "bm25_score": 213.9460906982422}, {"text": "The current outbreak of COVID-19 severe respiratory disease, which started in Wuhan, China, is an ongoing challenge, and a major threat to public health that requires surveillance, prompt diagnosis, and research efforts to understand this emergent pathogen and to develop an effective response. Due to the scientific community’s efforts, there is an increasing body of published studies describing the virus’ biology, its transmission and diagnosis, its clinical features, its radiological findings, and the development of candidate therapeutics and vaccines. Despite the decline in postmortem examination rate, autopsy remains the gold standard to determine why and how death happens. Defining the pathophysiology of death is not only limited to forensic considerations; it may also provide useful clinical and epidemiologic insights. Selective approaches to postmortem diagnosis, such as limited postmortem sampling over full autopsy, can also be useful in the control of disease outbreaks and provide valuable knowledge for managing appropriate control measures. In this scenario, we strongly recommend performing full autopsies on patients who died with suspected or confirmed COVID-19 infection, particularly in the presence of several comorbidities. Only by working with a complete set of histological samples obtained through autopsy can one ascertain the exact cause(s) of death, optimize clinical management, and assist clinicians in pointing out a timely and effective treatment to reduce mortality. Death can teach us not only about the disease, it might also help with its prevention and, above all, treatment.", "title": "COVID-19 Deaths: Are We Sure It Is Pneumonia? Please, Autopsy, Autopsy, Autopsy!", "pid": "g2llk2p0", "bm25_score": 213.93673706054688}, {"text": "Spain is one of the countries that has suffered the most from the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the strain that causes coronavirus disease 2019 (COVID-19). However, there is a lack of information on the characteristics of this disease in the Spanish population. The objective of this study has been to characterize our patients from an epidemiological point of view and to identify the risk factors associated with mortality in our geographical area. We performed a prospective, longitudinal study on 188 hospitalized cases of SARS-Cov-2 infection in Hospital Universitari de Sant Joan, in Reus, Spain, admitted between 15th March 2020 and 30th April 2020. We recorded demographic data, signs and symptoms and comorbidities. We also calculated the Charlson and McCabe indices. A total of 43 deaths occurred during the study period. Deceased patients were older than the survivors (77.7 ± 13.1 vs. 62.8 ± 18.4 years; p < 0.001). Logistic regression analyses showed that fever, pneumonia, acute respiratory distress syndrome, diabetes mellitus and cancer were the variables that showed independent and statistically significant associations with mortality. The Charlson index was more efficient than the McCabe index in discriminating between deceased and survivors. This is one of the first studies to describe the factors associated with mortality in patients infected with SARS-CoV-2 in Spain, and one of the few in the Mediterranean area. We identified the main factors independently associated with mortality in our population. Further studies in are needed to complete and confirm our findings.", "title": "Risk factors associated with mortality in hospitalized patients with SARS-CoV-2 infection. A prospective, longitudinal, unicenter study in Reus, Spain", "pid": "u7gbzyvx", "bm25_score": 213.9343719482422}, {"text": "BACKGROUND COVID-19 can cause a fatal outcome in elderly patients, as this case report illustrates. CASE PRESENTATION An active male in his nineties with a high level of function, despite several severe chronic diseases, was admitted to Oslo University Hospital after two days of fatigue, fever, dyspnoea and dry cough. He scored qSOFA 1 of 3 points due to high respiratory rate, and SIRS 2 of 4 points due to high respiratory rate and fever of 39.4º C. PCR for influenza virus was negative and he received benzylpenicillin for pneumonia. The chest X-ray taken initially showed no lung affection. On day 5 after symptom debut he was tested for COVID-19 which was positive. He had not been travelling to high-risk areas or been exposed to any known confirmed COVID-19 patients. On the same day, a chest CT scan was performed that showed ground-glass opacities. In subsequent days the patient's health rapidly deteriorated. He developed irreversible respiratory failure with hypoxia without hypercapnia despite substantial oxygen support. Chest X-ray taken on disease day 7 showed progression of consolidations. The patient died 9 days after symptom debut. INTERPRETATION This case illustrates a severe course of COVID-19 with fatal outcome. The patient was also one of the earliest admitted with COVID-19 in a Norwegian hospital and marked a new phase of the epidemic, as he had not been travelling to high-risk areas or been exposed to any confirmed COVID-19 patients.", "title": "A man in his nineties with fever and dry cough.", "pid": "yxps5psk", "bm25_score": 213.93287658691406}, {"text": "In the setting of the coronavirus disease 2019 (COVID-19) pandemic, only few data regarding lung pathology induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is available, especially without medical intervention interfering with the natural evolution of the disease. We present here the first case of forensic autopsy of a COVID-19 fatality occurring in a young woman, in the community. Diagnosis was made at necropsy and lung histology showed diffuse alveolar damage, edema, and interstitial pneumonia with a geographically heterogeneous pattern, mostly affecting the central part of the lungs. This death related to COVID-19 pathology highlights the heterogeneity and severity of central lung lesions after natural evolution of the disease.", "title": "Inside the lungs of COVID-19 disease", "pid": "pdz6j4hv", "bm25_score": 213.92446899414062}, {"text": "", "title": "Covid-19: Known risk factors fail to explain the increased risk of death among people from ethnic minorities", "pid": "e3d4fh5y", "bm25_score": 213.91744995117188}, {"text": "Abstract Nitrogen dioxide (NO2) is an ambient trace-gas result of both natural and anthropogenic processes. Long-term exposure to NO2 may cause a wide spectrum of severe health problems such as hypertension, diabetes, heart and cardiovascular diseases and even death. The objective of this study is to examine the relationship between long-term exposure to NO2 and coronavirus fatality. The Sentinel-5P is used for mapping the tropospheric NO2 distribution and the NCEP/NCAR reanalysis for evaluating the atmospheric capability to disperse the pollution. The spatial analysis has been conducted on a regional scale and combined with the number of death cases taken from 66 administrative regions in Italy, Spain, France and Germany. Results show that out of the 4443 fatality cases, 3487 (78%) were in five regions located in north Italy and central Spain. Additionally, the same five regions show the highest NO2 concentrations combined with downwards airflow which prevent an efficient dispersion of air pollution. These results indicate that the long-term exposure to this pollutant may be one of the most important contributors to fatality caused by the COVID-19 virus in these regions and maybe across the whole world.", "title": "Assessing nitrogen dioxide (NO2) levels as a contributing factor to coronavirus (COVID-19) fatality", "pid": "u4doukk7", "bm25_score": 213.91371154785156}, {"text": "", "title": "Why are more BAME people dying from COVID-19?", "pid": "2pjan40u", "bm25_score": 213.91258239746094}, {"text": "Forensic investigations generally contain extensive morphological examinations to accurately diagnose the cause of death. Thus, the appearance of a new disease often creates emerging challenges in morphological examinations due to the lack of available data from autopsy- or biopsy-based research. Since late December 2019, an outbreak of a novel seventh coronavirus disease has been reported in China caused by “severe acute respiratory syndrome coronavirus 2” (SARS-CoV-2). On March 11, 2020, the new clinical condition COVID-19 (Corona-Virus-Disease-19) was declared a pandemic by the World Health Organization (WHO). Patients with COVID-19 mainly have a mild disease course, but severe disease onset might result in death due to proceeded lung injury with massive alveolar damage and progressive respiratory failure. However, the detailed mechanisms that cause organ injury still remain unclear. We investigated the morphological findings of a COVID-19 patient who died during self-isolation. Pathologic examination revealed massive bilateral alveolar damage, indicating early-phase “acute respiratory distress syndrome” (ARDS). This case emphasizes the possibility of a rapid severe disease onset in previously mild clinical condition and highlights the necessity of a complete autopsy to gain a better understanding of the pathophysiological changes in SARS-CoV-2 infections.", "title": "Gross and histopathological pulmonary findings in a COVID-19 associated death during self-isolation", "pid": "onyryfty", "bm25_score": 213.9078826904297}, {"text": "The pandemia of coronavirus disease 2019 (COVID-19) has caused more than 355,000 confirmed deaths worldwide. However, publications on postmortem findings are scarce. We present the pulmonary findings in four cases of fatal COVID-19 with a spectrum of lung pathology reflecting disease course and duration, invasive therapies, and laboratory features. Early disease is characterized by neutrophilic, exudative capillaritis with microthrombosis and high levels of IL-1beta and IL-6. Later stages are associated with diffuse alveolar damage and ongoing intravascular thrombosis in small to medium-sized pulmonary vessels, occasionally with areas of infarction equivalents, accompanied by laboratory features of disseminated intravascular coagulation. In late stages, organizing pneumonia with extensive intra-alveolar proliferation of fibroblasts and marked metaplasia of alveolar epithelium can be observed. Viral RNA is encountered in the lung, with virus particles in endothelial cells and pneumocytes. In many patients, multi-organ failure with severe liver damage sets in finally, possibly as consequence of an early-onset pro-inflammatory cytokine storm and/or thrombotic microangiopathy. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00428-020-02881-x) contains supplementary material, which is available to authorized users.", "title": "The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation", "pid": "ywbyflas", "bm25_score": 213.89691162109375}, {"text": "Background A recently developing pneumonia caused by SARS-CoV-2 was originated in Wuhan, China, and has quickly spread across the world. We reported the clinical characteristics of 82 death cases with COVID-19 in a single center. Methods Clinical data on 82 death cases laboratory-confirmed as SARS-CoV-2 infection were obtained from a Wuhan local hospital′s electronic medical records according to previously designed standardized data collection forms. Findings All patients were local residents of Wuhan, and the great proportion of them were diagnosed as severe illness when admitted. Most of the death cases were male (65.9%). More than half of dead patients were older than 60 years (80.5%) and the median age was 72.5 years. The bulk of death cases had comorbidity (76.8%), including hypertension (56.1%), heart disease (20.7%), diabetes (18.3%), cerebrovascular disease (12.2%), and cancer (7.3%). Respiratory failure remained the leading cause of death (69.5%), following by sepsis syndrome/MOF (28.0%), cardiac failure (14.6%), hemorrhage (6.1%), and renal failure (3.7%). Furthermore, respiratory, cardiac, hemorrhage, hepatic, and renal damage were found in 100%, 89%, 80.5%, 78.0%, and 31.7% of patients, respectively. On the admission, lymphopenia (89.2%), neutrophilia (74.3%), and thrombocytopenia (24.3%) were usually observed. Most patients had a high neutrophil-to-lymphocyte ratio of >5 (94.5%), high systemic immune-inflammation index of >500 (89.2%), increased C-reactive protein level (100%), lactate dehydrogenase (93.2%), and D-dimer (97.1%). A high level of IL-6 (>10 pg/ml) was observed in all detected patients. Median time from initial symptom to death was 15 days (IQR 11-20), and a significant association between aspartate aminotransferase (p=0.002), alanine aminotransferase (p=0.037) and time from initial symptom to death were interestingly observed. Conclusion Older males with comorbidities are more likely to develop severe disease, even die from SARS-CoV-2 infection. Respiratory failure is the main cause of COVID-19, but either virus itself or cytokine release storm mediated damage to other organ including cardiac, renal, hepatic, and hemorrhage should be taken seriously as well.", "title": "Clinical characteristics of 82 death cases with COVID-19", "pid": "fcmzdcuh", "bm25_score": 213.8651123046875}, {"text": "", "title": "Excess Deaths From COVID-19 and Other Causes, March-April 2020.", "pid": "bs0yainl", "bm25_score": 213.86492919921875}, {"text": "Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined.Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan.Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management.Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-&#945;2b, respectively.Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.", "title": "Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study", "pid": "1qk77fqo", "bm25_score": 213.86456298828125}, {"text": "SARS-CoV-2 has rapidly spread across the United States, causing extensive morbidity and mortality, though the histopathologic basis of severe disease cases has yet to be studied in detail. Over the past century, autopsy has contributed significantly to our understanding of numerous disease processes, but for several reasons, autopsy reports following deaths related to SARS-CoV-2 have thus far been limited across the globe. We report on the relevant cardiopulmonary findings in the first series of autopsies in the United States, with the cause of death being due to SARS-CoV-2 infection. These cases identify key pathologic states potentially contributing to severe disease and decompensation in these patients.", "title": "Pulmonary and Cardiac Pathology in Covid-19: The First Autopsy Series from New Orleans", "pid": "iqgw6jaq", "bm25_score": 213.86416625976562}, {"text": "OBJECTIVE: This retrospective study aimed to analysis the clinical characteristics and complications in death cases with novel coronavirus disease-19 (COVID-19). METHOD: We collected the medical records of 92 patients with COVID-19 in Renmin Hospital of Wuhan University who died during January 6th to February 25th, 2020, summarized the clinical characteristics of complications. RESULTS: There were 91 death cases who developed different complications including acute respiratory distress syndrome (ARDS) (73/91), myocardial injury (31/91), liver injury (15/91), renal insufficiency (14/91), multiple organ dysfunction syndrome (MODS) (14/91) and pneumothorax (1/91). Among these patients, 83 patients had at least one complication. While 1 patient who died of recurrent gastrointestinal bleeding was not directly linked to COVID-19. CONCLUSION: The main complications of deceased patients with COVID-19 were ARDS, myocardial injury, liver injury, renal insufficiency and MODS. This article is protected by copyright. All rights reserved.", "title": "Analysis of 92 deceased patients with COVID-19", "pid": "dumf55yg", "bm25_score": 213.85394287109375}, {"text": "Findings from CCC19 and TERAVOLT suggest that patients with cancer may be more likely to die from COVID-19 than people in the general population. Additional mortality risk factors may include age, performance status, treatment with chemotherapy, and exposure to hydroxychloroquine plus azithromycin.", "title": "Registries Offer Insights on COVID-19-Cancer Connection.", "pid": "d4rphs30", "bm25_score": 213.83175659179688}, {"text": "COVID-19, the illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the deadliest pandemic to occur in this century. Common symptoms of COVID-19 include cough, myalgia, fever, chest pain, and headache. However, its clinical presentation ranges from completely asymptomatic to acute respiratory distress syndrome.[1] Pregnant women are susceptible to community spread of COVID-19 because they cannot postpone interactions with healthcare professionals and other women receiving obstetric care.", "title": "Maternal mortality from COVID-19 in Mexico.", "pid": "8noxjjuh", "bm25_score": 213.8282470703125}, {"text": "The ongoing outbreak of COVID-19 has been expanding worldwide. As of 17 April 2020, the death toll stands at a sobering 147,027 and over two million cases, this has been straining the health care systems all over. Respiratory failure has been cited as the major cause of death but here we present a case about a patient who instead succumbed to severe metabolic acidosis with multiple organ failure.", "title": "A fatal case of COVID-19 due to metabolic acidosis following dysregulate inflammatory response (cytokine storm)", "pid": "96v8owb9", "bm25_score": 213.82664489746094}, {"text": "By 27 February 2020, the outbreak of coronavirus disease 2019 (COVID-19) caused 82 623 confirmed cases and 2858 deaths globally, more than severe acute respiratory syndrome (SARS) (8273 cases, 775 deaths) and Middle East respiratory syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013, respectively. COVID-19 has spread to 46 countries internationally. Total fatality rate of COVID-19 is estimated at 3.46% by far based on published data from the Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID-19 is around 6.4 days, ranges from 0 to 24 days. The basic reproductive number (R0 ) of COVID-19 ranges from 2 to 3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID-19. Nosocomial transmission was another severe problem. A total of 3019 health workers were infected by 12 February 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID-19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID-19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID-19 and enhance our control measures in the future.", "title": "Unique epidemiological and clinical features of the emerging 2019 novel coronavirus pneumonia (COVID-19) implicate special control measures", "pid": "r63c7wqy", "bm25_score": 213.82530212402344}, {"text": "COVID-19 is a respiratory disease A recent report in Lancet examined, retrospectively, 137 patients with COVD-19 Patients that died had elevated IL-6 levels and acute respiratory distress syndrome These data have obvious implications for how to control mortality in COVID-19", "title": "COVID-19: is fibrosis the killer?", "pid": "b8bl5vq5", "bm25_score": 213.82217407226562}, {"text": "", "title": "Covid-19: risk factors for severe disease and death", "pid": "gfl22b5o", "bm25_score": 213.8195343017578}, {"text": "", "title": "COVID-19 and the liver-related deaths to come", "pid": "sftvwug9", "bm25_score": 213.8172607421875}, {"text": "", "title": "Neglected major causes of death much deadlier than COVID-19", "pid": "68vzzknt", "bm25_score": 213.81578063964844}, {"text": "Rationale: The current outbreak of coronavirus disease (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, spreads across national and international borders. The overall death rate of COVID-19 pneumonia in the Chinese population was 4%.Objectives: To describe the process of hospitalization and critical care of patients who died of COVID-19 pneumonia.Methods: This was a multicenter observational study of 109 decedents with COVID-19 pneumonia from three hospitals in Wuhan. Demographic, clinical, laboratory, and treatment data were collected and analyzed, and the final date of follow-up was February 24, 2020.Results: The mean age of 109 decedents with COVID-19 pneumonia was 70.7 years, 35 patients (32.1%) were female, and 85 patients (78.0%) suffered from one or more underlying comorbidities. Multiple organ failure, especially respiratory failure and heart failure, appeared in all patients even at the early stage of disease. Overall, the mean time from onset of symptoms to death was 22.3 days. All 109 hospitalized patients needed admission to an intensive care unit (ICU); however, because of limited availability, only 51 (46.8%) could be admitted. The period from hospitalization to death in the ICU group and non-ICU group was 15.9 days (standard deviation = 8.8 d) and 12.5 days (8.6 d, P = 0.044), respectively.Conclusions: Mortality due to COVID-19 pneumonia was concentrated in patients above the age of 65 years, especially those with major comorbidities. Patients who were admitted to the ICU lived longer than those who were not. Our findings should aid in the recognition and clinical management of such infections, especially with regard to ICU resource allocation.", "title": "Hospitalization and Critical Care of 109 Decedents with COVID-19 Pneumonia in Wuhan, China", "pid": "lywpbn1i", "bm25_score": 213.8122100830078}, {"text": "Rationale: The current outbreak of coronavirus disease (COVID-19) pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, spreads across national and international borders. The overall death rate of COVID-19 pneumonia in the Chinese population was 4%. Objectives: To describe the process of hospitalization and critical care of patients who died of COVID-19 pneumonia. Methods: This was a multicenter observational study of 109 decedents with COVID-19 pneumonia from three hospitals in Wuhan. Demographic, clinical, laboratory, and treatment data were collected and analyzed, and the final date of follow-up was February 24, 2020. Results: The mean age of 109 decedents with COVID-19 pneumonia was 70.7 years, 35 patients (32.1%) were female, and 85 patients (78.0%) suffered from one or more underlying comorbidities. Multiple organ failure, especially respiratory failure and heart failure, appeared in all patients even at the early stage of disease. Overall, the mean time from onset of symptoms to death was 22.3 days. All 109 hospitalized patients needed admission to an intensive care unit (ICU); however, because of limited availability, only 51 (46.8%) could be admitted. The period from hospitalization to death in the ICU group and non-ICU group was 15.9 days (standard deviation = 8.8 d) and 12.5 days (8.6 d, P = 0.044), respectively. Conclusions: Mortality due to COVID-19 pneumonia was concentrated in patients above the age of 65 years, especially those with major comorbidities. Patients who were admitted to the ICU lived longer than those who were not. Our findings should aid in the recognition and clinical management of such infections, especially with regard to ICU resource allocation.", "title": "Hospitalization and Critical Care of 109 Decedents with COVID-19 Pneumonia in Wuhan, China", "pid": "n75imevq", "bm25_score": 213.8122100830078}, {"text": "", "title": "Are COVID-19 Patients Dying of or with Cardiac Injury?", "pid": "ga0dzj3v", "bm25_score": 213.80935668945312}, {"text": "Rationale: The global death toll from coronavirus disease (COVID-19) virus as of May 12, 2020, exceeds 286,000. The risk factors for death were attributed to advanced age and comorbidities but have not been accurately defined. Objectives: To report the clinical features of 85 fatal cases of COVID-19 in two hospitals in Wuhan. Methods: Medical records were collected of 85 fatal cases of COVID-19 between January 9, 2020, and February 15, 2020. Information recorded included medical history, exposure history, comorbidities, symptoms, signs, laboratory findings, computed tomographic scans, and clinical management. Measurements and Main Results: The median age of the patients was 65.8 years, and 72.9% were male. Common symptoms were fever (78 [91.8%]), shortness of breath (50 [58.8%]), fatigue (50 [58.8%]), and dyspnea (60 [70.6%]). Hypertension, diabetes, and coronary heart disease were the most common comorbidities. Notably, 81.2% of patients had very low eosinophil counts on admission. Complications included respiratory failure (80 [94.1%]), shock (69 [81.2%]), acute respiratory distress syndrome (63 [74.1%]), and arrhythmia (51 [60%]), among others. Most patients received antibiotic (77 [90.6%]), antiviral (78 [91.8%]), and glucocorticoid (65 [76.5%]) treatments. A total of 38 (44.7%) and 33 (38.8%) patients received intravenous immunoglobulin and IFN-α2b, respectively. Conclusions: In this depictive study of 85 fatal cases of COVID-19, most cases were males aged over 50 years with noncommunicable chronic diseases. The majority of the patients died of multiple organ failure. Early onset of shortness of breath may be used as an observational symptom for COVID-19 exacerbations. Eosinophilopenia may indicate a poor prognosis. A combination of antimicrobial drugs did not offer considerable benefit to the outcome of this group of patients.", "title": "Clinical Features of 85 Fatal Cases of COVID-19 from Wuhan. A Retrospective Observational Study", "pid": "tp6qq2pu", "bm25_score": 213.80905151367188}, {"text": "The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the number of deaths not registered as Covid-19-related has increased compared to what would have been expected in the absence of the pandemic. Reasons behind this might include Covid-19 underreporting, avoiding visits to hospitals or GPs, and the effects of the lockdown. I used weekly ONS data on the number of deaths in England and Wales that did not officially involve Covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a difference-in-differences econometric approach to study whether there was a relative increase in deaths not registered as Covid-19-related during the pandemic, compared to a control. Results suggest that there were an additional 968 weekly deaths that officially did not involve Covid-19, compared to what would have otherwise been expected. It is possible that some people are dying from Covid-19 without being diagnosed, and/or that there are excess deaths due to other causes as a result of the pandemic. Analysing the cause of death for any excess non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.", "title": "Excess mortality during the Covid-19 pandemic: Early evidence from England and Wales.", "pid": "2jttlljm", "bm25_score": 213.80238342285156}, {"text": "Asthma is increasingly recognized as an underlying risk factor for severe respiratory disease in patients with coronavirus disease 2019 (COVID-19), particularly in the United States. Here, we report the postmortem lung findings from a 37-year-old man with asthma, who met the clinical criteria for severe acute respiratory distress syndrome and died of COVID-19 less than 2 weeks after presentation to the hospital. His lungs showed mucus plugging and other histologic changes attributable to asthma, as well as early diffuse alveolar damage and a fibrinous pneumonia. The presence of diffuse alveolar damage is similar to descriptions of autopsy lung findings from patients with severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus, and the absence of a neutrophil-rich acute bronchopneumonia differs from the histologic changes typical of influenza. The relative contribution of mucus plugging to his hypoxemia is unknown.", "title": "Postmortem Lung Findings in an Asthmatic Patient With Coronavirus Disease 2019", "pid": "u2jxwabq", "bm25_score": 213.7934112548828}, {"text": "As Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) spreads around the World, many questions about the disease are being answered; however, many more remain poorly understood. Although the situation is rapidly evolving, with datasets being continually corrected or updated, it is crucial to understand what factors may be driving transmission through different populations. While studies are beginning to highlight specific parameters that may be playing a role, few have attempted to thoroughly estimate the relative importance of these disparate variables that likely include: climate, population demographics, and imposed state interventions. In this report, we compiled a database of more than 28 potentially explanatory variables for each of the 50 U.S. states through early May 2020. Using a combination of traditional statistical and modern machine learning approaches, we identified those variables that were the most statistically significant, and, those that were the most important. These variables were chosen to be fiduciaries of a range of possible drivers for COVID-19 deaths in the USA. We found that population-weighted density (PWD), some \"stay at home\" metrics, monthly temperature and precipitation, race/ethnicity, and chronic low respiratory death rate, were all statistically significant. Of these, PWD and mobility metrics dominated. This suggests that the biggest impact on COVID-19 deaths was, at least initially, a function of where you lived, and not what you did. However, clearly, increasing social distancing has the net effect of (at least temporarily) reducing the effective PWD. Our results strongly support the idea that the loosening of \"lock-down\" orders should be tailored to the local PWD. In contrast to these variables, while still statistically significant, race/ethnicity, health, and climate effects could only account for a few percent of the variability in deaths. Where associations were anticipated but were not found, we discuss how limitations in the parameters chosen may mask a contribution that might otherwise be present.", "title": "COVID-19 Deaths: Which Explanatory Variables Matter the Most?", "pid": "q4jn5h00", "bm25_score": 213.7906494140625}, {"text": "BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. OBJECTIVE: To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes. DESIGN: Prospective autopsy study. SETTING: Single pathology department. PARTICIPANTS: 11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy). MEASUREMENTS: Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values. RESULTS: Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts. Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients. Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients. Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis. Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes. Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile. LIMITATION: The sample was small. CONCLUSION: COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism. PRIMARY FUNDING SOURCE: None.", "title": "Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome: Results From a Prospective, Single-Center, Clinicopathologic Case Series", "pid": "hfx418j6", "bm25_score": 213.7729034423828}, {"text": "Coronavirus disease 2019 (COVID-19) is a novel, viral-induced respiratory disease that in ∼10–15% of patients progresses to acute respiratory distress syndrome (ARDS) triggered by a cytokine storm. In this Perspective, autopsy results and literature are presented supporting the hypothesis that a little known yet powerful function of neutrophils—the ability to form neutrophil extracellular traps (NETs)—may contribute to organ damage and mortality in COVID-19. We show lung infiltration of neutrophils in an autopsy specimen from a patient who succumbed to COVID-19. We discuss prior reports linking aberrant NET formation to pulmonary diseases, thrombosis, mucous secretions in the airways, and cytokine production. If our hypothesis is correct, targeting NETs directly and/or indirectly with existing drugs may reduce the clinical severity of COVID-19.", "title": "Targeting potential drivers of COVID-19: Neutrophil extracellular traps", "pid": "37i62atc", "bm25_score": 213.77178955078125}, {"text": "SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first identified in December 2019 in Wuhan, China, and has since spread worldwide. On March 11, 2020, the World Health Organization declared COVID-19 a pandemic (1). That same day, the first confirmed COVID-19-associated fatality occurred in New York City (NYC). To identify confirmed COVID-19-associated deaths, defined as those occurring in persons with laboratory-confirmed SARS-CoV-2 infection, on March 13, 2020, the New York City Department of Health and Mental Hygiene (DOHMH) initiated a daily match between all deaths reported to the DOHMH electronic vital registry system (eVital) (2) and laboratory-confirmed cases of COVID-19. Deaths for which COVID-19, SARS-CoV-2, or an equivalent term is listed on the death certificate as an immediate, underlying, or contributing cause of death, but that do not have laboratory-confirmation of COVID-19 are classified as probable COVID-19-associated deaths. As of May 2, a total of 13,831 laboratory-confirmed COVID-19-associated deaths, and 5,048 probable COVID-19-associated deaths were recorded in NYC (3). Counting only confirmed or probable COVID-19-associated deaths, however, likely underestimates the number of deaths attributable to the pandemic. The counting of confirmed and probable COVID-19-associated deaths might not include deaths among persons with SARS-CoV-2 infection who did not access diagnostic testing, tested falsely negative, or became infected after testing negative, died outside of a health care setting, or for whom COVID-19 was not suspected by a health care provider as a cause of death. The counting of confirmed and probable COVID-19-associated deaths also does not include deaths that are not directly associated with SARS-CoV-2 infection. The objective of this report is to provide an estimate of all-cause excess deaths that have occurred in NYC in the setting of widespread community transmission of SARS-CoV-2. Excess deaths refer to the number of deaths above expected seasonal baseline levels, regardless of the reported cause of death. Estimation of all-cause excess deaths is used as a nonspecific measure of the severity or impact of pandemics (4) and public health emergencies (5). Reporting of excess deaths might provide a more accurate measure of the impact of the pandemic.", "title": "Preliminary Estimate of Excess Mortality During the COVID-19 Outbreak - New York City, March 11-May 2, 2020.", "pid": "6x33a6g6", "bm25_score": 213.76609802246094}, {"text": "AIMS: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly evolved into a sweeping pandemic. Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised. Autopsies are essential to elucidate COVID-19-associated organ alterations. METHODS AND RESULTS: This article reports the autopsy findings of 21 COVID-19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland. An in-corpore technique was performed to ensure optimal staff safety. The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation. Ten cases showed superimposed bronchopneumonia. Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1). Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy. Six patients were diagnosed with senile cardiac amyloidosis upon autopsy. Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus). Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively). All relevant histological slides are linked as open-source scans in supplementary files. CONCLUSIONS: This study provides an overview of postmortem findings in COVID-19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID-19. This provides a pathophysiological explanation for higher mortality rates among these patients.", "title": "Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction", "pid": "j8rtwy6l", "bm25_score": 213.7630157470703}, {"text": "INTRODUCTION: In the current study, we evaluated factors that increase the coronavirus disease (COVID-19) patient death rate by analyzing the data from two cohort hospitals. In addition, we studied whether underlying neurological diseases are risk factors for death. METHODS: In this retrospective cohort study, we included 103 adult inpatients (aged ≥ 18 years). We evaluated differences in demographic data between surviving and non-surviving COVID-19 patients. RESULTS: In a multivariate logistic analysis, age and the presence of chronic lung disease and Alzheimer’s dementia (AD) were the only significant parameters for predicting COVID-19 non-survival (p < 0.05). However, hypertension, coronary vascular disease, dyslipidemia, chronic kidney disease, diabetes, and history of taking angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors, as well as nonsteroidal anti-inflammatory drugs (NSAIDs), were not significantly associated with the death of COVID-19 patients. The optimal cutoff value obtained from the maximum Youden index was 70 (sensitivity, 80.77%; specificity, 61.04%), and the odds ratio of non-survival increased 1.055 fold for every year of age. CONCLUSIONS: Clinicians should closely monitor and manage the symptoms of COVID-19 patients who are over the age of 70 years or have chronic lung disease or AD.", "title": "Neurological diseases as mortality predictive factors for patients with COVID-19: a retrospective cohort study", "pid": "2530zdeq", "bm25_score": 213.760986328125}, {"text": "Autopsies of deceased with a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide important insights into the novel disease and its course. Furthermore, autopsies are essential for the correct statistical recording of the coronavirus disease 2019 (COVID-19) deaths. In the northern German Federal State of Hamburg, all deaths of Hamburg citizens with ante- or postmortem PCR-confirmed SARS-CoV-2 infection have been autopsied since the outbreak of the pandemic in Germany. Our evaluation provides a systematic overview of the first 80 consecutive full autopsies. A proposal for the categorisation of deaths with SARS-CoV-2 infection is presented (category 1: definite COVID-19 death; category 2: probable COVID-19 death; category 3: possible COVID-19 death with an equal alternative cause of death; category 4: SARS-CoV-2 detection with cause of death not associated to COVID-19). In six cases, SARS-CoV-2 infection was diagnosed postmortem by a positive PCR test in a nasopharyngeal or lung tissue swab. In the other 74 cases, SARS-CoV-2 infection had already been known antemortem. The deceased were aged between 52 and 96 years (average 79.2 years, median 82.4 years). In the study cohort, 34 deceased were female (38%) and 46 male (62%). Overall, 38% of the deceased were overweight or obese. All deceased, except for two women, in whom no significant pre-existing conditions were found autoptically, had relevant comorbidities (in descending order of frequency): (1) diseases of the cardiovascular system, (2) lung diseases, (3) central nervous system diseases, (4) kidney diseases, and (5) diabetes mellitus. A total of 76 cases (95%) were classified as COVID-19 deaths, corresponding to categories 1–3. Four deaths (5%) were defined as non-COVID-19 deaths with virus-independent causes of death. In eight cases, pneumonia was combined with a fulminant pulmonary artery embolism. Peripheral pulmonary artery embolisms were found in nine other cases. Overall, deep vein thrombosis has been found in 40% of the cases. This study provides the largest overview of autopsies of SARS-CoV-2-infected patients presented so far.", "title": "Dying with SARS-CoV-2 infection—an autopsy study of the first consecutive 80 cases in Hamburg, Germany", "pid": "elzyoefa", "bm25_score": 213.75155639648438}, {"text": "Notions of psychological frailty have been at the forefront of debates around the public response to the COVID-19 pandemic. In particular, there is the argument that collective selfishness, thoughtless behaviour, and over-reaction would make the effects of COVID-19 much worse. The same kinds of claims have been made in relation to other kinds of emergencies, such as fires, earthquakes, and sinking ships. We argue that in these cases as well as in the case of the COVID-19 pandemic, other factors are better explanations for fatalities - namely under-reaction to threat, systemic or structural factors, and mismanagement. Psychologizing disasters serves to distract from the real causes and thus from who might be held responsible. Far from being the problem, collective behaviour in emergencies - including the solidarity and cooperation so commonly witnessed among survivors - is the solution, one that should be harnessed more effectively in policy and practice.", "title": "COVID-19 in context: Why do people die in emergencies? It's probably not because of collective psychology", "pid": "jxja1fd4", "bm25_score": 213.7427215576172}, {"text": "SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), was first identified in December 2019 in Wuhan, China, and has since spread worldwide. On March 11, 2020, the World Health Organization declared COVID-19 a pandemic (1). That same day, the first confirmed COVID-19-associated fatality occurred in New York City (NYC). To identify confirmed COVID-19-associated deaths, defined as those occurring in persons with laboratory-confirmed SARS-CoV-2 infection, on March 13, 2020, the New York City Department of Health and Mental Hygiene (DOHMH) initiated a daily match between all deaths reported to the DOHMH electronic vital registry system (eVital) (2) and laboratory-confirmed cases of COVID-19. Deaths for which COVID-19, SARS-CoV-2, or an equivalent term is listed on the death certificate as an immediate, underlying, or contributing cause of death, but that do not have laboratory-confirmation of COVID-19 are classified as probable COVID-19-associated deaths. As of May 2, a total of 13,831 laboratory-confirmed COVID-19-associated deaths, and 5,048 probable COVID-19-associated deaths were recorded in NYC (3). Counting only confirmed or probable COVID-19-associated deaths, however, likely underestimates the number of deaths attributable to the pandemic. The counting of confirmed and probable COVID-19-associated deaths might not include deaths among persons with SARS-CoV-2 infection who did not access diagnostic testing, tested falsely negative, or became infected after testing negative, died outside of a health care setting, or for whom COVID-19 was not suspected by a health care provider as a cause of death. The counting of confirmed and probable COVID-19-associated deaths also does not include deaths that are not directly associated with SARS-CoV-2 infection. The objective of this report is to provide an estimate of all-cause excess deaths that have occurred in NYC in the setting of widespread community transmission of SARS-CoV-2. Excess deaths refer to the number of deaths above expected seasonal baseline levels, regardless of the reported cause of death. Estimation of all-cause excess deaths is used as a nonspecific measure of the severity or impact of pandemics (4) and public health emergencies (5). Reporting of excess deaths might provide a more accurate measure of the impact of the pandemic.", "title": "Preliminary Estimate of Excess Mortality During the COVID-19 Outbreak - New York City, March 11-May 2, 2020", "pid": "dmffqcq7", "bm25_score": 213.7406768798828}, {"text": "OBJECTIVE: The COVID-19 pandemic has caused much morbidity and mortality to patients but also health care providers. We tabulated the cases of physician deaths from COVID-19 associated with front-line work in hopes of mitigating future events. METHOD: On April 5, 2020, Google internet search was performed using the keywords doctor, physician, death, COVID, COVID-19, and coronavirus in English and Farsi, and in Chinese using the Baidu search engine. RESULTS: We found 198 physician deaths from COVID-19, but complete details were missing for 49 individuals. The average age of the physicians that died was 63.4 years (range 28 to 90 years) and the median age was 66 years of age. Ninety percent of the deceased physicians were male (175/194). General practitioners and emergency room doctors (78/192), respirologists (5/192), internal medicine specialists (11/192) and anesthesiologists (6/192) comprised 52% of those dying. Two percent of the deceased were epidemiologists (4/192), 2% were infectious disease specialists (4/192), 5% were dentists (9/192), 4% were ENT (8/192), and 4% were ophthalmologists (7/192). The countries with the most reported physician deaths were Italy (79/198), Iran (43/198), China (16/198), Philippines (14/198), United States (9/192) and Indonesia (7/192). CONCLUSION: Physicians from all specialties may die from COVID, and these deaths will likely increase as the pandemic progresses. Lack of personal protective equipment was cited as a common cause of death. Consideration should be made to exclude older physicians from front-line work.", "title": "Physician Deaths from Corona Virus Disease (COVID-19)", "pid": "lxkxgbun", "bm25_score": 213.736083984375}, {"text": "BACKGROUND: The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS–CoV-2), has caused more than 210 000 deaths worldwide. However, little is known about the causes of death and the virus's pathologic features. OBJECTIVE: To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests. DESIGN: Prospective cohort study. SETTING: Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction–confirmed diagnosis of COVID-19. PATIENTS: The first 12 consecutive COVID-19–positive deaths. MEASUREMENTS: Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed. Clinical data and medical course were evaluated. Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2). Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively). Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients. Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients. In all patients, SARS–CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart. LIMITATION: Limited sample size. CONCLUSION: The high incidence of thromboembolic events suggests an important role of COVID-19–induced coagulopathy. Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19–related death, as well as possible therapeutic interventions to reduce it. PRIMARY FUNDING SOURCE: University Medical Center Hamburg-Eppendorf.", "title": "Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study", "pid": "8efdzlc0", "bm25_score": 213.7322998046875}, {"text": "Autopsies of deceased with a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide important insights into the novel disease and its course. Furthermore, autopsies are essential for the correct statistical recording of the coronavirus disease 2019 (COVID-19) deaths. In the northern German Federal State of Hamburg, all deaths of Hamburg citizens with ante- or postmortem PCR-confirmed SARS-CoV-2 infection have been autopsied since the outbreak of the pandemic in Germany. Our evaluation provides a systematic overview of the first 80 consecutive full autopsies. A proposal for the categorisation of deaths with SARS-CoV-2 infection is presented (category 1: definite COVID-19 death; category 2: probable COVID-19 death; category 3: possible COVID-19 death with an equal alternative cause of death; category 4: SARS-CoV-2 detection with cause of death not associated to COVID-19). In six cases, SARS-CoV-2 infection was diagnosed postmortem by a positive PCR test in a nasopharyngeal or lung tissue swab. In the other 74 cases, SARS-CoV-2 infection had already been known antemortem. The deceased were aged between 52 and 96 years (average 79.2 years, median 82.4 years). In the study cohort, 34 deceased were female (38%) and 46 male (62%). Overall, 38% of the deceased were overweight or obese. All deceased, except for two women, in whom no significant pre-existing conditions were found autoptically, had relevant comorbidities (in descending order of frequency): (1) diseases of the cardiovascular system, (2) lung diseases, (3) central nervous system diseases, (4) kidney diseases, and (5) diabetes mellitus. A total of 76 cases (95%) were classified as COVID-19 deaths, corresponding to categories 1-3. Four deaths (5%) were defined as non-COVID-19 deaths with virus-independent causes of death. In eight cases, pneumonia was combined with a fulminant pulmonary artery embolism. Peripheral pulmonary artery embolisms were found in nine other cases. Overall, deep vein thrombosis has been found in 40% of the cases. This study provides the largest overview of autopsies of SARS-CoV-2-infected patients presented so far.", "title": "Dying with SARS-CoV-2 infection-an autopsy study of the first consecutive 80 cases in Hamburg, Germany", "pid": "bkntg9y0", "bm25_score": 213.7303924560547}, {"text": "The Covid-19 pandemic has claimed many lives in the UK and globally. The objective of this paper is to study whether the number of deaths not registered as Covid-19-related has increased compared to what would have been expected in the absence of the pandemic. Reasons behind this might include Covid-19 underreporting, avoiding visits to hospitals or GPs, and the effects of the lockdown. I used weekly ONS data on the number of deaths in England and Wales that did not officially involve Covid-19 over the period 2015-2020. Simply observing trends is not sufficient as spikes in deaths may occasionally occur. I thus followed a difference-in-differences econometric approach to study whether there was a relative increase in deaths not registered as Covid-19-related during the pandemic, compared to a control. Results suggest that there were an additional 968 weekly deaths that officially did not involve Covid-19, compared to what would have otherwise been expected. It is possible that some people are dying from Covid-19 without being diagnosed, and/or that there are excess deaths due to other causes as a result of the pandemic. Analysing the cause of death for any excess non-covid-19 deaths will shed light upon the reasons for the increase in such deaths and will help design appropriate policy responses to save lives.", "title": "Excess mortality during the Covid-19 pandemic: Early evidence from England and Wales", "pid": "qg4xl5w8", "bm25_score": 213.7168731689453}, {"text": "Background: The current outbreak of COVID-19 infection, which started in Wuhan, Hubei province, China, in December 2019, is an ongoing challenge and a significant threat to public health requiring surveillance, prompt diagnosis, and research efforts to understand a new, emergent, and unknown pathogen and to develop effective therapies. Despite the increasing number of published studies on COVID-19, in all the examined studies the lack of a well-defined pathophysiology of death among patients who died following COVID-19 infection is evident. Autopsy should be considered mandatory to define the exact cause of death, thus providing useful clinical and epidemiologic information as well as pathophysiological insights to further provide therapeutic tools. Methods: A literature review was performed on PubMed database, using the key terms: “COVID-19”, “nCov 19”, and “Sars Cov 2”. 9709 articles were retrieved; by excluding all duplicated articles, additional criteria were then applied: articles or abstracts in English and articles containing one of the following words: “death”, “died”, “comorbidity”, “cause of death”, “biopsy”, “autopsy”, or “pathological”. Results: A total of 50 articles met the inclusion criteria. However, only 7 of these studies reported autopsy-based data. Discussion: The analysis of the main data from the selected studies concerns the complete analysis of 12,954 patients, of whom 2269 died (with a mortality rate of 17.52%). Laboratory confirmation of COVID-19 infection was obtained in all cases and comorbidities were fully reported in 46 studies. The most common comorbidities were: cardiovascular diseases (hypertension and coronary artery disease), metabolic disorders (diabetes, overweight, or obesity), respiratory disorders (chronic obstructive pulmonary disease), and cancer. The most common reported complications were: acute respiratory distress syndrome (ARDS), acute kidney injury, cardiac injury, liver insufficiency, and septic shock. Only 7 papers reported histological investigations. Nevertheless, only two complete autopsies are described and the cause of death was listed as COVID-19 in only one of them. The lack of postmortem investigation did not allow a definition of the exact cause of death to determine the pathways of this infection. Based on the few histopathological findings reported in the analyzed studies, it seems to be a clear alteration of the coagulation system: frequently prothrombotic activity with consequent thromboembolism was described in COVID-19 patients. As a scientific community, we are called on to face this global threat, and to defeat it with all the available tools necessary. Despite the improvement and reinforcement of any method of study in every field of medicine and science, encouraging the autopsy practice as a tool of investigation could also therefore, help physicians to define an effective treatment to reduce mortality.", "title": "No Autopsies on COVID-19 Deaths: A Missed Opportunity and the Lockdown of Science", "pid": "f7cy5oad", "bm25_score": 213.7086181640625}, {"text": "BACKGROUND: From December 2019 to February 2020, 2019 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China. Related clinical features are needed. METHODS: We reviewed 69 patients who were hospitalized in Union hospital in Wuhan between January 16 to January 29, 2020. All patients were confirmed to be infected with SARS-CoV-2 and the final date of follow-up was February 4, 2020. RESULTS: The median age of 69 enrolled patients was 42.0 years (IQR 35.0-62.0), and 32 patients (46%) were men. The most common symptoms were fever (60[87%]), cough (38[55%]), and fatigue (29[42%]). Most patients received antiviral therapy (66 [98.5%] of 67 patients) and antibiotic therapy (66 [98.5%] of 67 patients). As of February 4, 2020, 18 (26.9%) of 67 patients had been discharged, and five patients had died, with a mortality rate of 7.5%. According to the lowest SpO2 during admission, cases were divided into the SpO2&#8805;90% group (n=55) and the SpO2<90% group (n=14). All 5 deaths occurred in the SpO2<90% group. Compared with SpO2&#8805;90% group, patients of the SpO2<90% group were older, and showed more comorbidities and higher plasma levels of IL6, IL10, lactate dehydrogenase, and c reactive protein. Arbidol treatment showed tendency to improve the discharging rate and decrease the mortality rate. CONCLUSIONS: COVID-19 appears to show frequent fever, dry cough, and increase of inflammatory cytokines, and induced a mortality rate of 7.5%. Older patients or those with underlying comorbidities are at higher risk of death.", "title": "Clinical Features of 69 Cases with Coronavirus Disease 2019 in Wuhan, China", "pid": "v7edybz4", "bm25_score": 213.70208740234375}, {"text": "", "title": "Cytokine Storm: is it the only major death factor in COVID-19 patients? Coagulation role", "pid": "8tfg0t6l", "bm25_score": 213.70175170898438}, {"text": "", "title": "Cytokine Storm: Is it the only major death factor in COVID-19 patients? Coagulation role", "pid": "kezdl13b", "bm25_score": 213.70175170898438}, {"text": "COVID-19 pandemic is an emergent cardiovascular risk factor and a major cause of mortality worldwide. Thromboembolism is highly suspected as a leading cause of death in these patients through vascular inflammation caused by SARS COV2. Until now there is no real treatment of COVID-19 and many proposed drugs are under clinical trials. Considering the high incidence of thromboembolic events in critically ill patients with COVID-19, prevention of this disorder should be essential in order to reduce mortality in these patients.", "title": "COVID-19 pandemic: do we need systematic screening of patients with cardiovascular risk factors in Low and Middle-Income Countries (LMICs) for preventing death?", "pid": "yml9wuer", "bm25_score": 213.6955108642578}, {"text": "INTRODUCTION: In the current study, we evaluated factors that increase the coronavirus disease (COVID-19) patient death rate by analyzing the data from two cohort hospitals. In addition, we studied whether underlying neurological diseases are risk factors for death. METHODS: In this retrospective cohort study, we included 103 adult inpatients (aged &#8805; 18 years). We evaluated differences in demographic data between surviving and non-surviving COVID-19 patients. RESULTS: In a multivariate logistic analysis, age and the presence of chronic lung disease and Alzheimer's dementia (AD) were the only significant parameters for predicting COVID-19 non-survival (p < 0.05). However, hypertension, coronary vascular disease, dyslipidemia, chronic kidney disease, diabetes, and history of taking angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme (ACE) inhibitors, as well as nonsteroidal anti-inflammatory drugs (NSAIDs), were not significantly associated with the death of COVID-19 patients. The optimal cutoff value obtained from the maximum Youden index was 70 (sensitivity, 80.77%; specificity, 61.04%), and the odds ratio of non-survival increased 1.055 fold for every year of age. CONCLUSIONS: Clinicians should closely monitor and manage the symptoms of COVID-19 patients who are over the age of 70 years or have chronic lung disease or AD.", "title": "Neurological diseases as mortality predictive factors for patients with COVID-19: a retrospective cohort study", "pid": "z5uf591v", "bm25_score": 213.6944122314453}, {"text": "A large percentage of the deaths from COVID-19 occur among residents of long-term care facilities. There are two possible reasons for this phenomenon. First, the structural features of such settings may lead to death. Alternatively, it is possible that individuals in these facilities are in poorer health than those living elsewhere, and that these individuals would have died even if they had not been in these facilities. Our findings show that, controlling for the population density and the percentage of older adults in the population, there is a significant positive association between the number of long-term care beds per capita and COVID-19 mortality rates. This finding provides support for the claim that long-term care living arrangements (of older people) are a significant risk factor for dying from COVID-19.", "title": "Long-Term Care Facilities as a Risk Factor for Death Due to COVID-19", "pid": "fhuugtq5", "bm25_score": 213.69314575195312}, {"text": "", "title": "Could the decrease in the endothelial nitric oxide (NO) production and NO bioavailability be the crucial cause of COVID-19 related deaths?", "pid": "jwdcz71h", "bm25_score": 213.68484497070312}]}
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"zy8qjaai": 0}, "bm25_results": [{"text": "The global pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has prompted multiple clinical trials to jumpstart search for anti-SARS-CoV-2 therapies from existing drugs, including those with reported in vitro efficacies as well as those ones that are not known to inhibit SARS-CoV-2, such as ritonavir/lopinavir and favilavir. Here we report that after screening 19 antiviral drugs that are either in clinical trials or with proposed activity against SARS-CoV-2, remdesivir was the most effective. Chloroquine only effectively protected virus-induced cytopathic effect at around 30 µM with a therapeutic index of 1.5. Our findings also suggest that velpatasvir, ledipasvir, ritonavir, litonavir, lopinavir, favilavir, sofosbuvir, danoprevir, and pocapavir do not have direct antiviral effect.", "title": "Evaluation of 19 antiviral drugs against SARS-CoV-2 Infection", "pid": "ai2zcke5", "bm25_score": 219.86376953125}, {"text": "The outbreak of a novel human coronavirus (SARS-CoV-2) has evolved into global health emergency, infecting hundreds of thousands of people worldwide. We have identified experimental data on the inhibitory activity of compounds tested against closely related (96% sequence identity, 100% active site conservation) protease of SARS-CoV and employed this data to build QSAR models for this dataset. We employed these models for virtual screening of all drugs from DrugBank, including compounds in clinical trials. Molecular docking and similarity search approaches were explored in parallel with QSAR modeling, but molecular docking failed to correctly discriminate between experimentally active and inactive compounds. As a result of our studies, we recommended 41 approved, experimental, or investigational drugs as potential agents against SARS-CoV-2 acting as putative inhibitors of Mpro. Ten compounds with feasible prices were purchased and are awaiting the experimental validation..", "title": "Computational Models Identify Several FDA Approved or Experimental Drugs as Putative Agents Against SARS-CoV-2.", "pid": "hchioraj", "bm25_score": 219.66873168945312}, {"text": "SARS-CoV-2 has been widely spread around the world and COVID-19 was declared a global pandemic by the World Health Organization. Limited clinically effective antiviral drugs are available now. The development of anti-SARS-CoV-2 drugs has become an urgent work worldwide. At present, potential therapeutic targets and drugs for SARS-CoV-2 are continuously reported, and many repositioning drugs are undergoing extensive clinical research, including remdesivir and chloroquine. On the other hand, structures of many important viral target proteins and host target proteins, including that of RdRp and Mpro were constantly reported, which greatly promoted structure-based drug design. This paper summarizes the current research progress and challenges in the development of anti-SARS-CoV-2 drugs, and proposes novel short-term and long-term drug research strategies.", "title": "Research progress on repositioning drugs and specific therapeutic drugs for SARS-CoV-2", "pid": "xb5p25gk", "bm25_score": 219.47825622558594}, {"text": "The current coronavirus (SARS-COV-2) pandemic and phenomenal spread to every nook and cranny of the world has raised major apprehensions about the modern public health care system. So far as a result of this epidemic, 4,434,653 confirmed cases and 302,169 deaths are reported. The growing infection rate and death toll demand the use of all possible approaches to design novel drugs and vaccines to curb this disease. In this study, we combined drugs repurposing and virtual drug screening strategies to target 3CLpro, which has an essential role in viral maturation and replication. A total of 31 FDA approved anti-HIV drugs, and Traditional Chinese medicines (TCM) database were screened to find potential inhibitors. As a result, Saquinavir, and five drugs (TCM5280805, TCM5280445, TCM5280343, TCM5280863, and TCM5458190) from the TCM database were found as promising hits. Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. Thus, we suggest that these compounds should be tested experimentally against the SARS-COV-2 as Saquinavir has been reported to inhibit HIV protease experimentally. Considering the intensity of coronavirus dissemination, the present research is in line with the idea of discovering the latest inhibitors against the coronavirus essential pathways to accelerate the drug development cycle.Communicated by Ramaswamy H. Sarma.", "title": "Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro)", "pid": "qp54spam", "bm25_score": 219.39430236816406}, {"text": "The current coronavirus (SARS-COV-2) pandemic and phenomenal spread to every nook and cranny of the world has raised major apprehensions about the modern public health care system. So far as a result of this epidemic, 4,434,653 confirmed cases and 302,169 deaths are reported. The growing infection rate and death toll demand the use of all possible approaches to design novel drugs and vaccines to curb this disease. In this study, we combined drugs repurposing and virtual drug screening strategies to target 3CLpro, which has an essential role in viral maturation and replication. A total of 31 FDA approved anti-HIV drugs, and Traditional Chinese medicines (TCM) database were screened to find potential inhibitors. As a result, Saquinavir, and five drugs (TCM5280805, TCM5280445, TCM5280343, TCM5280863, and TCM5458190) from the TCM database were found as promising hits. Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. Thus, we suggest that these compounds should be tested experimentally against the SARS-COV-2 as Saquinavir has been reported to inhibit HIV protease experimentally. Considering the intensity of coronavirus dissemination, the present research is in line with the idea of discovering the latest inhibitors against the coronavirus essential pathways to accelerate the drug development cycle. Communicated by Ramaswamy H. Sarma.", "title": "Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro)", "pid": "pwi48i20", "bm25_score": 219.39430236816406}, {"text": "COVID-19 is an emerging infectious disease and was recently declared as a pandemic by WHO. Currently, there is no vaccine or therapeutic available for this disease. Drug repositioning represents the only feasible option to address this global challenge and a panel of 48 FDA-approved drugs that have been pre-selected by an assay of SARS-CoV was screened to identify potential antiviral drug candidates against SARS-CoV-2 infection. We found a total of 24 drugs which exhibited antiviral efficacy (0.1 μM < IC50 < 10 μM) against SARS-CoV-2. In particular, two FDA-approved drugs - niclosamide and ciclesonide – were notable in some respects. These drugs will be tested in an appropriate animal model for their antiviral activities. In near future, these already FDA-approved drugs could be further developed following clinical trials in order to provide additional therapeutic options for patients with COVID-19.", "title": "Identification of antiviral drug candidates against SARS-CoV-2 from FDA-approved drugs", "pid": "5f95gve3", "bm25_score": 219.38754272460938}, {"text": "There are an urgent need for antivirals to treat the newly emerged SARS-CoV-2. To identify new candidates we screened a repurposing library of ~3,000 drugs. Screening in Vero cells found few antivirals, while screening in human Huh7.5 cells validated 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we found that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH-independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we found 9 drugs are antiviral in lung cells, 7 of which have been tested in humans, and 3 are FDA approved including Cyclosporine which we found is targeting Cyclophilin rather than Calcineurin for its antiviral activity. These antivirals reveal essential host targets and have the potential for rapid clinical implementation.", "title": "Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2", "pid": "hsc2x36j", "bm25_score": 219.38626098632812}, {"text": "SARS-CoV-2 emerged in China at the end of 2019 and has rapidly become a pandemic with roughly 2.7 million recorded COVID-19 cases and greater than 189,000 recorded deaths by April 23rd, 2020 (www.WHO.org). There are no FDA approved antivirals or vaccines for any coronavirus, including SARS-CoV-2. Current treatments for COVID-19 are limited to supportive therapies and off-label use of FDA approved drugs. Rapid development and human testing of potential antivirals is greatly needed. A quick way to test compounds with potential antiviral activity is through drug repurposing. Numerous drugs are already approved for human use and subsequently there is a good understanding of their safety profiles and potential side effects, making them easier to fast-track to clinical studies in COVID-19 patients. Here, we present data on the antiviral activity of 20 FDA approved drugs against SARS-CoV-2 that also inhibit SARS-CoV and MERS-CoV. We found that 17 of these inhibit SARS-CoV-2 at a range of IC50 values at non-cytotoxic concentrations. We directly follow up with seven of these to demonstrate all are capable of inhibiting infectious SARS-CoV-2 production. Moreover, we have evaluated two of these, chloroquine and chlorpromazine, in vivo using a mouse-adapted SARS-CoV model and found both drugs protect mice from clinical disease.", "title": "Broad anti-coronaviral activity of FDA approved drugs against SARS-CoV-2 in vitro and SARS-CoV in vivo", "pid": "jbc74lcu", "bm25_score": 219.17678833007812}, {"text": "Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC(50)s), and in particular, two FDA-approved drugs—niclosamide and ciclesonide—were notable in some respects.", "title": "Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs", "pid": "gka6f34c", "bm25_score": 219.13851928710938}, {"text": "Drug repositioning is the only feasible option to immediately address the COVID-19 global challenge. We screened a panel of 48 FDA-approved drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which were preselected by an assay of SARS-CoV. We identified 24 potential antiviral drug candidates against SARS-CoV-2 infection. Some drug candidates showed very low 50% inhibitory concentrations (IC50s), and in particular, two FDA-approved drugs-niclosamide and ciclesonide-were notable in some respects.", "title": "Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs", "pid": "2gvpn4zr", "bm25_score": 219.12567138671875}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), initially termed 2019-new CoV (2019-nCoV), is a novel coronavirus responsible for the severe respiratory illness currently ongoing worldwide from the beginning of December 2019. This beta gene virus, very close to bat coronaviruses (bat-CoV-RaTG13) and bat-SL-CoVZC45, causes a severe disease, similar to those caused by Middle East respiratory syndrome (MERS)-CoV and SARS-CoV viruses, featured by low to moderate mortality rate. Unfortunately, the antiviral drugs commonly used in clinical practice to treat viral infections, are not applicable to SARS-Cov-2 and no vaccine is available. Thus, it is extremely necessary to identify new drugs suitable for the treatment of the 2019-nCoV outbreak. Different preclinical studies conducted on other coronaviruses suggested that promising clinical outcomes for 2019-nCoV should be obtained by using alpha-interferon, chloroquine phosphate, arabinol, remdesivir, lopinavir/ritonavir, and anti-inflammatory drugs. Moreover, clinical trials with these suitable drugs should be performed on patients affected by SARS-Cov-2 to prove their efficacy and safety. Finally, a very promising therapeutic drug, tocilizumab, is discussed; it is currently used to treat patients presenting COVID-19 pneumonia. Herein, we recapitulate these experimental studies to highlight the use of antiviral drugs for the treatment of SARS-Cov-2 disease.", "title": "Potential Antiviral Drugs for SARS-Cov-2 Treatment: Preclinical Findings and Ongoing Clinical Research.", "pid": "lav2iavi", "bm25_score": 219.12355041503906}, {"text": "BACKGROUND: In December 2019, a new coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has emerged from China causing pneumonia outbreaks first in the Wuhan region and currently worldwide. In the light of the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the most efficient tool to find therapeutic solution. OBJECTIVES: The aim of this study was to summarize in vitro data of current agents used for the management of SARSCoV-2 all over the world. METHODS: A literature search of articles from January 2000 until April 2020 was performed using MEDLINE, EMBASE and the Cochrane Library to assess in vitro data of current or putative therapies for SARS-CoV-2. RESULTS: Although in vitro studies are scarce, data regarding chloroquine and hydroxychloroquine, remdesivir, nitazoxanide, teicoplanin, ivermectin, lopinavir, homoharringtonine and emetine seem promising. CONCLUSION: Scientist all over the world should work together and increase their efforts in order to find feasible and efficient solutions against this new global viral threat.", "title": "In vitro data of current therapies for SARS-CoV-2", "pid": "kfal7g2v", "bm25_score": 219.11767578125}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), initially termed 2019-new CoV (2019-nCoV), is a novel coronavirus responsible for the severe respiratory illness currently ongoing worldwide from the beginning of December 2019. This beta gene virus, very close to bat coronaviruses (bat-CoV-RaTG13) and bat-SL-CoVZC45, causes a severe disease, similar to those caused by Middle East respiratory syndrome (MERS)-CoV and SARS-CoV viruses, featured by low to moderate mortality rate. Unfortunately, the antiviral drugs commonly used in clinical practice to treat viral infections, are not applicable to SARS-Cov-2 and no vaccine is available. Thus, it is extremely necessary to identify new drugs suitable for the treatment of the 2019-nCoV outbreak. Different preclinical studies conducted on other coronaviruses suggested that promising clinical outcomes for 2019-nCoV should be obtained by using alpha-interferon, chloroquine phosphate, arabinol, remdesivir, lopinavir/ritonavir, and anti-inflammatory drugs. Moreover, clinical trials with these suitable drugs should be performed on patients affected by SARS-Cov-2 to prove their efficacy and safety. Finally, a very promising therapeutic drug, tocilizumab, is discussed; it is currently used to treat patients presenting COVID-19 pneumonia. Herein, we recapitulate these experimental studies to highlight the use of antiviral drugs for the treatment of SARS-Cov-2 disease.", "title": "Potential Antiviral Drugs for SARS-Cov-2 Treatment: Preclinical Findings and Ongoing Clinical Research", "pid": "7wbpj88g", "bm25_score": 219.1143341064453}, {"text": "COVID-19 pandemic has infected millions of people with mortality exceeding 300,000. There is an urgent need to find therapeutic agents that can help clear the virus to prevent the severe disease and death. Identifying effective and safer drugs can provide with more options to treat the COVID-19 infections either alone or in combination. Here we performed a high throughput screen of approximately 1700 US FDA approved compounds to identify novel therapeutic agents that can effectively inhibit replication of coronaviruses including SARS-CoV-2. Our two-step screen first used a human coronavirus strain OC43 to identify compounds with anti-coronaviral activities. The effective compounds were then screened for their effectiveness in inhibiting SARS-CoV-2. These screens have identified 24 anti-SARS-CoV-2 drugs including previously reported compounds such as hydroxychloroquine, amlodipine, arbidol hydrochloride, tilorone 2HCl, dronedarone hydrochloride, and merfloquine hydrochloride. Five of the newly identified drugs had a safety index (cytotoxic/effective concentration) of >600, indicating wide therapeutic window compared to hydroxychloroquine which had safety index of 22 in similar experiments. Mechanistically, five of the effective compounds were found to block SARS-CoV-2 S protein-mediated cell fusion. These FDA approved compounds can provide much needed therapeutic options that we urgently need in the midst of the pandemic.", "title": "Identification of potent and safe antiviral therapeutic candidates against SARS-CoV-2", "pid": "e9fjo7tl", "bm25_score": 219.0979461669922}, {"text": "With currently over 4 million confirmed cases worldwide, including more than 300’000 deaths, the current Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has a major impact on the economy and health care system. Currently, a limited amount of prophylactic or therapeutic intervention options are available against SARS-CoV-2. In this study, we screened 400 compounds from the antimicrobial ‘Pandemic Response Box’ library for inhibiting properties against SARS-CoV-2. We identified sixteen compounds that potently inhibited SARS-CoV-2 replication, of which five compounds displayed equal or even higher antiviral activity compared to Remdesivir. These results show that five compounds should be further investigated for their mode of action, safety and efficacy against SARS-CoV-2. Highlights 400 compounds from the pandemic response box were tested for antiviral activity against SARS-CoV-2. 5 compounds had an equal or higher antiviral efficacy towards SARS-CoV-2, compared to the nucleoside analogue Remdesivir.", "title": "Identification of five antiviral compounds from the Pandemic Response Box targeting SARS-CoV-2", "pid": "sj6ts2vo", "bm25_score": 219.06996154785156}, {"text": "BACKGROUND In December 2019, a new coronavirus, named Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has emerged from China causing pneumonia outbreaks first in the Wuhan region and currently worldwide. In the light of the lack of efficient and specific treatments and the need to contain the epidemic, drug repurposing appears to be the most efficient tool to find therapeutic solution. OBJECTIVES The aim of this study was to summarize in vitro data of current agents used for the management of SARSCoV-2 all over the world. METHODS A literature search of articles from January 2000 until April 2020 was performed using MEDLINE, EMBASE and the Cochrane Library to assess in vitro data of current or putative therapies for SARS-CoV-2. RESULTS Although in vitro studies are scarce, data regarding chloroquine and hydroxychloroquine, remdesivir, nitazoxanide, teicoplanin, ivermectin, lopinavir, homoharringtonine and emetine seem promising. CONCLUSION Scientist all over the world should work together and increase their efforts in order to find feasible and efficient solutions against this new global viral threat.", "title": "In vitro data of current therapies for SARS-CoV-2.", "pid": "de45x8q4", "bm25_score": 219.0251922607422}, {"text": "Different treatments are currently used for clinical management of SARS-CoV-2 infection, but little is known about their efficacy yet. Here we present ongoing results to compare currently available drugs for a variety of diseases to find out if they counteract SARS-CoV-2-induced cytopathic effect in vitro. Our goal is to prioritize antiviral activity to provide a solid evidence-driven rationale for forthcoming clinical trials. Since the most effective antiviral approaches are usually based on combined therapies that tackle the viral life cycle at different stages, we are also testing combinations of drugs that may be critical to reduce the emergence of resistant viruses. We will provide results as soon as they become available, so data should be interpreted with caution, clearly understanding the limitations of the in vitro model, that may not always reflect what could happen in vivo. Thus, our goal is to test the most active antivirals identified in adequate animal models infected with SARS-CoV-2, to add more information about possible in vivo efficacy. In turn, successful antivirals could be tested in clinical trials as treatments for infected patients, but also as pre-exposure prophylaxis to avoid novel infections until an effective and safe vaccine is developed.", "title": "Search for SARS-CoV-2 inhibitors in currently approved drugs to tackle COVID-19 pandemia", "pid": "ywaefpe8", "bm25_score": 219.01547241210938}, {"text": "Severe acute respiratory syndrome (SARS) is an infectious disease caused by a newly identified human coronavirus (SARS-CoV). Currently, no effective drug exists to treat SARS-CoV infection. In this study, we investigated whether a panel of commercially available antiviral drugs exhibit in vitro anti–SARS-CoV activity. A drug-screening assay that scores for virus-induced cytopathic effects on cultured cells was used. Tested were 19 clinically approved compounds from several major antiviral pharmacologic classes: nucleoside analogs, interferons, protease inhibitors, reverse transcriptase inhibitors, and neuraminidase inhibitors. Complete inhibition of cytopathic effects of SARS-CoV in culture was observed for interferon subtypes, β-1b, α-n1, α-n3, and human leukocyte interferon α. These findings support clinical testing of approved interferons for the treatment of SARS.", "title": "Inhibition of SARS Coronavirus Infection In Vitro with Clinically Approved Antiviral Drugs", "pid": "kcyao9i9", "bm25_score": 218.9688262939453}, {"text": "As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6,5 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified most potent sera from recovered patients for treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that combinations of virus-directed nelfinavir along with host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19.", "title": "Potential antiviral options against SARS-CoV-2 infection", "pid": "ucqago27", "bm25_score": 218.91873168945312}, {"text": "As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here, we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified the most potent sera from recovered patients for the treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that a combination of orally available virus-directed nelfinavir and host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19.", "title": "Potential Antiviral Options against SARS-CoV-2 Infection", "pid": "h8rg5umf", "bm25_score": 218.89747619628906}, {"text": "Novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lies behind the ongoing outbreak of coronavirus disease 2019 (COVID-19). There is a growing understanding of SARS-CoV-2 in virology, epidemiology, and clinical management strategies. However, no anti-SARS-CoV-2 drug or vaccine has been officially approved due to the absence of adequate evidence. Scientists are racing to develop a treatment for COVID-19. Recent studies have revealed many attractive therapeutic options, even if some of them remain to be further confirmed in rigorous preclinical models and clinical trials. In this minireview, we aim to summarize the updated potential approaches against SARS-CoV-2. We emphasize that further efforts are warranted to develop the safest and most effective approach.", "title": "Updated Approaches against SARS-CoV-2", "pid": "bgm4dlwz", "bm25_score": 218.88232421875}, {"text": "As of June 2020, the number of people infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) continues to skyrocket, with more than 6.7 million cases worldwide. Both the World Health Organization (WHO) and United Nations (UN) has highlighted the need for better control of SARS-CoV-2 infections. However, developing novel virus-specific vaccines, monoclonal antibodies and antiviral drugs against SARS-CoV-2 can be time-consuming and costly. Convalescent sera and safe-in-man broad-spectrum antivirals (BSAAs) are readily available treatment options. Here, we developed a neutralization assay using SARS-CoV-2 strain and Vero-E6 cells. We identified the most potent sera from recovered patients for the treatment of SARS-CoV-2-infected patients. We also screened 136 safe-in-man broad-spectrum antivirals against the SARS-CoV-2 infection in Vero-E6 cells and identified nelfinavir, salinomycin, amodiaquine, obatoclax, emetine and homoharringtonine. We found that a combination of orally available virus-directed nelfinavir and host-directed amodiaquine exhibited the highest synergy. Finally, we developed a website to disseminate the knowledge on available and emerging treatments of COVID-19.", "title": "Potential Antiviral Options against SARS-CoV-2 Infection.", "pid": "22366b81", "bm25_score": 218.8773193359375}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as the causative agent of the novel pandemic viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for safe, broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV), a monophosphoramidate prodrug of an adenosine analog, potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 μM). Weaker activity was observed in Vero E6 cells (EC50 = 1.65 μM) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminished lung viral load and improved pulmonary function as compared to vehicle treated animals. These data provide evidence that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.", "title": "Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice", "pid": "ghrlj6b2", "bm25_score": 218.8272705078125}, {"text": "Coronaviruses (CoVs) are a group of RNA viruses that are associated with different diseases in animals, birds, and humans. Human CoVs (HCoVs) have long been known to be the causative agents of mild respiratory illnesses. However, two HCoVs associated with severe respiratory diseases are Severe Acute Respiratory Syndrome-CoV (SARS-CoV) and Middle East Respiratory Syndrome-CoV (MERS-CoV). Both viruses resulted in hundreds of deaths after spreading to several countries. Most recently, SARS-CoV-2 has emerged as the third HCoV causing severe respiratory distress syndrome and viral pneumonia (known as COVID-19) in patients from Wuhan, China, in December 2019. Soon after its discovery, SARS-CoV-2 spread to all countries, resulting in millions of cases and thousands of deaths. Since the emergence of SARS-CoV, many research groups have dedicated their resources to discovering effective antivirals that can treat such life-threatening infections. The rapid spread and high fatality rate of SARS-CoV-2 necessitate the quick discovery of effective antivirals to control this outbreak. Since SARS-CoV-2 shares 79% sequence identity with SARS-CoV, several anti-SARS-CoV drugs have shown promise in limiting SARS-CoV-2 replication in vitro and in vivo. In this review, we discuss antivirals described for SARS-CoV and provide an update on therapeutic strategies and antivirals against SARS-CoV-2. The control of the current outbreak will strongly depend on the discovery of effective and safe anti-SARS-CoV-2 drugs.", "title": "SARS-CoV-2: An Update on Potential Antivirals in Light of SARS-CoV Antiviral Drug Discoveries.", "pid": "ydywrk62", "bm25_score": 218.74087524414062}, {"text": "SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.", "title": "Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods", "pid": "i1lyno9g", "bm25_score": 218.7384033203125}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global health pandemic. The lack of effective treatments, coupled with its etiology, has resulted in more than 400,000 deaths at the time of writing. The SARS-CoV-2 genome is highly homologous to that of SARS-CoV, the causative agent behind the 2003 SARS outbreak. Based on prior reports, clinicians have pursued the off-label use of several antiviral drugs, while the scientific community has responded by seeking agents against traditional targets, especially viral proteases. However, several avenues remain unexplored, including disrupting E and M protein oligomerization, outcompeting host glycan-virus interactions, interfering with the heparan sulfate proteoglycans-virus interaction, and others. In this review, we highlight some of these opportunities while summarizing the drugs currently in use against coronavirus 2019 (COVID-19).", "title": "Discovering small-molecule therapeutics against SARS-CoV-2", "pid": "cpg4q29v", "bm25_score": 218.72901916503906}, {"text": "Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 μM). Weaker activity is observed in Vero E6 cells (EC50 = 1.65 μM) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminishes lung viral load and improves pulmonary function compared to vehicle treated animals. These data demonstrate that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.", "title": "Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice.", "pid": "9sjdb7f3", "bm25_score": 218.6957244873047}, {"text": "Abstract Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may prevent spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic.", "title": "Candidate drugs against SARS-CoV-2 and COVID-19", "pid": "n0mz098o", "bm25_score": 218.6890106201172}, {"text": "Background The outbreak of SARS CoV-2 has caused ever-increasing attention and public panic all over the world. Currently, there is no specific treatment against the SARS CoV-2. Therefore, identifying effective antiviral agents to combat the disease is urgently needed. Previous studies found that indomethacin has the ability to inhibit the replication of several unrelated DNA and RNA viruses, including SARS-CoV. Methods SARS CoV-2 pseudovirus-infected African green monkey kidney VERO E6 cells treated with different concentrations of indomethacin or aspirin at 48 hours post infection (p.i). The level of cell infection was determined by luciferase activity. Anti-coronavirus efficacy in vivo was confirmed by evaluating the time of recovery in canine coronavirus (CCV) infected dogs treated orally with 1mg/kg body weight indomethacin. Results We found that indomethacin has a directly and potently antiviral activity against the SARS CoV-2 pseudovirus (reduce relative light unit to zero). In CCV-infected dogs, recovery occurred significantly sooner with symptomatic treatment + oral indomethacin (1 mg/kg body weight) daily treatments than with symptomatic treatment + ribavirin (10-15 mg/kg body weight) daily treatments (P =0.0031), but was not significantly different from that with symptomatic treatment + anti-canine coronavirus serum + canine hemoglobin + canine blood immunoglobulin + interferon treatments (P =0.7784). Conclusion The results identify indomethacin as a potent inhibitor of SARS CoV-2.", "title": "Indomethacin has a potent antiviral activity against SARS CoV-2 in vitro and canine coronavirus in vivo", "pid": "7joyaz7q", "bm25_score": 218.679443359375}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir/ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized controlled trials are showing the poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.", "title": "Clinical trials of repurposed antivirals for SARS-CoV-2", "pid": "yvlcorrg", "bm25_score": 218.6551971435547}, {"text": "On December 31, 2019 a pneumonia outbreak caused by a new coronavirus (SARS-CoV-2) was detected in the city of Wuhan (China) Due to the high capacity of diffusion and human infection it has become a new zoonotic pandemic The absence of a vaccine has determined the search for antiviral drugs with the capacity to inhibit the replication of the new virus Among them, remdesivir, an analogue of adenosine, is what seems to have a more promising future This drug has shown in vitro and in animals a high capacity to block infection and viral replication with attainable concentrations in human plasma Although all studies have been carried out with SARS-CoV and MERS-CoV, it seems that by virological and functional analogy, remdesivir is one of the few antiviral drugs with proven efficacy However, studies and clinical trials in humans are required to know the result of their application in them", "title": "Remdesivir, the antiviral hope against SARS-CoV-2/ Remdesivir, la esperanza antiviral frente al SARS-CoV-2", "pid": "puc13jf1", "bm25_score": 218.6544647216797}, {"text": "Outbreak and pandemic of coronavirus SARS-CoV-2 in 2019/2020 will challenge global health for the future. Because a vaccine against the virus will not be available in the near future, we herein try to offer a pharmacological strategy to combat the virus. There exists a number of candidate drugs that may inhibit infection with and replication of SARS-CoV-2. Such drugs comprise inhibitors of TMPRSS2 serine protease and inhibitors of angiotensin-converting enzyme 2 (ACE2). Blockade of ACE2, the host cell receptor for the S protein of SARS-CoV-2 and inhibition of TMPRSS2, which is required for S protein priming may prevent cell entry of SARS-CoV-2. Further, chloroquine and hydroxychloroquine, and off-label antiviral drugs, such as the nucleotide analogue remdesivir, HIV protease inhibitors lopinavir and ritonavir, broad-spectrum antiviral drugs arbidol and favipiravir as well as antiviral phytochemicals available to date may limit spread of SARS-CoV-2 and morbidity and mortality of COVID-19 pandemic.", "title": "Candidate drugs against SARS-CoV-2 and COVID-19", "pid": "xef6fr39", "bm25_score": 218.64376831054688}, {"text": "A novel coronavirus, named SARS-CoV-2, emerged in 2019 from Hubei region in China and rapidly spread worldwide. As no approved therapeutics exists to treat Covid-19, the disease associated to SARS-Cov-2, there is an urgent need to propose molecules that could quickly enter into clinics. Repurposing of approved drugs is a strategy that can bypass the time consuming stages of drug development. In this study, we screened the Prestwick Chemical Library® composed of 1,520 approved drugs in an infected cell-based assay. 90 compounds were identified. The robustness of the screen was assessed by the identification of drugs, such as Chloroquine derivatives and protease inhibitors, already in clinical trials. The hits were sorted according to their chemical composition and their known therapeutic effect, then EC50 and CC50 were determined for a subset of compounds. Several drugs, such as Azithromycine, Opipramol, Quinidine or Omeprazol present antiviral potency with 2<EC50<20µM. By providing new information on molecules inhibiting SARS-CoV-2 replication in vitro, this study could contribute to the short-term repurposing of drugs against Covid-19.", "title": "In vitro screening of a FDA approved chemical library reveals potential inhibitors of SARS-CoV-2 replication", "pid": "m7dwbheg", "bm25_score": 218.63743591308594}, {"text": "Aim: Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2), a pernicious viral disease, causes acute respiratory distress responsible for mortality and morbidity worldwide. To screen different immunomodulatory medicinal compounds to unravel their interaction with SARS-COV-2 viral proteins. Materials & methods: A library of immunomodulatory medicinal compounds with antiviral capability were analyzed against SARS proteases, spike protein and nonstructural proteins (NSP-9, 15) using Autodock vina. Results: Out of more than 300 medicinal compounds, only six compounds: arzanol, ferulic acid, genistein, resveratrol, rosmanol and thymohydroquinone showed significant interaction with the SARS viral proteins by forming hydrogen bonds with the active site residues with low binding energy. Further ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis showed good pharmacokinetic properties and low acute toxicity of these compounds. Conclusion: The current study provides convincing evidence that these medicinal compounds exert antiviral activity against the SARS-COV-2 virus and could be further exploited for the treatment of this disease.", "title": "Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-COV-2 inhibitors", "pid": "201ac32t", "bm25_score": 218.62396240234375}, {"text": "Recently, the SARS-CoV-2 was quickly identified as the causal pathogen leading to the outbreak of severe acute respiratory syndrome-like illness all over the world. As the SARS-CoV-2 infection pandemic proceeds, many efforts are being dedicated to the development of diverse treatment strategies. Increasing evidence showed potential therapeutic agents directly acting against SARS-CoV-2 virus, such as interferon, RNA-dependent RNA polymerase inhibitors, protease inhibitors, viral entry blockers, neuraminidase inhibitor, vaccine, antibody agent targeting the SARS-CoV-2 RNA genome, natural killer cells and nucleocytoplasmic trafficking inhibitor. To date, several direct anti-SARS-CoV-2 agents have demonstrated promising in vitro and clinical efficacy. This article reviews the current and future development of direct acting agents against SARS-CoV-2.", "title": "The pharmacological development of direct acting agents for emerging needed therapy against SARS-CoV-2.", "pid": "7ln7p715", "bm25_score": 218.62176513671875}, {"text": "SARS-COV-2 has recently emerged as a new public health threat. Herein, we report that the FDA-approved drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. Treatment of cells with auranofin resulted in a 95% reduction in the viral RNA at 48 h after infection. Auranofin treatment dramatically reduced the expression of SARS-COV-2-induced cytokines in human cells. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its antiviral, anti-inflammatory and anti-reactive oxygen species (ROS) properties. Further animal studies are warranted to evaluate the safety and efficacy of auranofin for the management of SARS-COV-2 associated disease.", "title": "The FDA-approved gold drug auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells", "pid": "d59dck5t", "bm25_score": 218.61553955078125}, {"text": "To identify drugs that are potentially used for the treatment of COVID-19, the potency of 1403 FDA-approved drugs were evaluated using a robust pseudovirus assay and the candidates were further confirmed by authentic SARS-CoV-2 assay. Four compounds, Clomiphene (citrate), Vortioxetine, Vortioxetine (hydrobromide) and Asenapine (hydrochloride), showed potent inhibitory effects in both pseudovirus and authentic virus assay. The combination of Clomiphene (citrate), Vortioxetine and Asenapine (hydrochloride) is much more potent than used alone, with IC50 of 0.34 μM.", "title": "Several FDA-approved drugs effectively inhibit SARS-CoV-2 infection in vitro", "pid": "4k7qymqd", "bm25_score": 218.57757568359375}, {"text": "The outbreak of novel coronavirus pneumonia (COVID-19) caused thousands of deaths worldwide, and the number of total infections is still rising. However, the development of effective vaccine for this novel virus would take a few months. Thus it is urgent to identify some potentially effective old drugs that can be used immediately. Fortunately, some compounds that can inhibit coronavirus in vitro have been reported. In this study, the coronavirus-specific dataset was used to fine-tune our pre-trained multi-task deep model. Next we used the re-trained model to select available commercial drugs against targeted proteins of SARS-CoV-2. The results show that abacavir, a powerful nucleoside analog reverse transcriptase inhibitor used to treat HIV, is predicted to have high binding affinity with several proteins of SARS-CoV-2. Almitrine mesylate and roflumilast which are used for respiratory diseases such as chronic obstructive pulmonary disease are also predicted to have inhibitory effect. Overall, ten drugs are listed as potential inhibitors and the important sites for these binding by our model are exhibited. We hope these results would be useful in the fight against SARS-CoV-2.", "title": "Prediction of potential commercially inhibitors against SARS-CoV-2 by multi-task deep model", "pid": "2fs8oui2", "bm25_score": 218.5470733642578}, {"text": "Recently, the SARS-CoV-2 was quickly identified as the causal pathogen leading to the outbreak of severe acute respiratory syndrome-like illness all over the world. As the SARS-CoV-2 infection pandemic proceeds, many efforts are being dedicated to the development of diverse treatment strategies. Increasing evidence showed potential therapeutic agents directly acting against SARS-CoV-2 virus, such as interferon, RNA-dependent RNA polymerase inhibitors, protease inhibitors, viral entry blockers, neuraminidase inhibitor, vaccine, antibody agent targeting the SARS-CoV-2 RNA genome, natural killer cells and nucleocytoplasmic trafficking inhibitor. To date, several direct anti-SARS-CoV-2 agents have demonstrated promising in vitro and clinical efficacy. This article reviews the current and future development of direct acting agents against SARS-CoV-2.", "title": "The pharmacological development of direct acting agents for emerging needed therapy against SARS-CoV-2", "pid": "el7d8lck", "bm25_score": 218.5367889404297}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir/ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized controlled trials are showing the poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.", "title": "Clinical trials of repurposed antivirals for SARS-CoV-2.", "pid": "5q5mele8", "bm25_score": 218.5173797607422}, {"text": "Here we report on the most recent updates on experimental drugs successfully employed in the treatment of the disease caused by SARS CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease 19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir (which is widely used to treat human immunodeficiency virus (HIV) infection) in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxychloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experimental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this virus. This also stresses the urgent need for the scientific community to devote its efforts to find other more specific antiviral strategies.", "title": "SARS CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and Other Drugs for the Treatment of the New Coronavirus.", "pid": "h450b2l5", "bm25_score": 218.48728942871094}, {"text": "The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.", "title": "Discovering drugs to treat coronavirus disease 2019 (COVID-19).", "pid": "8ruux4sw", "bm25_score": 218.4781951904297}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of CoV disease 2019 (COVID-19) is a highly pathogenic and transmissible CoV that is presently plaguing the global human population and economy. No proven effective antiviral therapy or vaccine currently exists, and supportive care remains to be the cornerstone treatment. Through previous lessons learned from SARS-CoV-1 and MERS-CoV studies, scientific groups worldwide have rapidly expanded the knowledge pertaining to SARS-CoV-2 virology that includes in vitro and in vivo models for testing of antiviral therapies and randomized clinical trials. In the present narrative, we review SARS-CoV-2 virology, clinical features, pathophysiology, and animal models with a specific focus on the antiviral and adjunctive therapies currently being tested or that require testing in animal models and randomized clinical trials.", "title": "A Review on SARS-CoV-2 Virology, Pathophysiology, Animal Models, and Anti-Viral Interventions", "pid": "30tftimd", "bm25_score": 218.43923950195312}, {"text": "Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.IMPORTANCE The SARS-CoV-2 pandemic continues to spread worldwide, with rapidly increasing numbers of mortalities, placing increasing strain on health care systems. Despite serious public health concerns, no effective vaccines or therapeutics have been approved by regulatory agencies. In this study, we tested the FDA-approved drugs lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir against SARS-CoV-2 infection in a highly susceptible ferret infection model. While most of the drug treatments marginally reduced clinical symptoms, they did not reduce virus titers, with the exception of emtricitabine-tenofovir treatment, which led to diminished virus titers in nasal washes at 8 dpi. Further, the azathioprine-treated immunosuppressed ferrets showed delayed virus clearance and low SN titers, resulting in a prolonged infection. As several FDA-approved or repurposed drugs are being tested as antiviral candidates at clinics without sufficient information, rapid preclinical animal studies should proceed to identify therapeutic drug candidates with strong antiviral potential and high safety prior to a human efficacy trial.", "title": "Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets", "pid": "7h3rrea7", "bm25_score": 218.43576049804688}, {"text": "Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is one of the most contagious diseases in human history that has already affected millions of lives worldwide. To date, no vaccines or effective therapeutics have been discovered yet that may successfully treat COVID-19 patients or contain the transmission of the virus. Scientific communities across the globe responded rapidly and have been working relentlessly to develop drugs and vaccines, which may require considerable time. In this uncertainty, repurposing the existing antiviral drugs could be the best strategy to speed up the discovery of effective therapeutics against SARS-CoV-2. Moreover, drug repurposing may leave some vital information on druggable targets that could be capitalized in target-based drug discovery. Information on possible drug targets and the progress on therapeutic and vaccine development also needs to be updated. In this review, we revisited the druggable targets that may hold promise in the development of the anti-SARS-CoV-2 agent. Progresses on the development of potential therapeutics and vaccines that are under the preclinical studies and clinical trials have been highlighted. We anticipate that this review will provide valuable information that would help to accelerate the development of therapeutics and vaccines against SARS-CoV-2 infection.", "title": "Revisiting potential druggable targets against SARS-CoV-2 and repurposing therapeutics under preclinical study and clinical trials: A comprehensive review", "pid": "a179xi5p", "bm25_score": 218.43560791015625}, {"text": "Due to the urgent need of a therapeutic treatment for coronavirus (CoV) disease 2019 (COVID-19) patients, a number of FDA-approved/repurposed drugs have been suggested as antiviral candidates at clinics, without sufficient information. Furthermore, there have been extensive debates over antiviral candidates for their effectiveness and safety against severe acute respiratory syndrome CoV 2 (SARS-CoV-2), suggesting that rapid preclinical animal studies are required to identify potential antiviral candidates for human trials. To this end, the antiviral efficacies of lopinavir-ritonavir, hydroxychloroquine sulfate, and emtricitabine-tenofovir for SARS-CoV-2 infection were assessed in the ferret infection model. While the lopinavir-ritonavir-, hydroxychloroquine sulfate-, or emtricitabine-tenofovir-treated group exhibited lower overall clinical scores than the phosphate-buffered saline (PBS)-treated control group, the virus titers in nasal washes, stool specimens, and respiratory tissues were similar between all three antiviral-candidate-treated groups and the PBS-treated control group. Only the emtricitabine-tenofovir-treated group showed lower virus titers in nasal washes at 8 days postinfection (dpi) than the PBS-treated control group. To further explore the effect of immune suppression on viral infection and clinical outcome, ferrets were treated with azathioprine, an immunosuppressive drug. Compared to the PBS-treated control group, azathioprine-immunosuppressed ferrets exhibited a longer period of clinical illness, higher virus titers in nasal turbinate, delayed virus clearance, and significantly lower serum neutralization (SN) antibody titers. Taken together, all antiviral drugs tested marginally reduced the overall clinical scores of infected ferrets but did not significantly affect in vivo virus titers. Despite the potential discrepancy of drug efficacies between animals and humans, these preclinical ferret data should be highly informative to future therapeutic treatment of COVID-19 patients.", "title": "Antiviral Efficacies of FDA-Approved Drugs against SARS-CoV-2 Infection in Ferrets", "pid": "l611eisi", "bm25_score": 218.43258666992188}, {"text": "Severe acute respiratory syndrome (SARS) is an infectious disease caused by a novel human coronavirus. Currently, no effective antiviral agents exist against this type of virus. A cell-based assay, with SARS virus and Vero E6 cells, was developed to screen existing drugs, natural products, and synthetic compounds to identify effective anti-SARS agents. Of >10,000 agents tested, approximately 50 compounds were found active at 10 microM; among these compounds, two are existing drugs (Reserpine 13 and Aescin 5) and several are in clinical development. These 50 active compounds were tested again, and compounds 2-6, 10, and 13 showed active at 3 microM. The 50% inhibitory concentrations for the inhibition of viral replication (EC(50)) and host growth (CC(50)) were then measured and the selectivity index (SI = CC(50)/EC(50)) was determined. The EC(50), based on ELISA, and SI for Reserpine, Aescim, and Valinomycin are 3.4 microM (SI = 7.3), 6.0 microM (SI = 2.5), and 0.85 microM (SI = 80), respectively. Additional studies were carried out to further understand the mode of action of some active compounds, including ELISA, Western blot analysis, immunofluorescence and flow cytometry assays, and inhibition against the 3CL protease and viral entry. Of particular interest are the two anti-HIV agents, one as an entry blocker and the other as a 3CL protease inhibitor (K(i) = 0.6 microM).", "title": "Small molecules targeting severe acute respiratory syndrome human coronavirus.", "pid": "biu8slfv", "bm25_score": 218.4205322265625}, {"text": "The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.", "title": "Discovering drugs to treat coronavirus disease 2019 (COVID-19)", "pid": "ey939w17", "bm25_score": 218.41920471191406}, {"text": "INTRODUCTION A novel coronavirus (CoV), unlike previous typical human coronaviruses (HCoVs), was identified as causative agent for severe acute respiratory syndrome (SARS). SARS first surfaced as a pandemic in late 2002 and originated in southern China. SARS-CoV rapidly spread to > 30 countries by 2003, infecting nearly 8,000 people and causing around 800 fatalities. After 10 years of silence, a 2012 report alarmed researchers about the emergence of a new strain of CoV causing SARS-like disease. AREAS COVERED To combat SARS, scientists applied for patents on various therapeutic agents, including small-molecule inhibitors targeting the essential proteases, helicase and other proteins of the virus, natural products, approved drugs, molecules binding to the virus, neutralizing antibodies, vaccines, anti-sense RNA, siRNA and ribozyme against SARS-CoV. In this article, the patents published from 2008 to the present for the new therapeutics that could potentially be used in the prophylaxis and treatment of SARS are reviewed. EXPERT OPINION The therapeutic interventions or prophylaxis discussed in this review seems to offer promising solutions to tackle SARS. Rather than being complacent about the results, we should envisage how to transform them into drug candidates that may be useful in combating SARS and related viral infections in the future.", "title": "Anti-SARS coronavirus agents: a patent review (2008 - present).", "pid": "2eezwumi", "bm25_score": 218.40301513671875}, {"text": "The present pandemic of SARS-CoV-2 has been a tough task for the whole world to deal with. With the absence of specific drugs or vaccines against SARS-CoV-2, the situation is very difficult to control. Apart from the absence of specific therapies, the lack of knowledge about potential therapeutic targets and individual perception is adding to the complications. The present review describes the novel SARS-CoV-2 structure, surface proteins, asymptomatic and symptomatic transmission in addition to the genotype and phenotype of SARS-CoV-2 along with genetic strains and similarity between SARS, MERS and SARS-CoV-2. Therapeutic strategies such as inhibition of the endocytic pathway and suppressing RNA polymerase activity by metal ions, which could be quite beneficial for controlling COVID-19, are outlined. The drug repurposing for SARS-CoV-2 is discussed in detail along with therapeutic classes such as antivirals, antibiotics, and amino quinolones and their probable role in suppressing SARS-CoV-2 with reference to case studies. The ongoing clinical trials both with respect to drug repurposing and vaccines are summarized along with a brief description. The recent advancements and future perspective of ongoing research for therapy and detection of SARS-CoV-2 are provided. The review, in brief, summarizes epidemiology, therapy and the current scenario for combating SARS-CoV-2.", "title": "Potential therapeutic targets for combating SARS-CoV-2: Drug repurposing, clinical trials and recent advancements", "pid": "0wh7x410", "bm25_score": 218.39962768554688}, {"text": "The novel coronavirus, later identified as SARS-CoV-2, originating from Wuhan in China in November 2019, quickly spread around the world becoming a pandemic. Despite the knowledge of previous coronaviruses, such as those responsible for the SARS and MERS-CoV epidemic, there is no drug or prophylaxis treatment to this day. The rapid succession of scientific findings on SARS-CoV-2 provides a significant number of potential drug targets. Nevertheless, at the same time, the high quantity of clinical data, generated by a large number of rapidly infected people, require accurate tests regarding effective medical treatments. Several in vitro and in vivo studies were rapidly initiated after the outbreak of the pandemic COVID-19. Initial clinical studies revealed the promising potential of remdesivir that demonstrated a powerful and specific in vitro antiviral activity for COVID-19. Promising effects appear to be attributable to hydroxychloroquine. Remdesivir and hydroxychloroquine are being tested in ongoing randomized trials. In contrast, oseltamivir was not effective and corticosteroids are not currently recommended. However, few data from ongoing clinical trials are identifying low molecular weight heparins, innate immune system stimulating agents, and inflammatory modulating agents as potential effective agents. The authors assume that the current pandemic will determine the need for a systematic approach based on big data analysis for identifying effective drugs to defeat SARS-Cov-2. This work is aimed to be a general reference point and to provide an overview as comprehensive as possible regarding the main clinical trials in progress at the moment.", "title": "Current pharmacological treatments for SARS-COV-2: A narrative review", "pid": "303b23dd", "bm25_score": 218.38853454589844}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global health pandemic. The lack of effective treatments, coupled with its etiology, has resulted in more than 400,000 deaths at the time of writing. The SARS-CoV-2 genome is highly homologous to that of SARS-CoV, the causative agent behind the 2003 SARS outbreak. Based on prior reports, clinicians have pursued the off-label use of several antiviral drugs, while the scientific community has responded by seeking agents against traditional targets, especially viral proteases. However, several avenues remain unexplored, including disrupting E and M protein oligomerization, outcompeting host glycan–virus interactions, interfering with the heparan sulfate proteoglycans–virus interaction, and others. In this review, we highlight some of these opportunities while summarizing the drugs current in use against coronavirus 2019 (COVID-19).", "title": "Discovering small-molecule therapeutics against SARS-CoV-2", "pid": "043w3zgy", "bm25_score": 218.3816375732422}, {"text": "Abstract A new disease, the severe acute respiratory distress syndrome (SARS), caused by the SARS coronavirus (SARS-CoV), emerged at the beginning of 2003 and rapidly spread throughout the world. Although the disease had disappeared in June 2003 its re-emergence cannot be excluded. The development of vaccines against SARS-CoV may take years. Therefore, the availability of effective antiviral drugs against SARS-CoV may be crucial for the control of future SARS outbreaks. In this review, experimental and clinical data about potential anti-SARS drugs is summarised and discussed. Animal model studies will be needed to help to determine which interventions warrant controlled clinical testing.", "title": "Development of antiviral therapy for severe acute respiratory syndrome", "pid": "9ujofcsm", "bm25_score": 218.3479766845703}, {"text": "Currently, the world suffers from a new coronavirus SARS-CoV-2 that causes COVID-19. Therefore, there is a need for the urgent development of novel drugs and vaccines for COVID-19. Since it can take years to develop new drugs against this disease, here we used a hybrid combined molecular modeling approach in virtual drug screening repurposing study to identify new compounds against this disease. One of the important SARS-CoV-2 targets namely type 2 transmembrane serine protease (TMPRSS2) was screened with NPC’s NIH small molecule library which includes approved drugs by FDA and compounds in clinical investigation. We used 6654 small molecules in molecular docking and top-50 docking scored compounds were initially used in short (10-ns) molecular dynamics (MD) simulations. Based on average MM/GBSA binding free energy results, long (100-ns) MD simulations were employed for the identified hits. Both binding energy results as well as crucial residues in ligand binding were also compared with a positive control TMPRSS2 inhibitor, Camostat mesylate. Based on these numerical calculations we proposed a compound (benzquercin) as strong TMPRSS2 inhibitor. If these results can be validated by in vitro and in vivo studies, benzquercin can be considered to be used as inhibitor of TMPRSS2 at the clinical studies.", "title": "Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target", "pid": "cl3nu5cm", "bm25_score": 218.3396453857422}, {"text": "COVID-19 is undoubtedly the most impactful viral disease of the current century, afflicting millions worldwide. As yet, there is not an approved vaccine, as well as limited options from existing drugs for treating this disease. We hypothesized that combining drugs with independent mechanisms of action could result in synergy against SARS-CoV-2. Using in silico approaches, we prioritized 73 combinations of 32 drugs with potential activity against SARS-CoV-2 and then tested them in vitro. Overall, we identified 16 synergistic and 8 antagonistic combinations, 4 of which were both synergistic and antagonistic in a dose-dependent manner. Among the 16 synergistic cases, combinations of nitazoxanide with three other compounds (remdesivir, amodiaquine and umifenovir) were the most notable, all exhibiting significant synergy against SARS-CoV-2. The combination of nitazoxanide, an FDA-approved drug, and remdesivir, FDA emergency use authorization for the treatment of COVID-19, demonstrate a strong synergistic interaction. Notably, the combination of remdesivir and hydroxychloroquine demonstrated strong antagonism. Overall, our results emphasize the importance of both drug repurposing and preclinical testing of drug combinations for potential therapeutic use against SARS-CoV-2 infections.", "title": "Discovery of Synergistic and Antagonistic Drug Combinations against SARS-CoV-2 In Vitro", "pid": "zbpk7sh0", "bm25_score": 218.33370971679688}, {"text": "Abstract Effective antiviral agents are urgently needed to combat the possible return of severe acute respiratory syndrome (SARS). Commercial antiviral agents and pure chemical compounds extracted from traditional Chinese medicinal herbs were screened against 10 clinical isolates of SARS coronavirus by neutralisation tests with confirmation by plaque reduction assays. Interferon-beta-1a, leukocytic interferon-alpha, ribavirin, lopinavir, rimantadine, baicalin and glycyrrhizin showed antiviral activity. The two interferons were only active if the cell lines were pre-incubated with the drugs 16h before viral inoculation. Results were confirmed by plaque reduction assays. Antiviral activity varied with the use of different cell lines. Checkerboard assays for synergy were performed showing combinations of interferon beta-1a or leukocytic interferon-alpha with ribavirin are synergistic. Since the clinical and toxicity profiles of these agents are well known, they should be considered either singly or in combination for prophylaxis or treatment of SARS in randomised placebo controlled trials in future epidemics.", "title": "In vitro susceptibility of 10 clinical isolates of SARS coronavirus to selected antiviral compounds", "pid": "ot5pvtbl", "bm25_score": 218.31753540039062}, {"text": "Abstract The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for SARS-CoV-2, various strategies are being tested in China, including drug repurposing. In this study, we used our pre-trained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of SARS-CoV-2. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 3C-like proteinase, followed by remdesivir (113.13 nM), efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of SARS-CoV-2 with an inhibitory potency with Kd < 1,000 nM. In addition, we also found that several antiviral agents, such as Kaletra (lopinavir/ritonavir), could be used for the treatment of SARS-CoV-2. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for SARS-CoV-2.", "title": "Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model", "pid": "zb434ve3", "bm25_score": 218.31590270996094}, {"text": "Severe Acute Respiratory Syndrome (SARS) is a life-threatening infectious disease caused by SARS-CoV. In the 2003 outbreak, it infected more than 8,000 people worldwide and claimed the lives of more than 900 victims. The high mortality rate resulted, at least in part, from the absence of definitive treatment protocols or therapeutic agents. Although the virus spreading has been contained, due preparedness and planning, including the successful development of antiviral drugs against SARS-CoV, is necessary for possible reappearance of SARS. In this review, we have discussed currently available strategies for antiviral drug discovery and how these technologies have been utilized to identify potential antiviral agents for the inhibition of SARS-CoV replication. Moreover, progress in the drug development based on different molecular targets is also summarized, including 1) Compounds that block the S protein-ACE2-mediated viral entry; 2) Compounds targeting SARS-CoV M(pro); 3) Compounds targeting papain-like protease 2 (PLP2); 4) Compounds targeting SARS-CoV RdRp; 5) Compounds targeting SARS-CoV helicase; 6) Active compounds with unspecified targets; and 7) Research on siRNA. This review aims to provide a comprehensive account of drug discovery on SARS. The experiences with the SARS outbreak and drug discovery would certainly be an important lesson for the drug development for any new viral outbreaks that may emerge in the future.", "title": "Antiviral drug discovery against SARS-CoV.", "pid": "1fy9edg3", "bm25_score": 218.3036346435547}, {"text": "The COVID-19 pandemic triggered by SARS-CoV-2 is a worldwide health disaster. Main protease is an attractive drug target among coronaviruses, due to its vital role in processing the polyproteins that are translated from the viral RNA. There is presently no exact drug or treatment for this diseases caused by SARS-CoV-2. In the present study, we report the potential inhibitory activity of some FDA approved drugs against SARS-CoV-2 main protease by molecular docking study to investigate their binding affinity in protease active site. Docking studies revealed that drug Oseltamivir (anti-H1N1 drug), Rifampin (anti-TB drug), Maraviroc, Etravirine, Indinavir, Rilpivirine (anti-HIV drugs) and Atovaquone, Quinidine, Halofantrine, Amodiaquine, Tetracylcine, Azithromycin, hydroxycholoroquine (anti-malarial drugs) among others binds in the active site of the protease with similar or higher affinity. However, the in-silico abilities of the drug molecules tested in this study, further needs to be validated by carrying out in vitro and in vivo studies. Moreover, this study spreads the potential use of current drugs to be considered and used to comprise the fast expanding SARS-CoV-2 infection.", "title": "In silico identification of clinically approved medicines against the main protease of SARS-CoV-2, causative agent of covid-19", "pid": "w9mij6c6", "bm25_score": 218.29486083984375}, {"text": "In this study, anti-SARS-CoV-2 activity of mycophenolic acid (MPA) and IMD-0354 was analyzed, these compounds were chosen based on their antiviral activities against other coronaviruses. Since they also inhibit Dengue virus (DENV) infection, other anti-DENV compounds/drugs were also assessed. Using SARS-CoV-2-infected VeroE6/TMPRSS2 cells, MPA and IMD-0354, but not other anti-DENV compounds/drugs, showed significant anti-SARS-CoV-2 activity. Although MPA reduced the viral RNA level by only ~100-fold, its EC50 was as low as 0.87µM, which is easily achievable at therapeutic doses of mycophenolate mofetil. MPA targets coronaviral papain-like protease and its study would be useful in the development of novel anti-SARS-CoV-2 drugs. This article is protected by copyright. All rights reserved.", "title": "Antiviral activities of mycophenolic acid and IMD-0354 against SARS-CoV-2", "pid": "fcxjt7qf", "bm25_score": 218.27493286132812}, {"text": "With the ongoing SARS-CoV-2 pandemic there is an urgent need for the discovery of a treatment for the coronavirus disease (COVID-19). Drug repurposing is one of the most rapid strategies for addressing this need and numerous compounds have been selected for in vitro testing by several groups already. These have led to a growing database of molecules with in vitro activity against the virus. Machine learning models can assist drug discovery through prediction of the best compounds based on previously published data. Herein we have implemented several machine learning methods to develop predictive models from recent SARS-CoV-2 in vitro inhibition data and used them to prioritize additional FDA approved compounds for in vitro testing selected from our in-house compound library. From the compounds predicted with a Bayesian machine learning model, CPI1062 and CPI1155 showed antiviral activity in HeLa-ACE2 cell-based assays and represent potential repurposing opportunities for COVID-19. This approach can be greatly expanded to exhaustively virtually screen available molecules with predicted activity against this virus as well as a prioritization tool for SARS-CoV-2 antiviral drug discovery programs. The very latest model for SARS-CoV-2 is available at www.assaycentral.org.", "title": "Machine Learning Models Identify Inhibitors of SARS-CoV-2", "pid": "vfd0su0w", "bm25_score": 218.2692413330078}, {"text": "As of April 9, 2020, a novel coronavirus (SARS-CoV-2) had caused 89,931 deaths and 1,503,900 confirmed cases worldwide, which indicates an increasingly severe and uncontrollable situation. Initially, little was known about the virus. As research continues, we now know the genome structure, epidemiological and clinical characteristics, and pathogenic mechanisms of SARS-CoV-2. Based on this knowledge, potential targets involved in the processes of virus pathogenesis need to be identified, and the discovery or development of drugs based on these potential targets is the most pressing need. Here, we have summarized the potential therapeutic targets involved in virus pathogenesis and discuss the advances, possibilities, and significance of drugs based on these targets for treating SARS-CoV-2. This review will facilitate the identification of potential targets and provide clues for drug development that can be translated into clinical applications for combating SARS-CoV-2.", "title": "Potential therapeutic targets and promising drugs for combating SARS-CoV-2", "pid": "zl1d3gf2", "bm25_score": 218.24111938476562}, {"text": "To identify potential therapeutic stop-gaps for SARS-CoV-2, we evaluated a library of 1,670 approved and reference compounds in an unbiased, cellular image-based screen for their ability to suppress the broad impacts of the SARS-CoV-2 virus on phenomic profiles of human renal cortical epithelial cells using deep learning. In our assay, remdesivir is the only antiviral tested with strong efficacy, neither chloroquine nor hydroxychloroquine have any beneficial effect in this human cell model, and a small number of compounds not currently being pursued clinically for SARS-CoV-2 have efficacy. We observed weak but beneficial class effects of β-blockers, mTOR/PI3K inhibitors and Vitamin D analogues and a mild amplification of the viral phenotype with β-agonists.", "title": "Identification of potential treatments for COVID-19 through artificial intelligence-enabled phenomic analysis of human cells infected with SARS-CoV-2", "pid": "27f9241x", "bm25_score": 218.23556518554688}, {"text": "BACKGROUND: The Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has now been reported on all inhabited continents. Hitherto, no antiviral drug is available to combat this viral outbreak. METHODS: Keeping in mind the urgency of the situation, the current study was designed to devise new strategies for drug discovery and/or repositioning against SARS-CoV-2. In the current study, RNA-dependent RNA polymerase (RdRp), which regulates viral replication, is proposed as a potential therapeutic target to inhibit viral infection. RESULTS: Evolutionary studies of whole-genome sequences of SARS-CoV-2 represent high similarity (> 90%) with other SARS viruses. Targeting the RdRp active sites, ASP760 and ASP761, by antiviral drugs could be a potential therapeutic option for inhibition of coronavirus RdRp, and thus viral replication. Target-based virtual screening and molecular docking results show that the antiviral Galidesivir and its structurally similar compounds have shown promise against SARS-CoV-2. CONCLUSIONS: The anti-polymerase drugs predicted here—CID123624208 and CID11687749—may be considered for in vitro and in vivo clinical trials.", "title": "Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach", "pid": "61nwk2sg", "bm25_score": 218.23106384277344}, {"text": "The disease caused by SARS-CoV2, covid-19, rapidly spreads worldwide, causing the greatest threat to global public health in the last 100 years. This scenario has become catastrophic as there are no approved vaccines to prevent the disease, and the main measures to contain the virus transmission are confinement and social distancing. One priority strategy is based on drug repurposing by pursuing antiviral chemotherapy that can control transmission and prevent complications associated with covid-19. With this aim, we performed a high content screening assay for the discovery of anti-SARS-CoV-2 compounds. From the 65 screened compounds, we have found four drugs capable to selectively inhibit SARS-CoV-2 in vitro infection: brequinar, abiraterone acetate, neomycin, and the extract of Hedera helix. Brequinar and abiraterone acetate had higher inhibition potency against SARS-CoV-2 than neomycin and Hedera helix extract, respectively. Drugs with reported antiviral activity and in clinical trials for covid-19, chloroquine, ivermectin, and nitazoxanide, were also included in the screening, and the last two were found to be non-selective. We used a data mining approach to build drug-host molecules-biological function-disease networks to show in a holistic way how each compound is interconnected with host node molecules and virus infection, replication, inflammatory response, and cell apoptosis. In summary, the present manuscript identified four drugs with active inhibition effect on SARS-CoV-2 in vitro infection, and by network analysis, we provided new insights and starting points for the clinical evaluation and repurposing process to treat SARS-CoV-2 infection. Summary sentence Discovery of drug repurposing candidates, inhibitors of SARS-CoV-2 infection in vitro, using a phenotypic screening strategy and network analysis.", "title": "Discovery of clinically approved drugs capable of inhibiting SARS-CoV-2 in vitro infection using a phenotypic screening strategy and network-analysis to predict their potential to treat covid-19", "pid": "40fz5r90", "bm25_score": 218.22792053222656}, {"text": "Herein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was to solvate the isolated S-protein in water for molecular dynamics (MD) simulation, being observed a transition from \"up\" to \"down\" conformation of receptor-binding domain (RBD) of the S-protein with angle of 54.3 and 43.0 degrees, respectively. The RBD region was more exposed to the solvent and to the possible drugs due to its enhanced surface area. From the equilibrated MD structure, virtual screening by docking calculations were performed using a library contained 9091 FDA approved drugs. Among them, 24 best-scored ligands (14 traditional herbal isolate and 10 approved drugs) with the binding energy below -8.1 kcal/mol were selected as potential candidates to inhibit the SARS-CoV-2 S-protein, preventing the human cell infection and their replication. For instance, the ivermectin drug (present in our list of promise candidates) was recently used successful to control viral replication in vitro. MD simulations were performed for the three best ligands@S-protein complexes and the binding energies were calculated using the MM/PBSA approach. Overall, it is highlighted an important strategy, some key residues, and chemical groups which may be considered on clinical trials for COVID-19 outbreak.", "title": "Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening", "pid": "5vgfliv0", "bm25_score": 218.21987915039062}, {"text": "A novel coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or 2019 novel coronavirus] has been identified as the pathogen of coronavirus disease 2019. The main protease (Mpro , also called 3-chymotrypsin-like protease) of SARS-CoV-2 is a potential target for treatment of COVID-19. A Mpro homodimer structure suitable for docking simulations was prepared using a crystal structure (PDB ID: 6Y2G; resolution 2.20 Å). Structural refinement was performed in the presence of peptidomimetic &#945;-ketoamide inhibitors, which were previously disconnected from each Cys145 of the Mpro homodimer, and energy calculations were performed. Structure-based virtual screenings were performed using the ChEMBL database. Through a total of 1 485 144 screenings, 64 potential drugs (11 approved, 14 clinical, and 39 preclinical drugs) were predicted to show high binding affinity with Mpro . Additional docking simulations for predicted compounds with high binding affinity with Mpro suggested that 28 bioactive compounds may have potential as effective anti-SARS-CoV-2 drug candidates. The procedure used in this study is a possible strategy for discovering anti-SARS-CoV-2 drugs from drug libraries that may significantly shorten the clinical development period with regard to drug repositioning.", "title": "Potential anti-SARS-CoV-2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease", "pid": "md75mnh8", "bm25_score": 218.17788696289062}, {"text": "SARS-COV-2 has recently emerged as a new public health threat. Herein, we report that the FDA-approved gold drug, auranofin, inhibits SARS-COV-2 replication in human cells at low micro molar concentration. Treatment of cells with auranofin resulted in a 95% reduction in the viral RNA at 48 hours after infection. Auranofin treatment dramatically reduced the expression of SARS-COV-2-induced cytokines in human cells. These data indicate that auranofin could be a useful drug to limit SARS-CoV-2 infection and associated lung injury due to its anti-viral, anti-inflammatory and anti-ROS properties. Auranofin has a well-known toxicity profile and is considered safe for human use.", "title": "The FDA- approved gold drug Auranofin inhibits novel coronavirus (SARS-COV-2) replication and attenuates inflammation in human cells", "pid": "vm0k7hfx", "bm25_score": 218.17718505859375}, {"text": "SARS-CoV-2 is a new generation of coronavirus, which was first determined in Wuhan, China, in December 2019. So far, however, there no effective treatment has been found to stop this new generation of coronavirus but discovering of the crystal structure of SARS-CoV-2 main protease (SARS-CoV-2 Mpro) may facilitate searching for new therapies for SARS-COV-2. The aim was to assess the effectiveness of available FDA approved drugs which can construct a covalent bond with Cys145 inside binding site SARS-CoV-2 main protease by using covalent docking screening. We conducted the covdock module MMGBSA module in the Schrodinger suite 2020-1, to examine the covalent bonding utilizing. Besides, we submitted the top three drugs to molecular dynamics simulations via Gromacs 2018.1. The covalent docking showed that saquinavir, ritonavir, remdesivir, delavirdine, cefuroxime axetil, oseltamivir and prevacid have the highest binding energies MMGBSA of -72.17, -72.02, -65.19, -57.65, -54.25, -51.8, and -51.14 kcal/mol, respectively. The 50 ns molecular dynamics simulation was conducted for saquinavir, ritonavir and remdesivir to evaluate the stability of these drugs inside the binding pocket of SARS-CoV-2 main protease. The current study provides a powerful in silico results, means for rapid screening of drugs as anti-protease medications and recommend that the above-mentioned drugs can be used in the treatment of SARS-CoV-2 in combined or sole therapy.Communicated by Ramaswamy H. Sarma.", "title": "Using integrated computational approaches to identify safe and rapid treatment for SARS-CoV-2", "pid": "ct4avetf", "bm25_score": 218.16647338867188}, {"text": "Abstract The severe acute respiratory syndrome (SARS) epidemic brought into the spotlight the need for rapid development of effective anti-viral drugs against newly emerging viruses. Researchers have leveraged the 20-year battle against AIDS into a variety of possible treatments for SARS. Most prominently, based solely on viral genome information, silencers of viral genes, viral-enzyme blockers and viral-entry inhibitors were suggested as potential therapeutic agents for SARS. In particular, inhibitors of viral entry, comprising therapeutic peptides, were based on the recently launched anti-HIV drug enfuvirtide. This could represent one of the most direct routes from genome sequencing to the discovery of antiviral drugs.", "title": "From genome to antivirals: SARS as a test tube", "pid": "dtaasxk1", "bm25_score": 218.13954162597656}, {"text": "The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.", "title": "A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.", "pid": "eje3i558", "bm25_score": 218.11683654785156}, {"text": "Coronavirus disease-19 (COVID-19) has reached pandemic proportions. Most of the drugs that are being tried for the treatment have not been evaluated in any randomized controlled trials. The purpose of this review was to summarize the in-vitro and in-vivo efficacy of these drugs on Severe Acute Respiratory Syndrome (SARS-CoV-2) and related viruses (SARS and Middle East Respiratory Syndrome) and evaluate their potential for re-purposing them in the management of COVID-19.", "title": "Battling COVID-19: using old weapons for a new enemy", "pid": "yn7x9uit", "bm25_score": 218.10105895996094}, {"text": "Severe acute respiratory syndrome (SARS) emerged in late 2002 and was controlled in July 2003 by public health measures. Its causative agent, SARS coronavirus (SARS-CoV) jumped from an animal reservoir to humans and has the potential to re-emerge. Following the sequencing of the genetic code and the deciphering of some of the functions of its proteins, including the cellular receptors and host proteins that participate in the life cycle of the virus, promising lead drugs and new uses of old drugs have been discovered. Patent applications for cathepsin L inhibitors have taken new relevance because of the role of cathepsin L in the entry of SARS-CoV into host cells. Likewise, patent applications for SARS-CoV protease inhibitors and interferon and mismatched dsRNA also need to be watched for potential application in treatment and prevention of SARS-CoV. Here, we review the recent advances and inventions that target SARS-CoV infection in humans.", "title": "SARS coronavirus anti-infectives.", "pid": "57y9ap3a", "bm25_score": 218.0991668701172}, {"text": "Since the emergence of CoVID-19 pandemic in China in late 2019, scientists are striving hard to explore non-toxic, viable anti-SARS-CoV-2 compounds or medicines. We determined In Vitro anti-SARS-CoV-2 activity of oral formulations (syrup and capsule) of an Iodine-complex (Renessans). A monolayer of vero cells were exposed to SARS-CoV-2 in the presence and absence of different concentrations (equivalent to 50, 05 and 0.5 μg/ml of I2) of Renessans. Anti-SARS-CoV-2 activity of each of the formulation was assessed in the form of cell survival, SARS-CoV-2-specific cytopathic effect (CPE) and genome quantization. With varying concentrations of syrup and capsule, a varying rate of inhibition of CPE, cells survival and virus replication was observed. Compared to 0.5 μg/ml concentration of Renessans syrup, 5 and 50 μg/ml showed comparable results where there was a 100% cell survival, no CPEs and a negligible viral replication (ΔCT= 0.11 and 0.13, respectively). This study indicates that Renessans, containing iodine, may have potential activity against SARS-CoV-2 which needs to be further investigated in human clinical trials.", "title": "An in vitro assessment of anti-SARS-CoV-2 activity of oral preparations of iodine complexes (RENESSANS)", "pid": "magsin78", "bm25_score": 218.0974884033203}, {"text": "In the current spread of novel coronavirus (SARS-CoV-2), antiviral drug discovery is of great importance. AutoDock Vina was used to screen potential drugs by molecular docking with the structural protein and non-structural protein sites of new coronavirus. Ribavirin, a common antiviral drug, remdesivir, chloroquine and luteolin were studied. Honeysuckle is generally believed to have antiviral effects in traditional Chinese medicine. In this study, luteolin (the main flavonoid in honeysuckle) was found to bind with a high affinity to the same sites of the main protease of SARS-CoV-2 as the control molecule. Chloroquine has been proved clinically effective and can bind to the main protease; this may be the antiviral mechanism of this drug. The study was restricted to molecular docking without validation by molecular dynamics simulations. Interactions with the main protease may play a key role in fighting against viruses. Luteolin is a potential antiviral molecule worthy of attention.", "title": "Computational screening of antagonists against the SARS-CoV-2 (COVID-19) coronavirus by molecular docking", "pid": "b19pjjib", "bm25_score": 218.09298706054688}, {"text": "Non-structural protein 1 (nsp1) is found in all Betacoronavirus genus, an important viral group that causes severe respiratory human diseases. This protein has significant role in pathogenesis and it is considered a probably major virulence factor. As it is absent in humans, it becomes an interesting target of study, especially when it comes to the rational search for drugs, since it increases the specificity of the target and reduces possible adverse effects that may be caused to the patient. Using approaches in silico we seek to study the behavior of nsp1 in solution to obtain its most stable conformation and find possible drugs with affinity to all of them. For this purpose, complete model of nsp1 of SARS-CoV-2 were predicted and its stability analyzed by molecular dynamics simulations in five different replicas. After main pocket validation using two control drugs and the main conformations of nsp1, molecular docking based on virtual screening were performed to identify novel potential inhibitors from DrugBank database. It has been found 16 molecules in common to all five nsp1 replica conformations. Three of them was ranked as the best compounds among them and showed better energy score than control molecules that have in vitro activity against nsp1 from SARS-CoV-2. The results pointed out here suggest new potential drugs for therapy to aid the rational drug search against COVID-19. Communicated by Ramaswamy H. Sarma.", "title": "Identification of potential drugs against SARS-CoV-2 non-structural protein 1 (nsp1).", "pid": "h4occy7h", "bm25_score": 218.08853149414062}, {"text": "Here we report on the most recent updates on experimental drugs successfully em- ployed in the treatment of the disease caused by SARS-CoV-2 coronavirus, also referred to as COVID-19 (COronaVIrus Disease 19). In particular, several cases of recovered patients have been reported after being treated with lopinavir/ritonavir (which is widely used to treat human immunodeficiency virus (HIV) infection) in combination with the anti-flu drug oseltamivir. In addition, remdesivir, which has been previously administered to Ebola virus patients, has also proven effective in the U.S. against coronavirus, while antimalarial chloroquine and hydroxy- chloroquine, favipiravir and co-administered darunavir and umifenovir (in patient therapies) were also recently recorded as having anti-SARS-CoV-2 effects. Since the recoveries/deaths ratio in the last weeks significantly increased, especially in China, it is clear that the experi- mental antiviral therapy, together with the availability of intensive care unit beds in hospitals and rigorous government control measures, all play an important role in dealing with this vi- rus. This also stresses the urgent need for the scientific community to devote its efforts to the development of other more specific antiviral strategies.", "title": "SARS-CoV-2: Recent Reports on Antiviral Therapies Based on Lopinavir/Ritonavir, Darunavir/Umifenovir, Hydroxychloroquine, Remdesivir, Favipiravir and Other Drugs for the Treatment of the New Coronavirus", "pid": "fgbilulc", "bm25_score": 218.08834838867188}, {"text": "The ongoing pandemic caused by severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2, also known as COVID-19) has led to unprecedented challenges for the global healthcare system. This novel coronavirus disease phenotype ranges from asymptomatic carriage to fulminant cytokine storm with respiratory failure, polyorgan dysfunction and death. Severe disease is characterised by exuberant inflammation resulting from high circulating cytokines such as interleukin-6 and tumour necrosis factor. These inflammatory mediators are responsible for the detrimental effects on the immune, hematologic, respiratory, renal, gastrointestinal and other body systems. In addition to inhibition of viral replication, blunting this inflammatory response before overt cytokine storm is important to improve outcomes. Although there are upcoming promising agents such as remdesivir and convalescent plasma, inexpensive, safe and widely available adjunct treatments to ameliorate disease burden would be welcome. Two potential anti-inflammatory agents include indomethacin, which has been shown in experimental models to decrease canine coronavirus levels in dogs and exhibit antiviral activity against several other viruses and the polyphenol, resveratrol, a potent antioxidant that has shown antiviral activity against several viruses.", "title": "Indomethacin and resveratrol as potential treatment adjuncts for SARS-CoV-2/COVID-19", "pid": "hezk9odp", "bm25_score": 218.0811767578125}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected near 5 million people and led to over 0.3 million deaths. Currently, there is no specific anti-SARS-CoV-2 medication. New drug discovery typically takes more than ten years. Drug repositioning becomes one of the most feasible approaches for combating COVID-19. This work curates the largest available experimental dataset for SARS-CoV-2 or SARS-CoV main protease inhibitors. Based on this dataset, we develop validated machine learning models with relatively low root mean square error to screen 1553 FDA-approved drugs as well as other 7012 investigational or off-market drugs in DrugBank. We found that many existing drugs might be potentially potent to SARS-CoV-2. The druggability of many potent SARS-CoV-2 main protease inhibitors is analyzed. This work offers a foundation for further experimental studies of COVID-19 drug repositioning.", "title": "Repositioning of 8565 existing drugs for COVID-19", "pid": "f2e4d3bz", "bm25_score": 218.0713653564453}, {"text": "Herein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was to solvate the isolated S-protein in water for molecular dynamics (MD) simulation, being observed a transition from “up” to “down” conformation of receptor-binding domain (RBD) of the S-protein with angle of 54.3 and 43.0 degrees, respectively. The RBD region was more exposed to the solvent and to the possible drugs due to its enhanced surface area. From the equilibrated MD structure, virtual screening by docking calculations were performed using a library contained 9091 FDA approved drugs. Among them, 24 best-scored ligands (14 traditional herbal isolate and 10 approved drugs) with the binding energy below –8.1 kcal/mol were selected as potential candidates to inhibit the SARS-CoV-2 S-protein, preventing the human cell infection and their replication. For instance, the ivermectin drug (present in our list of promise candidates) was recently used successful to control viral replication in vitro. MD simulations were performed for the three best ligands@S-protein complexes and the binding energies were calculated using the MM/PBSA approach. Overall, it is highlighted an important strategy, some key residues, and chemical groups which may be considered on clinical trials for COVID-19 outbreak.", "title": "Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening", "pid": "74xvvwrw", "bm25_score": 218.06857299804688}, {"text": "Since the outbreak of novel coronavirus pneumonia (COVID-19) in December 2019, more than 2,500,000 people worldwide have been diagnosed with SARS-CoV-2 as of April 22. In response to this epidemic, China has issued seven trial versions of diagnosis and treatment protocol for COVID-19. According to the information that we have collected so far, this article provides an overview of potential therapeutic drugs and compounds with much attention, including favipiravir and hydroxychloroquine, as well as traditional Chinese medicine, which have been reported with good clinical treatment effects. Moreover, with further understanding of SARS-CoV-2 virus, new drugs targeting specific SARS-CoV-2 viral components arise and investigations on these novel anti-SARS-CoV-2 agents are also reviewed.", "title": "Overview of therapeutic drug research for COVID-19 in China", "pid": "ldyg241o", "bm25_score": 218.06060791015625}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 7.1 million people and led to over 0.4 million deaths. Currently, there is no specific anti-SARS-CoV-2 medication. New drug discovery typically takes more than 10 years. Drug repositioning becomes one of the most feasible approaches for combating COVID-19. This work curates the largest available experimental data set for SARS-CoV-2 or SARS-CoV 3CL (main) protease inhibitors. On the basis of this data set, we develop validated machine learning models with relatively low root-mean-square error to screen 1553 FDA-approved drugs as well as another 7012 investigational or off-market drugs in DrugBank. We found that many existing drugs might be potentially potent to SARS-CoV-2. The druggability of many potent SARS-CoV-2 3CL protease inhibitors is analyzed. This work offers a foundation for further experimental studies of COVID-19 drug repositioning.", "title": "Repositioning of 8565 Existing Drugs for COVID-19", "pid": "78vo1jkc", "bm25_score": 218.05291748046875}, {"text": "COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.", "title": "Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials.", "pid": "oa8vzf02", "bm25_score": 218.04104614257812}, {"text": "BACKGROUND: New therapeutic options to address the ongoing coronavirus disease 2019 (COVID-19) pandemic are urgently needed. One possible strategy is the repurposing of existing drugs approved for other indications as antiviral agents for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Due to the commercial unavailability of SARS-CoV-2 drugs for treating COVID-19, we screened approximately 250 existing drugs or pharmacologically active compounds for their inhibitory activities against feline infectious peritonitis coronavirus (FIPV) and human coronavirus OC43 (HCoV-OC43), a human coronavirus in the same genus (Betacoronavirus) as SARS-CoV-2. METHODS: FIPV was proliferated in feline Fcwf-4 cells and HCoV-OC43 in human HCT-8 cells. Viral proliferation was assayed by visualization of cytopathic effects on the infected Fcwf-4 cells and immunofluorescent assay for detection of the nucleocapsid proteins of HCoV-OC43 in the HCT-8 cells. The concentrations (EC50) of each drug necessary to diminish viral activity to 50% of that for the untreated controls were determined. The viabilities of Fcwf-4 and HCT-8 cells were measured by crystal violet staining and MTS/PMS assay, respectively. RESULTS: Fifteen out of the 252 drugs or pharmacologically active compounds screened were found to be active against both FIPV and HCoV-OC43, with EC50 values ranging from 11 nM to 75 µM. They are all old drugs as follows, anisomycin, antimycin A, atovaquone, chloroquine, conivaptan, emetine, gemcitabine, homoharringtonine, niclosamide, nitazoxanide, oligomycin, salinomycin, tilorone, valinomycin, and vismodegib. CONCLUSION: All of the old drugs identified as having activity against FIPV and HCoV-OC43 have seen clinical use in their respective indications and are associated with known dosing schedules and adverse effect or toxicity profiles in humans. Those, when later confirmed to have an anti-viral effect on SARS-CoV-2, should be considered for immediate uses in COVID-19 patients.", "title": "Repurposing old drugs as antiviral agents for coronaviruses", "pid": "w8ta2qgh", "bm25_score": 218.03973388671875}, {"text": "The ongoing COVID-19 pandemic has forced the clinical and scientific community to try drug repurposing of existing antiviral agents as a quick option against SARS-CoV-2. Under this scenario, the interferon-ß 1a (IFN-ß 1a) whose antiviral potential is already known, and is a drug currently used in the clinical management of multiple sclerosis, may represent as a potential candidate. In this report, we demonstrate that IFN-ß 1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection.", "title": "Interferon-ß 1a inhibits SARS-CoV-2 in vitro when administered after virus infection", "pid": "1rvefpqz", "bm25_score": 218.02749633789062}, {"text": "The ongoing novel coronavirus disease (COVID-19) pandemic makes us painfully perceive that our bullet shells are blank so far for fighting against severe human coronavirus (HCoV). In spite of vast research work, it is crystal clear that the evident does not warrant the commercial blossoming of anti-HCoV drugs. In this circumstance, drug repurposing and/or screening of databases are the only fastest option. This study is an initiative to recapitulate the medicinal chemistry of severe acute respiratory syndrome (SARS)-CoV-2 (SARS-CoV-2). The aim is to present an exquisite delineation of the current research from the perspective of a medicinal chemist to allow the rapid development of anti-SARS-CoV-2 agents.", "title": "Fight against novel coronavirus: A perspective of medicinal chemists", "pid": "50db66ru", "bm25_score": 218.0240936279297}, {"text": "The focused drug repurposing of known approved drugs (such as lopinavir/ritonavir) has been reported failed for curing SARS-CoV-2 infected patients. It is urgent to generate new chemical entities against this virus. As a key enzyme in the life-cycle of coronavirus, the 3C-like main protease (3CLpro or Mpro) is the most attractive for antiviral drug design. Based on a recently solved structure (PDB ID: 6LU7), we developed a novel advanced deep Q-learning network with the fragment-based drug design (ADQN-FBDD) for generating potential lead compounds targeting SARS-CoV-2 3CLpro. We obtained a series of derivatives from those lead compounds by our structure-based optimization policy (SBOP). All the 47 lead compounds directly from our AI-model and related derivatives based on SBOP are accessible in our molecular library at https://github.com/tbwxmu/2019-nCov. These compounds can be used as potential candidates for researchers in their development of drugs against SARS-CoV-2.", "title": "AI-aided design of novel targeted covalent inhibitors against SARS-CoV-2", "pid": "qmg58cgr", "bm25_score": 218.0096435546875}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic with millions of human infections. One limitation to the evaluation of potential therapies and vaccines to inhibit SARS-CoV-2 infection and ameliorate disease is the lack of susceptible small animals in large numbers. Commercially available laboratory strains of mice are not readily infected by SARS-CoV-2 because of species-specific differences in their angiotensin-converting enzyme 2 (ACE2) receptors. Here, we transduced replication-defective adenoviruses encoding human ACE2 via intranasal administration into BALB/c mice and established receptor expression in lung tissues. hACE2-transduced mice were productively infected with SARS-CoV-2, and this resulted in high viral titers in the lung, lung pathology, and weight loss. Passive transfer of a neutralizing monoclonal antibody reduced viral burden in the lung and mitigated inflammation and weight loss. The development of an accessible mouse model of SARS-CoV-2 infection and pathogenesis will expedite the testing and deployment of therapeutics and vaccines.", "title": "A SARS-CoV-2 Infection Model in Mice Demonstrates Protection by Neutralizing Antibodies", "pid": "amsmd809", "bm25_score": 218.00509643554688}, {"text": "In March, a team of scientists reported that they had run and analyzed a computational screen that helped them pinpoint 69 compounds that might treat COVID-19, the disease caused by the novel coronavirus, SARS-CoV-2 They now have new data from lab experiments showing that some of those compounds can stop the virus from replicating in cells The hits include a cancer drug currently in clinical trials, an over-the-counter antihistamine, and a compound that’s never been tested in humans but outperformed hydroxychloroquine in the cell studies (Nature 2020, DOI: 10 1038/s41586-020-2286-9) The international group, led by molecular biologist Nevan Krogan of the University of California, San Francisco, identified the original 69 compounds by running a screen to look for human proteins that might interact with the virus’s proteins The program then searched for molecules that could disrupt those potential interactions", "title": "Cell studies follow up on previous SARS-CoV-2 studyCell studies follow up on previous SARS-CoV-2 study", "pid": "zedjs4lz", "bm25_score": 218.00477600097656}, {"text": "PURPOSE OF REVIEW The main purpose of this review is to summarize the current research (2006-2007) concerning the development of novel anticoronaviral strategies and compounds. RECENT FINDINGS Recent research led to the identification of several novel agents inhibiting coronaviral replication. The most promising compounds include carbohydrate-binding agents, neutralizing antibodies and drugs targeting a coronaviral envelope protein. SUMMARY Although initial outbreaks of coronavirus that causes severe acute respiratory syndrome (SARS-CoV) were controlled by public health measures, the development of vaccines and antiviral agents for SARS-CoV is essential for improving control and treatment of future outbreaks. Four years after the SARS-CoV epidemic, several compounds with an anticoronaviral activity have been identified.", "title": "Recent antiviral strategies against human coronavirus-related respiratory illnesses.", "pid": "g34v2oy7", "bm25_score": 218.0045166015625}, {"text": "The ongoing coronavirus disease 2019 pandemic has forced the clinical and scientific community to try drug repurposing of existing antiviral agents as a quick option against severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2). Under this scenario, interferon (IFN) β-1a, whose antiviral potential is already known, and which is a drug currently used in the clinical management of multiple sclerosis, may represent as a potential candidate. In this report, we demonstrate that IFN-β-1a was highly effective in inhibiting in vitro SARS-CoV-2 replication at clinically achievable concentration when administered after virus infection.", "title": "Interferon-β-1a Inhibition of Severe Acute Respiratory Syndrome–Coronavirus 2 In Vitro When Administered After Virus Infection", "pid": "8g40ukml", "bm25_score": 218.00038146972656}, {"text": "Since the infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was reported in China during December 2019, the coronavirus disease 2019 (COVID-19) has spread on a global scale, causing the World Health Organization (WHO) to issue a warning. While novel vaccines and drugs that target SARS-CoV-2 are under development, this review provides information on therapeutics which are under clinical trials or are proposed to antagonize SARS-CoV-2. Based on the information gained from the responses to other RNA coronaviruses, including the strains that cause severe acute respiratory syndrome (SARS)-coronaviruses and Middle East respiratory syndrome (MERS), drug repurposing might be a viable strategy. Since several antiviral therapies can inhibit viral replication cycles or relieve symptoms, mechanisms unique to RNA viruses will be important for the clinical development of antivirals against SARS-CoV-2. Given that several currently marketed drugs may be efficient therapeutic agents for severe COVID-19 cases, they may be beneficial for future viral pandemics and other infections caused by RNA viruses when standard treatments are unavailable.", "title": "COVID-19 Drug Discovery Using Intensive Approaches", "pid": "64ff1ksc", "bm25_score": 217.9893798828125}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for millions of infections and hundreds of thousands of deaths globally. There are no widely available licensed therapeutics against SARS-CoV-2, highlighting an urgent need for effective interventions. The virus enters host cells through binding of a receptor-binding domain within its trimeric spike glycoprotein to human angiotensin-converting enzyme 2. In this article, we describe the generation and characterization of a panel of murine mAbs directed against the receptor-binding domain. One mAb, 2B04, neutralized wild-type SARS-CoV-2 in vitro with remarkable potency (half-maximal inhibitory concentration of <2 ng/ml). In a murine model of SARS-CoV-2 infection, 2B04 protected challenged animals from weight loss, reduced lung viral load, and blocked systemic dissemination. Thus, 2B04 is a promising candidate for an effective antiviral that can be used to prevent SARS-CoV-2 infection.", "title": "A Potently Neutralizing Antibody Protects Mice against SARS-CoV-2 Infection.", "pid": "bwzcei28", "bm25_score": 217.98397827148438}, {"text": "A new coronavirus identified as SARS-CoV-2 virus has brought the world to a state of crisis, causing a major pandemic, claiming more than 433,000 lives and instigating major financial damage to the global economy. Despite current efforts, developing safe and effective treatments remains a major challenge. Moreover, new strains of the virus are likely to emerge in the future. To prevent future pandemics, several drugs with various mechanisms of action are required. Drug discovery efforts against the virus fall into two main categories: (a) monoclonal antibodies targeting the spike protein of the virus and blocking it from entry; (b) small molecule inhibitors targeting key proteins of the virus, interfering with replication and translation of the virus. In this study, we are presenting a computational investigation of a potential drug candidate that targets SARS-CoV-2 protease, a viral protein critical for replication and translation of the virus.", "title": "A small molecule drug candidate targeting SARS-CoV-2 main protease", "pid": "2rczhxp2", "bm25_score": 217.97898864746094}, {"text": "Severe acute respiratory syndrome (SARS) is caused by one of two recently discovered coronaviruses. The virus is emergent from South East (SE) Asian mammals: either the civet cat, a related species or a rat species. The virus has a long incubation period and low reproduction number (R0 value) and hence the first outbreak in 2004 was controlled by hygiene and quarantine. However, the healthcare system was compromised and the economic cost was extremely high. Fortunately, the virus is easily cultivated in Vero E6 cells and therefore the search for new antivirals and vaccines was initiated within weeks of the discovery of the virus using classic techniques of cell culture and electron microscopy. Molecular diagnostics facilitated rapid and accurate diagnosis, a key factor in containing the outbreak. The broad-spectrum molecule ribavirin was used in SE Asia in infected patients alongside corticosteroids. In retrospect, many patients survived due to careful nursing. The only currently accepted intervention is interferon. Coronavirus replicon systems should facilitate rapid screening of new inhibitors and the complex mechanism of viral replication will ensure that drugs are developed against at least five molecular targets, in particular the viral protease.", "title": "New antiviral drugs, vaccines and classic public health interventions against SARS coronavirus.", "pid": "e40xhnng", "bm25_score": 217.975830078125}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections. Communicated by Ramaswamy H. Sarma", "title": "Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase", "pid": "2ro2p77q", "bm25_score": 217.97093200683594}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections.Communicated by Ramaswamy H. Sarma.", "title": "Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase", "pid": "kjc3j7yz", "bm25_score": 217.96888732910156}, {"text": "The SARS-CoV-2 pandemic that originated from Wuhan, China, in December 2019 has impacted public health, society and economy and the daily lives of billions of people in an unprecedented manner. There are currently no specific registered antiviral drugs to treat or prevent SARS-CoV-2 infections. Therefore, drug repurposing would be the fastest route to provide at least a temporary solution while better, more specific drugs are being developed. Here we demonstrate that the antiparasitic drug suramin inhibits SARS-CoV-2 replication, protecting Vero E6 cells with an EC50 of ∼20 µM, which is well below the maximum attainable level in human serum. Suramin also decreased the viral load by 2-3 logs when Vero E6 cells or cells of a human lung epithelial cell line (Calu-3) were treated. Time of addition and plaque reduction assays performed on Vero E6 cells showed that suramin acts on early steps of the replication cycle, possibly preventing binding or entry of the virus. In a primary human airway epithelial cell culture model, suramin also inhibited the progression of infection. The results of our preclinical study warrant further investigation and suggest it is worth evaluating whether suramin provides any benefit for COVID-19 patients, which obviously requires safety studies and well-designed, properly controlled randomized clinical trials.", "title": "Suramin inhibits SARS-CoV-2 infection in cell culture by interfering with early steps of the replication cycle", "pid": "wf2tbbo2", "bm25_score": 217.96844482421875}, {"text": "Direct-acting antivirals are effective tools to control viral infections. SARS-CoV-2 is a coronavirus associated with the epidemiological outbreak in late 2019. Previous reports showed that HIV-1 protease inhibitors could block SARS-CoV main protease. Based on that and using an in silico approach, we evaluated SARS-CoV-2 main protease as a target for HIV-1 protease inhibitors to reveal the structural features related to their antiviral effect. Our results showed that several HIV inhibitors such as lopinavir, ritonavir, and saquinavir produce strong interaction with the active site of SARS-CoV-2 main protease. Furthermore, broad library protease inhibitors obtained from PubChem and ZINC (www.zinc.docking.org) were evaluated. Our analysis revealed 20 compounds that could be clustered into three groups based on their chemical features. Then, these structures could serve as leading compounds to develop a series of derivatives optimizing their activity against SARS-CoV-2 and other coronaviruses. Altogether, the results presented in this work contribute to gain a deep understanding of the molecular pharmacology of SARS-CoV-2 treatment and validate the use of protease inhibitors against SARS-CoV-2.", "title": "Unrevealing sequence and structural features of novel coronavirus using in silico approaches: The main protease as molecular target", "pid": "qdt90c22", "bm25_score": 217.96214294433594}, {"text": "SARS-CoV-2/novel coronavirus (2019-nCoV) is a new strain that has recently been confirmed in Wuhan City, Hubei Province of China, and spreads to more than 165 countries of the world including India. The virus infection leads to 245,922 confirmed cases and 10,048 deaths worldwide as of March 20, 2020. Coronaviruses (CoVs) are lethal zoonotic viruses, highly pathogenic in nature, and responsible for diseases ranging from common cold to severe illness such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) in humans for the past 15 years. Considering the severity of the current and previous outbreaks, no approved antiviral agent or effective vaccines are present for the prevention and treatment of infection during the epidemics. Although, various molecules have been shown to be effective against coronaviruses both in vitro and in vivo, but the antiviral activities of these molecules are not well established in humans. Therefore, this chapter is planned to provide information about available treatment and preventive measures for the coronavirus infections during outbreaks. This chapter also discusses the possible role of supportive therapy, repurposing drugs, and complementary and alternative medicines for the management of coronaviruses including COVID-19.", "title": "Therapeutic Development and Drugs for the Treatment of COVID-19", "pid": "9q7zbmwp", "bm25_score": 217.94924926757812}]}
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"2dyn9uez": 0, "yu89n6rq": 0, "yurxs7lj": 1, "yv5yz261": 2, "yvjxw39o": 2, "yvmrkl5s": 2, "yvsyo4l9": 0, "ywvk6gu6": 2, "ywwg00jj": 0, "yx99kks6": 0, "pkkj4udv": 0, "s91sz7c0": 1, "yzloau0d": 0, "z0sbztkw": 0, "z2y1ywdq": 2, "z470rn66": 0, "z4l3pk23": 2, "z5dy8kxf": 2, "z5itakx6": 2, "z6qqy858": 2, "z7r45291": 0, "z97nzbuu": 2, "zaaraiy7": 0, "zcktrmyg": 0, "7kidc16v": 0, "zends7v8": 0, "gk42nxrj": 0, "zhw8vh3e": 0, "zij2wbzs": 0, "zio8yhuy": 0, "zjg64lua": 0, "vz7p89zq": 2, "zloyie6z": 0, "zndtddty": 0, "zo9uzk52": 1, "jnhoau5v": 2, "zovj2vt5": 2, "ft15w83r": 0, "zph6r4il": 0, "pxt5aosp": 2, "zqh8t1ym": 2, "zqsy6r4i": 2, "zs18ez5q": 0, "xaw3t7tf": 1, "ztcij4wb": 0, "v0v0ahjh": 1, "zuedsaqg": 0, "zwbn44gz": 1, "bdfli7l0": 0, "zyrzfm40": 2, "zzc8dq9r": 2}, "bm25_results": [{"text": "We present an example of applying 'need-driven' product design principle to the development of a rapid test kit to detect SARS-COV-2 (COVID-19). The tests are intended for use in the field and, longer term, for home use. They detect whether a subject is currently infected with the virus and is infectious. The urgent need for large numbers of tests in field setting imposes constraints such as short test time and lack of access to specialist equipment, laboratories and skilled technicians to perform the test and interpret results. To meet these needs, an antigen test based on RT-LAMP with colorimetric readout was chosen. Direct use of swab sample with no RNA extraction was explored. After extensive experimental study (reported elsewhere), a rapid test kit has been fabricated to satisfy all design criteria.", "title": "Development of a rapid test kit for SARS-CoV-2: an example of product design", "pid": "52pw2vwx", "bm25_score": 216.86520385742188}, {"text": "We present an example of applying ‘need-driven’ product design principle to the development of a rapid test kit to detect SARS-COV-2 (COVID-19). The tests are intended for use in the field and, longer term, for home use. They detect whether a subject is currently infected with the virus and is infectious. The urgent need for large numbers of tests in field setting imposes constraints such as short test time and lack of access to specialist equipment, laboratories and skilled technicians to perform the test and interpret results. To meet these needs, an antigen test based on RT-LAMP with colorimetric readout was chosen. Direct use of swab sample with no RNA extraction was explored. After extensive experimental study (reported elsewhere), a rapid test kit has been fabricated to satisfy all design criteria.", "title": "Development of a rapid test kit for SARS-CoV-2: an example of product design", "pid": "5enmq7do", "bm25_score": 216.79933166503906}, {"text": "In January, Mologic, embarked on a product development pathway for COVID-19 diagnostics focusing on ELISA and rapid diagnostic tests (RDTs), with anticipated funding from Wellcome Trust and DFID. 755 clinical samples from known COVID-19 patients and hospital negative controls were tested on Mologics IgG ELISA. The reported sensitivity on 191 SGUL prospectively enrolled patients was 95% on day 7 or more post diagnosis, and 97% 10 days or more post-diagnosis. A specificity panel comprising 564 samples pre-December 2019 were tested to include most common respiratory pathogens, other types of coronavirus, and flaviviruses. Specificity in this panel was 97%. This is the first in a series of Mologic products for COVID-19, which will be deployed for COVID-19 diagnosis, contact tracing and sero-epidemiological studies to estimate disease burden and transmission with a focus on ensuring access, affordability, and availability to lowest resource settings.", "title": "Rapid development of COVID-19 rapid diagnostics for low resource settings: accelerating delivery through transparency, responsiveness, and open collaboration", "pid": "nol2n8fo", "bm25_score": 216.574462890625}, {"text": "Fast and widespread diagnosis is crucial to fighting against the outbreak of COVID-19. This work surveys the landscape of available and emerging biosensor technologies for COVID-19 testing. Molecular diagnostic assays based on quantitative reverse transcription polymerase chain reaction are used in most clinical laboratories. However, the COVID-19 pandemic has overwhelmed testing capacity and motivated the development of fast point-of-care tests and the adoption of isothermal DNA amplification. Antigenic and serological rapid tests based on lateral-flow immunoassays suffer from low sensitivity. Advanced digital systems enhance performance at the expense of speed and the need for large equipment. Emerging technologies, including CRISPR gene-editing tools, benefit from high sensitivity and specificity of molecular diagnostics and the easy use of lateral-flow assays. DNA sequencing and sample pooling strategies are highlighted to bring out the full capacity of the available biosensor technologies and accelerate mass testing.", "title": "Trends and Innovations in Biosensors for COVID-19 Mass Testing", "pid": "d5d10lwr", "bm25_score": 216.5121307373047}, {"text": "Fast and widespread diagnosis is crucial to fight against the outbreak of COVID-19. The present work surveys the landscape of available and emerging biosensor technologies for COVID-19 testing. Molecular diagnostic assays based on quantitative Reverse Transcription Polymerase Chain Reaction are used in most clinical laboratories. The COVID-19 pandemic has overwhelmed the testing capacity and motivated the development of fast point-of-care tests and the adoption of isothermal DNA amplification. Antigenic and serological rapid tests based on lateral flow immunoassays suffer from low sensitivity. Advanced digital systems enhance the performance at the expense of speed and large equipment requirement. Emerging technologies, including CRISPR gene-editing tools, benefit from high sensitivity and selectivity of molecular diagnostics and the easy use of lateral flow assays. DNA sequencing and sample pooling strategies are highlighted to bring out the full capacity of the available biosensor technologies and accelerate mass testing.", "title": "Trends and innovations in biosensors for COVID-19 mass testing.", "pid": "nswmhpzf", "bm25_score": 216.3757781982422}, {"text": "Novel Corona virus (COVID-19 or 2019-nCoV) is an emerging global health concern that requires a rapid diagnostic test. Quantitative reverse transcription PCR (qRT-PCR) is currently the standard for COVID-19 detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper field based testing at point-of-risk. The objective of this study was to develop a rapid screening diagnostic test that could be completed in under 30 minutes. Simulated patient samples were generated by spiking serum, urine, saliva, oropharyngeal swabs, and nasopharyngeal swabs with a portion of the COVID-19 nucleic sequence. The samples were tested using RT-LAMP as well as by conventional qRT-PCR. Specificity of the RT-LAMP was evaluated by also testing against other related coronaviruses. RT-LAMP specifically detected COVID-19 in simulated patient samples. This test was performed in under 30 minutes. This approach could be used for monitoring of exposed individuals or potentially aid with screening efforts in the field and potential ports of entry.", "title": "Rapid Detection of Novel Coronavirus (COVID-19) by Reverse Transcription-Loop-Mediated Isothermal Amplification", "pid": "6kpgt70s", "bm25_score": 216.3461456298828}, {"text": "There is widespread agreement that reliable, fast, and easy-to-produce diagnostic testing methods that have high sensitivity and specificity are essential for guiding appropriate responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak. At the present time, there are important unanswered questions about testing methods for SARS-CoV-2. This review article interprets recent findings related to the principal testing methods used to diagnose SARS-CoV-2, including reverse-transcription polymerase chain reaction (RT-PCR), chest imaging, and immunoassay. We discuss the value and limitations of these approaches and suggest directions for future research that can advance the understanding of diagnostic methods. Addressing areas of uncertainty will improve clinical outcomes and allow more effective policies to be implemented to control the disease.", "title": "What Do We Need to Know to Improve Diagnostic Testing Methods for the 2019 Novel Coronavirus?", "pid": "vzv0d5ry", "bm25_score": 216.16600036621094}, {"text": "In the last few months, an unprecedented number of laboratory tests for coronavirus disease 2019 (COVID-19) have been developed at a remarkable speed. With the rapid adoption of these tests into clinical practice, combined with the widespread publicity they received, questions arose related to the different types of tests, their utility, performance, and regulatory approval status. The aim of this publication is to provide a general landscape of laboratory testing for COVID-19 and offer a historical and regulatory perspective associated with them. Specifically, we aim to elaborate on the regulatory complexities of diagnostic testing in the United States and its implications to the present outbreak, as well as provide a synopsis of laboratory tests that have been developed for COVID-19. We will first address the detection of severe acute respiratory syndrome-coronavirus 2 directly by either nucleic acid amplification tests or by the detection of the viral protein for active infections. Subsequently, we will provide an overview of serological tests that can aid not only in diagnosis but additionally help to identify prior infections and potential immunity.", "title": "Testing For SARS-CoV-2: The Day the World Turned its Attention to the Clinical Laboratory", "pid": "r7glmi7p", "bm25_score": 216.1312255859375}, {"text": "Clinical laboratory testing routinely provides actionable results, which help direct patient care in the inpatient and outpatient settings. Since December 2019, a novel coronavirus (SARS-CoV-2) has been causing disease (COVID-19 [coronavirus disease 2019]) in patients, beginning in China and now extending worldwide. In this context of a novel viral pandemic, clinical laboratories have developed multiple novel assays for SARS-CoV-2 diagnosis and for managing patients afflicted with this illness. These include molecular and serologic-based tests, some with point-of-care testing capabilities. Herein, we present an overview of the types of testing available for managing patients with COVID-19, as well as for screening of potential plasma donors who have recovered from COVID-19.", "title": "Types of Assays for SARS-CoV-2 Testing: A Review.", "pid": "zyrzfm40", "bm25_score": 216.07798767089844}, {"text": "Clinical laboratory testing routinely provides actionable results, which help direct patient care in the inpatient and outpatient settings. Since December 2019, a novel coronavirus (SARS-CoV-2) has been causing disease (COVID-19 [coronavirus disease 2019]) in patients, beginning in China and now extending worldwide. In this context of a novel viral pandemic, clinical laboratories have developed multiple novel assays for SARS-CoV-2 diagnosis and for managing patients afflicted with this illness. These include molecular and serologic-based tests, some with point-of-care testing capabilities. Herein, we present an overview of the types of testing available for managing patients with COVID-19, as well as for screening of potential plasma donors who have recovered from COVID-19.", "title": "Types of Assays for SARS-CoV-2 Testing: A Review", "pid": "qexn0nuy", "bm25_score": 216.0537109375}, {"text": "Novel Corona virus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV), and the subsequent disease caused by the virus (coronavirus disease 2019 or COVID-19), is an emerging global health concern that requires a rapid diagnostic test. Quantitative reverse transcription PCR (qRT-PCR) is currently the standard for SARS-CoV-2 detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper field based testing at point-of-risk. The objective of this study was to develop a rapid screening diagnostic test that could be completed in 30-45 minutes. Simulated patient samples were generated by spiking serum, urine, saliva, oropharyngeal swabs, and nasopharyngeal swabs with a portion of the SARS-CoV-2 nucleic sequence. RNA isolated from nasopharyngeal swabs collected from actual COVID-19 patients was also tested. The samples were tested using RT-LAMP as well as by conventional qRT-PCR. Specificity of the RT-LAMP was evaluated by also testing against other related coronaviruses. RT-LAMP specifically detected SARS-CoV-2 in both simulated patient samples and clinical specimens. This test was performed in 30-45 minutes. This approach could be used for monitoring of exposed individuals or potentially aid with screening efforts in the field and potential ports of entry.", "title": "Rapid detection of novel coronavirus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by reverse transcription-loop-mediated isothermal amplification", "pid": "e54b5cbs", "bm25_score": 216.00711059570312}, {"text": "Novel Corona virus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2 or 2019-nCoV), and the subsequent disease caused by the virus (coronavirus disease 2019 or COVID-19), is an emerging global health concern that requires a rapid diagnostic test. Quantitative reverse transcription PCR (qRT-PCR) is currently the standard for SARS-CoV-2 detection; however, Reverse Transcription Loop-Mediated Isothermal Amplification (RT-LAMP) may allow for faster and cheaper field based testing at point-of-risk. The objective of this study was to develop a rapid screening diagnostic test that could be completed in 30–45 minutes. Simulated patient samples were generated by spiking serum, urine, saliva, oropharyngeal swabs, and nasopharyngeal swabs with a portion of the SARS-CoV-2 nucleic sequence. RNA isolated from nasopharyngeal swabs collected from actual COVID-19 patients was also tested. The samples were tested using RT-LAMP as well as by conventional qRT-PCR. Specificity of the RT-LAMP was evaluated by also testing against other related coronaviruses. RT-LAMP specifically detected SARS-CoV-2 in both simulated patient samples and clinical specimens. This test was performed in 30–45 minutes. This approach could be used for monitoring of exposed individuals or potentially aid with screening efforts in the field and potential ports of entry.", "title": "Rapid detection of novel coronavirus/Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by reverse transcription-loop-mediated isothermal amplification", "pid": "dci4jbyd", "bm25_score": 215.97154235839844}, {"text": "Objectives SARS-CoV-2, causing COVID-19, has emerged to cause a human pandemic. Detection of SARS-CoV-2 in respiratory samples by using PCR is the standard laboratory diagnostic tool. Our aim was to perform a limited evaluation of the diagnostic performance and user-friendliness of eleven rapid tests for detection of antibodies against SARS-CoV-2. Methods All participants were tested with PCR against SARS-CoV-2 at a clinical microbiology laboratory. Comparing with results from PCR tests, we evaluated the rapid tests' performances in three arms; 1) 20 hospitalized patients with PCR-confirmed COVID-19, 2) 23 recovered outpatients with former PCR-confirmed COVID-19, and 3) 49 participants with suspected COVID-19 presenting at a primary care emergency room. Results All eleven tests detected antibodies in hospitalized COVID-19 patients, though with varying sensitivities. In former outpatients recovered from COVID-19, there were differences between tests in the immunoglobulin type G (IgG) sensitivity, with five tests having a sensitivity below 65%. In participants with suspected COVID-19 infection, the rapid tests had very low sensitivities. Most rapid tests were easy to perform and interpret. Conclusions Rapid tests were not suited as stand-alone tests to detect present infection in a Norwegian primary care emergency room population. All the rapid tests were able to detect SARS-CoV-2 antibodies, although sensitivities varied and were generally higher in the study arm of more severely affected participants. Rapid tests with high IgG sensitivity (and specificity) may be useful for confirmation of past infection. An independent evaluation should be performed in the intended population before introducing a rapid test.", "title": "Evaluation of eleven rapid tests for detection of antibodies against SARS-CoV-2.", "pid": "7ur8hr23", "bm25_score": 215.9513397216797}, {"text": "SARS-CoV-2 is responsible for a highly contagious infection, known as COVID-19. SARS-CoV-2 was discovered in late December 2019 and, since then, has become a global pandemic. Timely and accurate COVID-19 laboratory testing is an essential step in the management of the COVID-19 outbreak. To date, assays based on the reverse-transcription polymerase chain reaction (RT-PCR) in respiratory samples are the gold standard for COVID-19 diagnosis. Unfortunately, RT-PCR has several practical limitations. Consequently, alternative diagnostic methods are urgently required, both for alleviating the pressure on laboratories and healthcare facilities and for expanding testing capacity to enable large-scale screening and ensure a timely therapeutic intervention. To date, few studies have been conducted concerning the potential utilization of rapid testing for COVID-19, with some conflicting results. Therefore, the present systematic review and meta-analysis was undertaken to explore the feasibility of rapid diagnostic tests in the management of the COVID-19 outbreak. Based on ten studies, we computed a pooled sensitivity of 64.8% (95%CI 54.5-74.0), and specificity of 98.0% (95%CI 95.8-99.0), with high heterogeneity and risk of reporting bias. We can conclude that: (1) rapid diagnostic tests for COVID-19 are necessary, but should be adequately sensitive and specific; (2) few studies have been carried out to date; (3) the studies included are characterized by low numbers and low sample power, and (4) in light of these results, the use of available tests is currently questionable for clinical purposes and cannot substitute other more reliable molecular tests, such as assays based on RT-PCR.", "title": "Point-of-Care Diagnostic Tests for Detecting SARS-CoV-2 Antibodies: A Systematic Review and Meta-Analysis of Real-World Data", "pid": "4ipuy7su", "bm25_score": 215.9317626953125}, {"text": "Quantitative reverse transcription polymerase chain reaction (RT-qPCR) assay is the gold standard recommended to test for acute SARS-CoV-2 infection. It has been used by the Centers for Disease Control and Prevention (CDC) and several other companies in their Emergency Use Authorization (EUA) assays. RT-qPCR requires expensive equipment such as RNA isolation instruments and real-time PCR thermal cyclers, which are not available in many low resource settings and developing countries. As a pandemic, COVID-19 has quickly spread to the rest of the world. Many underdeveloped and developing counties do not have the means for fast and accurate COVID-19 detection to control this outbreak. Using COVID-19 positive clinical specimens, we demonstrated that RT-PCR assays can be performed in as little as 12 minutes using untreated samples, heat-inactivated samples, or extracted RNA templates. Rapid RT-PCR was achieved using thin-walled PCR tubes and a setup including sous vide immersion heaters/circulators. Our data suggest that rapid RT-PCR can be implemented for sensitive and specific molecular diagnosis of COVID-19 in situations where sophisticated laboratory instruments are not available.", "title": "A Rapid COVID-19 RT-PCR Detection Assay for Low Resource Settings", "pid": "lqio7l8k", "bm25_score": 215.91929626464844}, {"text": "SARS-CoV-2 is responsible for a highly contagious infection, known as COVID-19. SARS-CoV-2 was discovered in late December 2019 and, since then, has become a global pandemic. Timely and accurate COVID-19 laboratory testing is an essential step in the management of the COVID-19 outbreak. To date, assays based on the reverse-transcription polymerase chain reaction (RT-PCR) in respiratory samples are the gold standard for COVID-19 diagnosis. Unfortunately, RT-PCR has several practical limitations. Consequently, alternative diagnostic methods are urgently required, both for alleviating the pressure on laboratories and healthcare facilities and for expanding testing capacity to enable large-scale screening and ensure a timely therapeutic intervention. To date, few studies have been conducted concerning the potential utilization of rapid testing for COVID-19, with some conflicting results. Therefore, the present systematic review and meta-analysis was undertaken to explore the feasibility of rapid diagnostic tests in the management of the COVID-19 outbreak. Based on ten studies, we computed a pooled sensitivity of 64.8% (95%CI 54.5–74.0), and specificity of 98.0% (95%CI 95.8–99.0), with high heterogeneity and risk of reporting bias. We can conclude that: (1) rapid diagnostic tests for COVID-19 are necessary, but should be adequately sensitive and specific; (2) few studies have been carried out to date; (3) the studies included are characterized by low numbers and low sample power, and (4) in light of these results, the use of available tests is currently questionable for clinical purposes and cannot substitute other more reliable molecular tests, such as assays based on RT-PCR.", "title": "Point-of-Care Diagnostic Tests for Detecting SARS-CoV-2 Antibodies: A Systematic Review and Meta-Analysis of Real-World Data", "pid": "tujxlve3", "bm25_score": 215.85867309570312}, {"text": "Objectives SARS-CoV-2, causing COVID-19, has emerged to cause a human pandemic. Detection of SARS-CoV-2 in respiratory samples by using PCR is the standard laboratory diagnostic tool. Our aim was to perform a limited evaluation of the diagnostic performance and user-friendliness of eleven rapid tests for detection of antibodies against SARS-CoV-2. Methods All participants were tested with PCR against SARS-CoV-2 at a clinical microbiology laboratory. Comparing with results from PCR tests, we evaluated the rapid tests' performances in three arms; 1) 20 hospitalized patients with PCR-confirmed COVID-19, 2) 23 recovered outpatients with former PCR-confirmed COVID-19, and 3) 49 participants with suspected COVID-19 presenting at a primary care emergency room. Results All eleven tests detected antibodies in hospitalized COVID-19 patients, though with varying sensitivities. In former outpatients recovered from COVID-19, there were differences between tests in the immunoglobulin type G (IgG) sensitivity, with five tests having a sensitivity below 65%. In participants with suspected COVID-19 infection, the rapid tests had very low sensitivities. Most rapid tests were easy to perform and interpret. Conclusions Rapid tests were not suited as stand-alone tests to detect present infection in a Norwegian primary care emergency room population. All the rapid tests were able to detect SARS-CoV-2 antibodies, although sensitivities varied and were generally higher in the study arm of more severely affected participants. Rapid tests with high IgG sensitivity (and specificity) may be useful for confirmation of past infection. An independent evaluation should be performed in the intended population before introducing a rapid test.", "title": "Evaluation of eleven rapid tests for detection of antibodies against SARS-CoV-2", "pid": "xa1v5t63", "bm25_score": 215.82086181640625}, {"text": "Abstract Rapid, scalable, point-of-need, COVID-19 diagnostic testing is necessary to safely re-open economies and prevent future outbreaks. We developed an assay that detects single copies of SARS-CoV-2 virus directly from saliva and swab samples in 30 min using a simple, one-step protocol that utilizes only a heat block and microcentrifuge tube prefilled with a mixture containing the necessary reagents and has a sensitivity and specificity of 97% and 100%, respectively.", "title": "Field-deployable, rapid diagnostic testing of saliva samples for SARS-CoV-2.", "pid": "8vp57c1o", "bm25_score": 215.81344604492188}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated Coronavirus disease 2019 (COVID-19) pandemic has demanded rapid upscaling of in-vitro diagnostic assays to enable mass screening and testing of high-risk groups, and simultaneous ascertainment of robust data on past SARS-CoV-2 exposure at an individual and population level. To meet the exponential demand in testing, there has been an accelerated development of both molecular and serological assays across a plethora of platforms. In the present review, we discuss the current literature on these modalities including the nucleic acid amplification tests, direct viral antigen tests and the rapidly expanding laboratory based and point of care serological tests. This suite of complementary tests will inform crucial decisions by healthcare providers and policy makers and understanding their strengths and limitations will be critical to their judicious application for the development of algorithmic approaches to treatment and public health strategies.", "title": "Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays", "pid": "8y0v6d2i", "bm25_score": 215.80479431152344}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated coronavirus disease 2019 (COVID-19) pandemic has demanded rapid upscaling of in-vitro diagnostic assays to enable mass screening and testing of high-risk groups, and simultaneous ascertainment of robust data on past SARS-CoV-2 exposure at an individual and a population level. To meet the exponential demand in testing, there has been an accelerated development of both molecular and serological assays across a plethora of platforms. The present review discusses the current literature on these modalities, including nucleic acid amplification tests, direct viral antigen tests and the rapidly expanding laboratory-based and point of care serological tests. This suite of complementary tests will inform crucial decisions by healthcare providers and policy makers, and understanding their strengths and limitations will be critical to their judicious application for the development of algorithmic approaches to treatment and public health strategies.", "title": "Testing for SARS-CoV-2 (COVID-19): a systematic review and clinical guide to molecular and serological in-vitro diagnostic assays", "pid": "3ea1ngo2", "bm25_score": 215.76644897460938}, {"text": "On March 11, 2020 the World Health Organization (WHO) upgraded the status of the coronavirus disease 2019 (COVID-19) outbreak from epidemic to a global pandemic. This infection is caused by a novel coronavirus, SARS-CoV-2. Several rapid diagnostic tests have been developed at an astonishing pace; however, COVID-19 requires more highly specific rapid point-of-care diagnostic tests. This review describes the currently available testing approaches, as well as the available test assays including the Xpert® Xpress SARS-CoV-2 test (takes (~)45 min) and Abbott ID COVID-19 test (5 min) as easy to use point-of-care tests for diagnosis of novel COVID-19 that have so far received the US Food and Drug Administration emergency use authorizations clearance. This review is correct as of the date published and will be updated as more diagnostic tests come to light.", "title": "Current and emerging diagnostic tests available for the novel COVID-19 global pandemic", "pid": "1dr4r3n4", "bm25_score": 215.73715209960938}, {"text": "OBJECTIVE: With the current SARS-CoV2 outbreak, countless tests need to be performed on potential symptomatic individuals, contacts and travellers. The gold standard is a quantitative polymerase chain reaction (qPCR)-based system taking several hours to confirm positivity. For effective public health containment measures, this time span is too long. We therefore evaluated a rapid test in a high-prevalence community setting. STUDY DESIGN: Thirty-nine randomly selected individuals at a COVID-19 screening centre were simultaneously tested via qPCR and a rapid test. Ten previously diagnosed individuals with known SARS-CoV-2 infection were also analysed. METHODS: The evaluated rapid test is an IgG/IgM-based test for SARS-CoV-2 with a time to result of 20 min. Two drops of blood are needed for the test performance. RESULTS: Of 49 individuals, 22 tested positive by repeated qPCR. In contrast, the rapid test detected only eight of those positive correctly (sensitivity: 36.4%). Of the 27 qPCR-negative individuals, 24 were detected correctly (specificity: 88.9%). CONCLUSION: Given the low sensitivity, we recommend not to rely on an antibody-based rapid test for public health measures such as community screenings.", "title": "Rapid point-of-care testing for SARS-CoV-2 in a community screening setting shows low sensitivity", "pid": "22kgwbz4", "bm25_score": 215.69090270996094}, {"text": "Abstract Objective With the current SARS-CoV2 outbreak, countless tests need to be performed on potential symptomatic individuals, contacts and travellers. The gold standard is a quantitative polymerase chain reaction (qPCR)–based system taking several hours to confirm positivity. For effective public health containment measures, this time span is too long. We therefore evaluated a rapid test in a high-prevalence community setting. Study design Thirty-nine randomly selected individuals at a COVID-19 screening centre were simultaneously tested via qPCR and a rapid test. Ten previously diagnosed individuals with known SARS-CoV-2 infection were also analysed. Methods The evaluated rapid test is an IgG/IgM–based test for SARS-CoV-2 with a time to result of 20 min. Two drops of blood are needed for the test performance. Results Of 49 individuals, 22 tested positive by repeated qPCR. In contrast, the rapid test detected only eight of those positive correctly (sensitivity: 36.4%). Of the 27 qPCR-negative individuals, 24 were detected correctly (specificity: 88.9%). Conclusion Given the low sensitivity, we recommend not to rely on an antibody-based rapid test for public health measures such as community screenings.", "title": "Rapid point-of-care testing for SARS-CoV-2 in a community screening setting shows low sensitivity", "pid": "k1adcls8", "bm25_score": 215.6803741455078}, {"text": "", "title": "Fast and simple high-throughput testing of COVID 19", "pid": "cjk0ggkt", "bm25_score": 215.64566040039062}, {"text": "The recent pandemic of COVID-19 has involved tens of thousands of patients in numerous countries and the causative virus, SARS COV-2 is highly transmissible. Molecular diagnostic tools are central to containment of the virus and initiating proper clinical care. Rapidity, user-friendliness, and high degree of sensitivity and specificity are desirable features of diagnostic assays for screening purposes. Herein, we present a single step reverse transcriptase LAMP assay (RT-LAMP), which can detect up to 500 viral copies in 30 minutes. We challenged our assay with a large number of clinical samples collected from 47 confirmed cases and 213 negative patients. Our LAMP assay showed a high degree of sensitivity and specificity compared to two commercialized qRT-PCR assay as gold standard. We present a rapid RT-LAMP assay that could extend the capacity of laboratories to process 2.5 more clinical samples relative to qRT-PCR and potentially could be used for high-throughput screening purposes.", "title": "Development and validation of a rapid single-step reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) system potentially to be used for reliable and high-throughput screening of COVID-19", "pid": "eo2pcgix", "bm25_score": 215.6410369873047}, {"text": "The ability to rapidly and accurately identify a patient's COVID-19 status has had significant impact on emergency departments (ED) and health systems globally. Since the identification of SARS-CoV-2 illness in the United States, there has been rapid development in patient testing capacity following initial challenges including sparse availability. This was made possible by increasing availability of diagnostic molecular tests in several formats, from laboratory based traditional, RT-PCR methods to near patient testing rapid point of care PCR tests.", "title": "Diagnostic Performance of a Rapid Point of Care Test for SARS-CoV-2 in an Urban ED Setting", "pid": "onhiptn7", "bm25_score": 215.62802124023438}, {"text": "An ongoing theme of the COVID-19 pandemic is the need for widespread availability of accurate and efficient diagnostic testing for detection of SARS-CoV-2 and antiviral antibodies in infected individuals. This report describes various assay techniques and tests for COVID-19 diagnosis. Most tests for early detection of SARS-CoV-2 RNA rely on the reverse transcription-polymerase chain reaction, but isothermal nucleic acid amplification assays, including transcription-mediated amplification and CRISPR-based methodologies, are promising alternatives. Identification of individuals who have developed antibodies to the SARS-CoV-2 virus requires serological tests, including enzyme-linked immunosorbent assay (ELISA) and lateral flow immunoassay. This report also provides an overview of current development in COVID-19 diagnostic techniques and products to facilitate future improvement and innovation.", "title": "Assay Techniques and Test Development for COVID-19 Diagnosis", "pid": "d7xq7x5g", "bm25_score": 215.61837768554688}, {"text": "As the novel coronavirus severe acute respiratory syndrome coronavirus 2 caused coronavirus disease 2019 cases in the United States, the initial test was developed and performed at the Centers for Disease Control and Prevention. As the number of cases increased, the demand for tests multiplied, leading the Centers for Disease Control and Prevention to use the Emergency Utilization Authorization to allow clinical and commercial laboratories to develop tests to detect the presence of the virus. Many nucleic acid tests based on RT-PCR were developed, each with different techniques, specifications, and turnaround time. As the illnesses turned into a pandemic, testing became more crucial. The test supply became inadequate to meet the need and so it had to be prioritized according to guidance. For surveillance, the need for serologic tests emerged. Here, we review the timeline of test development, the turnaround times, and the various approved tests, and compare them as regards the genes they detect. We concentrate on the point-of-care tests and discuss the basis for new serologic tests. We discuss the testing guidance for prioritization and their application in a hospital setting.", "title": "Clinical testing for COVID-19", "pid": "rw4ep4wh", "bm25_score": 215.607421875}, {"text": "These speed bumps are some of the reasons why many industry watchers and public health officials are praising the development of a 5 min bedside, or point-of-care, test produced by Abbott Laboratories Approved in late March, the test relies on PCR but uses a different method of copying genetic material, allowing it to be done at a constant temperature and quickly Other companies that use this method, called isothermal amplification, for infectious disease diagnostics have developed specialized enzymes that can copy viral RNA without the temperature cycling used in more traditional PCR It’s not clear exactly how Abbott is employing isothermal amplification, but the company says the test can be done in a small, portable machine that many hospitals already use to diagnose other infectious diseases Abbott says this test and another, more traditional PCR diagnostic it developed can perform up to 5 million COVID-19 tests per month total", "title": "Companies are racing to develop COVID-19 tests for the US. Will the tests help?", "pid": "hboafe4u", "bm25_score": 215.605224609375}, {"text": "Background: Rapid and extensive testing of large parts of the population and specific subgroups is crucial for proper management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decision-making in times of a pandemic outbreak. However, point-of-care (POC) testing in places such as emergency units, outpatient clinics, airport security points or the entrance of any public building is a major challenge. The need for thermal cycling and nucleic acid isolation hampers the use of standard PCR-based methods for this purpose. Methods: To avoid these obstacles, we tested PCR-independent methods for the detection of SARS-CoV-2 RNA from primary material (nasopharyngeal swabs) including loop-mediated isothermal amplification (LAMP) and specific high-sensitivity enzymatic reporter unlocking (SHERLOCK). Results: Whilst specificity of standard LAMP assays appears to be satisfactory, sensitivity does not reach the current gold-standard quantitative real-time polymerase chain reaction (qPCR) assays yet. We describe a novel multiplexed LAMP approach and validate its sensitivity on primary samples. This approach allows for fast and reliable identification of infected individuals. Primer optimization and multiplexing helps to increase sensitivity significantly. In addition, we directly compare and combine our novel LAMP assays with SHERLOCK. Conclusion: In summary, this approach reveals one-step multiplexed LAMP assays as a prime-option for the development of easy and cheap POC test kits.", "title": "Rapid SARS-CoV-2 testing in primary material based on a novel multiplex LAMP assay", "pid": "l91hiaao", "bm25_score": 215.5950927734375}, {"text": "Validated and accurate laboratory testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a crucial part of the timely management of Coronavirus Disease 2019 (COVID-19) disease, supporting the clinical decision-making process for infection control at the healthcare level and detecting asymptomatic cases. This would facilitate an appropriate treatment, a prompt isolation and consequently deceleration of the pandemic. Various laboratory tests can identify the genetic material of SARS-CoV-2 that causes COVID-19 in specimens, or specific anti-viral antibodies in blood/serum. Due to the current pandemic situation, a development of point-of-care diagnostics (POCD) allows us to substantially accelerate taking clinical decisions and implement strategic planning at the national level of preventative measures. This review summarizes and compares the available POCD and those currently under development, including quantitative reverse transcription PCR (RT-qPCR), serology immunoassays (SIAs) and protein microarray method (PMM) designed for standard and rapid COVID-19 diagnosis.", "title": "Molecular and Serological Tests for COVID-19. A Comparative Review of SARS-CoV-2 Coronavirus Laboratory and Point-of-Care Diagnostics", "pid": "tb1zsuw4", "bm25_score": 215.56658935546875}, {"text": "OBJECTIVES: We aimed to evaluate the role of rapid serological tests in the management of coronavirus disease 2019 (COVID-19) patients. METHODS: This retrospective study enrolled 16 real-time reverse transcription polymerase chain reaction-confirmed symptomatic patients with COVID-19 and 58 COVID-19 negative patients at a medical center in Taiwan over a 3-month period. Serial serum samples were collected and tested for antibody response using four point-of-care (POC) lateral flow immunoassays (LFIA) (ALLTEST 2019-nCoV IgG/IgM Rapid Test, Dynamiker 2019-nCoV IgG/IgM Rapid Test, ASK COVID-19 IgG/IgM Rapid Test, and Wondfo SARS-CoV-2 Antibody Test). Time-dependent detection sensitivity and timeliness of seroconversion were determined and compared between the four POC rapid tests. RESULTS: The overall sensitivity and specificity of the four tests for detecting anti-SARS-CoV-2 antibodies after 3 weeks of symptom onset were 100% and 100%, respectively. There was no significant difference between the rapid tests used for detection of IgM and IgG separately and those used for detection of combined total antibody (mainly IgM/IgG). There was no significant difference between the four POC rapid tests in terms of time required for determining seroconversion of COVID-19. Patients with COVID-19 with pneumonia demonstrated shorter seroconversion time than those without pneumonia. CONCLUSION: Though the POC antibody rapid tests based on LFIA showed reliable performance in the detection of SARS-CoV-2-specific antibodies, the results of these tests should be interpreted and applied appropriately in the context of antibody dynamic of COVID-19 infection. COVID-19 patients complicated with pneumonia exhibited earlier anti-SARS-CoV-2 antibody response than COVID-19 patients without pneumonia.", "title": "Four point-of-care lateral flow immunoassays for diagnosis of COVID-19 and for assessing dynamics of antibody responses to SARS-CoV-2", "pid": "gplcop2k", "bm25_score": 215.54835510253906}, {"text": "The 2019 novel coronavirus (COVID-19) is a newly emerged strain that has never been found in humans before. At present, the laboratory-based reverse transcription-polymerase chain reaction (RT-PCR) is the main method to confirm COVID-19 infection. The intensification of the COVID-19 epidemic overwhelms limited clinical resources in particular, but not only, in developing countries, resulting in many patients not being tested for the infection and in large queues of potentially infected individuals waiting to be tested while providing a breeding ground for the disease. We describe here a rapid, highly sensitive, point-of-care, molecular test amenable for use at home, in the clinic, and at points of entry by minimally trained individuals and with minimal instrumentation. Our test is based on loop mediated isothermal amplification (COVID-19 LAMP) and for higher sensitivity on nested nucleic acid, two stage isothermal amplification (COVID-19 Penn-RAMP). Both tests can be carried out in closed tubes with either fluorescence or colorimetric (e.g., leuco crystal violet LCV) detection. COVID-19 LAMP performs on par with COVID-19 RT-PCR. COVID-19 RAMP has 10 fold better sensitivity than COVID-19 LAMP and COVID-19 RT-PCR when testing purified targets and 100 times better sensitivity than COVID-19 LAMP and COVID-19 RT-PCR when testing rapidly prepared sample mimics. Due to fortunate scarcity of COVID-19 infections in the USA, we were not able to test our assays and methods with patient samples. We hope that such tests will be carried out by colleagues in impacted countries. Our Closed-Tube Penn-RAMP has the potential to significantly reduce false negatives while being amenable to use with minimal instrumentation and training.", "title": "A Single and Two-Stage, Closed-Tube, Molecular Test for the 2019 Novel Coronavirus (COVID-19) at Home, Clinic, and Points of Entry.", "pid": "7fgjoqgb", "bm25_score": 215.54331970214844}, {"text": "There is a need for widespread testing in India to stop the spread of the novel coronavirus in the population. While RT-PCR is the recommended diagnostic technique, its use is limited to well-equipped laboratories due to the need for specialized instrumentation, reagents and trained personnel. Immunodiagnostic tests are not yet recommended by the WHO for diagnosing active infections. There is a strong need for developing point-of-care molecular tests. Based on our past experience with paperfluidic devices for diagnosing bacterial infections by molecular tests, we propose the development of a diagnostic test for COVID-19. As a platform technology, it could be adapted to other viral outbreaks in future.", "title": "Developing a Point-of-Care Molecular Test to Detect SARS-CoV-2", "pid": "8siz9rb8", "bm25_score": 215.53309631347656}, {"text": "The emergence of the novel coronavirus SARS-CoV-2 has led to a pandemic infecting more than two million people worldwide in less than four months, posing a major threat to healthcare systems. This is compounded by the shortage of available tests causing numerous healthcare workers to unnecessarily self-isolate. We provide a roadmap instructing how a research institute can be repurposed in the midst of this crisis, in collaboration with partner hospitals and an established diagnostic laboratory, harnessing existing expertise in virus handling, robotics, PCR, and data science to derive a rapid, high throughput diagnostic testing pipeline for detecting SARS-CoV-2 in patients with suspected COVID-19. The pipeline is used to detect SARS-CoV-2 from combined nose-throat swabs and endotracheal secretions/ bronchoalveolar lavage fluid. Notably, it relies on a series of in-house buffers for virus inactivation and the extraction of viral RNA, thereby reducing the dependency on commercial suppliers at times of global shortage. We use a commercial RT-PCR assay, from BGI, and results are reported with a bespoke online web application that integrates with the healthcare digital system. This strategy facilitates the remote reporting of thousands of samples a day with a turnaround time of under 24 hours, universally applicable to laboratories worldwide.", "title": "Scalable and Resilient SARS-CoV2 testing in an Academic Centre", "pid": "nuw194wf", "bm25_score": 215.47216796875}, {"text": "COVID-19 testing as sufficient as needed is essential for healthcare workers, patients, and authorities to make informed decisions to confront and eventually defeat severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, diagnosis of COVID-19 relies on quantitative reverse-transcription PCR, which is low-throughput, laborious, and often false-negative, making it overwhelmingly challenging to meet testing needs even in industrialized countries. Here we propose a new strategy, which employs a modified loop-mediated isothermal amplification (LAMP) assay, a simple procedure requiring no sophisticated instruments, to index and amplify viral genes from individual specimens, of which the products are readily available for construction of multiplexed libraries for next-generation sequencing. Our strategy would allow precise diagnosis of thousands of specimens in 1-2 days with significantly lower operating expenses. Furthermore, this strategy will make it possible for patients to collect, process, and mail their own samples to facilities for a quick, reliable diagnosis at a population scale.", "title": "A high-throughput strategy for COVID-19 testing based on next-generation sequencing", "pid": "zms1o90x", "bm25_score": 215.45745849609375}, {"text": "The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19.", "title": "Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2.", "pid": "h2mloxuh", "bm25_score": 215.44412231445312}, {"text": "The recent outbreak of the Coronavirus disease 2019 (COVID-19) has quickly spread worldwide since its discovery in Wuhan city, China in December 2019. A comprehensive strategy, including surveillance, diagnostics, research, clinical treatment, and development of vaccines, is urgently needed to win the battle against COVID-19. The past three unprecedented outbreaks of emerging human coronavirus infections at the beginning of the 21st century have highlighted the importance of readily available, accurate, and rapid diagnostic technologies to contain emerging and re-emerging pandemics. Real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) based assays performed on respiratory specimens remain the gold standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging with high sensitivity and specificity as well. Even though excellent techniques are available for the diagnosis of symptomatic patients with COVID-19 in well-equipped laboratories; critical gaps still remain in screening asymptomatic people who are in the incubation phase of the virus, as well as in the accurate determination of live viral shedding during convalescence to inform decisions for ending isolation. This review article aims to discuss the currently available laboratory methods and surveillance technologies available for the detection of COVID-19, their performance characteristics and highlight the gaps in current diagnostic capacity, and finally, propose potential solutions. We also summarize the specifications of the majority of the available commercial kits (PCR, EIA, and POC) for laboratory diagnosis of COVID-19.", "title": "Challenges in Laboratory Diagnosis of the Novel Coronavirus SARS-CoV-2", "pid": "nm8a3jxt", "bm25_score": 215.43594360351562}, {"text": "", "title": "COVID-19 rapid antibody cassette point of care tests: practical considerations.", "pid": "djtebmio", "bm25_score": 215.43218994140625}, {"text": "Diagnostic testing to identify persons infected with severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection is central to control the global pandemic of COVID-19 that began in late 2019. In a few countries, the use of diagnostic testing on a massive scale has been a cornerstone of successful containment strategies. In contrast, the United States, hampered by limited testing capacity, has prioritized testing for specific groups of persons. Real-time reverse transcriptase polymerase chain reaction-based assays performed in a laboratory on respiratory specimens are the reference standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging. Although excellent tools exist for the diagnosis of symptomatic patients in well-equipped laboratories, important gaps remain in screening asymptomatic persons in the incubation phase, as well as in the accurate determination of live viral shedding during convalescence to inform decisions to end isolation. Many affluent countries have encountered challenges in test delivery and specimen collection that have inhibited rapid increases in testing capacity. These challenges may be even greater in low-resource settings. Urgent clinical and public health needs currently drive an unprecedented global effort to increase testing capacity for SARS-CoV-2 infection. Here, the authors review the current array of tests for SARS-CoV-2, highlight gaps in current diagnostic capacity, and propose potential solutions.", "title": "Diagnostic Testing for Severe Acute Respiratory Syndrome-Related Coronavirus 2: A Narrative Review", "pid": "wnt1v675", "bm25_score": 215.43124389648438}, {"text": "BACKGROUND: In January 2020 reports of unidentified severe respiratory illness were described in Wuhan, China. A rapid expansion in cases affecting most countries around the globe led to major changes in the way people live their daily lives. In the United Kingdom, the Department of Health and Social Care directed healthcare providers to establish additional resources to manage the anticipated surge in cases that could overwhelm the health services. A priority area was testing for SARS-CoV-2 RNA and its detection by qualitative RT-PCR. DESIGN: A laboratory workflow twinning research environment with clinical laboratory capabilities was implemented and validated in the University of Birmingham within 4 days of the project initiation. The diagnostic capability was centred on an IVD CE-marked RT-PCR kit and designed to provide surge capacity to the nearby Queen Elizabeth Hospital. The service was initially tasked with testing healthcare workers (HCW) using throat swabs, and subsequently the process investigated the utility of using saliva as an alternative sample type. RESULTS: Between the 8(th) April 2020 and the 30(th) April 2020, the laboratory tested a total of 1282 HCW for SARS-CoV-2 RNA in throat swabs. RNA was detected in 54% of those who reported symptoms compatible with COVID-19, but in only 4% who were asymptomatic. CONCLUSION: This capability was established rapidly and utilised a cold-chain free methodology, applicable to a wide range of settings, and which can provide surge capacity and support to clinical laboratories facing increasing pressure during periods of national crisis.", "title": "Rapid implementation and validation of a cold-chain free SARS-CoV-2 diagnostic testing workflow to support surge capacity", "pid": "twwpux1c", "bm25_score": 215.4097900390625}, {"text": "The current standard testing method for screening coronavirus disease 2019 (COVID-19) is through reverse real-time PCR assay (rRT-PCR), a common molecular-based assay that requires an average of four to six hours to provide results [...].", "title": "Combining Point-of-Care Diagnostics and Internet of Medical Things (IoMT) to Combat the COVID-19 Pandemic", "pid": "vy0x9hvr", "bm25_score": 215.40475463867188}, {"text": "The recently emerged coronavirus disease COVID-19 has now evolved into a global pandemic. Early detection is crucial for its effective control. Nucleic acid testing for viral pathogen and serological testing for host antibodies are playing important roles in current COVID-19 diagnosis. However, while nucleic acid testing is complicated, facility-restricted and time-consuming, antibody testing may result in high rates of false-negative diagnoses, especially during the early stages of viral infection. Thus, a more rapid and reliable test for both early COVID-19 diagnosis and whole-population screening is urgently needed. Here, we developed a novel nanozyme-based chemiluminescence paper assay for rapid and high-sensitive testing of SARS-CoV-2 spike antigen. Our paper test uses a newly established peroxidase-mimic Co-Fe@hemin nanozyme instead of natural HRP that catalytically amplifies the chemiluminescent signal, allowing for target concentrations to be as low as 0.1 ng/ml. Furthermore, our nanozyme-based chemiluminescence test exhibits a linear range that is 32-fold wider compared to ELISA tests. Importantly, testing is completed in less than 16 min, compared to 1-2 h required for ELISA or nucleic acid tests. Critically, signal detection is feasible using a smartphone camera. Ingredients for our test are simple and readily available, rendering overall cost considerably lower than those used in current diagnoses. In conclusion, our novel test provides a high-sensitive, point-of-care testing (POCT) approach for SARS-CoV-2 antigen detection, which should greatly increase current early screening capacities for suspected infections, and considerably lower demand for national healthcare resources.", "title": "Ultra-sensitive nanozyme-based chemiluminescence paper test for rapid diagnosis of SARS-CoV-2 infection", "pid": "sw23wf4b", "bm25_score": 215.38340759277344}, {"text": "Increasing evidence indicates immunity against severe acute respiratory syndrome coronavirus 2 (sars-cov-2) after covid-19, but it remains unclear for how long the protection remains Serology testing seems to have a higher sensitivity than molecular diagnostics from 8 days after onset of symtoms, and should be part of risk assessment and epidemiological studies of COVID-19 The performance of commercial serological point-of-care (POC) lateral flow tests are highly manufacturer-dependant Low sensitivity increases the risk of false negative results and could result in unnecessary quarantine of test persons with developed antibodies Low specificity increases the risk of false positive results and could lead to false assumptions of immunity Carefully selected serological POC tests for sars-cov-2 can be used in large scale testing but should only be used by licensed medical staff able to understand their limitations and interpret the results", "title": "Rapid point-of-care serology testing for sars-cov-2/ Snabbtest for covid-19-antikroppar bor utforas av utbildad personal", "pid": "m60w5dnl", "bm25_score": 215.3764190673828}, {"text": "Coronavirus disease 2019 (COVID-19), the current uncontrolled outbreak of infectious disease, has caused significant challenges throughout the world. A reliable rapid diagnostic test for COVID-19 is demanded worldwide. The real-time reverse transcriptase polymerase chain was one of the most quickly established methods in the novel viral pandemic and was considered as the gold standard for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this report, we illustrate our experience of applying a protocol from the Taiwan CDC and achieving assay optimization in the immediate circumstances to meet the urgent medical and public health needs.", "title": "Optimization of the CDC Protocol of Molecular Diagnosis of COVID-19 for Timely Diagnosis", "pid": "wt5o9sgm", "bm25_score": 215.36624145507812}, {"text": "Increasing evidence indicates immunity against severe acute respiratory syndrome coronavirus 2 (sars-cov-2) after covid-19, but it remains unclear for how long the protection remains. Serology testing seems to have a higher sensitivity than molecular diagnostics from 8 days after onset of symtoms, and should be part of risk assessment and epidemiological studies of COVID-19. The performance of commercial serological point-of-care (POC) lateral flow tests are highly manufacturer-dependant. Low sensitivity increases the risk of false negative results and could result in unnecessary quarantine of test persons with developed antibodies. Low specificity increases the risk of false positive results and could lead to false assumptions of immunity. Carefully selected serological POC tests for sars-cov-2 can be used in large scale testing but should only be used by licensed medical staff able to understand their limitations and interpret the results.", "title": "[Rapid point-of-care serology testing for sars-cov-2].", "pid": "91872v0l", "bm25_score": 215.36422729492188}, {"text": "An epidemic caused by an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China in December 2019 has since rapidly spread internationally, requiring urgent response from the clinical diagnostics community. We present a detailed overview of the clinical validation and implementation of the first laboratory-developed real-time reverse-transcription-PCR (rRT-PCR) test offered in the NewYork-Presbyterian Hospital system following the emergency use authority (EUA) guidance issued by the US Food and Drug Administration. Validation was performed on nasopharyngeal and sputum specimens (n=124) using newly designed dual-target rRT-PCR (altona RealStar SARS-CoV-2 Reagent) for detecting of SARS-CoV-2 in upper respiratory and lower respiratory tract specimens, including bronchoalveolar lavage and tracheal aspirates. Accuracy testing demonstrated excellent assay agreement between expected and observed values. The limit of detection (LOD) was 2.7 and 23.0 gene copies/reaction for nasopharyngeal and sputum specimens, respectively. Retrospective analysis of 1,694 tests from 1,571 patients revealed increased positivity in older patients and males compared to females, and an increasing positivity rate from approximately 20% at the start of testing to 50% at the end of testing three weeks later. Our findings demonstrate that the assay accurately and sensitively identifies SARS-CoV-2 in multiple specimen types in the clinical setting and summarizes clinical data from early in the epidemic in New York City.", "title": "Rapid implementation of SARS-CoV-2 emergency use authorization RT-PCR testing and experience at an academic medical institution", "pid": "mb784dam", "bm25_score": 215.36007690429688}, {"text": "The SARS-CoV-2 pandemic has evolved far more aggressively in countries lacking a robust testing strategy to identify infected individuals. Given the global demand for fast and reliable diagnosis to determine the carrier individuals, a stock-out scenario for a number of essential reagents/kits used along the diagnostic process has been foreseen by many organizations. Having identified the RNA extraction step as one of the key bottlenecks, we tested several alternatives that avoid the use of commercial kits for this step. The analysis showed that 2-propanol precipitation of the viral RNA, followed by one-step RT-qPCR results in a sensitivity and specificity comparable to that provided currently by automatized systems such as the COBAS 6800 system. Therefore, this simple protocol allows SARS-CoV-2 testing independently of commercial kit providers in a time and cost-effective manner. It can be readily implemented in research and/or diagnostic laboratories worldwide, provided that patient confidentiality and researcher safety are ensured. Scaling up the testing capabilities of hospitals and research facilities will identify larger numbers of infected individuals to paint a clear picture of the COVID-19 prevalence, a pre-requisite for informed policy decision making.", "title": "Fast SARS-CoV-2 detection protocol based on RNA precipitation and RT-qPCR in nasopharyngeal swab samples", "pid": "aa14tona", "bm25_score": 215.34552001953125}, {"text": "In the context of the Covid-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. We compared the performance of four rapid antigen detection tests for SARS-CoV-2 in respiratory samples. Immunochromatographic SARS-CoV-2 assays from RapiGEN, Liming bio, Savant, and Bioeasy were evaluated using universal transport medium containing naso-oropharyngeal swabs from suspected Covid-19 cases. The diagnostic accuracy was determined in comparison to SARS-CoV-2 RT-PCR. A total of 111 samples were included; 80 were RT-PCR positive. Median patients’ age was 40 years, 55% were female, and 88% presented within the first week after symptom onset. The evaluation of the Liming bio assay was discontinued due to insufficient performance. The overall sensitivity values of RapiGEN, Liming bio, and Bioeasy tests were 62.0% (CI95% 51.0–71.9), 16.7% (CI95% 10.0–26.5), and 85.0% (CI95% 75.6–91.2), respectively, with specificities of 100%. Sensitivity was significantly higher in samples with high viral loads (RapiGEN, 84.9%; Bioeasy, 100%). The study highlighted the significant heterogeneity of test performance among evaluated assays, which might have been influenced by the use of a non-validated sample material. The high sensitivity of some tests demonstrated that rapid antigen detection has the potential to serve as an alternative diagnostic method, especially in patients presenting with high viral loads in early phases of infection. This is particularly important in situations with limited access to RT-PCR or prolonged turnaround time. Further comparative evaluations are necessary to select products with high performance among the growing market of diagnostic tests for SARS-CoV-2.", "title": "Head-to-head comparison of four antigen-based rapid detection tests for the diagnosis of SARS-CoV-2 in respiratory samples", "pid": "3taykdr1", "bm25_score": 215.3311004638672}, {"text": "The ongoing novel coronavirus (COVID-19) outbreak as a global public health emergency infected by SARC-CoV-2 has caused devastating loss around the world. Currently, a lot of diagnosis methods have been used to detect the infection. The nucleic acid (NA) testing is reported to be the clinical standard for COVID-19 infection. Evidence shows that a faster and more convenient method to detect in the early phase will control the spreading of SARS-CoV-2. Here, we propose a method to detect SARC-Cov-2 infection within two hours combined with Loop-mediated Isothermal Amplification (LAMP) reaction and nanopore Flongle workflow. In this approach, RNA reverse transcription and nucleic acid amplification reaction with one step in 30 minutes at 60-65°C constant temperature environment, nanopore Flongle rapidly adapter ligated within 10 minutes. Flongle flow cell sequencing and analysis in real-time. This method described here has the advantages of rapid amplification, convenient operation and real-time detection which is the most important for rapid and reliable clinical diagnosis of COVID-19. Moreover, this approach not only can be used for SARS-CoV-2 detection but also can be extended to other respiratory viruses and pathogens.", "title": "Rapid detection of SARS-CoV-2 and other respiratory viruses by using LAMP method with Nanopore Flongle workflow", "pid": "pp0vlaye", "bm25_score": 215.32725524902344}, {"text": "Pooling of samples can increase lab capacity when using Polymerase chain reaction (PCR) to detect infections such as COVID-However, pool testing is typically performed via an adaptive testing strategy which requires a feedback loop in the lab and at least two PCR runs to confirm positive results. This can cost precious time. We discuss a non-adaptive testing method where each sample is distributed in a prescribed manner over several pools, and which yields reliable results after one round of testing. More precisely, assuming knowledge about the overall infection incidence rate, we calculate explicit error bounds on the number of false positives which scale very favourably with pool size and sample multiplicity. This allows for hugely streamlined PCR testing and cuts in detection times for a large-scale testing scenario. A viable consequence of this method could be real-time screening of entire communities, frontline healthcare workers and international flight passengers, for example, using the PCR machines currently in operation.", "title": "Rapid, Large-Scale, and Effective Detection of COVID-19 Via Non-Adaptive Testing", "pid": "twk5kvd3", "bm25_score": 215.32546997070312}, {"text": "As the COVID-19 outbreak has evolved in each country, the approach to the laboratory assessment of SARS-CoV-2 infection has had to evolve as well. This review addresses the evolving approach to the laboratory assessment of COVID-19 and discusses how algorithms for testing have been driven, in part, by the demand for testing overwhelming the capacity to accomplish such testing. This review focused on testing in the United States as this testing is evolving whereas in China and other countries such as South Korea testing is widely available and includes both molecular testing for SARS-CoV-2 as well as serological testing using both ELISA methodology and lateral flow immunoassay methodology. Although commercial testing systems are becoming available, there will likely be insufficient numbers of such tests due to high demand. Serological testing will be the next testing issue as the COVID-19 begins to subside. This will allow immunity testing as well as will allow the parameters of the COVID-19 outbreak to be defined. This article is protected by copyright. All rights reserved.", "title": "An Evolving Approach to the Laboratory Assessment of COVID-19", "pid": "k0f8jj0c", "bm25_score": 215.3167724609375}, {"text": "Rapid, reliable, and widespread testing is required to curtail the ongoing COVID-19 pandemic. Current gold standard diagnostic assays are hampered by supply shortages in critical reagents including nasal swabs, RNA extraction kits, personal protective equipment (PPE), instrumentation, and labor. Here we present an approach to overcome these challenges with the development of a rapid colorimetric assay using reverse-transcription loop-mediated isothermal amplification (RT-LAMP) optimized on human saliva samples without an RNA purification step. We describe our optimizations of the LAMP reaction and saliva pre-treatment protocols that enabled rapid and sensitive detection of < 10(2) viral genomes per reaction in contrived saliva controls. We also observed high performance of this assay on a limited number of clinical saliva samples. While thorough validation on additional clinical samples will be needed before such an assay can be widely used, these preliminary results demonstrate a promising approach to overcome the current bottlenecks limiting widespread testing.", "title": "Rapid and extraction-free detection of SARS-CoV-2 from saliva with colorimetric LAMP", "pid": "yvmrkl5s", "bm25_score": 215.2989501953125}, {"text": "Following the first reports of coronavirus disease-19 (COVID-19) by China to the World Health Organization (WHO) on 31st December 2019, more than 4,302,774 novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) cases have been reported by authorities in 212 countries and territories by 12th May 2020. The outbreak and spread of COVID-19 worldwide, highlights the critical need for developing rapid and accurate diagnostic testing methods for emerging human coronavirus (CoV) infections. Testing is crucial to track the spread of disease during a pandemic, and to swiftly permit public health interventions including isolation, quarantine, and appropriate clinical management of afflicted individuals. The key components of viral diagnostic tests are (1) collection of the appropriate sample (blood, nasal swab, and throat swab), (2) availability of the genetic and proteomic sequences of the novel virus for analysis, and (3) rapid and accurate laboratory testing methods. The current gold standard for the molecular diagnosis of SARS-CoV-2 infection is the real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for the qualitative and quantitative detection of viral nucleic acids. Other relevant laboratory methods include enzyme-linked immunoassays (EIA) for viral antibody and antigen detection, and serum viral neutralization (SVN) assays for antibody neutralization determination. The challenges faced in developing a diagnostic test for a novel pathogen are the ability to measure low viral loads for early detection, to provide low or no cross-reactivity with other viral strains and to deliver results rapidly. Several point-of-care molecular devices are currently being integrated for fast and accurate diagnosis of SARS-CoV-2 infections. This review discusses the current laboratory methods available to test for coronaviruses by focusing on the present COVID-19 outbreak.", "title": "Laboratory Testing Methods for Novel Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)", "pid": "401tisd3", "bm25_score": 215.29794311523438}, {"text": "We present here INSIGHT (Isothermal NASBA-Sequencing based hIGH-througput Test): a two-stage COVID-19 testing strategy, using a combination of an isothermal NASBA reaction and next generation sequencing. From commercially acquired human saliva with spiked-in viral RNA as input, the first stage employs isothermal amplification of viral RNA to give a rapid result in one to two hours, using either fluorescence detection or a dipstick readout, whilst simultaneously incorporating sample-specific barcodes into the amplification product. In the first stage, fluorescent viral RNA detection can be consistently achieved at 10-100 copies per 20 µl reaction. The second stage pools post-amplification barcoded products from multiple samples for scalable sequencing that could be centralised, to further improve the accuracy of the test in a massively parallel way. Our two-stage testing strategy is suitable for further development into a home-based or point-of-care assay, and is potentially scalable to population level. IMPORTANT This protocol has not been validated on patient samples and should not be used for clinical diagnosis without further validation and certification. ***This is ongoing research to develop a testing strategy for the SARS-CoV-2 virus. The Wellcome Sanger Institute is not in a position to develop this into a commercial product, but would be open to discussions with third parties about how they could develop this further to achieve the societal benefits of this work.***", "title": "INSIGHT: a scalable isothermal NASBA-based platform for COVID-19 diagnosis", "pid": "66192ajk", "bm25_score": 215.29478454589844}, {"text": "The current coronavirus disease 2019 (COVID-19) pandemic is largely driven by community transmission, after 2019 novel Coronavirus (2019-nCoV or SARS-CoV-2) crosses the borders. To stop the spread, rapid testing is required at community clinics and hospitals. These rapid tests should be comparable with the standard PCR technology. Isothermal amplification technology provides an excellent alternative that is highly amenable to resource limited settings, where expertise and infrastructure to support PCR are not available. In this review, we provide a brief description of isothermal amplification technology, its potential and the gaps that need to be considered for SARS-CoV-2 detection. Among this emerging technology, loop-mediated amplification (LAMP), recombinase polymerase amplification (RPA) and Nicking enzyme-assisted reaction (NEAR) technologies have been identified as potential platforms that could be implemented at community level, without samples referral to a centralized laboratory and prolonged turnaround time associated with the standard COVID-19 RT-PCR test. LAMP, for example, has recently been shown to be comparable with PCR and could be performed in less than 30 min by non-laboratory staff, without RNA extractions commonly associated with PCR. Interestingly, NEAR (ID NOW™ COVID-19 (Abbott, IL, USA) was able to detect the virus in 5 min. More so, isothermal platforms are cost effective and could easily be scaled up to resource limited settings. Diagnostics developers, scientific community and commercial companies could consider this alternative method to help stop the spread of COVID-19.", "title": "COVID-19 Infection Diagnosis: Potential Impact of Isothermal Amplification Technology to Reduce Community Transmission of SARS-CoV-2", "pid": "gi1dlail", "bm25_score": 215.2869873046875}, {"text": "The world needs mass at-home serological testing for antibodies elicited by SARS-CoV-2, and rapid and frequent point-of-care testing for the presence of the virus’ RNA in selected populations.", "title": "Humanity tested", "pid": "9mvk86q6", "bm25_score": 215.28237915039062}, {"text": "In the last few months, an unprecedented number of laboratory tests for COVID‐19 have been developed at a remarkable speed. With the rapid adoption of these tests into clinical practice, combined with the widespread publicity they received, questions arose related to the different types of tests, their utility, performance, and regulatory approval status. The aim of this publication is to provide a general landscape of laboratory testing for COVID‐19 and offer a historical and regulatory perspective associated with them. Specifically, we aim to elaborate on the regulatory complexities of diagnostic testing in the U.S. and its implications to the present outbreak, as well as provide a synopsis of laboratory tests that have been developed for COVID‐19. We will first address the detection of Sars‐Cov‐2 directly by either nucleic acid amplification tests (NAAT) or by the detection of the viral protein for active infections. Subsequently, we will provide an overview of serological tests that can aid not only in diagnosis but additionally help to identify prior infections and potential immunity.", "title": "Testing for SARS‐CoV‐2: the day the world turned its attention to the clinical laboratory", "pid": "x7v4y1ru", "bm25_score": 215.28170776367188}, {"text": "BACKGROUND: In January 2020 reports of unidentified severe respiratory illness were described in Wuhan, China. A rapid expansion in cases affecting most countries around the globe led to major changes in the way people live their daily lives. In the United Kingdom, the Department of Health and Social Care directed healthcare providers to establish additional resources to manage the anticipated surge in cases that could overwhelm the health services. A priority area was testing for SARS-CoV-2 RNA and its detection by qualitative RT-PCR. DESIGN: A laboratory workflow twinning research environment with clinical laboratory capabilities was implemented and validated in the University of Birmingham within 4 days of the project initiation. The diagnostic capability was centred on an IVD CE-marked RT-PCR kit and designed to provide surge capacity to the nearby Queen Elizabeth Hospital. The service was initially tasked with testing healthcare workers (HCW) using throat swabs, and subsequently the process investigated the utility of using saliva as an alternative sample type. RESULTS: Between the 8th April 2020 and the 30th April 2020, the laboratory tested a total of 1282 HCW for SARS-CoV-2 RNA in throat swabs. RNA was detected in 54 % of those who reported symptoms compatible with COVID-19, but in only 4% who were asymptomatic. CONCLUSION: This capability was established rapidly and utilised a cold-chain free methodology, applicable to a wide range of settings, and which can provide surge capacity and support to clinical laboratories facing increasing pressure during periods of national crisis.", "title": "Rapid implementation and validation of a cold-chain free SARS-CoV-2 diagnostic testing workflow to support surge capacity", "pid": "vi63t8mo", "bm25_score": 215.2754364013672}, {"text": "Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcription-polymerase chain reactions (rRT-PCR) can detect SARS-COV-2 by targeting open reading frame-1 antibodies (ORF1ab), envelope protein, nucleocapsid protein, RNA-dependent RNA polymerase genes, and the N1, N2, and N3 (3N) target genes. Therefore, rRT-PCR remains the primary method of diagnosing SARS-CoV-2 despite being limited by false-negative results, long turnaround, complex protocols, and a need for skilled personnel. Serological diagnosis of coronavirus disease 2019 (COVID-19) is simple and does not require complex techniques and equipment, rendering it suitable for rapid detection and massive screening. However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. Balancing the increased use of laboratory tests, risk of testing errors, need for tests, burden on healthcare systems, benefits of early diagnosis, and risk of unnecessary exposure is a significant and persistent challenge in diagnosing COVID-19.", "title": "In vitro diagnostics of coronavirus disease 2019: Technologies and application", "pid": "r1yf75bo", "bm25_score": 215.2573699951172}, {"text": "The recent outbreak of the novel coronavirus SARS-CoV-2, which causes COVID-19, can be diagnosed using RT-qPCR, but inadequate access to reagents and equipment has slowed disease detection and impeded efforts to mitigate viral spread. Alternative approaches based on combinations of isothermal amplification and CRISPR-mediated detection, such as the SHERLOCK (Specific High Sensitivity Enzymatic Reporter UnLOCKing) technique, offer reduced dependence on RT-qPCR equipment, but previously reported methods required multiple fluid handling steps, complicating their deployment outside clinical labs. Here we developed a simple test chemistry called STOP (SHERLOCK Testing in One Pot) for detecting SARS-CoV-2 in one hour that is suitable for point-of-care use. This simplified test, STOPCovid, provides sensitivity comparable to RT-qPCR-based SARS-CoV-2 tests and has a limit of detection of 100 copies of viral genome input in saliva or nasopharyngeal swabs per reaction. Using lateral flow readout, the test returns result in 70 minutes, and using fluorescence readout, the test returns result in 40 minutes. Moreover, we validated STOPCovid using nasopharyngeal swabs from COVID-19 patients and were able to correctly diagnose 12 positive and 5 negative patients out of 3 replicates. We envision that implementation of STOPCovid will significantly aid “test-trace-isolate” efforts, especially in low-resource settings, which will be critical for long-term public health safety and effective reopening of the society.", "title": "Point-of-care testing for COVID-19 using SHERLOCK diagnostics", "pid": "m9llic1q", "bm25_score": 215.2384796142578}, {"text": "The previous outbreaks of SARS-CoV and MERS-CoV have led researchers to study the role of diagnostics in impediment of further spread and transmission. With the recent emergence of the novel SARS-CoV-2, the availability of rapid, sensitive, and reliable diagnostic methods is essential for disease control. Hence, we have developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the specific detection of SARS-CoV-2. The primer sets for RT-LAMP assay were designed to target the nucleocapsid gene of the viral RNA, and displayed a detection limit of 102 RNA copies close to that of qRT-PCR. Notably, the assay has exhibited a rapid detection span of 30†min combined with the colorimetric visualization. This test can detect specifically viral RNAs of the SARS-CoV-2 with no cross-reactivity to related coronaviruses, such as HCoV-229E, HCoV-NL63, HCoV-OC43, and MERS-CoV as well as human infectious influenza viruses (type B, H1N1pdm, H3N2, H5N1, H5N6, H5N8, and H7N9), and other respiratory disease-causing viruses (RSVA, RSVB, ADV, PIV, MPV, and HRV). Furthermore, the developed RT-LAMP assay has been evaluated using specimens collected from COVID-19 patients that exhibited high agreement to the qRT-PCR. Our RT-LAMP assay is simple to perform, less expensive, time-efficient, and can be used in clinical laboratories for preliminary detection of SARS-CoV-2 in suspected patients. In addition to the high sensitivity and specificity, this isothermal amplification conjugated with a single-tube colorimetric detection method may contribute to the public health responses and disease control, especially in the areas with limited laboratory capacities.", "title": "Development of a reverse transcription-loop-mediated isothermal amplification as a rapid early-detection method for novel SARS-CoV-2", "pid": "77jpm4o0", "bm25_score": 215.2377471923828}, {"text": "Diagnostic testing to identify persons infected with severe acute respiratory syndrome–related coronavirus-2 (SARS–CoV-2) infection is central to control the global pandemic of COVID-19 that began in late 2019. In a few countries, the use of diagnostic testing on a massive scale has been a cornerstone of successful containment strategies. In contrast, the United States, hampered by limited testing capacity, has prioritized testing for specific groups of persons. Real-time reverse transcriptase polymerase chain reaction–based assays performed in a laboratory on respiratory specimens are the reference standard for COVID-19 diagnostics. However, point-of-care technologies and serologic immunoassays are rapidly emerging. Although excellent tools exist for the diagnosis of symptomatic patients in well-equipped laboratories, important gaps remain in screening asymptomatic persons in the incubation phase, as well as in the accurate determination of live viral shedding during convalescence to inform decisions to end isolation. Many affluent countries have encountered challenges in test delivery and specimen collection that have inhibited rapid increases in testing capacity. These challenges may be even greater in low-resource settings. Urgent clinical and public health needs currently drive an unprecedented global effort to increase testing capacity for SARS–CoV-2 infection. Here, the authors review the current array of tests for SARS–CoV-2, highlight gaps in current diagnostic capacity, and propose potential solutions.", "title": "Diagnostic Testing for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review", "pid": "ho5n7n90", "bm25_score": 215.2219696044922}, {"text": "The previous outbreaks of SARS-CoV and MERS-CoV have led researchers to study the role of diagnostics in impediment of further spread and transmission. With the recent emergence of the novel SARS-CoV-2, the availability of rapid, sensitive, and reliable diagnostic methods is essential for disease control. Hence, we have developed a reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for the specific detection of SARS-CoV-2. The primer sets for RT-LAMP assay were designed to target the nucleocapsid gene of the viral RNA, and displayed a detection limit of 10(2) RNA copies close to that of qRT-PCR. Notably, the assay has exhibited a rapid detection span of 30 min combined with the colorimetric visualization. This test can detect specifically viral RNAs of the SARS-CoV-2 with no cross-reactivity to related coronaviruses, such as HCoV-229E, HCoV-NL63, HCoV-OC43, and MERS-CoV as well as human infectious influenza viruses (type B, H1N1pdm, H3N2, H5N1, H5N6, H5N8, and H7N9), and other respiratory disease-causing viruses (RSVA, RSVB, ADV, PIV, MPV, and HRV). Furthermore, the developed RT-LAMP assay has been evaluated using specimens collected from COVID-19 patients that exhibited high agreement to the qRT-PCR. Our RT-LAMP assay is simple to perform, less expensive, time-efficient, and can be used in clinical laboratories for preliminary detection of SARS-CoV-2 in suspected patients. In addition to the high sensitivity and specificity, this isothermal amplification conjugated with a single-tube colorimetric detection method may contribute to the public health responses and disease control, especially in the areas with limited laboratory capacities.", "title": "Development of a reverse transcription-loop-mediated isothermal amplification as a rapid early-detection method for novel SARS-CoV-2", "pid": "sdde8bgd", "bm25_score": 215.21987915039062}, {"text": "The recent outbreak of a novel coronavirus SARS-CoV-2 (also known as 2019-nCoV) threatens global health, given serious cause for concern. SARS-CoV-2 is a human-to-human pathogen that caused fever, severe respiratory disease and pneumonia (known as COVID-19). By press time, more than 70,000 infected people had been confirmed worldwide. SARS-CoV-2 is very similar to the severe acute respiratory syndrome (SARS) coronavirus broke out 17 years ago. However, it has increased transmissibility as compared with the SARS-CoV, e.g. very often infected individuals without any symptoms could still transfer the virus to others. It is thus urgent to develop a rapid, accurate and onsite diagnosis methods in order to effectively identify these early infects, treat them on time and control the disease spreading. Here we developed an isothermal LAMP based method-iLACO (isothermal LAMP based method for COVID-19) to amplify a fragment of the ORF1ab gene using 6 primers. We assured the species-specificity of iLACO by comparing the sequences of 11 related viruses by BLAST (including 7 similar coronaviruses, 2 influenza viruses and 2 normal coronaviruses). The sensitivity is comparable to Taqman based qPCR detection method, detecting synthesized RNA equivalent to 10 copies of 2019-nCoV virus. Reaction time varied from 15-40 minutes, depending on the loading of virus in the collected samples. The accuracy, simplicity and versatility of the new developed method suggests that iLACO assays can be conveniently applied with for 2019-nCoV threat control, even in those cases where specialized molecular biology equipment is not available.", "title": "Rapid colorimetric detection of COVID-19 coronavirus using a reverse tran-scriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic plat-form: iLACO", "pid": "s7uqawbd", "bm25_score": 215.2191162109375}, {"text": "OBJECTIVES: To assess the diagnostic performance of rapid lateral flow immunochromatographic assays (LFAs) compared to an enzyme-linked immunosorbent assay (ELISA) and nucleic acid amplification tests (NATs) in suspected coronavirus disease 2019 (COVID-19) patients. METHODS: Patients presenting to a Dutch teaching hospital were eligible between March 17 and April 10, 2020, when they had respiratory symptoms that were suspected for COVID-19. The performances of six different LFAs were evaluated in plasma samples obtained on corresponding respiratory sample dates of NATs testing. Subsequently, the best performing LFA was evaluated in 228 patients and in 50 sera of a historical patient control group. RESULTS: In the pilot analysis sensitivity characteristics of LFA were heterogenous ranging from 2/20 (10%; 95% confidence interval (CI) 0-23) to 11/20 (55%; 95% CI 33-77). In the total cohort, Orient Gene Biotech COVID-19 IgG/IgM Rapid Test LFA had a sensitivity of 43/99 (43%; 95% CI 34-53) and specificity of 126/129 (98%; 95% CI 95-100). Sensitivity increased to 31/52 (60%; 95% CI 46-73) in patients with at least seven days of symptoms, and to 21/33 (64%; 95% CI 47-80) in patients with C-reactive protein (CRP) >100 mg/L. Sensitivity and specificity of Wantai SARS-CoV-2 Ab ELISA was 59/95 (62%; 95% CI 52-72) and 125/128 (98%; 95% CI 95-100) in all patients, respectively, but sensitivity increased to 38/48 (79%; 95% CI 68-91) in patients with at least seven days of symptoms. CONCLUSIONS: There is large variability in diagnostic test performance between rapid LFAs, but overall limited sensitivity and high specificity in acutely admitted patients. Sensitivity improved in patients with longer existing symptoms or high CRP. LFAs should only be considered as additional triage tools when these may lead to the improvement of hospital logistics.", "title": "Comparison of diagnostic accuracies of rapid serological tests and ELISA to molecular diagnostics in patients with suspected COVID-19 presenting to the hospital", "pid": "h7ikjgic", "bm25_score": 215.20803833007812}, {"text": "OBJECTIVES: To assess the diagnostic performance of rapid lateral flow immunochromatographic assays (LFAs) compared with an ELISA and nucleic acid amplification tests (NATs) in individuals with suspected coronavirus disease 2019 (COVID-19). METHODS: Patients presenting to a Dutch teaching hospital were eligible between 17 March and 10 April 2020, when they had respiratory symptoms that were suspected for COVID-19. The performances of six different LFAs were evaluated in plasma samples obtained on corresponding respiratory sample dates of NATs testing. Subsequently, the best performing LFA was evaluated in 228 patients and in 50 sera of a historical patient control group. RESULTS: In the pilot analysis, sensitivity characteristics of LFA were heterogeneous, ranging from 2/20 (10%; 95% CI 0%-23%) to 11/20 (55%; 95% CI 33%-77%). In the total cohort, Orient Gene Biotech COVID-19 IgG/IgM Rapid Test LFA had a sensitivity of 43/99 (43%; 95% CI 34%-53%) and specificity of 126/129 (98%; 95% CI 95%-100%). Sensitivity increased to 31/52 (60%; 95% CI 46%-73%) in patients with at least 7 days of symptoms, and to 21/33 (64%; 95% CI 47%-80%) in patients with C-reactive protein (CRP) &#8805;100 mg/L. Sensitivity and specificity of Wantai SARS-CoV-2 Ab ELISA was 59/95 (62%; 95% CI 52%-72%) and 125/128 (98%; 95% CI 95%-100%) in all patients, respectively, but sensitivity increased to 38/48 (79%; 95% CI 68%-91%) in patients with at least 7 days of symptoms. CONCLUSIONS: There is large variability in diagnostic test performance between rapid LFAs, but overall limited sensitivity and high specificity in acutely admitted patients. Sensitivity improved in patients with longer existing symptoms or high CRP. LFAs should only be considered as additional triage tools when these may lead to the improvement of hospital logistics.", "title": "Comparison of diagnostic accuracies of rapid serological tests and ELISA to molecular diagnostics in patients with suspected coronavirus disease 2019 presenting to the hospital", "pid": "156rsxrl", "bm25_score": 215.2070770263672}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for different types of diagnostics, comparative validation of new tests, faster approval by federal agencies, and rapid production of test kits to meet global demands. In this Perspective, we discuss the utility and challenges of current diagnostics for COVID-19.", "title": "COVID-19 diagnostics in context.", "pid": "n9ju3flv", "bm25_score": 215.19854736328125}, {"text": "COVID-19 pandemic is a serious global health issue today due to the rapid human to human transmission of SARS-CoV-2, a new type of coronavirus that causes fatal pneumonia. SARS -CoV-2 has a faster rate of transmission than other coronaviruses such as SARS and MERS and until now there are no approved specific drugs or vaccines for treatment. Thus, early diagnosis is crucial to prevent the extensive spread of the disease. The reverse transcription-polymerase chain reaction (RT-PCR) is the most routinely used method until now to detect SARS-CoV-2 infections. However, several other faster and accurate assays are being developed for the diagnosis of COVID-19 aiming to control the spread of infection through the identification of patients and immediate isolation. In this review, we will discuss the various detection methods of the SARS-CoV-2 virus including the recent developments in immunological assays, amplification techniques as well as biosensors.", "title": "Diagnostic techniques for COVID-19 and new developments", "pid": "0oak9ggm", "bm25_score": 215.19808959960938}, {"text": "The current COVID-19 pandemic presents a serious public health crisis, and a better understanding of the scope and spread of the virus would be aided by more widespread testing. Nucleic-acid based tests currently offer the most sensitive and early detection of COVID-19. However, the \"gold standard\" test pioneered by the United States Center for Disease Control & Prevention, takes several hours to complete and requires extensive human labor, materials such as RNA extraction kits that could become in short supply and relatively scarce qPCR machines. It is clear that a huge effort needs to be made to scale up current COVID-19 testing by orders of magnitude. There is thus a pressing need to evaluate alternative protocols, reagents, and approaches to allow nucleic-acid testing to continue in the face of these potential shortages. There has been a tremendous explosion in the number of papers written within the first weeks of the pandemic evaluating potential advances, comparable reagents, and alternatives to the \"gold-standard\" CDC RT-PCR test. Here we present a collection of these recent advances in COVID-19 nucleic acid testing, including both peer-reviewed and preprint articles. Due to the rapid developments during this crisis, we have included as many publications as possible, but many of the cited sources have not yet been peer-reviewed, so we urge researchers to further validate results in their own labs. We hope that this review can urgently consolidate and disseminate information to aid researchers in designing and implementing optimized COVID-19 testing protocols to increase the availability, accuracy, and speed of widespread COVID-19 testing.", "title": "Overcoming the bottleneck to widespread testing: A rapid review of nucleic acid testing approaches for COVID-19 detection.", "pid": "b3wp314u", "bm25_score": 215.18478393554688}, {"text": "The current COVID-19 pandemic presents a serious public health crisis, and a better understanding of the scope and spread of the virus would be aided by more widespread testing. Nucleic-acid-based tests currently offer the most sensitive and early detection of COVID-19. However, the \"gold standard\" test pioneered by the U.S. Centers for Disease Control and Prevention takes several hours to complete and requires extensive human labor, materials such as RNA extraction kits that could become in short supply, and relatively scarce qPCR machines. It is clear that a huge effort needs to be made to scale up current COVID-19 testing by orders of magnitude. There is thus a pressing need to evaluate alternative protocols, reagents, and approaches to allow nucleic-acid testing to continue in the face of these potential shortages. There has been a tremendous explosion in the number of papers written within the first weeks of the pandemic evaluating potential advances, comparable reagents, and alternatives to the \"gold-standard\" CDC RT-PCR test. Here we present a collection of these recent advances in COVID-19 nucleic acid testing, including both peer-reviewed and preprint articles. Due to the rapid developments during this crisis, we have included as many publications as possible, but many of the cited sources have not yet been peer-reviewed, so we urge researchers to further validate results in their own laboratories. We hope that this review can urgently consolidate and disseminate information to aid researchers in designing and implementing optimized COVID-19 testing protocols to increase the availability, accuracy, and speed of widespread COVID-19 testing.", "title": "Overcoming the bottleneck to widespread testing: a rapid review of nucleic acid testing approaches for COVID-19 detection", "pid": "opdva99w", "bm25_score": 215.1824493408203}, {"text": "The COVID-19 pandemic provides an urgent example where a gap exists between availability of state-of-the-art diagnostics and current needs. As assay details and primer sequences become widely known, many laboratories could perform diagnostic tests using methods such as RT-PCR or isothermal RT-LAMP amplification. A key advantage of RT-LAMP based approaches compared to RT-PCR is that RT-LAMP is known to be robust in detecting targets from unprocessed samples. In addition, RT-LAMP assays are performed at a constant temperature enabling speed, simplicity, and point-of-use testing. Here, we provide the details of an RT-LAMP isothermal assay for the detection of SARS-CoV-2 virus with performance comparable to currently approved tests using RT-PCR. We characterize the assay by introducing swabs in virus spiked synthetic nasal fluids, moving the swab to viral transport medium (VTM), and using a volume of that VTM for performing the amplification without an RNA extraction kit. The assay has a Limit-of-Detection (LOD) of 50 RNA copies/μL in the VTM solution within 20 minutes, and LOD of 5000 RNA copies/μL in the nasal solution. Additionally, we show the utility of this assay for real-time point-of-use testing by demonstrating detection of SARS-CoV-2 virus in less than 40 minutes using an additively manufactured cartridge and a smartphone-based reader. Finally, we explore the speed and cost advantages by comparing the required resources and workflows with RT-PCR. This work could accelerate the development and availability of SARS-CoV-2 diagnostics by proving alternatives to conventional laboratory benchtop tests.", "title": "Rapid Isothermal Amplification and Portable Detection System for SARS-CoV-2", "pid": "6epdh88j", "bm25_score": 215.18057250976562}, {"text": "The pandemic of novel coronavirus disease 2019 (COVID-19) seriously threatened the public health all over the world. A colloidal gold immunochromatography assay for IgM/IgG antibodies against the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S1 protein was established to assess its rapid diagnostic value. We first designed and manufactured all contents of the test cassette of SARS-CoV-2 rapid test kit: the colloidal gold-labeled mouse-antihuman lgM/lgG antibody, the recombinant SARS-CoV-2 antigen, the nitrocellulose membrane control line, and specimen diluents. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) assay, colloidal gold immunochromatography assay, serological validation of cross reaction with other common viruses, and clinical validation were performed. The kit was finally evaluated by 75 serum/plasma samples of SARS-CoV-2 infection cases and 139 healthy samples as control, with the result of that the sensitivity, specificity, and accuracy for IgM were 90.67%, 97.84%, and 95.33%, whereas for IgG were 69.33%, 99.28%, and 88.79%, respectively; the combination of IgM and IgG could improve the value: 92.00%, 97.12%, and 95.33%, respectively. Therefore, the rapid detection kit has high sensitivity and specificity, especially for IgM&IgG, showing a critical value in clinical application and epidemic control of COVID-19.", "title": "A new and rapid approach for detecting COVID-19 based on S1 protein fragments.", "pid": "xnj6slby", "bm25_score": 215.17938232421875}, {"text": "Background: The need for a fast and reliable test for COVID-19 is paramount in managing the current pandemic. A cost effective and efficient diagnostic tool as near to the point of care (PoC) as possible would be a game changer in current testing. We tested reverse transcription loop mediated isothermal amplification (RT-LAMP), a method which can produce results in under 30 minutes, alongside standard methods in a real-life clinical setting. Methods: This service improvement project piloted a research RT-LAMP method on nasal and pharyngeal swabs on 21 residents in an NHS Category 1 care home, with two index COVID-19 cases, and compared it to multiplex tandem reverse transcription polymerase chain reaction (RT-PCR). We calculated the sensitivity, specificity, positive and negative predictive values of a single RT-LAMP swab compared to RT-PCR, as per STARD guidelines. We also recorded vital signs of patients to correlate clinical and laboratory information. Findings: The novel method accurately detected 8/10 PCR positive cases and identified a further 3 positive cases. Eight further cases were negative using both methods. Using repeated RT-PCR as a 'gold standard', the sensitivity and specificity of the novel test were 80% and 73% respectively. Positive predictive value (PPV) was 73% and negative predictive value (NPV) was 83%. We also observed hypothermia to be a significant early clinical sign in a number of COVID-19 patients in this setting. Interpretation: RT-LAMP testing for SARS-CoV-2 was found to be promising, fast, easy to use and to work equivalently to RT-PCR methods. Definitive studies to evaluate this method in larger cohorts are underway. RT-LAMP has the potential to transform COVID-19 detection, bringing rapid and accurate testing to the point of care. This method could be deployed in mobile testing units in the community, care homes and hospitals to detect disease early and prevent spread.", "title": "Detecting SARS-CoV-2 at point of care: Preliminary data comparing Loop-mediated isothermal amplification (LAMP) to PCR", "pid": "ymdi0sed", "bm25_score": 215.17776489257812}, {"text": "There is an ongoing worldwide coronavirus disease 2019 (Covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At present, confirmatory diagnosis is by reverse transcription polymerase chain reaction (RT-PCR), typically taking several hours and requiring a molecular laboratory to perform. There is an urgent need for rapid, simplified, and cost-effective detection methods. We have developed and analytically validated a protocol for direct rapid extraction-free PCR (DIRECT-PCR) detection of SARS-CoV-2 without the need for nucleic acid purification. As few as six RNA copies per reaction of viral nucleocapsid (N) gene from respiratory samples such as sputum and nasal exudate can be detected directly using our one-step inhibitor-resistant assay. The performance of this assay was validated on a commercially available portable PCR thermocycler. Viral lysis, reverse transcription, amplification, and detection are achieved in a single-tube homogeneous reaction within 36 min. This minimizes hands-on time, reduces turnaround-time for sample-to-result, and obviates the need for RNA purification reagents. It could enable wider use of Covid-19 testing for diagnosis, screening, and research in countries and regions where laboratory capabilities are limiting.", "title": "Rapid Direct Nucleic Acid Amplification Test without RNA Extraction for SARS-CoV-2 Using a Portable PCR Thermocycler", "pid": "50cir0l6", "bm25_score": 215.15994262695312}, {"text": "There is an ongoing worldwide coronavirus disease 2019 (Covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At present, confirmatory diagnosis is by reverse transcription polymerase chain reaction (RT-PCR), typically taking several hours and requiring a molecular laboratory to perform. There is an urgent need for rapid, simplified, and cost-effective detection methods. We have developed and analytically validated a protocol for direct rapid extraction-free PCR (DIRECT-PCR) detection of SARS-CoV-2 without the need for nucleic acid purification. As few as six RNA copies per reaction of viral nucleocapsid (N) gene from respiratory samples such as sputum and nasal exudate can be detected directly using our one-step inhibitor-resistant assay. The performance of this assay was validated on a commercially available portable PCR thermocycler. Viral lysis, reverse transcription, amplification, and detection are achieved in a single-tube homogeneous reaction within 36 min. This minimizes hands-on time, reduces turnaround-time for sample-to-result, and obviates the need for RNA purification reagents. It could enable wider use of Covid-19 testing for diagnosis, screening, and research in countries and regions where laboratory capabilities are limiting.", "title": "Rapid Direct Nucleic Acid Amplification Test without RNA Extraction for SARS-CoV-2 Using a Portable PCR Thermocycler.", "pid": "p21ysly7", "bm25_score": 215.1560821533203}, {"text": "Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The rapid, sensitive and specific diagnosis of SARS-CoV-2 by fast and unambiguous testing is widely recognized to be critical in responding to the ongoing outbreak. Since the current testing capacity of RT-PCR-based methods is being challenged due to the extraordinary demand of supplies, such as RNA extraction kits and PCR reagents worldwide, alternative and/or complementary testing assays should be developed. Here, we exploit the potential of mass spectrometry technology combined with machine learning algorithms as an alternative fast tool for SARS-CoV-2 detection from nasopharyngeal swabs samples. According to our preliminary results, mass spectrometry-based methods combined with multivariate analysis showed an interesting potential as a complementary diagnostic tool and further steps should be focused on sample preparation protocols and the improvement of the technology applied.", "title": "A Combined approach of MALDI-TOF Mass Spectrometry and multivariate analysis as a potential tool for the detection of SARS-CoV-2 virus in nasopharyngeal swabs", "pid": "28ezisog", "bm25_score": 215.1490020751953}, {"text": "Summary The COVID-19 pandemic is a global public health crisis. Significant delays in the rapid development and distribution of diagnostic testing for SARS-CoV-2 infection have prevented adequate public health management of the disease, impacting the timely mapping of viral spread and the conservation of personal protective equipment. Furthermore, vulnerable populations such as those served by Boston Medical Center (BMC), the largest safety net hospital in New England, represent a high-risk group across multiple dimensions, including a higher prevalence of pre-existing conditions and substance use disorders, lower health maintenance, unstable housing, and a propensity for rapid community spread, highlighting the urgent need for expedient and reliable in-house testing. Here, we report the implementation of a SARS-CoV-2 diagnostic RT-PCR assay with rapid turnaround time enabling more informed decisions with personal and public health ramifications. This work provides a blueprint for academic centers and community hospitals lacking capital-intensive automated laboratory machinery to implement in-house testing.", "title": "Rapid Implementation of a SARS-CoV-2 Diagnostic qRT-PCR Test with Emergency Use Authorization at a Large Academic Safety-Net Hospital", "pid": "kco85lqn", "bm25_score": 215.14773559570312}, {"text": "Diagnosis of persons exposed to/infected with severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) is central to controlling the global pandemic of COVID-19. Currently, several diagnostic modalities are available for COVID-19, each with its own pros and cons. Although there is a global consensus to increase the testing capacity, it is also essential to prudently utilize these tests to control the pandemic. In this paper, we have reviewed the current array of diagnostics for SARS-CoV-2, highlighted the gaps in current diagnostic modalities, and their role in community surveillance and control of the pandemic. The different modalities of COVID-19 diagnosis discussed are: clinical and radiological, molecular based (laboratory based and point-of-care), Immunoassay based (ELISA, rapid antigen and antibody detection tests) and digital diagnostics (artificial intelligence based algorithms). The role of rapid antigen/antibody detection tests in community surveillance has also been described here. These tests can be used to identify asymptomatic persons exposed to the virus and in community based seroprevalence surveys to assess the epidemiology of spread of the virus. However, there are few concerns about the accuracy of these tests which needs to evaluated beforehand.", "title": "COVID 19 diagnostic multiplicity and its role in community surveillance and control.", "pid": "846t2t8g", "bm25_score": 215.14515686035156}, {"text": "The ongoing epidemic of caused by the coronavirus SARS-CoV-2 starting in December 2019 poses a serious public health threat globally. The virus is highly infectious and transmitted mainly through droplets and contacts, and is associated with a high risk of pneumonia. A small number of patients may present with acute respiratory distress syndrome with severe respiratory complications, which can lead even to death. The selection of appropriate detection techniques and methods for accurate and rapid identification of pathogens therefore plays a key role in improving the diagnosis and treatment of the patients and containing the outbreak. In this review, the authors gives an overview of the virus laboratory detection technology, including virus isolation and culture, real-time fluorescent PCR, gene sequencing, serological antibody detection, and the gene editing technology based on CRISPR/Cas13 system. These techniques are expected to provide valuable assistance in controlling the epidemic and new ideas for future researches.", "title": "[Laboratory testing techniques for SARS-CoV-2]", "pid": "945y9kfq", "bm25_score": 215.13973999023438}, {"text": "When South Florida became a hotspot for COVID-19 disease in March 2020, we faced an urgent need to develop test capability to detect SARS-CoV-2 infection. We assembled a transdisciplinary team of knowledgeable and dedicated physicians, scientists, technologists and administrators, who rapidly built a multi-platform, PCR- and serology- based detection program, established drive-thru facilities and drafted and implemented guidelines that enabled efficient testing of our patients and employees. This process was extremely complex, due to the limited availability of needed reagents, but outreach to our research scientists and to multiple diagnostic laboratory companies and government officials enabled us to implement both FDA authorized and laboratory developed testing (LDT)-based testing protocols. We analyzed our workforce needs and created teams of appropriately skilled and certified workers, to safely process patient samples and conduct SARS-CoV-2 testing and contact tracing. We initiated smart test ordering, interfaced all testing platforms with our electronic medical record, and went from zero testing capacity, to testing hundreds of healthcare workers and patients daily, within three weeks. We believe our experience can inform the efforts of others, when faced with a crisis situation.", "title": "A how-to-guide to building a robust SARS-CoV-2 testing program at a university-based health system", "pid": "23q7c15b", "bm25_score": 215.10818481445312}, {"text": "Timely detection and diagnosis are urgently needed to guide epidemiological measures, infection control, antiviral treatment, and vaccine research. In this review, biomarkers/indicators for diagnosis of coronavirus disease 2019 (COVID-19) or detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the environment are summarized and discussed. It is concluded that the detection methods targeting antibodies are not suitable for screening of early and asymptomatic cases since most patients had an antibody response at about 10 days after onset of symptoms. However, antibody detection methods can be combined with quantitative real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) to significantly improve the sensitivity and specificity of diagnosis, and boost vaccine research. Fast, sensitive and accurate detection methods targeting antigens need to be developed urgently. Various specimens for diagnosis or detection are compared and analyzed. Among them, deep throat saliva and induced sputum are desired for RT-qPCR test or other early detection technologies. Chest computerized tomography (CT) scan, RT-qPCR, lateral flow immunochromatographic strip (LFICS) for diagnosis of COVID-19 are summarized and compared. Specially, potential electrochemical biosensor, surface enhanced Raman scattering (SERS)-based biosensor, and artificial intelligence (AI) assisted diagnosis of COVID-19 are emphasized. Finally, some commercialized portable detection device, current challenges and future directions are discussed.", "title": "Diagnostic methods and potential portable biosensors for coronavirus disease 2019", "pid": "9204b4mx", "bm25_score": 215.09796142578125}, {"text": "Background The SARS-CoV-2 virus is responsible for the infectious respiratory disease called COVID-19 (COronaVIrus Disease). In response to the growing COVID-19 pandemic, Rapid Diagnostic Tests (RDTs) have been developed to detect specific antibodies, IgG and IgM, to SARS-CoV-2 virus in human whole blood. We conducted a real-life study to evaluate the performance of two RDTs, COVID-PRESTO and COVID-DUO, compared to the gold standard, RT-PCR. Methods RT-PCR testing of SARS-Cov-2 was performed from nasopharyngeal swab specimens collected in adult patients visiting the infectious disease department at the hospital (Orleans, France). Fingertip whole blood samples taken at different time points after onset of the disease were tested with RDTs. The specificity and sensitivity of the rapid test kits compared to test of reference (RT-PCR) were calculated. Results Among 381 patients with symptoms of COVID-19 who went to the hospital for a diagnostic, 143 patients were RT-PCR negative. Results of test with RDTs were all negative for these patients, indicating a specificity of 100% for both RDTs. In the RT-PCR positive subgroup (n=238), 133 patients were tested with COVID-PRESTO and 129 patients were tested with COVID-DUO (24 patients tested with both). The further the onset of symptoms was from the date of collection, the greater the sensitivity. The sensitivity of COVID-PRESTO test ranged from 10.00% for patients having experienced their 1st symptoms from 0 to 5 days ago to 100% in patients where symptoms had occurred more than 15 days before the date of tests. For COVID-DUO test, the sensitivity ranged from 35.71% [0-5 days] to 100% (> 15 days). Conclusion COVID-PRESTO and DUO RDTs turned out to be very specific (none false positive) and to be sensitive enough after 15 days from onset of symptom. These easy to use IgG/IgM combined test kits are the first ones allowing a screening with capillary blood sample, by typing from a finger prick. These rapid tests are particularly interesting for screening in low resource settings.", "title": "Evaluation of performance of two SARS-CoV-2 Rapid whole-blood finger-stick IgM-IgGCombined Antibody Tests", "pid": "85b4lwh3", "bm25_score": 215.09701538085938}, {"text": "Given the scale and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, known as 2019-nCov) infection (COVID-19), the ongoing global SARS-CoV-2 outbreak has become a huge public health issue. Rapid and precise diagnostic methods are thus immediately needed for diagnosing COVID-19, providing timely treatment and facilitating infection control. A one-step reverse transcription loop-mediated isothermal amplification (RT-LAMP) coupled with nanoparticles-based biosensor (NBS) assay (RT-LAMP-NBS) was successfully established for rapidly and accurately diagnosing COVID-19. A simple equipment (such as heating block) was required for maintaining a constant temperature (63 C) for only 40 min. Using two designed LAMP primer sets, F1ab (opening reading frame 1a/b) and np (nucleoprotein) genes of SARS-CoV-2 were simultaneously amplified and detected in a one-step and single-tube reaction, and the detection results were easily interpreted by NBS. The sensitivity of SARS-CoV-2 RT-LAMP-NBS was 12 copies (each of detection target) per reaction, and no cross-reactivity was generated from non-SARS-CoV-2 templates. Among clinically diagnosed COVID-19 patients, the analytical sensitivity of SARS-CoV-2 was 100% (33/33) in the oropharynx swab samples, and the assay's specificity was also 100% (96/96) when analyzed the clinical samples collected from non-COVID-19 patients. The total diagnosis test from sample collection to result interpretation only takes approximately 1 h. In sum, the RT-LAMP-NBS is a promising tool for diagnosing the current SARS-CoV-2 infection in first line field, public health and clinical laboratories, especially for resource-challenged regions.", "title": "Reverse transcription loop-mediated isothermal amplification combined with nanoparticles-based biosensor for diagnosis of COVID-19", "pid": "fq11rhab", "bm25_score": 215.09518432617188}, {"text": "Diagnostic tests for the coronavirus infection 2019 (COVID-19) are critical for prompt diagnosis, treatment and isolation to break the cycle of transmission A positive real-time reverse-transcriptase polymerase chain reaction (RT-PCR), in conjunction with clinical and epidemiologic data, is the current standard for diagnosis, but several challenges still exist Serological assays help to understand epidemiology better and to evaluate vaccine responses but they are unreliable for diagnosis in the acute phase of illness or assuming protective immunity Serology is gaining attention, mainly because of convalescent plasma gaining importance as treatment for clinically worsening COVID-19 patients We provide a narrative review of peer-reviewed research studies on RT-PCR, serology and antigen immune-assays for COVID-19, briefly describe their lab methods and discuss their limitations for clinical practice", "title": "Laboratory Tests for COVID-19: A Review of Peer-Reviewed Publications and Implications for Clinical UIse", "pid": "hgc4ymok", "bm25_score": 215.09378051757812}, {"text": "The COVID-19 pandemic is a global health emergency characterized by the high rate of transmission and ongoing increase of cases globally. Rapid point-of-care (PoC) diagnostics to detect the causative virus, SARS-CoV-2, are urgently needed to identify and isolate patients, contain its spread and guide clinical management. In this work, we report the development of a rapid PoC diagnostic test (< 20 min) based on reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) and semiconductor technology for the detection of SARS-CoV-2 from extracted RNA samples. The developed LAMP assay was tested on a real-time benchtop instrument (RT-qLAMP) showing a lower limit of detection of 10 RNA copies per reaction. It was validated against 183 clinical samples including 127 positive samples (screened by the CDC RT-qPCR assay). Results showed 90.55% sensitivity and 100% specificity when compared to RT-qPCR and average positive detection times of 15.45 {+/-} 4.43 min. For validating the incorporation of the RT-LAMP assay onto our PoC platform (RT-eLAMP), a subset of samples was tested (n=40), showing average detection times of 12.89 {+/-} 2.59 min for positive samples (n=34), demonstrating a comparable performance to a benchtop commercial instrument. Paired with a smartphone for results visualization and geo-localization, this portable diagnostic platform with secure cloud connectivity will enable real-time case identification and epidemiological surveillance.", "title": "A handheld point-of-care system for rapid detection of SARS-CoV-2 in under 20 minutes", "pid": "m9l8ntur", "bm25_score": 215.08970642089844}, {"text": "The pandemic of novel coronavirus disease 2019 (COVID-19) seriously threatened the public health all over the world. A colloidal gold immunochromatography assay for IgM/IgG antibodies against the receptor-binding domain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) S1 protein was established to assess its rapid diagnostic value. We first designed and manufactured all contents of the test cassette of SARS-CoV-2 rapid test kit: the colloidal gold-labeled mouse-antihuman lgM/lgG antibody, the recombinant SARS-CoV-2 antigen, the nitrocellulose membrane control line, and specimen diluents. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) assay, colloidal gold immunochromatography assay, serological validation of cross reaction with other common viruses, and clinical validation were performed. The kit was finally evaluated by 75 serum/plasma samples of SARS-CoV-2 infection cases and 139 healthy samples as control, with the result of that the sensitivity, specificity, and accuracy for IgM were 90.67%, 97.84%, and 95.33%, whereas for IgG were 69.33%, 99.28%, and 88.79%, respectively; the combination of IgM and IgG could improve the value: 92.00%, 97.12%, and 95.33%, respectively. Therefore, the rapid detection kit has high sensitivity and specificity, especially for IgM&IgG, showing a critical value in clinical application and epidemic control of COVID-19.", "title": "A new and rapid approach for detecting COVID-19 based on S1 protein fragments", "pid": "dt3982ox", "bm25_score": 215.08401489257812}, {"text": "Abstract Laboratory-based diagnostic measures including virological and serological tests are essential for detecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Real-time reverse transcription-polymerase chain reactions (rRT-PCR) can detect SARS-COV-2 by targeting open reading frame-1 antibodies (ORF1ab), envelope protein, nucleocapsid protein, RNA-dependent RNA polymerase genes, and the N1, N2, and N3 (3N) target genes. Therefore, rRT-PCR remains the primary method of diagnosing SARS-CoV-2 despite being limited by false-negative results, long turnaround, complex protocols, and a need for skilled personnel. Serological diagnosis of coronavirus disease 2019 (COVID-19) is simple and does not require complex techniques and equipment, rendering it suitable for rapid detection and massive screening. However, serological tests cannot confirm SARS-CoV-2, and results will be false-negative when antibody concentrations fall below detection limits. Balancing the increased use of laboratory tests, risk of testing errors, need for tests, burden on healthcare systems, benefits of early diagnosis, and risk of unnecessary exposure is a significant and persistent challenge in diagnosing COVID-19.", "title": "In vitro diagnostics of coronavirus disease 2019: technologies and application", "pid": "923jpec0", "bm25_score": 215.08236694335938}, {"text": "The ongoing epidemic of caused by the coronavirus SARS-CoV-2 starting in December 2019 poses a serious public health threat globally. The virus is highly infectious and transmitted mainly through droplets and contacts, and is associated with a high risk of pneumonia. A small number of patients may present with acute respiratory distress syndrome with severe respiratory complications, which can lead even to death. The selection of appropriate detection techniques and methods for accurate and rapid identification of pathogens therefore plays a key role in improving the diagnosis and treatment of the patients and containing the outbreak. In this review, the authors gives an overview of the virus laboratory detection technology, including virus isolation and culture, real-time fluorescent PCR, gene sequencing, serological antibody detection, and the gene editing technology based on CRISPR/Cas13 system. These techniques are expected to provide valuable assistance in controlling the epidemic and new ideas for future researches.", "title": "[Laboratory testing techniques for SARS-CoV-2].", "pid": "xu7ukti9", "bm25_score": 215.0794677734375}, {"text": "The outbreak of COVID-19 has taken a large number of lives since 2019 and the death toll continues to increase all over the world. Recent data reports that about 27 lacs of people are infected with this virus till date and around 2 lacs are dead due to this pandemic. The situation in India is no way better. In India, almost all the states have become victim of this deadly pandemic. Considering the enormous population in India, citizens here are facing acute shortage of detection kits and many are dying even before the knowledge of their infection. The present treatise proposes a molecularly imprinted polymer (MIP) based technique for simple and rapid detection of COVID-19. The technique will be inexpensive, selective, reusable and easy to handle. It has been already implemented in our laboratory in order to detect the taste contributing agents found in tea. This article discusses the detailed methodology and the resultant analytical characteristic of the sensors developed so far and also outlines the suitability of the MIP technique towards fabrication of testing kits for rapid detection of COVID-19.", "title": "A Molecularly Imprinted Polymer-Based Technology for Rapid Testing of COVID-19", "pid": "hmt9ojvc", "bm25_score": 215.0756378173828}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need for different types of diagnostics, comparative validation of new tests, faster approval by federal agencies, and rapid production of test kits to meet global demands. In this Perspective, we discuss the utility and challenges of current diagnostics for COVID-19.", "title": "COVID-19 diagnostics in context", "pid": "rk8pract", "bm25_score": 215.07476806640625}, {"text": "Abstract Recently, a novel coronavirus (SARS-CoV-2; coronavirus disease 2019, COVID-19) has emerged, rapidly spreading and severely straining the capacity of the global health community. Many nations are employing combinations of containment and mitigation strategies, where early diagnosis of COVID-19 is vital in controlling illness progression and limiting viral spread within the population. Thus, rapid and accurate methods of early detection are vital to contain COVID-19 and prevent further spread and predicted subsequent infectious waves of viral recurrence in future. Immediately after its initial characterization, Chinese and American Centers for Disease Control and Prevention (CDCs) rapidly employed molecular assays for detection of COVID-19, mostly employing real-time polymerase chain reaction (RT-PCR) methods. However, such methods require specific expensive items of equipment and highly trained analysts, requiring upwards of 4-8 hours to process. These requirements coupled with associated financial pressures may prevent effective deployment of such diagnostic tests. Loop mediated isothermal amplification(LAMP) is method of nucleic acid amplification which exhibits increased sensitivity and specificity are significantly rapid, and do not require expensive reagents or instruments, which aids in cost reduction for coronavirus detection. Studies have shown the successful application of LAMP assays in various forms to detect coronavirus RNA in patient samples, demonstrating that 1-10 copies of viral RNA template per reaction are sufficient for successful detection, ∼100-fold more sensitive than conventional RT-PCR methods. Importantly, studies have also now demonstrated the effectiveness of LAMP methodology in the detection of SARS-CoV-2 RNA at significantly low levels, particularly following numerous improvements to LAMP assay protocols. We hypothesise that recent advancements in enhanced LAMP protocols assay perhaps represent the best chance for a rapid and robust assay for field diagnosis of COVID-19, without the requirement of specialized equipment and highly trained professionals to interpret results. Herein, we present our arguments with a view to disseminate such findings, to assist the combat of this virus that is proving so devastating. We hope that this strategy could be applied rapidly, and confirmed for viability with clinical samples, before being rolled out for mass-diagnostic testing in these current times.", "title": "Loop mediated isothermal amplification (LAMP) assays as a rapid diagnostic for COVID-19", "pid": "wimsktta", "bm25_score": 215.07151794433594}, {"text": "COVID-19 has resulted in a global health crisis that may become even more acute over the upcoming months. One of the main reasons behind the current rapid growth of COVID-19 in the U.S. population is the limited availability of testing kits and the relatively-high cost of screening tests. In this draft, we demonstrate the effectiveness of group testing (pooling) ideas to accelerate testing for COVID-19. This draft is semi-tutorial in nature and is written for a broad audience with interest in mathematical formulations relevant to COVID-19 testing. Therefore, ideas are presented through illustrative examples rather than through purely theoretical formulations. The focus is also on pools of size less than 64 such as what is practical with current RT-PCR technology.", "title": "On Accelerated Testing for COVID-19 Using Group Testing", "pid": "m8n2p55z", "bm25_score": 215.06723022460938}, {"text": "OBJECTIVES: In the context of the Covid-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. We evaluated a novel rapid antigen detection test (RDT) for SARS-CoV-2 in respiratory samples. METHODS: The fluorescence immunochromatographic SARS-CoV-2 antigen test (Bioeasy Biotechnology Co., Shenzhen, China) was evaluated using universal transport medium with nasopharyngeal (NP) and oropharyngeal (OP) swabs from suspected Covid-19 cases. Diagnostic accuracy was determined in comparison to SARS-CoV-2 real time (RT)-PCR. RESULTS: A total of 127 samples were included; 82 were RT-PCR positive. Median patients' age was 38 years, 53.5% were male, and 93.7% were from the first week after symptom onset. Overall sensitivity and specificity were 93.9% (CI95% 86.5-97.4) and 100% (CI95% 92.1-100), respectively, with a diagnostic accuracy of 96.1% and Kappa coefficient of 0.9. Sensitivity was significantly higher in samples with high viral loads. CONCLUSIONS: The evaluated RDT showed a high sensitivity and specificity in samples mainly obtained during the first week of symptoms and with high viral loads, despite the use of a non-validated sample material. The assay has the potential to become an important tool for early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods.", "title": "Evaluation of novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples", "pid": "rtywrjo1", "bm25_score": 215.06338500976562}, {"text": "There is an ongoing worldwide coronavirus disease 2019 (Covid-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At present, confirmatory diagnosis is by reverse transcription polymerase chain reaction (RT-PCR), typically taking several hours and requiring a molecular laboratory to perform. There is an urgent need for rapid, simplified and cost-effective detection methods. We have developed and analytically validated a protocol for direct rapid extraction-free PCR (DIRECT-PCR) detection of SARS-CoV-2 without the need for nucleic acid purification. As few as 6 RNA copies per reaction of viral nucleocapsid (N) gene from respiratory samples such as sputum and nasal exudate can be detected directly using our one-step inhibitor-resistant assay. The performance of this assay was validated on a commercially available portable PCR thermocycler. Viral lysis, reverse transcription, amplification and detection are achieved in a single-tube homogeneous reaction within 36 minutes. This minimized hands-on time, reduces turnaround-time for sample-to-result and obviates the need for RNA purification reagents. It could enable wider use of Covid-19 testing for diagnosis, screening and research in countries and regions where laboratory capabilities are limiting.", "title": "Rapid direct nucleic acid amplification test without RNA extraction for SARS-CoV-2 using a portable PCR thermocycler", "pid": "e1oinu71", "bm25_score": 215.06222534179688}, {"text": "COVID-19 is the most rapidly growing pandemic in modern time, and the need for serological testing is most urgent. Although the diagnostics of acute patients by RT-PCR is both efficient and specific, we are also crucially in need of serological tools for investigating antibody responses and assessing individual and potential herd immunity. We evaluated a commercially available test developed for rapid (within 15 minutes) detection of SARS-CoV-2-specific IgM and IgG by 29 PCR-confirmed COVID-19 cases and 124 negative controls. The results revealed a sensitivity of 69% and 93.1% for IgM and IgG, respectively, based solely on PCR-positivity due to the absence of a serological gold standard. The assay specificities were shown to be 100% for IgM and 99.2% for IgG. This indicates that the test is suitable for assessing previous virus exposure, although negative results may be unreliable during the first weeks after infection. More detailed studies on antibody responses during and post infection are urgently needed.", "title": "Evaluation of a COVID-19 IgM and IgG rapid test; an efficient tool for assessment of past exposure to SARS-CoV-2", "pid": "knc0ruou", "bm25_score": 215.0439453125}, {"text": "OBJECTIVES: In the context of the Covid-19 pandemic, the development and validation of rapid and easy-to-perform diagnostic methods are of high priority. We evaluated a novel rapid antigen detection test (RDT) for SARS-CoV-2 in respiratory samples. METHODS: The fluorescence immunochromatographic SARS-CoV-2 antigen test (Bioeasy Biotechnology Co., Shenzhen, China) was evaluated using universal transport medium with nasopharyngeal (NP) and oropharyngeal (OP) swabs from suspected Covid-19 cases. Diagnostic accuracy was determined in comparison to SARS-CoV-2 real time (RT)-PCR. RESULTS: A total of 127 samples were included; 82 were RT-PCR positive. Median patients’ age was 38 years, 53.5% were male, and 93.7% were from the first week after symptom onset. Overall sensitivity and specificity were 93.9% (CI95% 86.5–97.4) and 100% (CI95% 92.1–100), respectively, with a diagnostic accuracy of 96.1% and Kappa coefficient of 0.9. Sensitivity was significantly higher in samples with high viral loads. CONCLUSIONS: The evaluated RDT showed a high sensitivity and specificity in samples mainly obtained during the first week of symptoms and with high viral loads, despite the use of a non-validated sample material. The assay has the potential to become an important tool for early diagnosis of SARS-CoV-2, particularly in situations with limited access to molecular methods.", "title": "Evaluation of novel antigen-based rapid detection test for the diagnosis of SARS-CoV-2 in respiratory samples", "pid": "n642wlsx", "bm25_score": 215.04257202148438}, {"text": "Recently, a novel coronavirus (SARS-CoV-2; coronavirus disease 2019, COVID-19) has emerged, rapidly spreading and severely straining the capacity of the global health community. Many nations are employing combinations of containment and mitigation strategies, where early diagnosis of COVID-19 is vital in controlling illness progression and limiting viral spread within the population. Thus, rapid and accurate methods of early detection are vital to contain COVID-19 and prevent further spread and predicted subsequent infectious waves of viral recurrence in future. Immediately after its initial characterization, Chinese and American Centers for Disease Control and Prevention (CDCs) rapidly employed molecular assays for detection of COVID-19, mostly employing real-time polymerase chain reaction (RT-PCR) methods. However, such methods require specific expensive items of equipment and highly trained analysts, requiring upwards of 4-8 h to process. These requirements coupled with associated financial pressures may prevent effective deployment of such diagnostic tests. Loop mediated isothermal amplification(LAMP) is method of nucleic acid amplification which exhibits increased sensitivity and specificity are significantly rapid, and do not require expensive reagents or instruments, which aids in cost reduction for coronavirus detection. Studies have shown the successful application of LAMP assays in various forms to detect coronavirus RNA in patient samples, demonstrating that 1-10 copies of viral RNA template per reaction are sufficient for successful detection, ~100-fold more sensitive than conventional RT-PCR methods. Importantly, studies have also now demonstrated the effectiveness of LAMP methodology in the detection of SARS-CoV-2 RNA at significantly low levels, particularly following numerous improvements to LAMP assay protocols. We hypothesise that recent advancements in enhanced LAMP protocols assay perhaps represent the best chance for a rapid and robust assay for field diagnosis of COVID-19, without the requirement of specialized equipment and highly trained professionals to interpret results. Herein, we present our arguments with a view to disseminate such findings, to assist the combat of this virus that is proving so devastating. We hope that this strategy could be applied rapidly, and confirmed for viability with clinical samples, before being rolled out for mass-diagnostic testing in these current times.", "title": "Loop mediated isothermal amplification (LAMP) assays as a rapid diagnostic for COVID-19", "pid": "ax8qn0ci", "bm25_score": 215.03955078125}, {"text": "Abstract The ongoing pandemic of SARS-CoV-2 is a one of the most devastating outbreaks witnessed in the last 100 years. The outbreak started in China's hinterland and spread rapidly to almost every country culminating in woefully overwhelmed healthcare systems in most countries. The only approved diagnostic test to accompany radiographic evaluation is the reverse-transcriptase PCR. However, the applicability of this test in diagnosis and surveillance is challenged by global shortage in reagents and unavailability of well-equipped laboratories with specialized staff in several low- and middle-income countries. The need for development of accurate and rapid diagnostic assays became apparent. Handful of immunodiagnostic tests and other molecular approaches were developed and tested. Other recently developed point-of-care molecular tests are expected to be helpful in pandemic management since no particular skills are required from the operator. Fortunately, handful of serological tests have granted authorization to be used under emergency situation by FDA in diagnosis of SARS-CoV-2.", "title": "Laboratory diagnosis of SARS-CoV-2: available approaches and limitations", "pid": "voc0eqb9", "bm25_score": 215.02354431152344}, {"text": "", "title": "Rapid detection of COVID-19 coronavirus using a reverse transcriptional loop-mediated isothermal amplification (RT-LAMP) diagnostic platform", "pid": "f7sjd5wh", "bm25_score": 215.0227813720703}]}
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"zknngzt2": 0, "zksa523r": 0, "vz7p89zq": 0, "znm5ibc1": 0, "zo9uzk52": 2, "jnhoau5v": 0, "zovj2vt5": 2, "zqjiiy4l": 0, "zroufl2t": 0, "zrtfyz8s": 0, "zrw8dk5r": 2, "zs86lyxq": 0, "zstfdmkl": 2, "zsvdn8o3": 2, "xaw3t7tf": 2, "zvj00qjj": 2, "zwhavf4h": 2, "zzljrkbf": 2}, "bm25_results": [{"text": "OBJECTIVE To develop an simple and sensitive method for detecting anti-coronavirus IgG antibodies in bat sera based on enzyme-linked immunosorbent assay (ELISA). METHODS A commercial ELISA kit for detecting SARS-CoV antibody was modified for detecting coronavirus antibodies in bat serum samples. The second antibody in the kit was replaced with horseradish peroxidase-conjugated protein-A (HRP-SPA) based on the characteristics of binding between Staphylococcus aureus protein A (SPA) and mammal IgG Fc fragment. The sera of 55 fulvous fruit bats (Rousettus dasymallus) were tested using the SPA-ELISA. RESULTS The test results of the positive and negative controls in the kit and the serum samples from convalescent ;patient were consistent with expectation. Coronavirus antibody was detected in 2 out of the 55 bat serum samples. Serum neutralization test confirmed the validity of the SPA-ELISA method. CONCLUSION This SPA-ELISA method is applicable for detecting coronavirus antibody in bat sera.", "title": "[Development of a SPA-ELISA method for detecting anti-coronavirus IgG antibodies in serum samples from fulvous fruit bats].", "pid": "vwy25qah", "bm25_score": 219.654296875}, {"text": "We developed and validated 2 species-independent protein-based assays to detect Middle East respiratory syndrome coronavirus functional antibodies that can block virus receptor-binding or sialic acid-attachment. Antibody levels measured in both assays correlated strongly with virus-neutralizing antibody titers, proving their use for serologic confirmatory diagnosis of Middle East respiratory syndrome.", "title": "Serologic Detection of Middle East Respiratory Syndrome Coronavirus Functional Antibodies", "pid": "blrfn8qh", "bm25_score": 218.83584594726562}, {"text": "The immunochromatographic assay (ICA) is a simple antibody–antigen detection method, the results of which can be rapidly obtained at a low cost. We designed an ICA to detect anti-feline coronavirus (FCoV) antibodies. A colloidal gold-labeled recombinant FCoV nucleocapsid protein (rNP) is used as a conjugate. The Protein A and affinity-purified cat anti-FCoV IgG are blotted on the test line and the control line, respectively, of the nitrocellulose membrane. The specific detection of anti-FCoV antibodies was possible in all heparin-anticoagulated plasma, serum, whole blood, and ascitic fluid samples from anti-FCoV antibody positive cats, and nonspecific reaction was not noted in samples from anti-FCoV antibody negative cats.", "title": "Serological Diagnosis of Feline Coronavirus Infection by Immunochromatographic Test", "pid": "wfy5kz63", "bm25_score": 218.64295959472656}, {"text": "Abstract An enzyme-linked immunosorbent assay (Elisa), using as antigen canine coronavirus-infected CrFK cell supernatant, was developed to detect antibodies against canine coronavirus (CCoV). Out of a total of 109 dog serum samples, 80 which were positive by routine virus neutralisation test were also Elisa positive. Seventeen samples which were negative by the virus neutralisation test, were positive by Elisa and by the confirmatory Western blotting test. The Elisa was substantially more sensitive than the virus neutralisation test in detecting antibodies to CCoV and may be used as an alternative technique to virus neutralisation.", "title": "Prevalence of canine coronavirus antibodies by an enzyme-linked immunosorbent assay in dogs in the south of Italy", "pid": "j36vajdi", "bm25_score": 218.44879150390625}, {"text": "We report the evaluation of recombinant severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) nucleocapsid protein enzyme-linked immunosorbent assay (ELISA)-based antibody tests for serodiagnosis of SARS-CoV pneumonia and compare the sensitivities and specificities of this ELISA for detection of immunoglobulin G (IgG), IgM, IgA, and their combinations with serum samples from 149 healthy blood donors who donated blood 3 years ago as controls and 106 SARS-CoV pneumonia patients in Hong Kong. The specificities of the ELISA for IgG, IgM, and IgA detection were 95.3, 96.6, and 96.6%, respectively, with corresponding sensitivities of 94.3, 59.4, and 60.4%, respectively. The present ELISA appears to be a sensitive test for serodiagnosis of SARS-CoV pneumonia, is much more economical and less labor-intensive than the indirect immunofluorescence assay, and does not require cultivation of SARS-CoV.", "title": "Detection of specific antibodies to severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein for serodiagnosis of SARS coronavirus pneumonia.", "pid": "b1qnfl41", "bm25_score": 218.44192504882812}, {"text": "The serological response profile of severe acute respiratory syndrome (SARS) coronavirus (CoV) infection was defined by neutralization tests and subclass-specific immunofluorescent (IF) tests using serial sera from 20 patients. SARS CoV total immunoglobulin (Ig) (IgG, IgA, and IgM [IgGAM]) was the first antibody to be detectable. There was no difference in time to seroconversion between the patients who survived (n = 14) and those who died (n = 6). Although SARS CoV IgM was still detectable by IF tests with 8 of 11 patients at 7 months postinfection, the geometric mean titers dropped from 282 at 1 month postinfection to 19 at 7 months (P = 0.001). In contrast, neutralizing antibody and SARS CoV IgGAM and IgG antibody titers remained stable over this period. The SARS CoV antibody response was sometimes associated with an increase in preexisting IF IgG antibody titers for human coronaviruses OC43, 229E, and NL63. There was no change in IF IgG titer for virus capsid antigen from the herpesvirus that was used as an unrelated control, Epstein-Barr virus. In contrast, patients who had OC43 infections, and probably also 229E infections, without prior exposure to SARS CoV had increases of antibodies specific for the infecting virus but not for SARS CoV. There is a need for awareness of cross-reactive antibody responses between coronaviruses when interpreting IF serology.", "title": "Serological responses in patients with severe acute respiratory syndrome coronavirus infection and cross-reactivity with human coronaviruses 229E, OC43, and NL63.", "pid": "q41plzqq", "bm25_score": 218.43966674804688}, {"text": "The sensitivity of a radioimmunoassay (RIA), an enzyme-linked immunosorbent assay (ELISA), and a serum neutralization assay (SN) for detecting antibodies to bovine coronavirus in serum and colostrum were compared. Although there proved to be a good correlation among all three assays (r = 0.915 and 0.964 for RIA with SN and ELISA, respectively), RIA and ELISA proved to be at least 10 times more sensitive than neutralization tests. By using these techniques, it was possible to detect a time-dependent decrease in antibody levels in bovine colostrum after parturition. Using ELISA, we demonstrated that 12 of 12 herds in Saskatchewan, and 109 of 110 animals tested, and antibody to bovine coronavirus. There was no elevated antibody response in serum or lacteal secretions of cows vaccinated once or twice with a commercially available modified live rota-coronavirus vaccine. In addition to being more sensitive than SN, ELISA and RIA proved to have other advantages for measuring antibody levels to bovine coronavirus and therefore warrant wider use as tools in diagnostic virology.", "title": "Detection by radioimmunoassay and enzyme-linked immunosorbent assay of coronavirus antibodies in bovine serum and lacteal secretions.", "pid": "grahy9up", "bm25_score": 218.43753051757812}, {"text": "A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein-specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2-infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.", "title": "Severe Acute Respiratory Syndrome Coronavirus 2-Specific Antibody Responses in Coronavirus Disease Patients", "pid": "83odb66l", "bm25_score": 218.4315185546875}, {"text": "A total of 2238 feline serum samples submitted to the New York State Diagnostic Laboratory over a 1-year period were tested for the presence of coronavirus antibodies, using the computer-assisted, kinetics-based enzyme-linked immunosorbent assay (KELA). Cats from which sera were obtained were categorized by sex, age, breed, and disease status, and variations in mean antibody titers for different sub-classifications within each category were analyzed by computerized statistical analysis. As expected, higher mean antibody titers were recorded for cats with feline infectious peritonitis, and for cats with a recent history of possible coronavirus exposure. However, an unexpected inverse relationship between coronavirus antibody titer and age was also found. Certain cattery-oriented pure breeds appeared to have higher mean antibody titers, because their sample populations contained a higher percentage of younger cats and cats of unknown age-groups which, over-all, had higher mean titers. Taken together, the data substantiated the efficacy of the computer-assisted KELA for routine detection of serum coronavirus antibodies in cats.", "title": "Coronavirus antibody detection in cats by computer-assisted kinetics-based enzyme-linked immunosorbent assay (KELA): field studies.", "pid": "il7x4l4u", "bm25_score": 218.40306091308594}, {"text": "We comparatively assessed sensitivities and specificities of 4 commercial enzyme-linked immunosorbent assays (ELISAs) and 2 rapid tests in 77 patients with polymerase chain reaction-confirmed severe acute respiratory syndrome coronavirus 2 infection, grouped by interval since symptom onset. Although test sensitivities were low (<40%) within the first 5 days after disease onset, immunoglobulin (Ig) M, IgA, and total antibody ELISAs increased in sensitivity to >80% between days 6 and 10 after symptom onset. The evaluated tests (including IgG and rapid tests) provided positive results in all patients at or after the 11th day after onset of disease. The specificities of the ELISAs were 83% (IgA), 98% (IgG), and 97% (IgM and total antibody).", "title": "Performance of Severe Acute Respiratory Syndrome Coronavirus 2 Antibody Assays in Different Stages of Infection: Comparison of Commercial Enzyme-Linked Immunosorbent Assays and Rapid Tests", "pid": "ub1t0wwq", "bm25_score": 218.2842254638672}, {"text": "Background. Severe acute respiratory syndrome (SARS) is a novel infectious disease. No information is currently available on host-specific immunity against the SARS coronavirus (CoV), and detailed characteristics of the epidemiology of SARS CoV infection have not been identified. Methods. ELISA was used to detect antibody to SARS CoV. Reverse-transcriptase polymerase chain reaction was used to detect SARS CoV RNA. T cells in peripheral blood of patients were quantified by flow cytometry. Results. Of 36 patients with probable SARS CoV infection, 30 (83.3%) were positive for IgG antibody to SARS CoV; in contrast, only 3 of 48 patients with suspected SARS CoV infection, 0 of 112 patients with fever but without SARS, and 0 of 96 healthy control individuals were positive for it. IgG antibody to SARS CoV was first detected between day 5 and day 47 after onset of illness (mean ± SD, 18.7±10.4). Conclusion. Detection of antibody to SARS CoV is useful in the diagnosis of SARS; however, at the incubation and initial phases of the illness, serological assay is of little value, because of late seroconversion in most patients.", "title": "Serology of Severe Acute Respiratory Syndrome: Implications for Surveillance and Outcome", "pid": "nrtrhq1f", "bm25_score": 218.2057342529297}, {"text": "Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.", "title": "Serodiagnostics for Severe Acute Respiratory Syndrome-Related Coronavirus-2: A Narrative Review", "pid": "01mo6yo9", "bm25_score": 218.10755920410156}, {"text": "Recombinant severe acute respiratory syndrome (SARS) nucleocapsid and spike protein-based immunoglobulin G immunoassays were developed and evaluated. Our assays demonstrated high sensitivity and specificity to the SARS coronavirus in sera collected from patients as late as 2 years postonset of symptoms. These assays will be useful not only for routine SARS coronavirus diagnostics but also for epidemiological and antibody kinetic studies.", "title": "Recombinant protein-based assays for detection of antibodies to severe acute respiratory syndrome coronavirus spike and nucleocapsid proteins.", "pid": "qfsxuyow", "bm25_score": 218.0928955078125}, {"text": "We present a serological assay for the specific detection of IgM and IgG antibodies against the emerging human coronavirus hCoV-EMC and the SARS-CoV based on protein microarray technology. The assay uses the S1 receptor-binding subunit of the spike protein of hCoV-EMC and SARS-CoV as antigens. The assay has been validated extensively using putative cross-reacting sera of patient cohorts exposed to the four common hCoVs and sera from convalescent patients infected with hCoV-EMC or SARS-CoV.", "title": "Specific serology for emerging human coronaviruses by protein microarray.", "pid": "79bzd4nl", "bm25_score": 218.091552734375}, {"text": "OBJECTIVE: As the severe acute respiratory syndrome-coronavirus-2 pandemic develops, assays to detect the virus and infection caused by it are needed for diagnosis and management. To describe to clinicians how each assay is performed, what each assay detects, and the benefits and limitations of each assay. DATA SOURCES: Published literature and internet. STUDY SELECTION: As well done, relevant and recent as possible. DATA EXTRACTION: Sources were read to extract data from them. DATA SYNTHESIS: Was synthesized by all coauthors. CONCLUSIONS: Available assays test for current or previous severe acute respiratory syndrome-coronavirus-2 infection. Nucleic acid assays such as quantitative, or real-time, polymerase chain reaction and loop-mediated isothermal amplification are ideal for acute diagnosis with polymerase chain reaction testing remaining the “gold standard” to diagnose acute infection by severe acute respiratory syndrome-coronavirus-2, specifically the presence of viral RNA. Assays that detect serum antibodies can theoretically diagnose both acute and remote infection but require time for the patient to develop immunity and may detect nonspecific antibodies. Antibody assays that quantitatively measure neutralizing antibodies are needed to test efficacy of convalescent plasma therapy but are more specialized.", "title": "Review of Viral Testing (Polymerase Chain Reaction) and Antibody/Serology Testing for Severe Acute Respiratory Syndrome-Coronavirus-2 for the Intensivist", "pid": "uxeaaski", "bm25_score": 218.07928466796875}, {"text": "Abstract From the reasons that canine coronavirus (CCV) grows more efficiently than feline coronavirus in a cell culture and they are mutually related in their antigenicities, an enzyme-linked immunosorbent assay (ELISA) using CCV-infected feline kidney (CRFK) cells as substrate antigens was developed for detection of anti-coronavirus antibodies in cats. It was indispensable for generating coronavirus-specific ELISA antibody activities that the sample was applied to the mock-infected, normal CRFK cells in parallel with the CCV-infected cells and then the optical density values given by the mock-infected cell antigen were subtracted from those given by the virus-infected cell antigen. On the basis of ELISA antibody titers obtained in sera from the cats experimentally infected with CCV and from the spontaneous feline infectious peritonitis (FIP) cases, the ELISA described in the present study was found to be applicable as a simple and easy serologic test which was able to detect anti-coronavirus antibodies as efficiently as the indirect immunofluorescence assay with homologous FIP virus.", "title": "An enzyme-linked immunosorbent assay using canine coronavirus-infected CRFK cells as antigen for detection of anti-coronavirus antibody in cat", "pid": "uyqqalyv", "bm25_score": 218.04580688476562}, {"text": "A rapid and reproducible enzyme linked immunosorbent assay (ELISA) was developed for detection of canine coronavirus (CCV) specific antibodies directed to both the nucleocapsid (NC) and the spike (S) proteins. The coating antigen, a methanol-treated, S-protein enriched preparation, was produced by subjecting infected cells to Triton X-114 detergent followed by phase separation. The sensitivity of this assay was determined by following the course of infection in dogs experimentally infected with CCV. The specificity of the antibody response was determined by Western blot analysis and supported the increased magnitude of the ELISA response and the presence of serum neutralizing (SN) antibody. Due to the sensitivity and specificity of the IgG response detected by this assay it can be used to determine both virus exposure and vaccine efficacy.", "title": "Development and evaluation of an ELISA to measure antibody responses to both the nucleocapsid and spike proteins of canine coronavirus.", "pid": "tyav4ue1", "bm25_score": 218.035888671875}, {"text": "Study of coronavirus OC43 infections has been limited because of the lack of sensitive cell culture systems and serologic assays. To improve this circumstance, we developed an indirect enzyme immunoassay (EIA) to detect serum antibody to OC43. Antigen (100 ng) prepared by polyethylene glycol precipitation provided optimal results without a postcoat procedure. Evaluation of intraplate variation indicated that a > or = 2.5-fold increase in serum titer was significant. Sixteen of 18 (89%) paired serum samples with previously identified, reproducible increases in the level of hemagglutination inhibition (HAI) antibody to OC43 also showed significant increases as detected by EIA. Specificity for the EIA was established with paired sera obtained from persons given influenza immunizations or experiencing a respiratory infection. No rise in antibody titers occurred among 33 persons with documented coronavirus 229E infection. EIA was then performed on each of 419 paired serum samples from ambulatory chronic obstructive pulmonary disease patients and healthy older adults, from asthmatic adults presenting for emergency room treatment, and from persons hospitalized with acute respiratory symptoms. Twenty-three antibody rises to OC43 were detected; only nine of these were detected by the HAI test, and the HAI test did not detect any increases in antibody titers that were not detected by EIA. Nineteen of 25 coronavirus OC43 infections for which a month of infection could be assigned occurred between November and February. Overall, 4.4% of acute respiratory illnesses in the studied populations were associated with a coronavirus OC43 infection.", "title": "Development and application of an enzyme immunoassay for coronavirus OC43 antibody in acute respiratory illness.", "pid": "gzf2b2y0", "bm25_score": 218.02816772460938}, {"text": "Since there is no available serological methods to detect antibodies to ferret coronavirus (FRCoV), an enzyme-linked immunosorbent assay (ELISA) using recombinant partial nucleocapsid (N) proteins of the ferret coronavirus (FRCoV) Yamaguchi-1 strain was developed to establish a serological method for detection of FRCoV infection. Many serum samples collected from ferrets recognized both a.a. 1–179 and a.a. 180–374 of the N protein, but two serum samples did not a.a. 180–374 of the N protein. This different reactivity was also confirmed by immunoblot analysis using the serum from the ferret.Therefore, the a.a. 1–179 of the N protein was used as an ELISA antigen. Serological test was carried out using sera or plasma of ferrets in Japan. Surprisingly, 89% ferrets in Japan had been infected with FRCoV. These results indicated that our established ELISA using a.a. 1–179 of the N protein is useful for detection of antibody to FRCoV for diagnosis and seroepidemiology of FRCoV infection.", "title": "Establishment of serological test to detect antibody against ferret coronavirus", "pid": "3g75spkc", "bm25_score": 217.99530029296875}, {"text": "Abstract The membrane (M) protein of canine coronavirus (CCoV) was cloned and expressed in E. coli. The purified recombinant protein was then evaluated for its antigenicity and reliability in an enzyme-linked immunosorbent assay (ELISA) for detection of CCoV antibodies in dog sera. Fifty serum samples, screened previously by whole virus ELISA and Western blotting, were tested. When the performance of the new test was compared with those of whole virus ELISA and Western blotting, an excellent correlation was found with the latter two assays. The ELISA based on recombinant M protein represents an alternative and valid test for detection of antibodies to CCoV in dog sera.", "title": "Recombinant M protein-based ELISA test for detection of antibodies to canine coronavirus", "pid": "5pl5oqwf", "bm25_score": 217.97268676757812}, {"text": "OBJECTIVE To identify patients with SARS coronavirus infection who have only mild symptoms. METHOD Enzyme-linked immunosorbent assay was employed to detect serum antibody against SARS coronavirus in the lysate of whole SARS coronavirus from 19 SARS patients and 200 medical staff members without obvious SARS symptoms after possible exposure to the virus during routine medical practice. RESULTS Serum IgG antibody against SARS coronavirus was detected in all the 19 SARS patients, and among the 200 staff members, 20 (10%) were found positive for the antibody but with no obvious or only mild symptoms. CONCLUSION Serum IgG antibody against SARS coronavirus is positive in a small proportion (around 10%) of the medical staff members exposed to the virus in our hospital, but may not cause obvious symptoms, suggesting SARS coronavirus infection might in some cases have mild or even no clinical manifestations.", "title": "[Some medical staff positive for serum SARS coronavirus antibody IgG have only mild symptoms].", "pid": "dza80e8o", "bm25_score": 217.9700469970703}, {"text": "A new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged to cause a human pandemic. Although molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are needed for contact tracing, identifying the viral reservoir, and epidemiologic studies. We developed serologic assays for detection of SARS-CoV-2 neutralizing, spike protein–specific, and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed SARS-CoV-2 infections, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrated that most PCR-confirmed SARS-CoV-2–infected persons seroconverted by 2 weeks after disease onset. We found that commercial S1 IgG or IgA ELISAs were of lower specificity, and sensitivity varied between the 2 assays; the IgA ELISA showed higher sensitivity. Overall, the validated assays described can be instrumental for detection of SARS-CoV-2–specific antibodies for diagnostic, seroepidemiologic, and vaccine evaluation studies.", "title": "Severe Acute Respiratory Syndrome Coronavirus 2−Specific Antibody Responses in Coronavirus Disease Patients", "pid": "mryazbnq", "bm25_score": 217.9644012451172}, {"text": "", "title": "The researchers taking a gamble with antibody tests for coronavirus.", "pid": "1tc0i21c", "bm25_score": 217.9615478515625}, {"text": "The current practice for diagnosis of SARS-CoV-2 infection relies on PCR testing of nasopharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk. This testing strategy likely underestimates the true prevalence of infection, creating the need for serologic methods to detect infections missed by the limited testing to date. Here, we describe the development of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A preliminary study of human sera collected prior to the SARS-CoV-2 pandemic demonstrates overall high IgG reactivity to common human coronaviruses and low IgG reactivity to epidemic coronaviruses including SARS-CoV-2, with some cross-reactivity of conserved antigenic domains including S2 domain of spike protein and nucleocapsid protein. This array can be used to answer outstanding questions regarding SARS-CoV-2 infection, including whether baseline serology for other coronaviruses impacts disease course, how the antibody response to infection develops over time, and what antigens would be optimal for vaccine development.", "title": "Analysis of Serologic Cross-Reactivity Between Common Human Coronaviruses and SARS-CoV-2 Using Coronavirus Antigen Microarray", "pid": "lw12h047", "bm25_score": 217.90438842773438}, {"text": "A seroepidemiological study for detection of antibody to human coronaviruses OC43, 229E, and neonatal calf diarrhea coronavirus (NCDCV), has been carried out using sera collected from hospitalized patients or healthy persons through routine laboratory tests in Northern Italy. Patients tested were children and adults with different pathological diseases. Antibody detection was performed by using an indirect immunoperoxidase staining technique (for all viruses) and, in the case of OC43 and NCDCV, antibody detection was obtained even with a hemagglutination inhibition test and a plaque reduction neutralization assay. Results obtained show a significant difference in the prevalence of antibody to 229E between children and adult group. Furthermore, a different titer was observed, within the two groups, between patients affected by hematological diseases (leukemia) and patients with other diseases. Finally, our data seem to confirm previous studies reporting a very high prevalence of antibody to coronavirus OC43 but a less detectable seropositivity to coronavirus 229E.", "title": "Prevalence of antibody to human coronaviruses 229E, OC43 and neonatal calf diarrhea coronavirus (NCDCV) in patients of Northern Italy", "pid": "576xiuz8", "bm25_score": 217.90301513671875}, {"text": "Sera from patients with multiple sclerosis and carefully matched controls were tested for antibodies to three strains of coronavirus. There was no significant difference in the levels of antibody in the patients vs the controls. We conclude that unless the strains of coronaviruses recently reported to have been isolated from patients with multiple sclerosis express important serological differences from those used in these studies, coronaviruses are not associated with the cause of multiple sclerosis.", "title": "Coronavirus antibodies in sera from patients with multiple sclerosis and matched controls.", "pid": "o0y0xiq6", "bm25_score": 217.89527893066406}, {"text": "The need for accurate antibody testing in patients following symptomatic or asymptomatic infections with SARS-CoV-2 is well documented.….", "title": "Patients with Common Cold Coronaviruses Tested Negative for IgG Antibody to SARS-CoV-2.", "pid": "o9bx1gn7", "bm25_score": 217.88189697265625}, {"text": "OBJECTIVE To examine the presence of severe acute respiratory syndrome (SARS) coronavirus-specific antibodies in the sera from non-SARS children. METHODS Indirect immunofluorescent assay and double-antigen sandwich enzyme-linked immunosorbent assay (ELISA) were used to detect the virus-specific antibodies in sera of 1,060 non-SARS children in Guangzhou. RESULTS All the serum samples from the 1,060 non-SARS children were negative for both IgG and IgM antibodies against SARS coronavirus as determined by indirect immunofluorescent assay, with only two serum samples showing weak positivity for SARS coronavirus-specific antibodies identified by double-antigen sandwich ELISA. CONCLUSION No SARS coronavirus-specific antibody are present in the sera of non-SARS children.", "title": "[Detection and analysis of SARS coronavirus-specific antibodies in sera from non-SARS children].", "pid": "w0ceb715", "bm25_score": 217.87806701660156}, {"text": "Abstract Most coronaviruses infecting humans cause mild diseases, whereas severe acute respiratory syndrome (SARS)-associated coronavirus is an extremely dangerous pathogen. Here, we report the development of a serologic assay for detection of antibodies to human coronaviruses (HCoVs) based on recombinant nucleocapsid (N) proteins of all known pathogenic strains (229E, NL63, OC43, HKU1, SARS). The novel immunoassay is highly useful for epidemiologic surveys, where use of nucleic acid diagnostics often is limited. Purified recombinant antigens were immobilized on nitrocellulose membranes and applied in a line immunoassay, which allows rapid detection of antibodies to 5 different HCoVs in a single experiment. For assay evaluation, serum samples from persons infected with 229E or OC43 (acute/convalescent), recovered SARS patients and healthy donors were analyzed. Screening for nucleocapsid (N)-specific immunoglobulin G (IgG) in convalescent sera reached 100% sensitivity. With this new technique, we found that recently identified NL63 and HKU1 contribute significantly to the overall spectrum of coronavirus infections. Possibly, cross-reactive antibody responses were observed using 229E and OC43 serum pairs. However, the potential of this assay could clearly be demonstrated employing SARS-positive serum samples, where nonspecific binding to nucleocapsids of other HCoVs was not observed. This coronavirus strain-specific line immunoassay represents a powerful tool for serologic diagnostics.", "title": "A line immunoassay utilizing recombinant nucleocapsid proteins for detection of antibodies to human coronaviruses", "pid": "m400cal3", "bm25_score": 217.8560028076172}, {"text": "A new coronavirus, SARS-CoV-2, has recently emerged to cause a human pandemic. Whereas molecular diagnostic tests were rapidly developed, serologic assays are still lacking, yet urgently needed. Validated serologic assays are important for contact tracing, identifying the viral reservoir and epidemiological studies. Here, we developed serological assays for the detection of SARS-CoV-2 neutralizing, spike- and nucleocapsid-specific antibodies. Using serum samples from patients with PCR-confirmed infections of SARS-CoV-2, other coronaviruses, or other respiratory pathogenic infections, we validated and tested various antigens in different in-house and commercial ELISAs. We demonstrate that most PCR-confirmed SARS-CoV-2 infected individuals seroconverted, as revealed by sensitive and specific in-house ELISAs. We found that commercial S1 IgG or IgA ELISAs were of lower specificity while sensitivity varied between the two, with IgA showing higher sensitivity. Overall, the validated assays described here can be instrumental for the detection of SARS-CoV-2-specific antibodies for diagnostic, seroepidemiological and vaccine evaluation studies.", "title": "SARS-CoV-2 specific antibody responses in COVID-19 patients", "pid": "9595vm0k", "bm25_score": 217.84573364257812}, {"text": "", "title": "Testing for Novel Coronavirus Antibodies: A Necessary Adjunct", "pid": "fdfearkn", "bm25_score": 217.84059143066406}, {"text": "The seroprevalence of feline coronavirus (FCoV) antibodies was studied in cats in southern Italy. One hundred twenty sera collected from cats belonging to catteries or community shelters and to households were tested for FCoV type I and II antibodies. The virus neutralization (VN) was performed and compared with indirect fluorescent antibody test (IFAT) and enzyme-linked immunosorbent assay (ELISA). Ninety-six sera tested positive for FCoV antibodies by VN and ELISA. Interestingly, ELISA revealed 2 more positive sera than did the VN test and 3 more positive sera than did the IFAT. All results were confirmed by Western blotting. ELISA proved to be more sensitive and detected a seroprevalence of about 82%. Considering the cross-reactivity of FCoV type I and type II, ELISA was able to detect antibodies against both serotypes, allowing the use of the assay as a reference test for sera screening. The high prevalence of antibodies observed indicates that FCoVs are common in southern Italian cat populations.", "title": "Comparison of serologic techniques for the detection of antibodies against feline coronaviruses.", "pid": "xrjuma7x", "bm25_score": 217.8209228515625}, {"text": "Using paired serum samples obtained from patients with illness associated with increases in anti-human coronavirus OC43 (HCoV-OC43) or anti-HCoV-229E antibodies, we examined the possibility of false-positive results detected in a recombinant severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) nucleocapsid protein immunoglobulin G enzyme-linked immunosorbent assay (ELISA). Three of the 21 and 1 of the 7 convalescent-phase serum samples from persons with increases in antibodies against HCoV-OC43 and HCoV-229E, respectively, tested positive by the recombinant SARS-CoV nucleocapsid protein-based ELISA. None of these samples were found to contain a specific antibody in the recombinant SARS-CoV spike polypeptide-based Western blot assay.", "title": "False-positive results in a recombinant severe acute respiratory syndrome-associated coronavirus (SARS-CoV) nucleocapsid enzyme-linked immunosorbent assay due to HCoV-OC43 and HCoV-229E rectified by Western blotting with recombinant SARS-CoV spike polypeptide.", "pid": "pjyfz0pm", "bm25_score": 217.8134765625}, {"text": "In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by SARS-CoV-2, multiple diagnostic tests are required for acute disease diagnosis, contact tracing, monitoring asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed. Unlike PCR tests which are highly specific, cross-reactivity is a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. SARS-CoV is genetically related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus in the genus Betacoronavirus of family Coronaviridae. We developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. There is significant cross-reactivity when N protein of either virus is used. The S1 or RBD regions from the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. We found that SARS survivors all have significant levels of antibodies remaining in their blood 17 years after infection. Anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity.", "title": "Serological differentiation between COVID-19 and SARS infections", "pid": "9skvbk8m", "bm25_score": 217.81280517578125}, {"text": "Recognized in 2019 in Wuhan, China, the new SARS-CoV-2 coronavirus is responsible for the occurrence of a global pandemic disease called COVID-19. So far, confirmation of infection is based on the detection of virus RNA in a sample taken from a person meeting the suspected case definition. However, in the laboratory diagnosis of SARS-CoV-2 infections, in addition to genetic tests, serological methods can also be used to detect specific antibodies of the IgM, IgG and IgA class produced after contact with antigens or to detect viral antigen. Currently, a number of rapid immunochromatographic, chemiluminescent and ELISA immunoassay tests developed by different manufacturers for the diagnosis of COVID-19 are available on the market. Despite this fact, so far there is no WHO or ECDC recommendations or even reliable research regarding the usefulness of serological investigations in the laboratory diagnosis of infections caused by SARS-CoV-2.", "title": "Characteristics and assessment of the usefulness of serological tests in the diagnostic of infections caused by coronavirus SARS-CoV-2 on the basis of available manufacturer's data and literature review", "pid": "84yjdlab", "bm25_score": 217.79547119140625}, {"text": "Recognized in 2019 in Wuhan, China, the new SARS-CoV-2 coronavirus is responsible for the occurrence of a global pandemic disease called COVID-19. So far, confirmation of infection is based on the detection of virus RNA in a sample taken from a person meeting the suspected case definition. However, in the laboratory diagnosis of SARS-CoV-2 infections, in addition to genetic tests, serological methods can also be used to detect specific antibodies of the IgM, IgG and IgA class produced after contact with antigens or to detect viral antigen. Currently, a number of rapid immunochromatographic, chemiluminescent and ELISA immunoassay tests developed by different manufacturers for the diagnosis of COVID-19 are available on the market. Despite this fact, so far there is no WHO or ECDC recommendations or even reliable research regarding the usefulness of serological investigations in the laboratory diagnosis of infections caused by SARS-CoV-2.", "title": "Characteristics and assessment of the usefulness of serological tests in the diagnostic of infections caused by coronavirus SARS-CoV-2 on the basis of available manufacturer's data and literature review.", "pid": "82iy2prw", "bm25_score": 217.7862091064453}, {"text": "Accurate serologic tests to detect host antibodies to severe acute respiratory syndrome–related coronavirus-2 (SARS-CoV-2) will be critical for the public health response to the coronavirus disease 2019 pandemic. Many use cases are envisaged, including complementing molecular methods for diagnosis of active disease and estimating immunity for individuals. At the population level, carefully designed seroepidemiologic studies will aid in the characterization of transmission dynamics and refinement of disease burden estimates and will provide insight into the kinetics of humoral immunity. Yet, despite an explosion in the number and availability of serologic assays to test for antibodies against SARS-CoV-2, most have undergone minimal external validation to date. This hinders assay selection and implementation, as well as interpretation of study results. In addition, critical knowledge gaps remain regarding serologic correlates of protection from infection or disease, and the degree to which these assays cross-react with antibodies against related coronaviruses. This article discusses key use cases for SARS-CoV-2 antibody detection tests and their application to serologic studies, reviews currently available assays, highlights key areas of ongoing research, and proposes potential strategies for test implementation.", "title": "Serodiagnostics for Severe Acute Respiratory Syndrome–Related Coronavirus-2: A Narrative Review", "pid": "ofd2ipvs", "bm25_score": 217.73553466796875}, {"text": "Eight different tests for antibodies to feline coronavirus (FCoV) were evaluated for attributes that are important in situations in veterinary practice. We compared four indirect immunofluorescent antibody tests (IFAT), one enzyme-linked immunosorbent assay (ELISA) (FCoV Immunocomb; Biogal) and three rapid immunochromatographic (RIM) tests against a panel of samples designated by consensus as positive or negative. Specificity was 100% for all but the two IFATs based on transmissible gastroenteritis virus (TGEV), at 83.3% and 97.5%. The IFAT and ELISA tests were best for obtaining an antibody titre and for working in the presence of virus. The RIM tests were the best for obtaining a result quickly (10-15 mins); of these, the Speed F-Corona was the most sensitive, at 92.4%, followed by FASTest feline infectious peritonitis (FIP; 84.6%) and Anigen Rapid FCoV antibody test (64.1%). Sensitivity was 100% for the ELISA, one FCoV IFAT and one TGEV IFAT; and 98.2% for a second TGEV IFA and 96.1% for a second FCoV IFAT. All tests worked with effusions, even when only blood products were stipulated in the instruction manual. The ELISA and Anigen RIM tests were best for small quantities of sample. The most appropriate FCoV antibody test to use depends on the reason for testing: in excluding a diagnosis of FIP, sensitivity, specificity, small sample quantity, rapidity and ability to work in the presence of virus all matter. For FCoV screening, speed and sensitivity are important, and for FCoV elimination antibody titre is essential.", "title": "Utility of feline coronavirus antibody tests.", "pid": "93ea9u03", "bm25_score": 217.7103271484375}, {"text": "Coronaviruses (CoVs) are widespread among mammals and birds and known for their potential for cross-species transmission. In cats, infections with feline coronaviruses (FCoVs) are common. Several non-feline coronaviruses have been reported to infect feline cells as well as cats after experimental infection, supported by their ability to engage the feline receptor ortholog for cell entry. However, whether cats might become naturally infected with CoVs of other species is unknown. We analyzed coronavirus infections in cats by serological monitoring. In total 137 cat serum samples and 25 FCoV type 1 or type 2-specific antisera were screened for the presence of antibodies against the S1 receptor binding subunit of the CoV spike protein, which is immunogenic and possesses low amino acid sequence identity among coronavirus species. Seventy-eight sera were positive for antibodies that recognized one or more coronavirus S1s whereas 1 serum exclusively reacted with human coronavirus 229E (HCoV-229E) and two sera exclusively reacted with porcine delta coronavirus (PDCoV). We observed antigenic cross-reactivity between S1s of type 1 and type 2 FCoVs, and between FCoV type 1 and porcine epidemic diarrhea virus (PEDV). Domain mapping of antibody epitopes indicated the presence of conserved epitope(s) particularly in the CD domains of S1. The cross-reactivity of FCoV type 1 and PEDV was also observed at the level of virus neutralization. To conclude, we provide the first evidence of antigenic cross-reactivity among S1 proteins of coronaviruses, which should be considered in the development of serological diagnoses. In addition, the potential role of cats in cross-species transmission of coronaviruses cannot be excluded.", "title": "Serological Screening for Coronavirus Infections in Cats", "pid": "eiobmxp2", "bm25_score": 217.68515014648438}, {"text": "The study presented here was conducted to evaluate the performance of a double-antigen sandwich ELISA to detect antibodies in human serum against the coronavirus associated with severe acute respiratory syndrome (SARS). A recombinant partial nucleocapsid protein of SARS-associated coronavirus was used as a serodiagnostic antigen in the ELISA. A total of 2892 clinical serum samples were tested with the ELISA kit, which positively identified 25 of 35 (71.4%) samples of patients with confirmed SARS infection, 286 of 407 (70%) samples of patients suspected of having SARS, 229 of 302 (75.8%) samples of convalescent SARS patients, and 0 of 544 samples obtained from healthcare workers; only 1 of 1604 clinical samples obtained from patients with other diseases demonstrated a weakly positive result. These results indicate that the double-antigen sandwich ELISA is an effective screening method for the serodiagnosis of SARS-associated coronavirus.", "title": "Double-antigen sandwich ELISA for detection of antibodies to SARS-associated coronavirus in human serum", "pid": "epd1zeif", "bm25_score": 217.66604614257812}, {"text": "Abstract Two methods of enzyme-linked immunosorbent assay (ELISA) were developed for the diagnosis of canine coronavirus (CCV) infection in dogs. One ELISA, in which CCV-infected CRFK cell lysate is used as antigen, is for the detection and titration of antibody against CCV, and the other ELISA uses the double antibody sandwich method for the detection of CCV antigen. The first ELISA procedure demonstrated antibody responses in dogs inoculated with CCV, as did the virus neutralization test; the second ELISA detected specific CCV antigen in feces and organ homogenates of inoculated dogs.", "title": "Enzyme-linked immunosorbent assay for the detection of canine coronavirus and its antibody in dogs", "pid": "ldeylpne", "bm25_score": 217.65304565429688}, {"text": "Corona Virus Disease 2019 (COVID-19) has spread rapidly to more than 70 countries and regions overseas and over 80000 cases have been infected, resulting in more than three thousand deaths. Rapid diagnosis of patients remains a bottleneck in containing the progress of the epidemic. We used automated chemiluminescent immunoassay to detect serum IgM and IgG antibodies to 2019-nCoV of 736 subjects. COVID-19 patients were becoming reactive(positive) for specific antibodies from 7-12 days after the onset of morbidity. Specific IgM and IgG increased with the progression of the disease. The areas under the ROC curves of IgM and IgG were 0.988 and 1.000, respectively. Specific antibody detection has good sensitivity and specificity. Detection of specific antibodies in patients with fever can be a good distinction between COVID-19 and other diseases, so as to be a complement to nucleic acid diagnosis to early diagnosis of suspected cases.", "title": "Serological detection of 2019-nCoV respond to the epidemic: A useful complement to nucleic acid testing", "pid": "na8odvj7", "bm25_score": 217.63418579101562}, {"text": "OBJECTIVES: To examine and summarize the current literature on serologic methods for the detection of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: A literature review was performed using searches in databases including PubMed, medRxiv, and bioRxiv. Thirty-two peer-reviewed papers and 23 preprints were examined. RESULTS: The studies included lateral flow immunoassay, enzyme-linked immunosorbent assay, chemiluminescence immunoassay, and neutralizing antibody assays. The use of all major SARS-CoV-2 antigens was demonstrated to have diagnostic value. Assays measuring total antibody reactivity had the highest sensitivity. In addition, all the methods provided opportunities to characterize the humoral immune response by isotype. The combined use of IgM and IgG detection resulted in a higher sensitivity than that observed when detecting either isotype alone. Although IgA was rarely studied, it was also demonstrated to be a sensitive marker of infection, and levels correlated with disease severity and neutralizing activity. CONCLUSIONS: The use of serologic testing, in conjunction with reverse transcription polymerase chain reaction testing, was demonstrated to significantly increase the sensitivity of detection of patients infected with SARS-CoV-2. There was conflicting evidence regarding whether antibody titers correlated with clinical severity. However, preliminary investigations indicated some immunoassays may be a surrogate for the prediction of neutralizing antibody titers and the selection of recovered patients for convalescent serum donation.", "title": "Review of Current Advances in Serologic Testing for COVID-19", "pid": "77rcr30x", "bm25_score": 217.60308837890625}, {"text": "The need for accurate antibody testing in patients following symptomatic or asymptomatic infections with SARS-CoV-2 is well documented. .", "title": "Patients with Common Cold Coronaviruses Tested Negative for IgG Antibody to SARS-CoV-2", "pid": "k7bpx2cu", "bm25_score": 217.60284423828125}, {"text": "", "title": "The researchers taking a gamble with antibody tests for coronavirus", "pid": "yseooaiw", "bm25_score": 217.59561157226562}, {"text": "In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by the SARS-CoV-2 virus, multiple diagnostic tests are required globally for acute disease diagnosis, contact tracing, monitoring of asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed to fulfil the other requirements. Unlike PCR tests which are highly specific for each virus, cross-reactivity could potentially be a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. Among the human pathogens, SARS-CoV is genetically most related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus (SARSr-CoV) in the genus Betacoronavirus of family Coronaviridae. In this study, we developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. Our results indicate that there is a significant cross-reactivity when N protein of either SARS-CoV or SARS-CoV-2 is used. The S1 or RBD derived the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. Finally, we found that SARS survivors all have significant level of antibodies remaining in their blood 17 years after infection. We discovered that anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity.", "title": "Serological differentiation between COVID-19 and SARS infections", "pid": "0yj3xp9s", "bm25_score": 217.59474182128906}, {"text": "", "title": "Antibody tests suggest that coronavirus infections vastly exceed official counts.", "pid": "qkqi484x", "bm25_score": 217.58580017089844}, {"text": "To monitor severe acute respiratory syndrome (SARS) infection, a coronavirus protein microarray that harbors proteins from SARS coronavirus (SARS-CoV) and five additional coronaviruses was constructed. These microarrays were used to screen approximately 400 Canadian sera from the SARS outbreak, including samples from confirmed SARS-CoV cases, respiratory illness patients, and healthcare professionals. A computer algorithm that uses multiple classifiers to predict samples from SARS patients was developed and used to predict 206 sera from Chinese fever patients. The test assigned patients into two distinct groups: those with antibodies to SARS-CoV and those without. The microarray also identified patients with sera reactive against other coronavirus proteins. Our results correlated well with an indirect immunofluorescence test and demonstrated that viral infection can be monitored for many months after infection. We show that protein microarrays can serve as a rapid, sensitive, and simple tool for large-scale identification of viral-specific antibodies in sera.", "title": "Severe acute respiratory syndrome diagnostics using a coronavirus protein microarray.", "pid": "qud2syw4", "bm25_score": 217.57803344726562}, {"text": "Severe acute respiratory syndrome (SARS) has raised a global alert since March 2003. After its causative agent, SARS-associated coronavirus (SARS-CoV), was confirmed, laboratory methods, including virus isolation, reverse transcriptase–polymerase chain reaction (RT-PCR), and serologic methods, have been quickly developed. In this study, we evaluated four serologic tests ( neutralization test, enzyme-linked immunosorbent assay [ELISA], immunofluorescent assay [IFA], and immunochromatographic test [ICT]) for detecting antibodies to SARS-CoV in sera of 537 probable SARS case-patients with correlation to the RT-PCR . With the neutralization test as a reference method, the sensitivity, specificity, positive predictive value, and negative predictive value were 98.2%, 98.7%, 98.7%, and 98.4% for ELISA; 99.1%, 87.8%, 88.1% and 99.1% for IFA; 33.6%, 98.2%, 95.7%, and 56.1% for ICT, respectively. We also compared the recombinant-based western blot with the whole virus–based IFA and ELISA; the data showed a high correlation between these methods, with an overall agreement of >90%. Our results provide a systematic analysis of serologic and molecular methods for evaluating SARS-CoV infection.", "title": "Serologic and Molecular Biologic Methods for SARS-associated Coronavirus Infection, Taiwan", "pid": "zo9uzk52", "bm25_score": 217.54379272460938}, {"text": "An indirect immunofluorescence test, using cultured cells infected with two strains of mouse hepatitis virus, was developed for detection of antibody to rodent coronaviruses. The immunofluorescence test detected serum antibody to mouse hepatitis virus and rat sialodacryoadenitis virus earlier than the neutralization test. In the case of mouse hepatitis virus, the results of the immunofluorescence test closely paralleled those obtained with a commercially available enzyme-linked immunosorbent assay.", "title": "An immunofluorescence test for detection of serum antibody to rodent coronaviruses.", "pid": "agtm3afi", "bm25_score": 217.5403289794922}, {"text": "In response to the coronavirus disease 2019 (COVID-19) outbreak, caused by the SARS-CoV-2 virus, multiple diagnostic tests are required globally for acute disease diagnosis, contact tracing, monitoring of asymptomatic infection rates and assessing herd immunity. While PCR remains the frontline test of choice in the acute diagnostic setting, serological tests are urgently needed to fulfil the other requirements. Unlike PCR tests which are highly specific for each virus, cross-reactivity could potentially be a major challenge for COVID-19 antibody tests considering there are six other coronaviruses known to infect humans. Among the human pathogens, SARS-CoV is genetically most related to SARS-CoV-2 sharing approximately 80% sequence identity and both belong to the species SARS related coronavirus (SARSr-CoV) in the genus Betacoronavirus of family Coronaviridae. In this study, we developed and compared the performance of four different serological tests to comprehensively assess the cross-reactivity between COVID-19 and SARS patient sera. Our results indicate that there is a significant cross-reactivity when N protein of either SARS-CoV or SARS-CoV-2 is used. The S1 or RBD derived the spike (S) protein offers better specificity. Amongst the different platforms, capture ELISA performed best. Finally, we found that SARS survivors all have significant level of antibodies remaining in their blood 17 years after infection. We discovered that anti-N antibodies waned more than anti-RBD antibodies, and the latter is known to play a more important role in providing protective immunity.", "title": "Serological differentiation between COVID-19 and SARS infections.", "pid": "0jl6qu0i", "bm25_score": 217.53269958496094}, {"text": "In many parts of the United States, SARS-CoV-2 cases have reached peak infection rates, prompting administrators to create protocols to resume elective cases. As elective procedures and surgeries get scheduled, ASCs must implement some form of widespread testing in order to ensure the safety of both the ASC staff as well as the patients being seen. The CDC recently announced the approval of new serological testing for SARS-CoV-2, a test that can indicate the presence of IgM and IgG antibodies in the serum against viral particles. However, the possibility for reinfection raises questions about the utility of this new serological test, as the presence of IgG may not correspond to long-term immunity. The coronavirus has been known to form escape mutations, which may correspond to reduction in immunoglobulin binding capacity. Patients who develop more robust immune responses with formation of memory CD8+ T-cells and helper CD4+ T-cells will be the most equipped if exposed to the virus, but unfortunately the serology test will not help us in distinguishing those individuals. Given the inherent disadvantages of serological testing, antibody testing alone should not be used when deciding patient care and should be combined with PCR testing.", "title": "Efficacy of Serology Testing in Predicting Reinfection in Patients with SARS-CoV-2", "pid": "m71ut1sd", "bm25_score": 217.52618408203125}, {"text": "Cross-reactivity between antibodies to different human coronaviruses (HCoVs) has not been systematically studied. By use of Western blot analysis, indirect immunofluorescence assay (IFA), and enzyme-linked immunosorbent assay (ELISA), antigenic cross-reactivity between severe acute respiratory syndrome (SARS)—associated coronavirus (SARS-CoV) and 2 HCoVs (229E and OC43) was demonstrated in immunized animals and human serum. In 5 of 11 and 10 of 11 patients with SARS, paired serum samples showed a ⩾4-fold increase in antibody titers against HCoV-229E and HCoV-OC43, respectively, by IFA. Overall, serum samples from convalescent patients who had SARS had a 1-way cross-reactivity with the 2 known HCoVs. Antigens of SARS-CoV and HCoV-OC43 were more cross-reactive than were those of SARS-CoV and HCoV-229E.", "title": "Antigenic Cross-Reactivity between Severe Acute Respiratory Syndrome—Associated Coronavirus and Human Coronaviruses 229E and OC43", "pid": "w5sub348", "bm25_score": 217.5115966796875}, {"text": "Turkey coronavirus (TCoV) infection continues to threaten turkey industry. Because specific treatment and effective vaccination program are not available, rapid and cost-effective detection of antibodies to TCoV infection is an important control measure to monitor the disease status in the fields. Two antibody-capture enzyme-linked immunosorbent assay (ELISA) procedures for detection of antibodies to TCoV are outlined in this chapter. One ELISA method uses chicken infectious bronchitis coronavirus (IBV) as the coating antigen based on antigenic cross-reactivity between TCoV and IBV. The other method relies on a recombinant TCoV nucleocapsid protein. Both methods are useful for serological diagnosis of TCoV infection in the turkey flocks.", "title": "Antibody-Capture Enzyme-Linked Immunosorbent Assay for Detection of Antibody to Turkey Coronavirus Using Infectious Bronchitis Virus or Recombinant Nucleocapsid Protein as Coating Antigen", "pid": "0te5ybjv", "bm25_score": 217.51043701171875}, {"text": "An enzyme‐linked immunosorbent assay (ELISA) was developed for diagnosing human coronavirus (HCV) infections in children. One hundred and seventy seven nose swabs, throat swabs, and nasopharyngeal aspirates were collected from 30 children suffering from acute respiratory infections. These samples were tested for HCV antigens by ELISA and 28.2% of the samples were shown to be HCV positive. These results indicate that our ELISA should prove useful in the diagnosis of HCV infections in children. Further studies are in progress to extend the ELISA to detect HCVs in experimentally and naturally acquired infections in adults.", "title": "Diagnosis of human coronavirus infections in children using enzyme‐linked immunosorbent assay", "pid": "qtz3r5di", "bm25_score": 217.48333740234375}, {"text": "The current practice for diagnosis of COVID-19, based on SARS-CoV-2 PCR testing of pharyngeal or respiratory specimens in a symptomatic patient at high epidemiologic risk, likely underestimates the true prevalence of infection. Serologic methods can more accurately estimate the disease burden by detecting infections missed by the limited testing performed to date. Here, we describe the validation of a coronavirus antigen microarray containing immunologically significant antigens from SARS-CoV-2, in addition to SARS-CoV, MERS-CoV, common human coronavirus strains, and other common respiratory viruses. A comparison of antibody profiles detected on the array from control sera collected prior to the SARS-CoV-2 pandemic versus convalescent blood specimens from virologically confirmed COVID-19 cases demonstrates complete discrimination of these two groups. This array can be used as a diagnostic tool, as an epidemiologic tool to more accurately estimate the disease burden of COVID-19, and as a research tool to correlate antibody responses with clinical outcomes.", "title": "Analysis of SARS-CoV-2 Antibodies in COVID-19 Convalescent Plasma using a Coronavirus Antigen Microarray", "pid": "ax9btc74", "bm25_score": 217.47604370117188}, {"text": "Background: The SARS-CoV-2 shares 74.5% genome identity with SARS-CoV, both exhibiting a similar well conserved structure. Therefore, antibodies produced in COVID-19 and SARS patients should not be that dissimilar. We evaluated SARS-CoV test assays to detect for the presence of antibodies to SARS-CoV-2 and tried to determine the timing of appearance of these antibodies by testing serial sera from these patients. Methods: Tests were carried out using ELISA (total antibodies) and indirect immunofluorescence (IIFA) (IgM & IgG) methods on serial sera from patients confirmed with SARS-CoV-2 infection. Results: Cross-reactivity was seen in these two test assays with sera from COVID-19 patients and was detected in 6 out of 7 patients from 7 days after onset of symptoms. Five of the patients had detectable antibodies by the 3rd week into their illness and there was evidence of seroconversion in 4 patients. The IIFA method was marginally more sensitive compared to the ELISA assay, however the IIFA IgM test was not useful in the early phase of the illness with poor sensitivity. Conclusions: Existing diagnostic assays for SARS-CoV can detect antibodies in patients who were diagnosed with COVID-19. These assays maybe be utilized as an interim measure in epidemiological investigations for contact tracing and to determine the extent of community spread of this new emerging virus pending the availability of specific serology tests for SARS-CoV-2.", "title": "Cross-reaction of sera from COVID-19 patients with SARS-CoV assays.", "pid": "lv5xjfk4", "bm25_score": 217.4727783203125}, {"text": "The serum antibodies to severe acute respiratory syndrome (SARS) coronavirus of 18 SARS patients were checked at 1 month and every 3 months after disease onset. All of them except one, who missed blood sampling at 1 month, tested positive for the immunoglobulin G (IgG) antibody at 1 month. Fifteen out of 17 tested positive for the IgM antibody at 1 month. The serum IgM antibody of most patients became undetectable within 6 months after the onset of SARS. The IgG antibody of all 17 patients, whose serum was checked 1 year after disease onset, remained positive.", "title": "Longitudinal analysis of Severe Acute Respiratory Syndrome (SARS) coronavirus-specific antibody in SARS patients.", "pid": "7gt4ok6v", "bm25_score": 217.4668731689453}, {"text": "In many parts of the United States, SARS-CoV-2 cases have reached peak infection rates, prompting administrators to create protocols to resume elective cases. As elective procedures and surgeries get scheduled, ASCs must implement some form of widespread testing in order to ensure the safety of both the ASC staff as well as the patients being seen. The CDC recently announced the approval of new serological testing for SARS-CoV-2, a test that can indicate the presence of IgM and IgG antibodies in the serum against viral particles. However, the possibility for reinfection raises questions about the utility of this new serological test, as the presence of IgG may not correspond to long-term immunity. The coronavirus has been known to form escape mutations, which may correspond to reduction in immunoglobulin binding capacity. Patients who develop more robust immune responses with formation of memory CD8+ T-cells and helper CD4+ T-cells will be the most equipped if exposed to the virus, but unfortunately the serology test will not help us in distinguishing those individuals. Given the inherent disadvantages of serological testing, antibody testing alone should not be used when deciding patient care and should be combined with PCR testing.", "title": "Efficacy of Serology Testing in Predicting Reinfection in Patients with SARS-CoV-2.", "pid": "g1dij8ty", "bm25_score": 217.4468994140625}, {"text": "Abstract Human coronaviruses are one of the main causes of upper respiratory tract infections in humans. While more often responsible for mild illness, they have been associated with illnesses that require hospitalization. In this study, an assay for one of the human coronaviruses, OC43, was developed using a truncated recombinant nucleocapsid (N) protein antigen in an enzyme immunosorbent assay (ELISA) and evaluated using serum collected from HCoV-OC43-infected patients, healthy adults, and patients with other respiratory virus infections. Results showed that the diagnostic sensitivity and specificity of the assay were 90.9% (10/11) and 82.9% (39/47), respectively. To evaluate the clinical utility of the ELISA, serum samples collected from patients during an outbreak of HCoV-OC43 infection and previously identified as positive by HCoV-OC43 whole N ELISA were screened resulting in 100% diagnosis agreement between the testing methods. These results suggest that this assay offers a reliable method to detect HCoV-OC43 infection and may be a useful tool in coronavirus seroepidemiological studies.", "title": "Development of a recombinant truncated nucleocapsid protein based immunoassay for detection of antibodies against human coronavirus OC43", "pid": "ok3h4w7f", "bm25_score": 217.44662475585938}, {"text": "A sensitive and highly specific enzyme-linked immunosorbent assay (ELISA) system for detection of bovine coronavirus was developed using monoclonal antibodies, which showed both neutralization and hemagglutination inhibition activities. A monoclonal antibody was coated onto microplates for capturing antigen and a mixture of two monoclonal antibodies served as detecting antibodies. Using this assay, 40 of 202 fecal specimens from 29 herds were shown to be positive for viral antigen. From 10 ELISA positive specimens from 5 herds, the virus was isolated after several passages on human rectal adenocarcinoma (HRT-18) cell culture.", "title": "Detection of bovine coronavirus by enzyme-linked immunosorbent assay using monoclonal antibodies.", "pid": "sza605p7", "bm25_score": 217.4374237060547}, {"text": "Abstract An enzyme-linked immunosorbent assay (ELISA) which detects rhinovirus specific antibody in human sera and nasal secretions, has been developed. This sandwich ELISA utilizes a rabbit antirhinovirus hyperimmune serum as the capture antibody and was found to be very sensitive, detecting rhinovirus specific antibody in the serum at dilutions of 1:106 and 1:103.5 and IgA immunoglobulins, respectively. Thus, this new assay is 102–104 times more sensitive than our standard neutralization test. Furthermore, this increase in sensitivity has enabled us to reliably detect rhinovirus specific immunoglobulins in unconcentrated nasal washings, which are thought to be particularly important for protection against rhinovirus reinfection. A preliminary study of the immune response in human volunteers challenged with rhinovirus using this new ELISA system is presented and further applications and potential of the method are also discussed.", "title": "An ELISA for the detection of rhinovirus specific antibody in serum and nasal secretion", "pid": "jdvzqre6", "bm25_score": 217.43414306640625}, {"text": "Known human coronaviruses (hCoV) usually cause mild to moderate upper-respiratory tract illnesses, except SARS-CoV and MERS-CoV, which, in addition to mild illness can also be associated with severe respiratory diseases and high mortality rates. Well-characterized multiplexed serologic assays are needed to aid in rapid detection and surveillance of hCoVs. The present study describes development and evaluation of a multiplexed magnetic microsphere immunoassay (MMIA) to simultaneously detect immunoglobulin G (IgG) antibodies specific for recombinant nucleocapsid proteins (recN) from hCoVs 229E, NL63, OC43, HKU1, SARS-CoV, and MERS-CoV. We used paired human sera to screen for IgG with reactivity against six hCoVs to determine assay sensitivity, specificity and reproducibility. We found no signal interference between monoplex and multiplex assay formats (R(2) range = 0.87–0.97). Screening of paired human sera using MMIA, resulted in 92 of 106 (sensitivity: 86%) as positive and 68 of 80 (specificity: 84%) as negative. This study serves as a proof of concept that it is feasible to develop and use a multiplexed microsphere immunoassay as a next generation screening tool for use in large scale seroprevalence studies of hCoVs.", "title": "Development and Evaluation of a Multiplexed Immunoassay for Simultaneous Detection of Serum IgG Antibodies to Six Human Coronaviruses", "pid": "3qky7l9k", "bm25_score": 217.41395568847656}, {"text": "Antibody-screening methods to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) need to be validated. We evaluated SARS-CoV-2 IgG and IgA ELISAs in conjunction with the EUROLabworkstation (Euroimmun, Lübeck, Germany). Overall specificities were 91.9% and 73.0% for IgG and IgA ELISAs, respectively. Of 39 coronavirus disease patients, 13 were IgG and IgA positive and 11 IgA alone at sampling. IgGs and IgAs were respectively detected at a median of 12 and 11 days after symptom onset.", "title": "Evaluation of commercial and automated SARS-CoV-2 IgG and IgA ELISAs using coronavirus disease (COVID-19) patient samples", "pid": "5najee33", "bm25_score": 217.40936279296875}, {"text": "OBJECTIVE To study the serum anti-coronavirus antibody titer in medical personnel who had closely contacted with severe acute respiratory syndrome (SARS) patients. METHODS The serum anti-coronavirus IgG antibody titer in medical personnel who had closely contacted with SARS patients, healthy individuals, patients with community acquired pneumonia and patients recovered from SARS was detected by using an enzyme-linked immunosorbent assay (ELISA) method. The antibody titer was expressed as the value of absorbency (A) with common logarithm conversion. RESULTS The serum anti-coronavirus IgG antibody titer in patients recovered from SARS was 0.07 +/- 0.13, which was significantly higher as compared with those in other groups. The antibody titer in medical personnel was -1.18 +/- 0.20, which was also significantly higher as compared with those in community acquired pneumonia patients and healthy persons. In the healthy persons, the antibody titer of serum samples obtained from Beijing in May, 2003 was -1.61 +/- 0.13, which was significantly higher than that of samples obtained from Beijing in 2001 when SARS was not found -1.76 +/- 0.25 and that of samples from Shandong province where SARS was not found in May, 2003 -1.95 +/- 0.44. There was no significant difference in the antibody titer between patients of bacterial pneumonia and patients of atypical pneumonia, which was -1.99 +/- 0.31 and -2.05 +/- 0.23 respectively. CONCLUSION Close contact with SARS patients can cause the serum anti-coronavirus antibody titer to increase significantly in medical personnel, a phenomenon deserves further study.", "title": "[The quantitative detection of anti-coronavirus antibody titer in medical personnel closely contacted with severe acute respiratory syndrome patients].", "pid": "vbqnt8p9", "bm25_score": 217.39321899414062}, {"text": "Of paired serum samples of 196 cattle with respiratory disease from 37 herds which were tested for hemagglutination inhibiting antibodies against coronavirus (BCV) 185 of the first specimens and 190 of the second ones gave positive results. This difference was due to five animals of five different farms showing seroconversions between the time of the blood collections. A significant rise in antibody titer (no less than 4-fold) was evident in 28 cattle from 3 of the above mentioned and 12 other farms. Altogether serological indication of acute coronavirus infections were gained in 33 (16.8%) of animals with respiratory diseases which derived from 17 of 37 herds. Most of these infections (about 35%) occurred in animals older than 6 months while calves up to 3 or 6 months were only affected in a ratio of ca. 10%, respectively.", "title": "[Serological diagnostic studies of the occurrence of coronavirus infections in cattle with respiratory diseases].", "pid": "vsy97xb3", "bm25_score": 217.37063598632812}, {"text": "Rhinovirus‐specific antibodies have traditionally been detected by their ability to neutralise the homologous rhinovirus serotype in tissue culture. Recently, however, we have described an enzyme‐linked immunosorbent assay that detects rhinovirus‐specific antibodies in sera and nasal secretions [Barclay and Al‐Nakib, 1987]. Here we describe an evaluation of the ELISA in a study involving 71 adult volunteers inoculated intranasally with human rhinovirus type 2 (HRV‐2). Pre‐and post‐inoculation serum samples and pre‐inoculation nasal washings were tested for the presence of HRV‐2‐specific antibodies by ELISA. Such antibodies were associated with protection against infection when present locally in nasal secretions, but when also present in the serum they were associated with protection against both infection and the development of illness. The antibody concentrations showed strong correlation with each other and with that of antibodies detected by the neutralisation test. Following HRV‐2 infection, rises in HRV‐2‐specific IgA in sera detected by ELISA occurred more frequently than rises in neutralizing antibody. These results suggest that the ELISA is a sensitive and reliable indicator of recent infection, as well as a predictor of homologous immune status.", "title": "Evaluation of an enzyme‐linked immunosorbent assay that measures rhinovirus‐specific antibodies in human sera and nasal secretions", "pid": "3cyz6o9c", "bm25_score": 217.36769104003906}, {"text": "In order to fight the SARS-CoV-2 pandemic infection, there is a growing need and demand for diagnostic tools that are complementary and different from the RT-PCR currently in use. Multiple serological tests are or will be very soon available but need to be evaluated and validated. We have thus tested 4 immunochromatographic tests for the detection of antibodies to SARS-CoV-2. In addition, we assessed the kinetics of antibody appearance using these assays in 22 patients after they were tested positive by RT-PCR. We observed great heterogeneity in antibody detection post-symptom onset. The median antibody detection time was between 8 and 10 days according to the manufacturers. All the tests showed a sensitivity of 60 to 80% on day 10 and 100% on day 15. In addition, a single cross-reaction was observed with other human coronavirus infections. Thus, immunochromatographic tests for the detection of anti-SARS-CoV-2 antibodies may have their place for the diagnostic panel of COVID-19.", "title": "Dynamic profile for the detection of anti-SARS-CoV-2 antibodies using four immunochromatographic assays", "pid": "wf5cozst", "bm25_score": 217.36605834960938}, {"text": "Six coronaviruses isolated in the U.S.A. have been inoculated into volunteers and all produced colds. Between 10 and 20% of infected volunteers developed heterologous antibody responses after these and other experimental infections with coronaviruses. The haemagglutination-inhibition test with the OC43 virus strain was found to detect antibody rises after infection with a variety of strains.Studies on normal adult sera taken between 1965 and 1970 revealed a high frequency of neutralizing antibody to one strain (229 E) and a frequency of HI antibody to strain OC43 which fluctuated from year to year. Complement-fixing antibodies to these two viruses were also found, revealing an apparent increase in the activity of coronaviruses in the general population of the U.K., during the winter of 1968-9.", "title": "Coronative antibody tires in sera of healthy adults and experimentally infected volunteers.", "pid": "utnqvdvl", "bm25_score": 217.33197021484375}, {"text": "Recombinant severe acute respiratory syndrome (SARS) coronavirus nucleocapsid protein was employed to establish an antigen-capturing enzyme-linked immunosorbent assay (ELISA). Antinucleocapsid protein antibodies could be detected in 68.4% of probable SARS patients 6 to 10 days after illness and in 89.6% of the patients 11 to 61 days after illness. No false-positive results were observed in 20 non-SARS fever patients, 24 non-SARS respiratory illness patients, and 20 health care workers. Among 940 other non-SARS clinical serum samples, only 1 was found to be weakly positive. This method provides a new, sensitive, and specific approach for SARS diagnosis.", "title": "Diagnosis of severe acute respiratory syndrome (SARS) by detection of SARS coronavirus nucleocapsid antibodies in an antigen-capturing enzyme-linked immunosorbent assay.", "pid": "ygkwdrxl", "bm25_score": 217.3306121826172}, {"text": "We developed a monoclonal antibody-based, antigen capture sandwich enzyme-linked immunosorbent assay (ELISA) for bovine coronavirus. We compared the ELISA with electron microscopy and the hemagglutination test and found a close correlation between them. The sensitivity of the ELISA was 10(4) bovine coronavirus particles per ml of 10% fecal suspension. Compared with electron microscopy, bovine coronavirus ELISA had 96% specificity.", "title": "Development and applications of a bovine coronavirus antigen detection enzyme-linked immunosorbent assay.", "pid": "6r0gfdma", "bm25_score": 217.29977416992188}, {"text": "Serum antibodies against human coronavirus OC43 in different age groups were measured by complement fixation (CF), haemagglutination inhibition (HI), radial diffusion haemolysis‐in‐gel (HIG), and solid‐phase radioimmunoassay (RIA) methods. Antigen grown in suckling mouse brain was used in all tests. Results obtained by the CF and HIG tests, and the RIA, were in good agreement with regard to the presence or absence of antibodies. Similar results were also obtained with the HI test if nonspecific haemagglutination inhibitors were first removed by treatment with phospholipase C and only titers of 1:20 or greater were considered positive. Children 6–23 months of age (n = 45) were without measurable coronavirus antibodies in all four assays. A rapid increase in the prevalence of antibodies then occurred in subsequent age groups, and practically all persons 6 years of age or older were found to have OC43 antibodies as measured by the HIG test or the RIA. The mean antibody levels determined by these two methods continued to increase, however, up to the age group of 10–14 years. This increase in antibody levels after the initial antibody incidence plateau may be due to boosting effects caused by related coronavirus strains, since OC43 antigens are known to cross‐react with antibodies induced by other human coronaviruses. Taken together, these data suggest that OC43 virus, or an antigenically related coronavirus strain, is very common in Finland.", "title": "OC43 strain‐related coronavirus antibodies in different age groups", "pid": "1e3n1bfy", "bm25_score": 217.29937744140625}, {"text": "We present a rigorously validated and highly sensitive confirmatory real-time RT-PCR assay (1A assay) that can be used in combination with the previously reported upE assay. Two additional RT-PCR assays for sequencing are described, targeting the RdRp gene (RdRpSeq assay) and N gene (NSeq assay), where an insertion/deletion polymorphism might exist among different hCoV-EMC strains. Finally, a simplified and biologically safe protocol for detection of antibody response by immunofluorescence microscopy was developed using convalescent patient serum.", "title": "Assays for laboratory confirmation of novel human coronavirus (hCoV-EMC) infections.", "pid": "0kx3d3ml", "bm25_score": 217.27577209472656}, {"text": "Antibodies to coronavirus were detected by an indirect fluorescent antibody test in rabbit sera from six rabbitries. The prevalence ranged from 3 to 40% in different rabbitries and most seropositive rabbits were more than 4 months old. A rabbitry with high prevalence of antibodies and high incidence of diarrhea could serve as a source of virus and aid in studying the natural history of coronavirus infection in rabbits.", "title": "Prevalence of coronavirus antibodies in rabbits.", "pid": "hn69l5mq", "bm25_score": 217.24566650390625}, {"text": "Background These last months, dozens of SARS-CoV-2 serological tests have become available with varying performances. A major effort was completed to compare 17 serological tests. Methods In a preliminary phase, we compared 17 IgG, IgM, IgA and pan Ig serological tests including ELISA, LFA, CLIA and ECLIA on a panel of 182 sera, comprising 113 sera from hospitalized patients with a positive RT-PCR, and 69 sampled before 1st November 2019, expected to give a positive and negative results, respectively. In a second phase, the five best performing and most available tests were further evaluated on a total of 582 sera (178 and 404 expected positive and negative, respectively), allowing the assessment of 20 possible cross-reactions with other virus. Results In the preliminary phase, among eight IgG/pan-Ig ELISA or CLIA/ECLIA tests, four had a sensitivity and specificity above 90% and 98% respectively, and on six IgM/IgA tests, only one was acceptable. Only one LFA test on three showed good performances for both IgG and IgM. For all the tests IgM and IgG aroused concomitantly. In the second phase, no tests showed particular cross-reaction. We observed an important heterogeneity in the development of the antibody response, and that anti-nucleocapside (anti-N) antibodies appeared earlier than the anti-spike (anti-S) proteins. Conclusions The identified SARS-CoV-2 serology tests may be used for the diagnostic of CoviD-19 for negative RT-PCR patients presenting severe to mild suggestive symptoms or particular clinical presentation. Detection of both anti-N and anti-S could be complementary to increase the sensitivity of the analysis.", "title": "Comparison of SARS-CoV-2 serological tests with different antigen targets", "pid": "le35ak9m", "bm25_score": 217.24266052246094}, {"text": "SARS-Cov-2 (severe acute respiratory disease coronavirus 2), which causes Coronavirus Disease 2019 (COVID19) was first detected in China in late 2019 and has since then caused a global pandemic. While molecular assays to directly detect the viral genetic material are available for the diagnosis of acute infection, we currently lack serological assays suitable to specifically detect SARS-CoV-2 antibodies. Here we describe serological enzyme-linked immunosorbent assays (ELISA) that we developed using recombinant antigens derived from the spike protein of SARS-CoV-2. Using negative control samples representing pre-COVID 19 background immunity in the general adult population as well as samples from COVID19 patients, we demonstrate that these assays are sensitive and specific, allowing for screening and identification of COVID19 seroconverters using human plasma/serum as early as two days post COVID19 symptoms onset. Importantly, these assays do not require handling of infectious virus, can be adjusted to detect different antibody types and are amendable to scaling. Such serological assays are of critical importance to determine seroprevalence in a given population, define previous exposure and identify highly reactive human donors for the generation of convalescent serum as therapeutic. Sensitive and specific identification of coronavirus SARS-Cov-2 antibody titers may, in the future, also support screening of health care workers to identify those who are already immune and can be deployed to care for infected patients minimizing the risk of viral spread to colleagues and other patients.", "title": "A serological assay to detect SARS-CoV-2 seroconversion in humans", "pid": "ntra3jhs", "bm25_score": 217.24002075195312}, {"text": "Feline infectious peritonitis and other coronavirus infections of cats are briefly reviewed. Interpretation and applications of feline coronavirus antibody tests are described, and general recommendations are provided for practitioners. Some of the major unresolved questions regarding coronavirus infections of cats are delineated.", "title": "Cats, coronaviruses and coronavirus antibody tests", "pid": "j061ywrl", "bm25_score": 217.2147674560547}, {"text": "Abstract A capture enzyme-enhanced chemiluminescence immunoassay (ECLIA) based on three specific monoclonal antibodies to detect the nucleocapsid (N) protein of severe acute respiratory syndrome (SARS) associated coronavirus (SARS-CoV) in the serial serum samples from SARS patients was developed. The anti-SARS-CoV IgG and the viral RNA were also detected in the sera by ELISA and RT-PCR, respectively. During the first 10 days after onset, anti-SARS-CoV IgG, SARS-CoV RNA and the N protein were detected in 21.4, 42.9, and 90% of the patients’ sera, respectively. The detection rate of the N protein during days 11–15 of the disease was still significantly higher than those of anti-SARS-CoV IgG and SARS-CoV RNA. The data demonstrated that detection of the N protein with the capture ECLIA appears to be more useful than detection of other viral makers for rapid diagnosis of SARS in patients.", "title": "Detection of the nucleocapsid protein of severe acute respiratory syndrome coronavirus in serum: Comparison with results of other viral markers", "pid": "tgowzrqo", "bm25_score": 217.19158935546875}, {"text": "Serologic virus neutralization tests, indirect immunofluorescence tests, and ELISA, using tissue culture-adapted feline infectious peritonitis virus (FIPV) or feline enteric coronavirus (FECV) were compared for their ability to distinguish specific virus exposure in cats. Sera of specific-pathogen-free cats inoculated with virulent or modified FIPV or FECV were used to compare the sensitivity and specificity of the homologous assays to a heterologous assay that measures antibody reactivity with transmissible gastroenteritis virus of swine. The geometric means of the serologic titers in FIPV and FECV assays were higher for FIPV- or FECV-infected specific-pathogen-free cats than the geometric means of the transmissible gastroenteritis virus assays for most groups. None of the assays was specific enough to discern the virus to which a cat had been exposed. However, the FIPV virus neutralization test appeared to be more sensitive for detection of an early response to FIPV infection than did the FIPV immunofluorescence test or FIPV-ELISA.", "title": "Comparison of serologic assays for measurement of antibody response to coronavirus in cats.", "pid": "8g5s381b", "bm25_score": 217.18312072753906}, {"text": "The emergence of Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 made imperative the need for diagnostic tests that can identify the infection. Although Nucleic Acid Test (NAT) is considered to be the gold standard, serological tests based on antibodies could be very helpful. However, individual studies are usually inconclusive, thus, a comparison of different tests is needed. We performed a systematic review and meta-analysis in PubMed, medRxiv and bioRxiv. We used the bivariate method for meta-analysis of diagnostic tests pooling sensitivities and specificities. We evaluated IgM and IgG tests based on Enzyme-linked immunosorbent assay (ELISA), Chemiluminescence Enzyme Immunoassays (CLIA), Fluorescence Immunoassays (FIA), and the Lateral Flow Immunoassays (LFIA). We identified 38 studies containing data from 7848 individuals. Tests using the S antigen are more sensitive than N antigen-based tests. IgG tests perform better compared to IgM ones and show better sensitivity when the samples were taken longer after the onset of symptoms. Moreover, a combined IgG/IgM test seems to be a better choice in terms of sensitivity than measuring either antibody alone. All methods yield high specificity with some of them (ELISA and LFIA) reaching levels around 99%. ELISA- and CLIA-based methods perform better in terms of sensitivity (90%–94%) followed by LFIA and FIA with sensitivities ranging from 80% to 89%. ELISA tests could be a safer choice at this stage of the pandemic. LFIA tests are more attractive for large seroprevalence studies but show lower sensitivity, and this should be taken into account when designing and performing seroprevalence studies.", "title": "Antibody Tests in Detecting SARS-CoV-2 Infection: A Meta-Analysis", "pid": "3aoxplp3", "bm25_score": 217.15692138671875}, {"text": "The sensitivities and specificities of an immunofluorescence assay and an enzyme immunoassay for detection of antibodies specific for severe acute respiratory syndrome coronavirus (SARS-CoV) were compared for 148 laboratory-confirmed SARS cases. The appearance and persistence of SARS-CoV-specific antibodies were assessed, with immunoglobulin G detected in 59% of samples collected within 14 days and persisting for 60 to 95 days after the onset of illness.", "title": "Kinetics of severe acute respiratory syndrome (SARS) coronavirus-specific antibodies in 271 laboratory-confirmed cases of SARS.", "pid": "e28phe9y", "bm25_score": 217.14859008789062}, {"text": "Feline coronavirus genetic elements were detected by polymerase chain reaction from blood, fecal samples, and effusive fluid collected from 33 cheetahs in the U.S.A. Feline coronavirus-specific serum antibodies were also measured by indirect immunofluorescence. Ten cheetahs were positive for viral shedding by polymerase chain reaction, whereas 13 were seropositive by immunofluorescence. Results of serology did not consistently correlate with shedding of virus, and the capture antigen used for detection of feline coronavirus-specific antibodies had a significant impact on results. Testing of samples from one population over a 1-yr period indicated chronic infection in some animals. These relatively healthy carrier animals were a source of virus for contact animals. Screening programs in cheetah populations for feline coronavirus infection may be most reliable if a combination of serologic analysis and viral detection by polymerase chain reaction is used.", "title": "Detection of feline coronavirus infection in captive cheetahs (Acinonyx jubatus) by polymerase chain reaction.", "pid": "j083hy74", "bm25_score": 217.14581298828125}, {"text": "Of 1200 human sera tested by enzyme-linked immunosorbent assay (ELISA), 53% contained antibodies to human coronavirus (HCV) 229E and 88% to HCV OC43. The sera were from persons aged 13 months to 80 years, both males and females, and were collected in four different regions in 1986. The percentage of positives increased with increasing age and tended to vary according to the geographic area. Additional paired human sera from 218 patients with acute respiratory diseases (ARD) were collected between October 1986 and June 1987 in Prague. Significant antibody rises to HCV strain 229E were detected in 7 (3.2%) patients 9 months to 17 years old, to HCV strain OC43 in 4 (1.8%) patients under 2 years of age.", "title": "Antibodies to human coronaviruses 229E and OC43 in the population of C.R.", "pid": "y6gd1zku", "bm25_score": 217.14405822753906}, {"text": "An indirect immunofluorescent assay (Euroimmun AG, Luebeck, Germany) was used to investigate the avidity of immunoglobulin G (IgG), IgM, IgA, and total Ig (IgGAM) antibody responses to severe acute respiratory syndrome coronavirus (SARS CoV) infections. Serial serum samples from eight patients collected during the first, third, and ninth months after the onset of infection were evaluated. It was found that low-avidity IgG antibodies were detected in 15/15 (100%), 1/5 (20%), and 0/8 (0%) serum samples collected during the first, third, and ninth months after the onset of symptoms, respectively. Low-avidity antibodies of IgA and IgM subclasses were detected in 14/14 (100%) and 3/14 (21%) serum samples, respectively, collected in the first month after the onset of infection. However, IgA antibodies remained low in avidity in a proportion of patients even during late convalescence. As a consequence, IgG antibody avidity assays gave better discrimination between acute-phase and late-convalescent-phase serum samples than IgM, IgA, or IgGAM assays. In two of these patients, sequential serum samples were also tested for IgG avidity against human CoV strains OC43 and 229E in parallel. While SARS CoV infections induced an anamnestic IgG antibody response to the 229E and OC43 viruses, these cross-reactive antibodies remained of high avidity from early (the first month) postinfection. The results showed that assays to detect low-avidity antibody may be useful for discriminating early from late antibody responses and also for distinguishing anamnestic cross-reactive antibody responses from primary specific responses. This may be useful in some clinical situations.", "title": "Use of antibody avidity assays for diagnosis of severe acute respiratory syndrome coronavirus infection.", "pid": "4rbtif2y", "bm25_score": 217.14068603515625}, {"text": "Abstract Three types of immunochromatographic assays (ICAs) were designed to detect anti-feline coronavirus (FCoV) antibodies. Recombinant FCoV nucleocapsid protein (rNP) was used as a conjugate or test line in all 3 ICA kits (CJIgG/TNP, CJNP/TNP, and CJNP/TPA). All three ICA kits were capable of detecting anti-FCoV antibodies; however, non-specific positive reactions of anti-FCoV antibody-negative plasma samples with the test line were observed in 2 ICA kits (CJIgG/TNP and CJNP/TNP), in which rNP was used as the test line. On the other hand, the specific detection of anti-FCoV antibodies was possible in all plasma, serum, whole blood, and ascitic fluid samples using the ICA kit with protein A blotted as the test line (CJNP/TPA). In addition, the specificity and sensitivity of ICA (CJNP/TPA) were equivalent to those of the reference ELISA. The development of simple antibody test methods using the principle of ICA (CJNP/TPA) for other coronavirus and feline viral infections is expected in the future.", "title": "Use of recombinant nucleocapsid proteins for serological diagnosis of feline coronavirus infection by three immunochromatographic tests", "pid": "k6wkpmpn", "bm25_score": 217.1298065185547}, {"text": "Rabbit antisera were prepared against coronavirus strains 229E and OC43 and used successfully to detect viral antigen in epithelial cells shed from the nasopharynx of symptomatic volunteers who had received coronavirus inocula three to four days before. The same serologic reagents were applied to nasopharyngeal secretion cells obtained from 106 infants and children hospitalized with respiratory tract disease and apparently not infected with conventional respiratory viruses. No coronavirus infections were detected by this method. It appears that coronavirus OC43 or 229E infections were not common in children in Tyneside hospitals during the period of study. However, fluorescence is a useful method for detection of coronavirus infections in symptomatic human subjects.", "title": "Diagnosis of human coronavirus infection by immunofluorescence: Method and application to respiratory disease in hospitalized children", "pid": "y27aa1b6", "bm25_score": 217.12123107910156}, {"text": "Abstract Antibodies to a transmissible gastroenteritis virus (TGEV)-related coronavirus have been demonstrated in mink sera by indirect immunofluorescence, peroxidase-linked antibody assays and immunoblotting. This is the first serological evidence of a specific coronavirus infection in mink. The putative mink coronavirus (MCV) seems to be widespread in the Danish mink population with a prevalence approaching 100%. Analysis by immunoblotting has shown that MCV is closely related to TGEV by the spike (S), matrix (M) and nucleoprotein (N) polypeptides. Furthermore, antibodies to MCV also cross-reacted with N and M polypeptides of porcine epidemic diarrhea virus (PEDV). Thus MCV may occupy an intermediate position between the TGEV group of coronaviruses and PEDV. The possibility that MCV may be associated with syndromes of acute enteritis in preweaning mink is discussed.", "title": "Coronavirus infection in mink (Mustela vision). Serological evidence of infection with a coronavirus related to transmissible gastroenteritis virus and porcine epidemic diarrhea virus", "pid": "fxhkfjl6", "bm25_score": 217.1168975830078}, {"text": "Using clinical samples from patients with severe acute respiratory syndrome, we showed that the sensitivities of a quantitative reverse transcription–polymerase chain reaction (80% for fecal samples and 25% for urine samples) were higher than those of the polyclonal (50% and 5%) and monoclonal (35% and 8%) antibody-based nucleocapsid antigen capture enzyme-linked immunosorbent assays.", "title": "SARS Coronavirus Detection Methods", "pid": "qm3qfvry", "bm25_score": 217.11570739746094}, {"text": "Abstract In order to fight the SARS-CoV-2 pandemic infection, there is a growing need and demand for diagnostic tools that are complementary and different from the RT-PCR currently in use. Multiple serological tests are or will be very soon available but need to be evaluated and validated. We have thus tested 4 immunochromatographic tests for the detection of antibodies to SARS-CoV-2. In addition, we assessed the kinetics of antibody appearance using these assays in 22 patients after they were tested positive by RT-PCR. We observed great heterogeneity in antiboy detection post-symptom onset. The median antibody detection time was between 8 and 10 days according to the manufacturers. All the tests showed a sensitivity of 60 to 80% on day 10 and 100% on day 15. In addition, a single cross-reaction was observed with other human coronavirus infections. Thus, immunochromatographic tests for the detection of anti-SARS-CoV-2 antibodies may have their place for the diagnostic panel of COVID-19.", "title": "Dynamic profile for the detection of anti-SARS-CoV-2 antibodies using four immunochromatographic assays", "pid": "m9yv4qkm", "bm25_score": 217.1133270263672}, {"text": "Abstract Human coronaviruses are known to be a common cause of respiratory infections in man. However, the diagnosis of human coronavirus infections is not carried out routinely, primarily because the isolation and propagation of these viruses in tissue culture is difficult and time consuming. The aim of this study was to evaluate the use of recombinant, bacterial expressed proteins in the serodiagnosis of coronavirus infections. Two proteins were examined: the human coronavirus 229E nucleocapsid protein (N), expressed as a fusion protein in the vector pUR and the coronavirus 229E surface glycoprotein (S), expressed as a fusion protein in the vector pROS. The recombinant proteins were used as antigens in Western blot (WB) assays to detect the 229E-specific IgG antibodies and the results were compared with a standard serological method, indirect immunofluorescence. Serum samples of 51 paediatric patients, suffering from acute respiratory illness, and 10 adults, voluntarily infected with human coronavirus, were tested. The serum samples of the adult group had coronavirus-specific IgG antibodies in both test systems. In contrast, only 8 51 sera of the paediatric group were positive for coronavirus-specific IgG by both WB and IF and 20 51 sera were positive by WB, but not by IF. The overall incidence of human coronavirus infections in the paediatric age group was 55% evaluated by WB analysis and 16% evaluated by IF. This study shows that recombinant human coronavirus 229E proteins are suitable reagents for the epidemiological screening of coronavirus 229E infections.", "title": "Detection of human coronavirus 229E-specific antibodies using recombinant fusion proteins", "pid": "gbyyehbu", "bm25_score": 217.10865783691406}, {"text": "Sera collected from 90 multiple sclerosis patients and 148 age-matched normal subjects were examined for the presence of antibodies against human coronaviruses (HCV) 229E and OC43 by enzyme immunoassay (EIA). The results demonstrated no significant difference between the MS patients and the normal subjects in their antibody titer to HCV 229E and HCV OC43. Further analysis of these 238 sera indicated that a stronger EIA reaction was generally observed against HCV OC43 (mean EIA value at an optical density of 492 nm = 0.896) than against HCV 229E (mean EIA value at an optical density of 492 nm = 0.346).", "title": "Detection of antibodies to human coronaviruses 229E and OC43 in the sera of multiple sclerosis patients and normal subjects.", "pid": "cm7uvtg0", "bm25_score": 217.10848999023438}, {"text": "A new enzyme-linked immunosorbent assay (ELISA)-based immunoglobulin G (IgG)-plus-IgM antibody detection test for severe acute respiratory syndrome (SARS) has been developed by using a cocktail of four recombinant polypeptides as the antigen. These recombinant fragments were designed as parts of two different structural proteins from SARS-associated coronavirus (SARS-CoV). One recombinant polypeptide, S251-683, was designed as part of the spike glycoprotein, and the other three polypeptides comprised almost the whole nucleocapsid protein, avoiding the last 25 C-terminal amino acids. Immunization with a cocktail of these four polypeptides yielded a specific polyclonal antibody that is able to recognize SARS-CoV-infected cells by an immunofluorescence assay. This polypeptide cocktail was also used to set up an ELISA-based IgG-plus-IgM antibody detection test, which showed 99% specificity and 90% sensitivity upon evaluation using sera from 100 healthy negative controls and 20 SARS patients. Separate immunoreactivity assays with each recombinant polypeptide demonstrated that a combination of N and S protein fragments was more suitable than the individual peptides for developing a serological assay for SARS-CoV.", "title": "Development of an enzyme-linked immunosorbent assay-based test with a cocktail of nucleocapsid and spike proteins for detection of severe acute respiratory syndrome-associated coronavirus-specific antibody.", "pid": "pt3k01vx", "bm25_score": 217.1070556640625}, {"text": "BACKGROUND: A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently emerged and caused the rapid spread of coronavirus disease 2019 (COVID-19) worldwide. METHODS: We did a retrospective study and included COVID-19 patients admitted to Renmin Hospital of Wuhan University between 1 February and 29 February 2020. Antibody assay was conducted to detect COVID-19 envelope protein E and nucleocapsid protein N antigen. RESULTS: One hundred twelve patients were recruited with symptoms of fever, cough, fatigue, myalgia, and diarrhea. All patients underwent antibody tests. Fifty-eight (51.79%) were positive for both immunoglobulin M (IgM) and immunoglobulin G (IgG), 7 (6.25%) were negative for both antibodies, 1 (0.89%) was positive for only IgM, and 46 (41.07%) were positive for only IgG. IgM antibody appeared within a week post-disease onset, lasted for 1 month, and gradually decreased, whereas IgG antibody was produced 10 days after infection and lasted for a longer time. However, no significant difference in levels of IgM and IgG antibodies between positive and negative patients of nucleic acid test after treatment was found. CONCLUSIONS: Our results indicate that serological tests could be a powerful approach for the early diagnosis of COVID-19.", "title": "Longitudinal Change of Severe Acute Respiratory Syndrome Coronavirus 2 Antibodies in Patients with Coronavirus Disease 2019", "pid": "r356sn9t", "bm25_score": 217.1058349609375}, {"text": "", "title": "Will antibody tests for the coronavirus really change everything?", "pid": "tu5hoitm", "bm25_score": 217.1014862060547}, {"text": "Multiple sclerosis (MS) and matched control sera had similar antibody titers to coronaviruses OC43 and 229E when tested by a radioimmunoassay method. In contrast, cerebrospinal fluid from MS patients contained coronavirus antibodies more frequently and in higher titers than matched controls. Intrathecal antibody synthesis to OC43 and 229E viruses was detected in 41% (9/22) and 26% (7/27) of MS patients, respectively, but was not found in any of the neurologic control patients. This intrathecal antibody synthesis may mean that coronaviruses play an etiologic or pathogenic role in MS. Alternatively, intrathecal synthesis of coronavirus antibodies may be but part of a generalized and variable intrathecal antibody synthesis that is typical for MS patients.", "title": "Antibodies to coronaviruses OC43 and 229E in multiple sclerosis patients.", "pid": "da35k2t2", "bm25_score": 217.07289123535156}, {"text": "In what appears to be a first, disease trackers in Singapore have used an experimental antibody test for COVID-19 to confirm that a suspected patient was infected with the coronavirus The patient was one of two people who together formed a missing link between two clusters of cases that each occurred in a Singaporean church Researchers around the world are racing to develop antibody tests, also called serological tests, that can confirm whether someone was infected even after their immune system has cleared the virus that causes COVID-19 The group that developed the test, at Duke-NUS Medical School in Singapore, is among the front-runners, although its assay has to be validated before it is taken into production and deployed widely", "title": "Singapore claims first use of antibody test to track coronavirus infections ;Science ;AAAS", "pid": "g693adjd", "bm25_score": 217.06442260742188}, {"text": "Emergence of the novel pathogenic coronavirus Sars-CoV-2 and its rapid pandemic spread presents numerous questions and challenges that demand immediate attention. Among these is the urgent need for a better understanding of humoral immune response against the virus and assessment of seroprevalence levels in the population, both of which form the basis for developing public health strategies to control viral spread. For this, sensitive, specific and quantitative serological assays are required. Here we describe the development of a semi-quantitative high-content microscopy-based assay for detection of three major classes (IgG, IgA and IgM) of SARS-CoV-2 specific antibodies in human samples. The possibility to detect antibodies against the entire viral proteome together with a robust semi-automated image analysis workflow resulted in improvement of sensitivity and specificity compared to an approved ELISA-based diagnostic test. Combining both methods resulted in maximum specificity in a negative control cohort, while maintaining high sensitivity. The procedure described here is compatible with high-throughput microscopy approaches and may be applied for serological analysis of other virus infections.", "title": "Microscopy-based assay for semi-quantitative detection of SARS-CoV-2 specific antibodies in human sera", "pid": "scd3f8vk", "bm25_score": 217.05921936035156}, {"text": "About 14,000 paired sera, from patients with various types of acute infectious diseases with suspected viral origin, were screened by complement fixation against a wide set of viral antigens, including coronavirus OC43. A significant change in OC43 antibodies was recorded in 33 cases and a constant high titre, defined as a titre occurring in the respective age group in less than 1 % of all sera examined, was found in 45 cases. On the basis of careful retrospective analysis of hospital case records it was concluded that in 28 cases with an increase of OC43 antibody litres, and in two with titre decrease, a disease could be associated with an acute coronavirus infection. In 16 cases the disease was dominated by respiratory symptoms. Eight of these patients, four children and four adults, had pneumonia. Three of the eight pneumonia patients had, however, another concomitant infection, too. Four patients had neurological symptoms, one had severe perimyocarditis, and in five cases fever was the only symptom recorded. Among the patients with a statistically significant high titre of OC43 antibodies, there were 14 cases where a suggestive association with a disease could be envisaged on the basis of hospital records. Five of these patients had pneumonia. These results suggest that human coronaviruses, so far considered only as one group of causative agents of the common cold, may also be associated with other and more severe diseases in all age groups.", "title": "Coronavirus infections of man associated with diseases other than the common cold", "pid": "tsb6gul8", "bm25_score": 217.04478454589844}, {"text": "The Centers for Disease Control and Prevention (CDC) algorithm for detecting presence of serum antibodies against Middle East Respiratory Syndrome coronavirus (MERS-CoV) in subjects with potential infections with the virus has included screening by indirect ELISA against recombinant nucleocapsid (N) protein and confirmation by immunofluorescent staining of infected monolayers and/or micro-neutralization titration. Other international groups include indirect ELISA assays using the spike (S) protein, as part of their serological determinations. In the current study, we describe development and validation of an indirect MERS-CoV S ELISA to be used as part of our serological determination for evidence of previous exposure to the virus.", "title": "Inclusion of MERS-spike protein ELISA in algorithm to determine serologic evidence of MERS-CoV infection", "pid": "mha7zs08", "bm25_score": 217.03640747070312}, {"text": "In order to establish immunological detection methods for severe acute respiratory syndrome coronavirus (SARS-CoV), we established monoclonal antibodies directed against structural components of the virus. B cell hybridomas were generated from mice that were hyper-immunized with inactivated SARS-CoV virion. By screening 2,880 generated hybridomas, we established three hybridoma clones that secreted antibodies specific for nucleocapsid protein (N) and 27 clones that secreted antibodies specific for spike protein (S). Among these, four S-protein specific antibodies had in vitro neutralization activity against SARS-CoV infection. These monoclonal antibodies enabled the immunological detection of SARS-CoV by immunofluorescence staining, Western blot or immunohistology. Furthermore, a combination of monoclonal antibodies with different specificities allowed the establishment of a highly sensitive antigen-capture sandwich ELISA system. These monoclonal antibodies would be a useful tool for rapid and specific diagnosis of SARS and also for possible antibody-based treatment of the disease.", "title": "Immunological detection of severe acute respiratory syndrome coronavirus by monoclonal antibodies.", "pid": "r8vgj7m5", "bm25_score": 217.0286407470703}]}
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understand the scope and development of the COVID-19 pandemic, knowledge of the number of infected persons is essential. Often, the number of \"confirmed cases\", which is based on positive RT-PCR test results, is regarded as a reasonable indicator. However, limited COVID-19 test capacities in many countries are restricting the amount of testing that can be done. This can lead to the implementation of testing policies that restrict access to COVID-19 tests, and to testing backlogs and delays. As a result, confirmed case numbers can be significantly lower than the actual number of infections, especially during rapid growth phases of the epidemic. This study examines the quantitative relation between infections and reported confirmed case numbers for two different testing strategies, \"limited\" and \"inclusive\" testing, in relation to the growth rate of the epidemic. The results indicate that confirmed case numbers understate the actual number of infections substantially; during rapid growth phases where the daily growth rate can reach or exceed 30%, as has been seen in many countries, the confirmed case numbers under-report actual infections by up to 50 to 100-fold.", "title": "Severe underestimation of COVID-19 case numbers: effect of epidemic growth rate and test restrictions", "pid": "p0rqg7uk", "bm25_score": 217.50790405273438}, {"text": "Abstract Since the novel coronavirus disease (COVID-19) emerged in December 2019 in China, it has rapidly propagated to around the world, leading to one of the most significant pandemic events of recent history. Deriving reliable estimates of the COVID-19 epidemic growth rate is quite important to guide the timing and intensity of intervention strategies. Indeed, many studies have quantified the epidemic growth rate using time-series of reported cases during the early phase of the outbreak to estimate the basic reproduction number, R 0. Using daily time series of COVID-19 incidence, we illustrate how epidemic curves of reported cases may not always reflect the true epidemic growth rate due to changes in testing rates, which could be influenced by limited diagnostic testing capacity during the early epidemic phase.", "title": "Changes in testing rates could mask the novel coronavirus disease (COVID-19) growth rate", "pid": "dz1lfwzp", "bm25_score": 216.92333984375}, {"text": "Since the novel coronavirus disease (COVID-19) emerged in December 2019 in China, it has rapidly spread around the world, leading to one of the most significant pandemic events of recent history. Deriving reliable estimates of the COVID-19 epidemic growth rate is quite important to guide the timing and intensity of intervention strategies. Indeed, many studies have quantified the epidemic growth rate using time-series of reported cases during the early phase of the outbreak to estimate the basic reproduction number, R0. Using daily time series of COVID-19 incidence, we illustrate how epidemic curves of reported cases may not always reflect the true epidemic growth rate due to changes in testing rates, which could be influenced by limited diagnostic testing capacity during the early epidemic phase.", "title": "Changes in testing rates could mask the novel coronavirus disease (COVID-19) growth rate", "pid": "79gozr1p", "bm25_score": 216.88833618164062}, {"text": "To design effective disease control strategies, it is critical to understand the incidence of diseases. In the Covid-19 epidemic in the United States (caused by outbreak of the SARS-CoV-2 virus), testing capacity was initially very limited and has been increasing at the same time as the virus has been spreading. When estimating the incidence, it can be difficult to distinguish whether increased numbers of positive tests stem from increases in the spread of the virus or increases in testing. This has made it very difficult to identify locations in which the epidemic poses the largest public health risks. Here, we use a probabilistic model to quantify beliefs about testing strategies and understand implications regarding incidence. We apply this model to estimate the incidence in each state of the United States, and find that: (1) the Covid-19 epidemic is likely to be more widespread than reported by limited testing, (2) the Covid-19 epidemic growth in the summer months is likely smaller than it was during the spring months, and (3) the regions which are at highest risk of Covid-19 epidemic outbreaks are not always those with the largest number of positive test results.", "title": "Disentangling Increased Testing From Covid-19 Epidemic Spread", "pid": "l7jme343", "bm25_score": 216.6663818359375}, {"text": "Accurate estimates of the burden of SARS-CoV-2 infection are critical to informing pandemic response. Current confirmed COVID-19 case counts in the U.S. do not capture the total burden of the pandemic because testing has been primarily restricted to individuals with moderate to severe symptoms due to limited test availability. Using a semi-Bayesian probabilistic bias analysis to account for incomplete testing and imperfect diagnostic accuracy, we estimated 6,275,072 cumulative infections compared to 721,245 confirmed cases (1.9% vs. 0.2% of the population) as of April 18, 2020. Accounting for uncertainty, the number of infections was 3 to 20 times higher than the number of confirmed cases. 86% (simulation interval: 64-99%) of this difference was due to incomplete testing, while 14% (0.3-36%) was due to imperfect test accuracy. Estimates of SARS-CoV-2 infections that transparently account for testing practices and diagnostic accuracy reveal that the pandemic is larger than confirmed case counts suggest.", "title": "Substantial underestimation of SARS-CoV-2 infection in the United States due to incomplete testing and imperfect test accuracy", "pid": "ehcikhnw", "bm25_score": 216.5342254638672}, {"text": "BACKGROUND: Under the unique Japanese policy to restrict reverse transcriptase-polymerase chain reaction (RT-PCR) testing against severe acute respiratory syndrome coronavirus 2, a nationwide number of its confirmed cases and mortality remains to be low. Yet the information is lacking on geographical differences of these measures and their associated factors. AIM: Evaluation of prefecture-based geographical differences and associated predictors for the incidence and number of RT-PCR tests for COVID-19. DESIGN: Cross-sectional study using regression and correlation analysis. METHODS: We retrieved domestic laboratory-confirmed cases, deaths, and the number of RT-PCR testing for COVID-19 from January 15 to April 6, 2020 in 47 prefectures in Japan, using publicly-available data by the Ministry of Health, Labour and Welfare. We did descriptive analyses of these three measures and identified significant predictors for the incidence and RT-PCR testing through multiple regression analyses and correlates with the number of deaths through correlation analysis. RESULTS: The median prefectural-level incidence and number of RT-PCR testing per 100,000 population were 1.14 and 38.6, respectively. Multiple regression analyses revealed that significant predictors for the incidence were prefectural-level population (p < 0.001) and the number of RT-PCR testing (p = 0.03); and those for RT-PCR testing were the incidence (p = 0.025), available beds (p = 0.045) and cluster infections (p = 0.034). CONCLUSION: Considering bidirectional association between the incidence and RT-PCR testing, there may have been an underdiagnosed population for the infection. The restraint policy for RT-PCR testing should be revisited to meet the increasing demand under the COVID-19 epidemic.", "title": "Underestimation of COVID-19 cases in Japan: an analysis of RT-PCR testing for COVID-19 among 47 prefectures in Japan", "pid": "nwfbo4zj", "bm25_score": 216.40423583984375}, {"text": "Many statisticians, epidemiologists, economists and data scientists have registered serious reservations regarding the reported coronavirus case-counts. Limited testing capacity across the country has been widely identified as a key driver of suppressed coronavirus case-counts. The calls to increase testing capacity are well-justified as they become a more frequent point of discussion in the public sphere. While expanded testing is a laudable goal, selection bias will impact estimates of disease prevalence and the effective reproduction number until the entire population is sampled. Moreover, tests are imperfect as false positive/negative rates interact in complex ways with selection bias. In this paper, we attempt to clarify this interaction. Through simple calculations, we demonstrate pitfalls and paradoxes that can arise when considering case-count data in the presence of selection bias and measurement error. The discussion guides several suggestions on how to improve current case-count reporting.", "title": "The Hypothesis of Testing: Paradoxes arising out of reported coronavirus case-counts", "pid": "u5s5heqm", "bm25_score": 216.27407836914062}, {"text": "BACKGROUND Under the unique Japanese policy to restrict reverse transcriptase-polymerase chain reaction (RT-PCR) testing against severe acute respiratory syndrome coronavirus 2, a nationwide number of its confirmed cases and mortality remains to be low. Yet the information is lacking on geographical differences of these measures and their associated factors. AIM Evaluation of prefecture-based geographical differences and associated predictors for the incidence and number of RT-PCR tests for COVID-19. DESIGN Cross-sectional study using regression and correlation analysis. METHODS We retrieved domestic laboratory-confirmed cases, deaths, and the number of RT-PCR testing for COVID-19 from January 15 to April 6, 2020 in 47 prefectures in Japan, using publicly-available data by the Ministry of Health, Labour and Welfare. We did descriptive analyses of these three measures and identified significant predictors for the incidence and RT-PCR testing through multiple regression analyses and correlates with the number of deaths through correlation analysis. RESULTS The median prefectural-level incidence and number of RT-PCR testing per 100,000 population were 1.14 and 38.6, respectively. Multiple regression analyses revealed that significant predictors for the incidence were prefectural-level population (p < 0.001) and the number of RT-PCR testing (p = 0.03); and those for RT-PCR testing were the incidence (p = 0.025), available beds (p = 0.045) and cluster infections (p = 0.034). CONCLUSION Considering bidirectional association between the incidence and RT-PCR testing, there may have been an underdiagnosed population for the infection. The restraint policy for RT-PCR testing should be revisited to meet the increasing demand under the COVID-19 epidemic.", "title": "Underestimation of COVID-19 cases in Japan: an analysis of RT-PCR testing for COVID-19 among 47 prefectures in Japan.", "pid": "7gmacx72", "bm25_score": 216.185302734375}, {"text": "Estimates of the reproductive number for novel pathogens such as SARS-CoV-2 are essential for understanding the potential trajectory of the epidemic and the level of intervention that is needed to bring the epidemic under control. However, most methods for estimating the basic reproductive number (R(0)) and time-varying effective reproductive number (R(t)) assume that the fraction of cases detected and reported is constant through time. We explore the impact of secular changes in diagnostic testing and reporting on estimates of R(0) and R(t) using simulated data. We then compare these patterns to data on reported cases of COVID-19 and testing practices from different United States (US) states. We find that changes in testing practices and delays in reporting can result in biased estimates of R(0) and R(t). Examination of changes in the daily number of tests conducted and the percent of patients testing positive may be helpful for identifying the potential direction of bias. Changes in diagnostic testing and reporting processes should be monitored and taken into consideration when interpreting estimates of the reproductive number of COVID-19.", "title": "The impact of changes in diagnostic testing practices on estimates of COVID-19 transmission in the United States", "pid": "e5q27vpw", "bm25_score": 216.1604766845703}, {"text": "Standard measures such as quarantining suspects and contact tracing could not contain the ongoing COVID-19 pandemic. Unlike for other recent epidemics where such instruments were successful, in the present case a large fraction of the infected have only mild unspecific symptoms. By employing network models we here show that even for near perfect contact tracing and unlimited suspect testing, containment starts to fail when more than approximately half of the carriers fall into the weak-symptom category. The situation becomes considerably more severe if the number of daily available tests is limited. In this case the epidemic transition becomes discontinuous and a much larger percentage of the population becomes infected. While moderate levels of social distancing can bring the situation back under control, the limited number of daily tests introduces a finite time horizon: If social distancing is implemented after the cut off date, containment catastrophically breaks down resulting in an exponential disease spread.", "title": "Catastrophic failure of outbreak containment: Limited testing causes discontinuity in epidemic transition", "pid": "ekglbwrl", "bm25_score": 216.1112823486328}, {"text": "The Coronavirus disease 2019(COVID-19) outbreak has caused havoc across the world. Subsequently, research on COVID-19 has focused on number of cases and deaths and predicted projections have focused on these parameters. We propose that the number of tests performed is a very important denominator in understanding the COVID-19 data. We analysed the number of diagnostic tests performed in proportion to the number of cases and subsequently deaths across different countries and projected pandemic outcomes. We obtained real time COVID-19 data from the reference website Worldometer at 0900 BST on Saturday 4th April, 2020 and collated the information obtained on the top 50 countries with the highest number of COVID 19 cases. We analysed this data according to the number of tests performed as the main denominator. Country wise population level pandemic projections were extrapolated utilising three models - 1) inherent case per test and death per test rates at the time of obtaining the data (4/4/2020 0900 BST) for each country; 2) rates adjusted according to the countries who conducted at least 100000 tests and 3) rates adjusted according to South Korea. We showed that testing rates impact on the number of cases and deaths and ultimately on future projections for the pandemic across different countries. We found that countries with the highest testing rates per population have the lowest death rates and give us an early indication of an eventual COVID-19 mortality rate. It is only by continued testing on a large scale that will enable us to know if the increasing number of patients who are seriously unwell in hospitals across the world are the tip of the iceberg or not. Accordingly, obtaining this information through a rapid increase in testing globally is the only way which will enable us to exit the COVID-19 pandemic and reduce economic and social instability.", "title": "Making sense of the Global Coronavirus Data: The role of testing rates in understanding the pandemic and our exit strategy", "pid": "1kxxg0s9", "bm25_score": 216.10719299316406}, {"text": "Abstract Background With continuous global COVID-19 outbreak, differing case numbers and mortality rates are observed. While actual case numbers appear vague, mortality numbers related to COVID-19 seem more precise. In this study, we used the mortality rate as the main indicator to evaluate the extent of underreporting and underdetection of COVID-19 cases. Methods We have analyzed all available data provided by the World Health Organization on the development of international COVID-19 cases and mortality numbers on March 17th, 2020. A crude case-fatality risk (cCFR) and adjusted case-fatality risk (aCFR) was calculated for China, South Korea, Japan, Italy, France, Spain, Germany, Iran and the United States. Additionally, a fold-change (FC) was derived for each country. Results The highest aCFR and FC were detected for Spain. Based on their FC values, an extremely high number of undetected COVID-19 cases was displayed in France, the United States, Italy and Spain. For these countries, our findings indicate a detection rate of only 1-2% of total actual COVID-19 cases. Conclusions Due to limited testing capacities, mortality numbers may serve as a better indicator for COVID-19 case spread in many countries. Our data indicate that countries like France, Italy, the United States, Iran and Spain have extremely high numbers of undetected and underreported cases. Differences in testing availability and capacity, containment as well as overall health care and medical infrastructure result in significantly different mortality rates and COVID-19 case numbers for each respective country.", "title": "Evaluating the massive underreporting and undertesting of COVID-19 cases in multiple global epicenters", "pid": "ckecol7i", "bm25_score": 216.06753540039062}, {"text": "BACKGROUND: With continuous global COVID-19 outbreak, differing case numbers and mortality rates are observed. While actual case numbers appear vague, mortality numbers related to COVID-19 seem more precise. In this study, we used the mortality rate as the main indicator to evaluate the extent of underreporting and underdetection of COVID-19 cases. METHODS: We have analyzed all available data provided by the World Health Organization on the development of international COVID-19 cases and mortality numbers on March 17th, 2020. A crude case-fatality risk (cCFR) and adjusted case-fatality risk (aCFR) was calculated for China, South Korea, Japan, Italy, France, Spain, Germany, Iran and the United States. Additionally, a fold-change (FC) was derived for each country. RESULTS: The highest aCFR and FC were detected for Spain. Based on their FC values, an extremely high number of undetected COVID-19 cases was displayed in France, the United States, Italy and Spain. For these countries, our findings indicate a detection rate of only 1-2% of total actual COVID-19 cases. CONCLUSIONS: Due to limited testing capacities, mortality numbers may serve as a better indicator for COVID-19 case spread in many countries. Our data indicate that countries like France, Italy, the United States, Iran and Spain have extremely high numbers of undetected and underreported cases. Differences in testing availability and capacity, containment as well as overall health care and medical infrastructure result in significantly different mortality rates and COVID-19 case numbers for each respective country.", "title": "Evaluating the massive underreporting and undertesting of COVID-19 cases in multiple global epicenters", "pid": "hnbatlj0", "bm25_score": 216.00936889648438}, {"text": "We used multi-agent simulations to estimate the testing capacity required to find and isolate a number of infections sufficient to break the chain of transmission of SARS-CoV-2. Depending on the mitigation policies in place, a daily capacity between 0.7 to 3.6 tests per thousand was required to contain the disease. However, if contact tracing and testing efficacy dropped below 60% (e.g. due to false negatives or reduced tracing capability), the number of infections kept growing exponentially, irrespective of any testing capacity. Under these conditions, the population’s geographical distribution and travel behaviour could inform sampling policies to aid a successful containment.", "title": "Containment of future waves of COVID-19: simulating the impact of different policies and testing capacities for contact tracing, testing, and isolation", "pid": "q6l9zu7b", "bm25_score": 215.8930206298828}, {"text": "Real-time estimates of the true size and trajectory of local COVID-19 epidemics are key metrics to guide policy responses. We developed a Bayesian nowcasting approach that explicitly accounts for reporting delays and secular changes in case ascertainment to generate real-time estimates of COVID-19 epidemiology on the basis of reported cases and deaths. Using this approach, we estimate time trends in infections, symptomatic cases, and deaths for all 50 US states and the District of Columbia from early-March through June 11, 2020. At the beginning of June, our best estimates of the effective reproduction number (Rt) are close to 1 in most states, indicating a stabilization of incidence, but there is considerable variability in the level of incidence and the estimated proportion of the population that has already been infected.", "title": "Bayesian nowcasting with adjustment for delayed and incomplete reporting to estimate COVID-19 infections in the United States", "pid": "bge7btzz", "bm25_score": 215.8788604736328}, {"text": "Effectively designing and evaluating public health responses to the ongoing COVID-19 pandemic requires accurate estimation of the weekly incidence of COVID-19. Unfortunately, a lack of systematic testing across the United States (US) due to equipment shortages and varying testing strategies has hindered the usefulness of the reported positive COVID-19 case counts. We introduce three complementary approaches to estimate the cumulative incidence of symptomatic COVID-19 during the early outbreak in each state in the US as well as in New York City, using a combination of excess influenza-like illness reports, COVID-19 test statistics, and COVID-19 mortality reports. Instead of relying on an estimate from a single data source or method that may be biased, we provide multiple estimates, each relying on different assumptions and data sources. Across our three approaches, there is a consistent conclusion that estimated state-level COVID-19 symptomatic case counts from March 1 to April 4, 2020 varied from 5 to 50 times greater than the official positive test counts. Nationally, our estimates of COVID-19 symptomatic cases in the US as of April 4 have a likely range of 2.2 to 5.1 million cases, with possibly as high as 8.1 million cases, up to 26 times greater than the cumulative confirmed cases of about 311,000. Extending our method to May 16, 2020, we estimate that cumulative symptomatic incidence ranges from 6.0 to 12.2 million, which compares with 1.5 million positive test counts. Our approaches demonstrate the value of leveraging existing influenza-like-illness surveillance systems during the flu season for measuring the burden of new diseases that share symptoms with influenza-like-illnesses. Our methods may prove useful in assessing the burden of COVID-19 during upcoming flu seasons in the US and other countries with comparable influenza surveillance systems.", "title": "Estimating the Early Outbreak Cumulative Incidence of COVID-19 in the United States: Three Complementary Approaches", "pid": "4i0gici7", "bm25_score": 215.839111328125}, {"text": "The new corona virus disease -- COVID-2019 -- is rapidly spreading through the world. The availability of unbiased timely statistics of trends in disease events are a key to effective responses. But due to reporting delays, the most recently reported numbers are frequently underestimating of the total number of infections, hospitalizations and deaths creating an illusion of a downward trend. Here we describe a statistical methodology for predicting true daily quantities and their uncertainty, estimated using historical reporting delays. The methodology takes into account the observed distribution pattern of the lag. It is derived from the removal method, a well-established estimation framework in the field of ecology.", "title": "Nowcasting Covid-19 statistics reported withdelay: a case-study of Sweden", "pid": "zjnr7vwm", "bm25_score": 215.8346710205078}, {"text": "The COVID-19 virus has spread worldwide in a matter of a few months, while healthcare systems struggle to monitor and report current cases. Testing results have struggled with the relative capabilities, testing policies and preparedness of each affected country, making their comparison a non-trivial task. Since severe cases, which more likely lead to fatal outcomes, are detected at a higher rate than mild cases, the reported virus mortality is likely inflated in most countries. Lockdowns and changes in human behavior modulate the underlying growth rate of the virus. Under-sampling of infection cases may lead to the under-estimation of total cases, resulting in systematic mortality estimation biases. For healthcare systems worldwide it is important to know the expected number of cases that will need treatment. In this manuscript, we identify a generalizable growth rate decay reflecting behavioral change. We propose a method to correct the reported COVID-19 cases and death numbers by using a benchmark country (South Korea) with near-optimal testing coverage, with considerations on population demographics. We extrapolate expected deaths and hospitalizations with respect to observations in countries that passed the exponential growth curve. By applying our correction, we predict that the number of cases is highly under-reported in most countries and a significant burden on worldwide hospital capacity.", "title": "Correcting under-reported COVID-19 case numbers: estimating the true scale of the pandemic", "pid": "gttuxtw6", "bm25_score": 215.8278350830078}, {"text": "", "title": "Covid-19: Lack of test and trace data are frustrating government scrutiny.", "pid": "4amnl029", "bm25_score": 215.81723022460938}, {"text": "Accurate forecasts for COVID-19 are necessary for better preparedness and resource management. Specifically, deciding the response over months or several months requires accurate long-term forecasts which is particularly challenging as the model errors accumulate with time. A critical factor that can hinder accurate long-term forecasts, is the number of unreported/asymptomatic cases. While there have been early serology tests to estimate this number, more tests need to be conducted for more reliable results. To identify the number of unreported/asymptomatic cases, we take an epidemiology data-driven approach. We show that we can identify lower bounds on this ratio or upper bound on actual cases as a factor of reported cases. To do so, we propose an extension of our prior heterogeneous infection rate model, incorporating unreported/asymptomatic cases. We prove that the number of unreported cases can be reliably estimated only from a certain time period of the epidemic data. In doing so, we construct an algorithm called Fixed Infection Rate method, which identifies a reliable bound on the learned ratio. We also propose two heuristics to learn this ratio and show their effectiveness on simulated data. We use our approaches to identify the upper bounds on the ratio of actual to reported cases for New York City and several US states. Our results demonstrate with high confidence that the actual number of cases cannot be more than 35 times in New York, 40 times in Illinois, 38 times in Massachusetts and 29 times in New Jersey, than the reported cases.", "title": "Data-driven Identification of Number of Unreported Cases for COVID-19: Bounds and Limitations", "pid": "bm7q56mp", "bm25_score": 215.8067626953125}, {"text": "In May 2020 the UK introduced a Test, Trace, Isolate programme in response to the COVID-19 pandemic. The programme was first rolled out on the Isle of Wight and included Version 1 of the NHS contact tracing app. We used COVID-19 daily case data to infer incidence of new infections and estimate the reproduction number R for each of 150 Upper Tier Local Authorities in England, and at the National level, before and after the launch of the programme on the Isle of Wight. We used Bayesian and Maximum-Likelihood methods to estimate R, and compared the Isle of Wight to other areas using a synthetic control method. We observed significant decreases in incidence and R on the Isle of Wight immediately after the launch. These results are robust across each of our approaches. Our results show that the sub-epidemic on the Isle of Wight was controlled significantly more effectively than the sub-epidemics of most other Upper Tier Local Authorities, changing from having the third highest reproduction number R (of 150) before the intervention to the tenth lowest afterwards. The data is not yet available to establish a causal link. However, the findings highlight the need for further research to determine the causes of this reduction, as these might translate into local and national non-pharmaceutical intervention strategies in the period before a treatment or vaccination becomes available.", "title": "COVID-19 incidence and R decreased on the Isle of Wight after the launch of the Test, Trace, Isolate programme", "pid": "hf54ic40", "bm25_score": 215.79794311523438}, {"text": "Abstract When the novel coronavirus disease SARS-CoV2 (COVID-19) was officially declared a pandemic by the WHO in March 2020, the scientific community had already braced up in the effort of making sense of the fast-growing wealth of data gathered by national authorities all over the world. However, despite the diversity of novel theoretical approaches and the comprehensiveness of many widely established models, the official figures that recount the course of the outbreak still sketch a largely elusive and intimidating picture. Here we show unambiguously that the dynamics of the COVID-19 outbreak belongs to the simple universality class of the SIR model and extensions thereof. Our analysis naturally leads us to establish that there exists a fundamental limitation to any theoretical approach, namely the unpredictable non-stationarity of the testing frames behind the reported figures. However, we show how such bias can be quantified self-consistently and employed to mine useful and accurate information from the data. In particular, we describe how the time evolution of the reporting rates controls the occurrence of the apparent epidemic peak, which typically follows the true one in countries that were not vigorous enough in their testing at the onset of the outbreak. The importance of testing early and resolutely appears as a natural corollary of our analysis, as countries that tested massively at the start clearly had their true peak earlier and less deaths overall.", "title": "COVID-19: The unreasonable effectiveness of simple models", "pid": "qf4v02lv", "bm25_score": 215.77464294433594}, {"text": "When the novel coronavirus disease SARS-CoV2 (COVID-19) was officially declared a pandemic by the WHO in March 2020, the scientific community had already braced up in the effort of making sense of the fast-growing wealth of data gathered by national authorities all over the world. However, despite the diversity of novel theoretical approaches and the comprehensiveness of many widely established models, the official figures that recount the course of the outbreak still sketch a largely elusive and intimidating picture. Here we show unambiguously that the dynamics of the COVID-19 outbreak belongs to the simple universality class of the SIR model and extensions thereof. Our analysis naturally leads us to establish that there exists a fundamental limitation to any theoretical approach, namely the unpredictable non-stationarity of the testing frames behind the reported figures. However, we show how such bias can be quantified self-consistently and employed to mine useful and accurate information from the data. In particular, we describe how the time evolution of the reporting rates controls the occurrence of the apparent epidemic peak, which typically follows the true one in countries that were not vigorous enough in their testing at the onset of the outbreak. The importance of testing early and resolutely appears as a natural corollary of our analysis, as countries that tested massively at the start clearly had their true peak earlier and less deaths overall.", "title": "COVID-19: The unreasonable effectiveness of simple models", "pid": "nda1toup", "bm25_score": 215.77435302734375}, {"text": "When assessing the relative prevalence of the novel coronavirus (COVID-19), observers often point to the number of COVID-19 cases that have been confirmed through viral testing. However, comparisons based on confirmed case counts alone can be misleading since a higher case count may reflect either a higher disease prevalence or a better rate of disease detection. Using weekly records of viral test results for each state in the US, I demonstrate how confirmed case counts can be adjusted based on the percentage of COVID-19 tests that come back positive. A regression analysis indicates that case counts track better with future hospitalizations and deaths when employing this simple adjustment for testing coverage. Viral testing results can be used as a leading indicator of COVID-19 prevalence, but data reporting standards should be improved, and care should be taken to account for testing coverage when comparing confirmed case counts.", "title": "Adjusting confirmed COVID-19 case counts for testing volume", "pid": "g096k79u", "bm25_score": 215.77029418945312}, {"text": "The COVID-19 pandemic has created a public health crisis. Because SARS-CoV-2 can spread from individuals with pre-symptomatic, symptomatic, and asymptomatic infections, the re-opening of societies and the control of virus spread will be facilitated by robust surveillance, for which virus testing will often be central. After infection, individuals undergo a period of incubation during which viral titers are usually too low to detect, followed by an exponential growth of virus, leading to a peak viral load and infectiousness, and ending with declining viral levels and clearance. Given the pattern of viral load kinetics, we model surveillance effectiveness considering test sensitivities, frequency, and sample-to-answer reporting time. These results demonstrate that effective surveillance, including time to first detection and outbreak control, depends largely on frequency of testing and the speed of reporting, and is only marginally improved by high test sensitivity. We therefore conclude that surveillance should prioritize accessibility, frequency, and sample-to-answer time; analytical limits of detection should be secondary.", "title": "Test sensitivity is secondary to frequency and turnaround time for COVID-19 surveillance", "pid": "q44yuued", "bm25_score": 215.73265075683594}, {"text": "By March 2020, COVID-19 led to thousands of deaths and disrupted economic activity worldwide. As a result of narrow case definitions and limited capacity for testing, the number of unobserved SARS-CoV-2 infections during its initial invasion of the US remains unknown. We developed an approach for estimating the number of unobserved infections based on data that are commonly available shortly after the emergence of a new infectious disease. The logic of our approach is, in essence, that there are bounds on the amount of exponential growth of new infections that can occur during the first few weeks after imported cases start appearing. Applying that logic to data on imported cases and local deaths in the US through March 12, we estimated that 22,876 (95% posterior predictive interval: 7,451 - 53,044) infections occurred in the US by this date. By comparing the model's predictions of symptomatic infections to local cases reported over time, we obtained daily estimates of the proportion of symptomatic infections detected by surveillance. This revealed that detection of symptomatic infections decreased throughout February as exponential growth of infections outpaced increases in testing. Between February 21 and March 12, we estimated an increase in detection of symptomatic infections, which was strongly correlated (median: 0.97, 95% PPI: 0.85 - 0.98) with increases in testing. These results suggest that testing was a major limiting factor in assessing the extent of SARS-CoV-2 transmission during its initial invasion of the US.", "title": "Estimating unobserved SARS-CoV-2 infections in the United States", "pid": "4q5lkzz7", "bm25_score": 215.72564697265625}, {"text": "Background: In the pandemic, testing for SARS-CoV-2 by RT-PCR in one of the pillars on which countermeasures are based. Factors limiting the output of laboratories interfere with the effectiveness of public health measures. Conserving reagents by pooling samples in low-probability settings is proposed, but may cause dilution and loss of sensitivity. Methods: We tested an alternate approach (FACT) by simultaneously incubating multiple respiratory swabs in a single tube. This protocol was evaluated by serial incubation of a respiratory swab in up to 10 tubes. The analytics validity of this concept was demonstrated in a five-sample mini pool set-up. It was consequently applied in the testing of 50 symptomatic patients (five-sample pools) as well as 100 asymptomatic residents of a nursing home (ten-sample pools). Results: Serial incubation of a respiratory swab in up to 10 tubes did not lead to a significant decline in viral concentration. The novel FACT-protocol did not cause a false negative result in a five-sample mini-pool setup, with non-significantly differing Ct values between single sample and mini-pool NAT. In two routine applications, all mini pools containing positive patient samples were correctly identified. Conclusions: Our proposed FACT- protocol did not cause a significant loss in analytic or diagnostic sensitivity compared to single sample testing in multiple setups. It reduced the amount of reagents needed by up to 40%, and also reduced hands-on time. This method could enhance testing efficiency, especially in groups with a low pretest-probability, such as systemically relevant professional groups.", "title": "FACT- Frankfurt adjusted COVID-19 testing- a novel method enables high-throughput SARS-CoV-2 screening without loss of sensitivity", "pid": "zgehbwve", "bm25_score": 215.7200469970703}, {"text": "SARS-CoV-2 transmission risk generally increases with proximity of those shedding the virus to those susceptible to infection. Thus, this risk is a function of both number of people and the area which they occupy. However, the latter continues to evade COVID-19 testing policy. Increased testing in areas with lower population density, has the potential to induce a false sense of security even as cases continue to rise sharply overall.", "title": "COVID-19: Saving lives and livelihoods using population density driven testing", "pid": "netozhv1", "bm25_score": 215.58914184570312}, {"text": "Differences in COVID-19 testing and tracing across countries, as well as changes in testing within each country over time, make it difficult to estimate the true (population) infection rate based on the confirmed number of cases obtained through RNA viral testing. We applied a backcasting approach, coupled with Monte Carlo methods, to estimate a distribution for the true (population) cumulative number of infections (infected and recovered) for 15 countries where reliable data are available. We find a positive relationship between the testing rate per 1,000 people and the implied true detection rate of COVID-19, and a negative relationship between the proportion who test positive and the implied true detection rate. Our estimates suggest that the true number of people infected across our sample of 15 developed countries is 18.2 (5-95% CI: 11.9-39.0) times greater than the reported number of cases. In individual countries, the true number of cases exceeds the reported figure by factors that range from 1.7 (5-95% CI: 1.1-3.6) for Australia to 35.6 (5-95% CI: 23.2-76.3) for Belgium.", "title": "Estimating the true (population) infection rate for COVID-19: A Backcasting Approach with Monte Carlo Methods", "pid": "vq7k0gma", "bm25_score": 215.5755157470703}, {"text": "With the increasing spread of COVID-19, it is important to systematically test more and more people. The current strategy for test-kit allocation is mostly rule-based, focusing on individuals having (a) symptoms for COVID-19, (b) travel history or (c) contact history with confirmed COVID-19 patients. Such testing strategy may miss out on detecting asymptomatic individuals who got infected via community spread. Thus, it is important to allocate a separate budget of test-kits per day targeted towards preventing community spread and detecting new cases early on. In this report, we consider the problem of allocating test-kits and discuss some solution approaches. We believe that these approaches will be useful to contain community spread and detect new cases early on. Additionally, these approaches would help in collecting unbiased data which can then be used to improve the accuracy of machine learning models trained to predict COVID-19 infections.", "title": "COVID-19: Strategies for Allocation of Test Kits", "pid": "pr8flgd2", "bm25_score": 215.54806518554688}, {"text": "Since its emergence in Wuhan, China in December 2019, novel Coronavirus disease - 2019 (COVID-19) has rapidly spread worldwide, achieving pandemic status on 11 (th) March, 2020. As of 1 (st) April 2020, COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), had infected over 800,000 people and caused over 40,000 deaths in 205 countries and territories. COVID-19 has had its heaviest toll on Europe, United States and China. As of 1 (st) of April 2020, the number of confirmed COVID-19 cases in Africa was relatively low, with the highest number registered by South Africa, which had reported 1,380 confirmed cases. On the same date (also the date of this review), Africa had reported 5,999 confirmed cases, of which 3,838 (almost 65%) occurred in South Africa, Algeria, Egypt, Morocco and Tunisia, with the remaining 2,071 cases distributed unevenly across the other African countries. We speculate that while African nations are currently experiencing much lower rates of COVID-19 relative to other continents, their significantly lower testing rates may grossly underestimate incidence rates. Failure to grasp the true picture may mean crucial windows of opportunity shut unutilized, while limited resources are not deployed to maximum effect. In the absence of extensive testing data, an overestimation of spread may lead to disproportionate measures being taken, causing avoidable strain on livelihoods and economies. Here, based on the African situation, we discuss COVID-19 diagnostic challenges and how they may blunt responses.", "title": "COVID-19: Are Africa’s diagnostic challenges blunting response effectiveness?", "pid": "i9ndb71n", "bm25_score": 215.54486083984375}, {"text": "", "title": "Covid-19: Lack of test and trace data are frustrating government scrutiny", "pid": "zscviypa", "bm25_score": 215.50997924804688}, {"text": "Testing and case identification are key strategies in controlling the COVID-19 pandemic. Contact tracing and isolation are only possible if cases have been identified. The effectiveness of testing must be tracked, but a single comprehensive metric is not available to assess testing effectiveness, and no timely estimates of case detection rate are available globally, making inter-country comparisons difficult. The purpose of this paper was to propose a single, comprehensive metric, called the COVID-19 Testing Index (CovTI) scaled from 0 to 100, that incorporated several testing metrics. The index was based on case-fatality rate, test positivity rate, active cases, and an estimate of the detection rate. It used parsimonious modeling to estimate the true total number of COVID-19 cases based on deaths, testing, health system capacity, and government transparency. Publicly reported data from 188 countries and territories were included in the index. Estimates of detection rates aligned with previous estimates in literature (R2=0.97). As of June 3, 2020, the states with the highest CovTI included Iceland, Australia, New Zealand, Hong Kong, and Thailand, and some island nations. Globally, CovTI increased from April 20 ([x]=43.2) to June 3 ([x]=52.2) but declined in ca. 10% of countries. Bivariate analyses showed the average in countries with open public testing policies (59.7, 95% CI 55.6-63.8) were significantly higher than countries with no testing policy (30.2, 95% CI 18.1-42.3) (p<0.0001). A multiple linear regression model assessed the association of independent grouping variables with CovTI. Open public testing and extensive contact tracing were shown to significantly increase CovTI, after adjusting for extrinsic factors, including geographic isolation and centralized forms of government. This tool may be useful for policymakers to assess testing effectiveness, inform decisions, and identify model countries. It may also serve as a tool for researchers in analyses by combining it with other databases.", "title": "A novel comprehensive metric to assess COVID-19 testing outcomes: Effects of geography, government, and policy response", "pid": "6ed3two6", "bm25_score": 215.50540161132812}, {"text": "Testing representative populations to determine the prevalence or percent of the population with active SARS-Cov-2 (COVID-19) infection and/or antibodies to infection is being recommended as essential for making public policy decisions to open-up or to continue enforcing national, state and local government rules to shelter-in-place. However, all laboratory tests are imperfect and have estimates of sensitivity and specificity less than 100% - in some cases considerably less than 100%. That error will lead to biased prevalence estimates. If the true prevalence of COVID-19 is low, possibly in the range of 1-5%, then testing error will lead to a constant background of bias that will most likely be larger and possibly much larger than the true prevalence itself. As a result, what is needed is a method for adjusting prevalence estimates for testing error. In this paper we outline methods for adjusting prevalence estimates for testing error both prospectively in studies being planned and retrospectively in studies that have been conducted. The methods if employed would also help to harmonize study results within countries and around the world. Adjustment can lead to more accurate prevalence estimates and to better policy decisions.", "title": "Adjusting Coronavirus prevalence estimates for laboratory test kit error", "pid": "1xjgtj0t", "bm25_score": 215.50244140625}, {"text": "The pandemic spread of the COVID-19 virus has, as of 20th of April 2020, reached most countries of the world. In an effort to design informed public health policies, many modelling studies have been performed to predict crucial outcomes of interest, including ICU solicitation, cumulated death counts, etc... The corresponding data analyses however, mostly rely on restricted (openly available) data sources, which typically include daily death rates and confirmed COVID cases time series. In addition, many of these predictions are derived before the peak of the outbreak has been observed yet (as is still currently the case for many countries). In this work, we show that peak phase and data paucity have a substantial impact on the reliability of model predictions. Although we focus on a recent model of the COVID pandemics, our conclusions most likely apply to most existing models, which are variants of the so-called 'Susceptible-Infected-Removed' or SIR framework. Our results highlight the need for performing systematic reliability evaluations for all models that currently inform public health policies. They also motivate a plea for gathering and opening richer and more reliable data time series (e.g., ICU occupancy, negative test rates, social distancing commitment reports, etc).", "title": "On the reliability of model-based predictions in the context of the current COVID epidemic event: impact of outbreak peak phase and data paucity", "pid": "ej8fx52u", "bm25_score": 215.4923553466797}, {"text": "The number of new infections per day is a key quantity for effective epidemic management. It can be estimated by testing of random population samples. Without such direct epidemiological measurement, other approaches are required to infer whether the number of new cases is likely to be increasing or decreasing: for example, estimating the pathogen reproductive rate, R, using data gathered from the clinical response to the disease. For COVID-19 such R estimation is heavily dependent on modelling assumptions, because the available clinical case data are opportunistic observational data subject to severe temporal confounding. Given this difficulty it is useful to reconstruct the time course of infections from the least compromised available data, using minimal prior assumptions. A Bayesian inverse problem approach applied to UK data on COVID-19 deaths and the disease duration distribution suggests that infections were in decline before UK lockdown, and that infections in Sweden started to decline only a short time later.", "title": "Did COVID-19 infections decline before UK lockdown?", "pid": "bu59aji5", "bm25_score": 215.49130249023438}, {"text": "In attempting to predict the further course of the novel coronavirus disease (COVID-19) pandemic caused by SARS-CoV-2, mathematical models of different types are frequently employed and calibrated to reported case numbers. Among the major challenges in interpreting these data is the uncertainty about the amount of undetected infections, or conversely: the detection ratio. As a result, some models make assumptions about the percentage of detected cases among total infections while others completely neglect undetected cases. Here, we illustrate how model projections about case and fatality numbers vary significantly under varying assumptions on the detection ratio. Uncertainties in model predictions can be significantly reduced by representative testing, both for antibodies and active virus RNA, to uncover past and current infections that have gone undetected thus far.", "title": "The significance of case detection ratios for predictions on the outcome of an epidemic - a message from mathematical modelers", "pid": "5djl6b40", "bm25_score": 215.4864501953125}, {"text": "The Coronavirus Disease (Covid-19) pandemic is caused by the severe acute respiratory syndrome virus 2 and was first identified in Wuhan, China, in December 2019. The disease spread globally, leading to the World Health Organization declaring it a pandemic in March 2020. The condition is often fatal in its severe form. As it is a previously unknown virus, no treatment is identified or any vaccine available. The burden of disease control and containment, therefore, falls upon a robust and geographically appropriate testing strategy. Testing policies are modified, in turn, by the rapidly evolving patterns of the disease in various nations and by the evolving nature of tests in development. It is, therefore, helpful to study different national models to learn from the experience of different countries. This article compares testing strategies in the UK and India as the two countries travel different paths in controlling the pandemic. The UK is one of the most severely affected countries in the world. Initially restricted to hospitalised patients, the UK has broadened the scope of testing to many categories of individuals. In contrast, India appears to have a lower prevalence of the infection. However, the large Indian population and relatively insufficient testing capacities so far have led India to adopt a different testing trajectory, with the testing currently focused on high-risk groups in the community and hospitals. Owing to the rapidly changing nature of the disease, there can be no ‘one-size-fits-all’ policy but should be based on country-specific circumstances.", "title": "Testing times in Coronavirus disease (Covid-19): A tale of two nations", "pid": "03z7tarm", "bm25_score": 215.44491577148438}, {"text": "Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading at a rapid pace throughout the world, and the World Health Organization (WHO) declared it as pandemic on March 11, 2020. We present a case of COVID-19 patient whose reverse transcription-polymerase chain reaction (RT-PCR) initially was false negative and later turned positive, which will stress the importance of a comprehensive approach while evaluating a patient with a differential of COVID-19. The clinicians should be aware of the sensitivity and specificities of these tests which can have grave implications on the patient and community if the diagnosis is missed just based on the laboratory tests due to the highly contagious nature of the disease.", "title": "A Comprehensive Approach Is Vital for Diagnosing COVID-19: A Case of False Negative", "pid": "cj46yfye", "bm25_score": 215.44168090820312}, {"text": "We propose a novel testing and containment strategy in order to contain the spread of SARS-CoV2 while permitting large parts of the population to resume social and economic activity. Our approach recognises the fact that testing capacities are severely constrained in many countries. In this setting, we show that finding the best way to utilise this limited number of tests during a pandemic can be formulated concisely as an allocation problem. Our problem formulation takes into account the heterogeneity of the population and uses pooled testing to identify and isolate individuals while prioritising key workers and individuals with a higher risk of spreading the disease. In order to demonstrate the efficacy of our testing and containment mechanism, we perform simulations using a network-based SIR model. Our simulations indicate that applying our mechanism on a population of $100,000$ individuals with only $16$ tests per day reduces the peak number of infected individuals by approximately $20\\%$, when compared to the scenario where no intervention is implemented.", "title": "Maximising the Benefits of an Acutely Limited Number of COVID-19 Tests", "pid": "c9oodqpw", "bm25_score": 215.44082641601562}, {"text": "The recent emergence of the COVID-19 pandemic has posed an unprecedented healthcare challenge and catastrophic economic and social consequences to the countries across the world. The situation is even worse for emerging economies like India. WHO recommends mass scale testing as one of the most effective ways to contain its spread and fight the pandemic. But, due to the high cost and shortage of test kits, specifically in India, the testing is restricted to only those who are symptomatic. In this context, pooled testing is recommended by some experts as a partial solution to overcome this problem. In this article, we explain the basic statistical theory behind the pooled testing procedure for screening as well as prevalence estimation. In real world situations, the tests are imperfect, and lead to false positive and false negative results. We provide theoretical explanation of the impact of these diagnostic errors on the performances of individual testing and pooled testing procedures. Finally, we study the effect of misspecification of sensitivity and specificity of tests on the estimate of prevalence, an issue, which is debated a lot among the scientists in the context of COVID-19. Our theoretical investigations lead to some interesting and precise understanding of some of these issues.", "title": "Application of pooled testing in screening and estimating the prevalence of Covid-19", "pid": "dbzpcy5v", "bm25_score": 215.4220428466797}, {"text": "The COVID-19 pandemic has plagued the world for months. The U.S. has taken measures to counter it. On a daily basis, newly confirmed cases have been reported. In the early days, these numbers showed an increasing trend. Recently, the numbers have been generally flattened out. This report tries to estimate the hidden number of currently alive infections in the population by using the confirmed cases. A major result indicates an existing infections estimate at about 10-50 times the daily confirmed new cases, with the stringent social distancing policy tipping to the upper end of this range. It clarifies the relationship between the infection rate and the test rate to put the epidemic under control, which says that the test rate shall keep up at the same pace as infection rate to prevent an outbreak. This relationship is meaningful in the wake of business re-opening in the U.S. and the world. The report also reveals the connections of all the measures taken to the epidemic spread. A stratified sampling method is proposed to add to the current tool kits of epidemic control. Again, this report is a summary of some straight observations and thoughts, not through a thorough study backed with field data. The results appear obvious and suitable for general education to interested policymakers and the public.", "title": "Controlling the Hidden Growth of COVID-19", "pid": "z0lvcb3z", "bm25_score": 215.39671325683594}, {"text": "I estimate plausible true positive (TP) rates for the number of COVID-19 tests per day, most relevant when the number of test is on the same order of magnitude as number of infected persons. I then modify a standard SEIR model to model current growth patterns and detection rates in South Korea and New York state. Although reducing transmission rates have the largest impact, increasing TP rates by ~10% in New York can have an impact equal to adding tens of thousands of new tests per day. Increasing both TP rates and tests per day together can have significant impacts and likely be more easily sustained than social distancing restrictions. Systematic and standardized data collection, even beyond contact tracking, should be ongoing and quickly made available for research teams to maximize the efficacy of testing.", "title": "Predicting Whom to Test is More Important Than More Tests - Modeling the Impact of Testing on the Spread of COVID-19 Virus By True Positive Rate Estimation", "pid": "06vc2y9y", "bm25_score": 215.3966522216797}, {"text": "Detection of SARS-CoV-2 infections to date has relied heavily on RT-PCR testing. However, limited test availability, high false-negative rates, and the existence of asymptomatic or sub-clinical infections have resulted in an under-counting of the true prevalence of SARS-CoV-2. Here, we show how influenza-like illness (ILI) outpatient surveillance data can be used to estimate the prevalence of SARS-CoV-2. We found a surge of non-influenza ILI above the seasonal average in March 2020 and showed that this surge correlated with COVID-19 case counts across states. If 1/3 of patients infected with SARS-CoV-2 in the US sought care, this ILI surge would have corresponded to more than 8.7 million new SARS-CoV-2 infections across the US during the three-week period from March 8 to March 28, 2020. Combining excess ILI counts with the date of onset of community transmission in the US, we also show that the early epidemic in the US was unlikely to have been doubling slower than every 4 days. Together these results suggest a conceptual model for the COVID-19 epidemic in the US characterized by rapid spread across the US with over 80% infected patients remaining undetected. We emphasize the importance of testing these findings with seroprevalence data and discuss the broader potential to use syndromic surveillance for early detection and understanding of emerging infectious diseases.", "title": "Using influenza surveillance networks to estimate state-specific prevalence of SARS-CoV-2 in the United States", "pid": "szvb2gsf", "bm25_score": 215.38623046875}, {"text": "The COVID-19 pandemic (SARS-CoV-2 virus) is the defying global health crisis of our time. The absence of mass testing and the relevant presence of asymptomatic individuals causes the available data of the COVID-19 pandemic in Brazil to be largely under-reported regarding the number of infected individuals and deaths. We propose an adapted Susceptible-Infected-Recovered (SIR) model which explicitly incorporates the under-reporting and the response of the population to public policies (such as confinement measures, widespread use of masks, etc) to cast short-term and long-term predictions. Large amounts of uncertainty could provide misleading models and predictions. In this paper, we discuss the role of uncertainty in these prediction, which is illustrated regarding three key aspects. First, assuming that the number of infected individuals is under-reported, we demonstrate an anticipation regarding the peak of infection. Furthermore, while a model with a single class of infected individuals yields forecasts with increased peaks, a model that considers both symptomatic and asymptomatic infected individuals suggests a decrease of the peak of symptomatic. Second, considering that the actual amount of deaths is larger than what is being register, then demonstrate the increase of the mortality rates. Third, when consider generally under-reported data, we demonstrate how the transmission and recovery rate model parameters change qualitatively and quantitatively. We also investigate the effect of the\"COVID-19 under-reporting tripod\", i.e. the under-reporting in terms of infected individuals, of deaths and the true mortality rate. If two of these factors are known, the remainder can be inferred, as long as proportions are kept constant. The proposed approach allows one to determine the margins of uncertainty by assessments on the observed and true mortality rates.", "title": "The COVID-19 (SARS-CoV-2) Uncertainty Tripod in Brazil: Assessments on model-based predictions with large under-reporting", "pid": "8cw3bjxh", "bm25_score": 215.3856201171875}, {"text": "Background In response to the SARS-CoV2 pandemic, governments have adopted a variety of public health measures. There are variations in how much testing has been done across countries. South Korea, Germany, and Iceland take the bet of massive testing of their population. Whereas tests were not performed widely in southern European countries. As the former undergo a lower case-fatality rate due to the COVID-19 than the latter, the impact of the testing strategy must be investigated. In this study, we aimed to evaluate the impact of testing on the case fatality rate. Methods We use data on inpatients across French geographic areas and propose a novel methodology that exploits policy discontinuities at region borders to estimate the effect of COVID-19 tests on the case-fatality rate. In France, testing policies are determined locally. We compare all contiguous department pairs located on the opposite sides of a region border. The heterogeneity in testing rate between department pairs together with the similarities in other dimensions allow us to mimic the existence of treatment and control groups and to identify the impact of testing on mortality. Results The increase of one percentage point in the test rate is associated with a decrease of 0.001 percentage point in the death rate. In other words, for each additional 1000 tests, one person would have remained alive. Conclusion Massive population testing could have a significant effect on mortality in different ways. Mass testing may help decision-makers to implement healthcare measures to limit the spread of the disease.", "title": "Impact of virus testing on COVID-19 case fatality rate: estimate using a fixed-effects model", "pid": "0l4pec0z", "bm25_score": 215.37771606445312}, {"text": "Confirmed cases in Australia notified up to 17 May 2020: notifications = 7,075; deaths = 100. The incidence of new cases of COVID-19 has reduced dramatically since a peak in mid-March. Social distancing measures, public health action and the reduction in international travel have likely been effective in slowing the spread of the disease, in the Australian community. Testing rates over the past week have increased markedly, with a continued very low proportion of people testing positive. These low rates of detection are indicative of low levels of COVID-19 transmission. It is important that testing rates and community adherence to public health measures remain high to support the continued suppression of the virus, particularly in vulnerable high-risk groups and settings. New cases of COVID-19 are currently being reported by by only some jurisdictions, albeit at relatively low rates. Although case numbers are low, new cases tend to still be a mix of overseas-acquired and locally-acquired infections. Most locally-acquired cases can be linked back to a known case or cluster. Although the proportion of locally-acquired cases has increased, the overall rate of new cases, regardless of place of acquisition, continues to decrease. The crude case fatality rate in Australia remains low (1.4%), compared with the WHO reported global rate (6.9%). The low case fatality rate is likely reflective of high case detection and high quality of health care services in Australia. Deaths from COVID-19 in Australia have occurred predominantly among the elderly and those with comorbidities, with no deaths occurring in those under 40 years. The highest rate of COVID-19 continues to be among people aged 60-79 years. One third of all cases in this age group have been associated with several outbreaks linked to cruise ships. The lowest rate of disease is in young children, a pattern reflected in international reports. Internationally, while the number of new cases each day remains relatively stable at the global level, some areas such as Brazil and India are showing a dramatic rise in reported cases. Although some low-income countries have so far reported few cases, it is possible that this is due to limited diagnostic and public health capacity, and may not be reflective of true disease incidence.", "title": "COVID-19, Australia: Epidemiology Report 16 (Reporting week to 23:59 AEST 17 May 2020).", "pid": "8cw12q7i", "bm25_score": 215.37603759765625}, {"text": "Studies aimed at characterizing the evolution of COVID-19 disease often rely on case-based surveillance data publicly released by health authorities, that can be incomplete and prone to errors. Here, we quantify the biases caused by the use of inaccurate data in the estimation of the Time-Varying Reproduction Number R(t). By focusing on Italy and Spain, two of the hardest-hit countries in Europe and worldwide, we show that if the symptoms' onset time-series is inferred from the notification date series, the R(t) curve cannot capture nor describe accurately the early dynamics of the epidemic. Furthermore, the effectiveness of the containment measures that were implemented, such as national lockdowns, can be properly evaluated only when R(t) is estimated using the real time-series of dates of symptoms' onset. Our findings show that extreme care should be taken when a pivotal quantity like R(t) is used to make decisions and to evaluate different alternatives.", "title": "Impact of the accuracy of case-based surveillance data on the estimation of time-varying reproduction numbers", "pid": "chbdqxk8", "bm25_score": 215.36489868164062}, {"text": "As the COVID-19 pandemic spreads across the world, it is important to understand its features and responses to public health interventions in real-time. The field of infectious diseases epidemiology has highly advanced modeling strategies that yield relevant estimates. These include the doubling time of the epidemic and various other representations of the numbers of cases identified over time. Crude estimates of these quantities suffer from dependence on the underlying testing strategies within communities. We clarify the functional relationship between testing and the epidemic parameters, and thereby derive sensitivity analyses that explore the range of possible truths under various testing dynamics. We derive the required adjustment to the estimates of interest for New York City. We demonstrate that crude estimates that assume stable testing or complete testing can be biased.", "title": "Accounting for incomplete testing in the estimation of epidemic parameters", "pid": "u0prnwk6", "bm25_score": 215.34542846679688}, {"text": "Confirmed cases in Australia notified up to 17 May 2020: notifications = 7,075; deaths = 100. The incidence of new cases of COVID-19 has reduced dramatically since a peak in mid-March. Social distancing measures, public health action and the reduction in international travel have likely been effective in slowing the spread of the disease, in the Australian community. Testing rates over the past week have increased markedly, with a continued very low proportion of people testing positive. These low rates of detection are indicative of low levels of COVID-19 transmission. It is important that testing rates and community adherence to public health measures remain high to support the continued suppression of the virus, particularly in vulnerable high-risk groups and settings. New cases of COVID-19 are currently being reported by by only some jurisdictions, albeit at relatively low rates. Although case numbers are low, new cases tend to still be a mix of overseas-acquired and locally-acquired infections. Most locally-acquired cases can be linked back to a known case or cluster. Although the proportion of locally-acquired cases has increased, the overall rate of new cases, regardless of place of acquisition, continues to decrease. The crude case fatality rate in Australia remains low (1.4%), compared with the WHO reported global rate (6.9%). The low case fatality rate is likely reflective of high case detection and high quality of health care services in Australia. Deaths from COVID-19 in Australia have occurred predominantly among the elderly and those with comorbidities, with no deaths occurring in those under 40 years. The highest rate of COVID-19 continues to be among people aged 60-79 years. One third of all cases in this age group have been associated with several outbreaks linked to cruise ships. The lowest rate of disease is in young children, a pattern reflected in international reports. Internationally, while the number of new cases each day remains relatively stable at the global level, some areas such as Brazil and India are showing a dramatic rise in reported cases. Although some low-income countries have so far reported few cases, it is possible that this is due to limited diagnostic and public health capacity, and may not be reflective of true disease incidence.", "title": "COVID-19, Australia: Epidemiology Report 16 (Reporting week to 23:59 AEST 17 May 2020)", "pid": "megipjpn", "bm25_score": 215.3309783935547}, {"text": "We paired high-resolution travel-time metrics with a SARS-CoV-2 testing location database in the United States. Median travel time to testing sites is longer in counties with lower population density, and a higher percent of minority and uninsured individuals. Differential geographic accessibility to testing can recapitulate healthcare disparities and bias transmission estimates.", "title": "Geographic access to United States SARS-CoV-2 testing sites highlights healthcare disparities and may bias transmission estimates", "pid": "goup6xtg", "bm25_score": 215.30197143554688}, {"text": "Abstract Background With its epicenter in Wuhan, China, the COVID-19 outbreak was declared a pandemic by the World Health Organization (WHO). While many countries have implemented flight restrictions to China, an increasing number of cases with or without travel background to China are confirmed daily. These developments support concerns on possible unidentified and unreported international COVID-19 cases, which could lead to new local disease epicenters. Methods We have analyzed all available data on the development of international COVID-19 cases from January 20th, 2020 until February 18th, 2020. COVID-19 cases with and without travel history to China were divided into cohorts according to the Healthcare Access and Quality Index (HAQ-Index) of each country. Chi-square and Post-hoc testing were performed. Results While COVID-19 cases with travel history to China seem to peak for each HAQ-cohort, the number of non-travel related COVID-19 cases seem to continuously increase in the HAQ-cohort of countries with higher medical standards. Further analyses demonstrate a significantly lower proportion of reported COVID-19 cases without travel history to China in countries with lower HAQ (HAQ I vs. HAQ II, posthoc p < 0.01). Conclusions Our data indicate that countries with lower HAQ-index may either underreport COVID-19 cases or are unable to adequately detect them. Although our data may be incomplete and must be interpreted with caution, inconsistencies in reporting COVID-19 cases is a serious problem which might sabotage efforts to contain the virus.", "title": "Internationally lost COVID-19 cases", "pid": "l0zv0xuw", "bm25_score": 215.29922485351562}, {"text": "The publicly available data on COVID-19 cases provides an opportunity to better understand this new disease. However, strong attention needs to be paid to the limitations of the data to avoid making inaccurate conclusions. This article, which focuses on the relationship between the weather and COVID-19, raises the concern that the same factors influencing the spread of the disease might also affect the number of tests performed and who gets tested. For example, weather conditions impact the prevalence of respiratory diseases with symptoms similar to COVID-19, and this will likely influence the number of tests performed. This general limitation could severely undermine any similar analysis using existing COVID-19 data or similar epidemiological data, which could, therefore, mislead decision-makers on questions of great policy relevance.", "title": "The Challenge of Using Epidemiological Case Count Data: The Example of Confirmed COVID-19 Cases and the Weather", "pid": "0jm73t0s", "bm25_score": 215.29905700683594}, {"text": "Since the beginning of March 2020, the cumulative numbers of cases of infection with the novel coronavirus SARS-CoV-2 in Germany have been reported on a daily basis. The reports originate from national laws, according to which positive test findings must be submitted to the Federal Health Authorities, the Robert Koch Institute, via the local health authorities. Since an enormous number of unreported cases can be expected, the question of how widespread the disease has been in the population cannot be answered based on these administrative reports. Using mathematical modeling, however, estimates can be made. These estimates indicate that the small numbers of diagnostic tests carried out at the beginning of the outbreak overlooked considerable parts of the infection. In order to cover the initial phase of future waves of the disease, wide-spread and comprehensive tests are recommended.", "title": "Estimation of the actual disease occurrence based on official case numbers during a COVID outbreak in Germany 2020", "pid": "d8gl78lg", "bm25_score": 215.29217529296875}, {"text": "Background: In December 2019, an outbreak of respiratory illness caused by a novel coronavirus (2019-nCoV) emerged in Wuhan, China and has swiftly spread to other parts of China and a number of foreign countries. The 2019-nCoV cases might have been under-reported roughly from 1 to 15 January 2020, and thus we estimated the number of unreported cases and the basic reproduction number, R(0), of 2019-nCoV. Methods: We modelled the epidemic curve of 2019-nCoV cases, in mainland China from 1 December 2019 to 24 January 2020 through the exponential growth. The number of unreported cases was determined by the maximum likelihood estimation. We used the serial intervals (SI) of infection caused by two other well-known coronaviruses (CoV), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) CoVs, as approximations of the unknown SI for 2019-nCoV to estimate R(0). Results: We confirmed that the initial growth phase followed an exponential growth pattern. The under-reporting was likely to have resulted in 469 (95% CI: 403–540) unreported cases from 1 to 15 January 2020. The reporting rate after 17 January 2020 was likely to have increased 21-fold (95% CI: 18–25) in comparison to the situation from 1 to 17 January 2020 on average. We estimated the R(0) of 2019-nCoV at 2.56 (95% CI: 2.49–2.63). Conclusion: The under-reporting was likely to have occurred during the first half of January 2020 and should be considered in future investigation.", "title": "Estimating the Unreported Number of Novel Coronavirus (2019-nCoV) Cases in China in the First Half of January 2020: A Data-Driven Modelling Analysis of the Early Outbreak", "pid": "l8bv5t3o", "bm25_score": 215.28717041015625}, {"text": "", "title": "Covid-19: Lack of testing in Brazil is a \"major failure,\" says MSF.", "pid": "luqlfphw", "bm25_score": 215.28021240234375}, {"text": "Background: COVID-19 originated in China and has quickly spread worldwide causing a pandemic. Countries need rapid data on the prevalence of the virus in communities to enable rapid containment. However, the equipment, human and laboratory resources required for conducting individual RT-PCR is prohibitive. One technique to reduce the number of tests required is the pooling of samples for analysis by RT-PCR prior to testing. Methods: We conducted a mathematical analysis of pooling strategies for infection rate classification using group testing and for the identification of individuals by testing pooled clusters of samples. Findings: On the basis of the proposed pooled testing strategy we calculate the probability of false alarm, the probability of detection, and the average number of tests required as a function of the pool size. We find that when the sample size is 256, with a maximum pool size of 64, with only 7.3 tests on the average, we can distinguish between prevalences of 1% and 5% with a probability of detection of 95% and probability of false alarm of 4%. Interpretation: The pooling of RT-PCR samples is a cost-effective technique for providing much-needed course-grained data on the prevalence of COVID-19. This is a powerful tool in providing countries with information that can facilitate a response to the pandemic that is evidence-based and saves the most lives possible with the resources available.", "title": "Pooling RT-PCR or NGS samples has the potential to cost-effectively generate estimates of COVID-19 prevalence in resource limited environments", "pid": "6ob3u2e2", "bm25_score": 215.27076721191406}, {"text": "Speed is critical in the response to COVID-19 So why has the United States been so slow in its attempt to develop reliable diagnostic tests and use them widely? The World Health Organization (WHO) has shipped testing kits to 57 countries China had five commercial tests on the market 1 month ago and can now do up to 1 6 million tests a week;South Korea has tested 65,000 people so far The U S Centers for Disease Control and Prevention (CDC), in contrast, has done only 459 tests since the epidemic began The rollout of a CDC-designed test kit to state and local labs has become a fiasco because it contained a faulty reagent Labs around the country eager to test more suspected cases—and test them faster—have been unable to do so No commercial or state labs have the approval to use their own tests In what is already an infamous snafu, CDC initially refused a request to test a patient in Northern California who turned out to be the first probable COVID19 case without known links to an infected person", "title": "The United States badly bungled coronavirus testing—but things may soon improve ;Science ;AAAS", "pid": "lxjhz079", "bm25_score": 215.26905822753906}, {"text": "Background: Cases with negative reverse transcription-polymerase chain reaction (RT-PCR) results at initial testing for suspicion of SARS-CoV-2 infection, and found to be positive in a subsequent test, are considered as RT-PCR false-negative cases. False-negative cases have important implications for COVID-19 management, isolation, and risk of transmission. We aimed to review and critically appraise evidence about the proportion of RT-PCR false-negatives at initial testing for COVID-19. Methods: We performed a systematic review and critical appraisal of literature with high involvement of stakeholders in the review process. We searched on MEDLINE, EMBASE, LILACS, the WHO database of COVID-19 publications, the EPPI-Centre living systematic map of evidence about COVID-19, and the living systematic review developed by the University of Bern (ISPM). Two authors screened and selected studies according to the eligibility criteria and collected data of included studies (no-independent verification). Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. We calculated the false-negative proportion with the corresponding 95% CI using a multilevel mixed-effect logistic regression model using STATA 16. Certainty of the evidence about false-negative cases was rated using the GRADE approach for tests and strategies. The information is current up to 6 April 2020. Findings: Five studies enrolling 957 patients were included. All studies were affected by several biases and applicability concerns. Pooled estimation of false-negative proportion was 0.085 (95% CI= 0.034 to 0.196; tau-squared = 1.08; 95% CI= 0.27 to 8.28; p<0.001); however, this estimation is highly affected by unexplained heterogeneity, and its interpretation should be avoided. The certainty of the evidence was judged as very low, due to the risk of bias, indirectness, and inconsistency issues. Conclusions: The collected evidence has several limitations, including risk of bias issues, high heterogeneity, and concerns about its applicability. Nonetheless, our findings reinforce the need for repeated testing in patients with suspicion of SARS-Cov-2 infection given that up to 29% of patients could have an initial RT-PCR false-negative result. Systematic review registration: Protocol available on OSF website: https://osf.io/gp38w/", "title": "FALSE-NEGATIVE RESULTS OF INITIAL RT-PCR ASSAYS FOR COVID-19: A SYSTEMATIC REVIEW", "pid": "g8h6trql", "bm25_score": 215.26858520507812}, {"text": "Background: A novel coronavirus disease 2019 (COVID-19) broke out in Wuhan of Hubei province and had spread throughout the world since December 2019. Because the clinically diagnosed cases in Hubei province were reported for the first time on February 13, 2020, a very high peak of new cases in China was observed. The reason why so many clinically diagnosed cases appeared was not clear. Methods: All data of new cases in China were acquired from WHO situation reports. Linear fitting was used to infer the ability to detect COVID-19 infections. Primer-BLAST and nucleotide blast were applied to check the specificity of primers. Expression data of human mRNA in different tissues was obtained from Human Protein Atlas. Finding: Based on the data and analysis of changes of new laboratory-confirmed cases and new clinically diagnosed cases, it was inferred that there were many false-negative results in all clinically diagnosed cases in Hubei province. There were eight non-specific primers in dozens of primers used in clinical or research detection of COVID-19. Among them, a pair of primer for the ORF1ab regions of SARS-CoV-2 genome, which widely applied to detect SARS-CoV-2 virus in China, well matched some human mRNAs such as Cathepsin C transcripts. Compared to other transcripts, Cathepsin C mRNA had a high abundance in tonsil, lung and small intestine. Interpretation: Some non-specific RT-PCR primers could cause the serious interference during RT-PCR amplification so as to increase the risk of false-negative diagnoses for COVID-19 infections. Funding Key Research Project of the Higher Education of Henan Province", "title": "Non-specific Primers Reveal False-negative Risk in Detection of COVID-19 Infections", "pid": "g1hczx54", "bm25_score": 215.2649688720703}, {"text": "There is some consensus in Europe and Asia about testing rates being crucial to controlling COVID-19 pandemics. There are though misconceptions on what means an effective high testing rate. This paper demonstrates that the rate of tests per detected case (Tests/Case) is the important variable, correlating negatively with the number of deaths. The higher the Tests/Case rate, the lower the death rate, as this predictor is causally related to contact tracing and isolation of the vectors of the disease. Doubling Tests/Case typically divides by three the number of deaths. On the other hand, per capita testing rate is a poor predictor for the performance of policies to fight the pandemics. The number of tests per 1,000 inhabitants (Tests/1,000) tends to correlate positively with the number of deaths. In some cases, high levels of Tests/1,000 just mean an epidemic that ran out of control, with an explosion of cases that demands high testing rates just to confirm the diagnosis of the very sick.", "title": "Testing for tracing or testing just for treating? A comparative analysis between strategies to face COVID-19 pandemic.", "pid": "rjzther1", "bm25_score": 215.2550506591797}, {"text": "COVID-19 testing studies have become a standard approach for estimating prevalence and fatality rates which then assist in public health decision making to contain and mitigate the spread of the disease. The sampling designs used are often biased in that they do not reflect the true underlying populations. For instance, individuals with strong symptoms are more likely to be tested than those with no symptoms. This results in biased estimates of prevalence (too high) and over-estimation of fatality rates. Typical post-sampling corrections are not always possible. Here we present a simple bias correction methodology derived and adapted from a correction for publication bias in meta analysis studies. The methodology is general enough to allow a wide variety of customization making it more useful in practice. Implementation is easily done using already collected information. We show via an example that the bias corrections can provide dramatic reductions in estimation error.", "title": "Estimation of testing bias in covid-19", "pid": "ee22gcx1", "bm25_score": 215.24984741210938}, {"text": "As of January 22, 2020, \"disease caused by a novel coronavirus\" became a reportable disease of public health significance in Ontario. Public health units were provided with guidance on the entry of patients tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus causing 2019 coronavirus disease (COVID-19), into the provincial public health information system. Between January 22 and February 22, 2020, there were 359 individuals who had a negative test result recorded and three confirmed cases of COVID-19. Of those who tested negative, 51% were female and 71% were under 50 years of age. The most common symptoms reported were cough (55%), fever (37%) and sore throat (35%). The majority were tested within three days of symptom onset, but over one-quarter tested more than seven days after symptom onset. Over the first month of reportability, reported travel history shifted from China to an increasing proportion with travel outside of China.", "title": "Surveillance of persons-who tested negative for COVID-19 in Ontario, January 22-February 22, 2020.", "pid": "z2zt4fs2", "bm25_score": 215.24420166015625}, {"text": "The world is suffering from a pandemic called COVID-19, caused by the SARS-CoV-2 virus. National governments have problems evaluating the reach of the epidemic, due to having limited resources and tests at their disposal. This problem is especially acute in low and middle-income countries (LMICs). Hence, any simple, cheap and flexible means of evaluating the incidence and evolution of the epidemic in a given country with a reasonable level of accuracy is useful. In this paper, we propose a technique based on (anonymous) surveys in which participants report on the health status of their contacts. This indirect reporting technique, known in the literature as network scale-up method, preserves the privacy of the participants and their contacts, and collects information from a larger fraction of the population (as compared to individual surveys). This technique has been deployed in the CoronaSurveys project, which has been collecting reports for the COVID-19 pandemic for more than two months. Results obtained by CoronaSurveys show the power and flexibility of the approach, suggesting that it could be an inexpensive and powerful tool for LMICs.", "title": "CoronaSurveys: Using Surveys with Indirect Reporting to Estimate the Incidence and Evolution of Epidemics", "pid": "e1ovtngw", "bm25_score": 215.22093200683594}, {"text": "Reverse transcription-polymerase chain reaction (RT-PCR) assays are used to test patients and key workers for infection with the causative SARS-CoV-2 virus. RT-PCR tests are highly specific and the probability of false positives is low, but false negatives can occur if the sample contains insufficient quantities of the virus to be successfully amplified and detected. The amount of virus in a swab is likely to vary between patients, sample location (nasal, throat or sputum) and through time as infection progresses. Here, we analyse publicly available data from patients who received multiple RT-PCR tests and were identified as SARS-CoV-2 positive at least once. We identify that the probability of a positive test decreases with time after symptom onset, with throat samples less likely to yield a positive result relative to nasal samples. Empirically derived distributions of the time between symptom onset and hospitalisation allowed us to comment on the likely false negative rates in cohorts of patients who present for testing at different clinical stages. We further estimate the expected numbers of false negative tests in a group of tested individuals and show how this is affected by the timing of the tests. Finally, we assessed the robustness of these estimates of false negative rates to the probability of false positive tests. This work has implications both for the identification of infected patients and for the discharge of convalescing patients who are potentially still infectious.", "title": "Estimating false-negative detection rate of SARS-CoV-2 by RT-PCR", "pid": "qolbq8ul", "bm25_score": 215.20748901367188}, {"text": "The reported number of new cases underestimates the real spread of COVID-19 pandemic because of non-tested asymptomatic people and limited global access to reliable diagnostic tests. In this context, COVID-19 mortality with confirmed diagnosis becomes an attractive source of information to be included in the analysis of perspectives and proposals. Objective data are required to calculate the capacity of resources provided by health systems. New strategies are needed to stabilize or minimize the mortality surge. However, we will not afford this goal until more alternatives were available. We still need an effective treatment, an affordable vaccine, or a collective achievement of sufficient immunity (reaching up to 70% of the whole population). At any time, the arriving waves of the pandemic are testing the capacity of governments. The health services struggle to keep the plateau in a steady-state below 100 deaths per million inhabitants. Therefore, it is necessary to increase the alternatives and supplies based on the current and near-future expected demands imposed by the number of deaths by COVID-19. Estimating COVID-19 mortality in various scenarios with the gradual release of social constraints will help predict the magnitude of those arriving waves.", "title": "COVID-19 Waves: Importance of Accumulative Mortality per Million Inhabitants.", "pid": "qdxccgea", "bm25_score": 215.20579528808594}, {"text": "In December-2019 China reported several cases of a novel coronavirus later called COVID-19. In this work, we will use a probabilistic method for approximating the true daily numbers of infected. Based on two distribution functions to describe the spontaneous recovered cases on the one hand and the detected cases on the other hand. The impact of the underlying variables of these functions is discussed. The detected rate is predicted to be between 5.3% and 10,8%, which means that there would be about 38 million infected until now (10-May 2020), rather than the officially declared number of 3.99 million worldwide cases.", "title": "On the true numbers of COVID-19 infections: behind the available data", "pid": "o66rchhw", "bm25_score": 215.20416259765625}, {"text": "Different COVID-19 testing approaches have been implemented among Italian regions, reflected in heterogeneous testing rates. We analysed the number COVID-19-related deaths in relation to the number of tests performed among the most hit Italian regions. We showed that regions with the highest number of tests performed (Veneto and Toscana) had the lowest 30-day crude mortality rate per 100,000 inhabitants. In addition, an inverse association between crude mortality rates and tests performed (mortality rate ratio for unit increase in tests per 1,000 inhabitants: 0.92; 95% CI 0.89-0.94) was observed. Early identification and isolation of active cases (including asymptomatic or mildly symptomatic subjects) could have had an important effect in lowering COVID-19 mortality.", "title": "Higher testing coverage is associated with lower COVID-19 mortality rate: insights from Italian regions.", "pid": "th2byzpj", "bm25_score": 215.1956024169922}, {"text": "As of January 22, 2020, \"disease caused by a novel coronavirus\" became a reportable disease of public health significance in Ontario. Public health units were provided with guidance on the entry of patients tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus causing 2019 coronavirus disease (COVID-19), into the provincial public health information system. Between January 22 and February 22, 2020, there were 359 individuals who had a negative test result recorded and three confirmed cases of COVID-19. Of those who tested negative, 51% were female and 71% were under 50 years of age. The most common symptoms reported were cough (55%), fever (37%) and sore throat (35%). The majority were tested within three days of symptom onset, but over one-quarter tested more than seven days after symptom onset. Over the first month of reportability, reported travel history shifted from China to an increasing proportion with travel outside of China.", "title": "Surveillance of persons-who tested negative for COVID-19 in Ontario, January 22-February 22, 2020", "pid": "cgk8dxv5", "bm25_score": 215.18936157226562}, {"text": "OBJECTIVES: To determine the public health surveillance severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing volume needed, both for acute infection and seroprevalence. METHODS: Required testing volumes were developed using standard statistical methods based on test analytical performance, disease prevalence, desired precision, and population size. RESULTS: Widespread testing for individual health management cannot address surveillance needs. The number of people who must be sampled for public health surveillance and decision making, although not trivial, is potentially in the thousands for any given population or subpopulation, not millions. CONCLUSIONS: While the contributions of diagnostic testing for SARS-CoV-2 have received considerable attention, concerns abound regarding the availability of sufficient testing capacity to meet demand. Different testing goals require different numbers of tests and different testing strategies; testing strategies for national or local disease surveillance, including monitoring of prevalence, receive less attention. Our clinical laboratory and diagnostic infrastructure are capable of incorporating required volumes for many local, regional, and national public health surveillance studies into their current and projected testing capacity. However, testing for surveillance requires careful design and randomization to provide meaningful insights.", "title": "Linking Statistics With Testing Policy to Manage COVID-19 in the Community", "pid": "istyeebn", "bm25_score": 215.18325805664062}, {"text": "Confirmed Case Data have been widely cited during the current COVID-19 pandemic as an estimate of the spread of the SARS-CoV-2 virus. However, their central role in media, official reports and decision-making may be undeserved and misleading. Previously published Infection Fatality Rates were weighted by age structure in the 50 countries with more reported deaths to obtain country-specific rates. For each country, the number of infections up to the Infection Date (23 days ago = Incubation Period + Onset to Death period) and the present percentage of immune population were estimated using Infection Fatality Rate, the number of reported deaths (which is less prone to undersampling), and projecting back to Infection Date. We then estimated a Detection Index for each country as the percentage of estimated infections that confirmed cases represent. Assuming that detection remains constant after Infection Date, we estimated the number of deaths and the estimated percentage of the population of each country expected to be immune up to 23 days into the future. Estimated Infection Fatality Rates are higher in Europe. In most countries, confirmed cases currently represent less than 30% of estimated infections on Infection Date, and this value decreases with time. Countries with flat curves throughout the pandemic show the lowest immunity percentages and these values seem unlikely to change in the near future, suggesting that they remain vulnerable to new outbreaks. Estimates for some countries with low Infection Fatality Rates suggest a still steep increase in the number of casualties in the next three weeks. Countries that did not control initial outbreaks seem to have reached higher immunity percentages, although mostly still under 5%. We provide the code to monitor the trajectories of these estimates in 178 countries throughout the COVID-19 pandemic.", "title": "The misleading illusion of COVID-19 confirmed case data: alternative estimates and a monitoring tool", "pid": "z9r5i0ky", "bm25_score": 215.18304443359375}, {"text": "We estimate the number of COVID-19 cases from newly reported deaths in a population without previous reports. Our results suggest that by the time a single death occurs, hundreds to thousands of cases are likely to be present in that population. This suggests containment via contact tracing will be challenging at this point, and other response strategies should be considered. Our approach is implemented in a publicly available, user-friendly, online tool.", "title": "Inferring the number of COVID-19 cases from recently reported deaths", "pid": "zklwovba", "bm25_score": 215.16693115234375}, {"text": "Policymakers need a clear and fast assessment of the real spread of the epidemic of COVID-19 in each of their respective countries. Standard measures of the situation provided by the governments include reported positive cases and total deaths. While total deaths immediately indicate that countries like Italy and Spain have the worst situation as of mid April 2020, on its own, reported cases do not provide a correct picture of the situation. The reason is that different countries diagnose diversely and present very distinctive reported case fatality rate (CFR). The same levels of reported incidence and mortality might hide a very different underlying picture. Here we present a straightforward and robust estimation of the diagnostic rate in each European country. From that estimation we obtain an uniform unbiased incidence of the epidemic. The method to obtain the diagnostic rate is transparent and empiric. The key assumption of the method is that the real CFR in Europe of COVID-19 is not strongly country-dependent. We show that this number is not expected to be biased due to demography nor the way total deaths are reported. The estimation protocol has a dynamic nature, and it has been giving converging numbers for diagnostic rates in all European countries as of mid April 2020. From this diagnostic rate, policy makers can obtain an Effective Potential Growth (EPG) updated everyday providing an unbiased assessment of the countries with more potential to have an uncontrolled situation. The method developed will be used to track possible improvements on the diagnostic rate in European countries as the epidemic evolves.", "title": "Robust estimation of diagnostic rate and real incidence of COVID-19 for European policymakers", "pid": "oj3v1x99", "bm25_score": 215.16322326660156}, {"text": "To optimize epidemiologic interventions, predictors of mortality should be identified. The US COVID-19 epidemic data, reported up to 31 March 2020, were analyzed using kernel regularized least squares regression. Six potential predictors of mortality were investigated: (i) the number of diagnostic tests performed in testing week I; (ii) the proportion of all tests conducted during week I of testing; (iii) the cumulative number of (test-positive) cases through 3-31-2020, (iv) the number of tests performed/million citizens; (v) the cumulative number of citizens tested; and (vi) the apparent prevalence rate, defined as the number of cases/million citizens. Two metrics estimated mortality: the number of deaths and the number of deaths/million citizens. While both expressions of mortality were predicted by the case count and the apparent prevalence rate, the number of deaths/million citizens was {approx}3.5 times better predicted by the apparent prevalence rate than the number of cases. In eighteen states, early testing/million citizens/population density was inversely associated with the cumulative mortality reported by 31 March, 2020. Findings support the hypothesis that early and massive testing saves lives. Other factors --e.g., population density-- may also influence outcomes. To optimize national and local policies, the creation and dissemination of high resolution geo-referenced, epidemic data is recommended.", "title": "Early and massive testing saves lives: COVID-19 related infections and deaths in the United States during March of 2020", "pid": "z2zwdxrk", "bm25_score": 215.15248107910156}, {"text": "", "title": "Covid-19: Lack of capacity led to halting of community testing in March, admits deputy chief medical officer.", "pid": "w0sb4qnl", "bm25_score": 215.1473388671875}, {"text": "Confirmed cases in Australia notified up to 24 May 2020: notifications = 7,135; deaths = 102. The incidence of COVID-19 has markedly reduced since a peak in mid-March. There have been no cases reported in SA, the NT or the ACT in the last four weeks. The numbers of new cases reported from other jurisdictions continue to be very low. Testing rates have been higher across all jurisdictions, with Victoria reporting an 85% testing rate increase and NSW a 40% increase over this period. The positivity rate nationally continues to remain very low at less than 0.1% over the reporting period. Continued high rates of testing are necessary to detect and mitigate the spread of COVID-19 in the community. Over the past fortnight, 45% of cases acquired their infection overseas. Of cases considered to be locally acquired over this period, most were associated with contacts of confirmed cases or were associated with known outbreaks. The highest rate of COVID-19 continues to be among people aged 65-79 years. Three-quarters of all cases in this age group have been associated with overseas travel, including several outbreaks linked to cruise ships. The lowest rate of disease is in children under 18, a pattern reflected in international reports. A small proportion of cases overall have experienced severe disease, requiring hospitalisation or intensive care with some fatalities. The crude case fatality rate amongst Australian cases is 1.4%. People who are older and have one or more comorbidities are more likely to experience severe disease. A combination of early case identification, physical distancing, public health measures and a reduction in international travel have likely been effective in slowing the spread of the disease in Australia. In addition, the median number of days between symptom onset and diagnostic testing has improved considerably from 7 days in the early phase of the outbreak to 1 day in the latest phase of the epidemic. Internationally, as at 24 May 2020, there have been recent increases in the number of daily cases reported globally. The largest numbers of both cases and deaths have been reported in the United States. Of the confirmed cases reported globally, the case fatality rate is approximately 6.5%. Countries in South America are starting to see rapid acceleration, while the United States is seeing a very slow decline in its daily new case numbers. In the South East Asia region, India and Bangladesh are seeing accelerating epidemics, compounded by the recovery from Cyclone Amphan. Increasing numbers of cases are also being reported in Africa, although the numbers are much smaller. In the Pacific there are very few daily new cases reported.", "title": "COVID-19, Australia: Epidemiology Report 17 (Fortnightly reporting period ending 24 May 2020)", "pid": "hnc8thas", "bm25_score": 215.1467742919922}, {"text": "This article offers a reflection on the testing strategies deployed in the generation of epidemiological data in the European Union (EU). I will argue that, while in the early days of the pandemic, Member States proceeded to testing in a rather scattered way, the shortage of resources seems to have acted as a driver of coordination, which is now increasingly being discussed at EU level. I will examine the legal and institutional framework supporting such embryonic coordination efforts and offer a preliminary assessment of their implications for a European approach to epidemiological knowledge-making.", "title": "I Just Can’t Get Enough (of Experts): The Numbers of COVID-19 and the Need for a European Approach to Testing", "pid": "25v2z9jn", "bm25_score": 215.1343231201172}, {"text": "The relative case fatality rates (CFRs) between groups and countries are key measures of relative risk that guide policy decisions regarding scarce medical resource allocation during the ongoing COVID-19 pandemic. In the middle of an active outbreak when surveillance data is the primary source of information, estimating these quantities involves compensating for competing biases in time series of deaths, cases, and recoveries. These include time- and severity- dependent reporting of cases as well as time lags in observed patient outcomes. In the context of COVID-19 CFR estimation, we survey such biases and their potential significance. Further, we analyze theoretically the effect of certain biases, like preferential reporting of fatal cases, on naive estimators of CFR. We provide a partially corrected estimator of these naive estimates that accounts for time lag and imperfect reporting of deaths and recoveries. We show that collection of randomized data by testing the contacts of infectious individuals regardless of the presence of symptoms would mitigate bias by limiting the covariance between diagnosis and death. Our analysis is supplemented by theoretical and numerical results and a simple and fast open-source codebase at https://github.com/aangelopoulos/cfr-covid-19 .", "title": "On Identifying and Mitigating Bias in the Estimation of the COVID-19 Case Fatality Rate", "pid": "29izbpf8", "bm25_score": 215.1329345703125}, {"text": "The number of confirmed cases of COVID-19 is often used as a proxy for the actual number of ground truth COVID-19 infected cases in both public discourse and policy making. However, the number of confirmed cases depends on the testing policy, and it is important to understand how the number of positive cases obtained using different testing policies reveals the unknown ground truth. We develop an agent-based simulation framework in Python that can simulate various testing policies as well as interventions such as lockdown based on them. The interaction between the agents can take into account various communities and mobility patterns. A distinguishing feature of our framework is the presence of another `flu'-like illness with symptoms similar to COVID-19, that allows us to model the noise in selecting the pool of patients to be tested. We instantiate our model for the city of Bengaluru in India, using census data to distribute agents geographically, and traffic flow mobility data to model long-distance interactions and mixing. We use the simulation framework to compare the performance of three testing policies: Random Symptomatic Testing (RST), Contact Tracing (CT), and a new Location Based Testing policy (LBT). We observe that if a sufficient fraction of symptomatic patients come out for testing, then RST can capture the ground truth quite closely even with very few daily tests. However, CT consistently captures more positive cases. Interestingly, our new LBT, which is operationally less intensive than CT, gives performance that is comparable with CT. In another direction, we compare the efficacy of these three testing policies in enabling lockdown, and observe that CT flattens the ground truth curve maximally, followed closely by LBT, and significantly better than RST.", "title": "How Reliable are Test Numbers for Revealing the COVID-19 Ground Truth and Applying Interventions?", "pid": "7bvsf5dk", "bm25_score": 215.1322784423828}, {"text": "", "title": "Covid-19: Lack of capacity led to halting of community testing in March, admits deputy chief medical officer", "pid": "srpgfh3h", "bm25_score": 215.12413024902344}, {"text": "Confirmed cases in Australia notified up to 24 May 2020: notifications = 7,135; deaths = 102. The incidence of COVID-19 has markedly reduced since a peak in mid-March. There have been no cases reported in SA, the NT or the ACT in the last four weeks. The numbers of new cases reported from other jurisdictions continue to be very low. Testing rates have been higher across all jurisdictions, with Victoria reporting an 85% testing rate increase and NSW a 40% increase over this period. The positivity rate nationally continues to remain very low at less than 0.1% over the reporting period. Continued high rates of testing are necessary to detect and mitigate the spread of COVID-19 in the community. Over the past fortnight, 45% of cases acquired their infection overseas. Of cases considered to be locally acquired over this period, most were associated with contacts of confirmed cases or were associated with known outbreaks. The highest rate of COVID-19 continues to be among people aged 65-79 years. Three-quarters of all cases in this age group have been associated with overseas travel, including several outbreaks linked to cruise ships. The lowest rate of disease is in children under 18, a pattern reflected in international reports. A small proportion of cases overall have experienced severe disease, requiring hospitalisation or intensive care with some fatalities. The crude case fatality rate amongst Australian cases is 1.4%. People who are older and have one or more comorbidities are more likely to experience severe disease. A combination of early case identification, physical distancing, public health measures and a reduction in international travel have likely been effective in slowing the spread of the disease in Australia. In addition, the median number of days between symptom onset and diagnostic testing has improved considerably from 7 days in the early phase of the outbreak to 1 day in the latest phase of the epidemic. Internationally, as at 24 May 2020, there have been recent increases in the number of daily cases reported globally. The largest numbers of both cases and deaths have been reported in the United States. Of the confirmed cases reported globally, the case fatality rate is approximately 6.5%. Countries in South America are starting to see rapid acceleration, while the United States is seeing a very slow decline in its daily new case numbers. In the South East Asia region, India and Bangladesh are seeing accelerating epidemics, compounded by the recovery from Cyclone Amphan. Increasing numbers of cases are also being reported in Africa, although the numbers are much smaller. In the Pacific there are very few daily new cases reported.", "title": "COVID-19, Australia: Epidemiology Report 17 (Fortnightly reporting period ending 24 May 2020).", "pid": "6q883j4f", "bm25_score": 215.122802734375}, {"text": "Background: Rapid testing for an infection is paramount during a pandemic to prevent continued viral spread and excess morbidity and mortality. This study aimed to determine whether alternative testing strategies based on sample pooling can increase the speed and throughput of screening for SARS-CoV-2. Methods: A mathematical modelling approach was chosen to simulate six different testing strategies based on key input parameters (infection rate, test characteristics, population size, testing capacity etc.). The situations in five countries (US, DE, UK, IT and SG) currently experiencing COVID-19 outbreaks were simulated to reflect a broad variety of population sizes and testing capacities. The primary study outcome measurements that were finalised prior to any data collection were time and number of tests required; number of cases identified; and number of false positives. Findings: The performance of all tested methods depends on the input parameters, i.e. the specific circumstances of a screening campaign. To screen one tenth of each country's population at an infection rate of 1% - e.g. when prioritising frontline medical staff and public workers -, realistic optimised testing strategies enable such a campaign to be completed in ca. 29 days in the US, 71 in the UK, 25 in Singapore, 17 in Italy and 10 in Germany (ca. eight times faster compared to individual testing). When infection rates are considerably lower, or when employing an optimal, yet logistically more complex pooling method, the gains are more pronounced. Pool-based approaches also reduces the number of false positive diagnoses by 50%. Interpretation: The results of this study provide a clear rationale for adoption of pool-based testing strategies to increase speed and throughput of testing for SARS-CoV-2. The current individual testing approach unnecessarily wastes valuable time and resources.", "title": "Evaluation of Pool-based Testing Approaches to Enable Population-wide Screening for COVID-19", "pid": "vf3vexi1", "bm25_score": 215.120849609375}, {"text": "Background: Following a consistent decline in COVID-19-related deaths in the UK throughout May 2020, it is recognised that contact tracing will be vital to relaxing physical distancing measures. The increasingly evident role of asymptomatic and pre-symptomatic transmission means testing is central to control, but test sensitivity estimates are as low as 65%. Methods: We extend an existing UK-focused branching process model for contact tracing, adding diagnostic testing and refining parameter estimates to demonstrate the impact of poor test sensitivity and suggest mitigation methods. We also investigate the role of super-spreading events, providing estimates of the relationship between infections, cases detected and hospitalisations, and consider how tracing coverage and speed affects outbreak risk. Findings: Incorporating poor sensitivity testing into tracing protocols could reduce efficacy, due to false negative results impacting isolation duration. However, a 7-day isolation period for all negative-testing individuals could mitigate this effect. Similarly, reducing delays to testing following exposure has a negligible impact on the risk of future outbreaks, but could undermine control if negative-testing individuals immediately cease isolating. Even 100% tracing of contacts will miss cases, which could prompt large localised outbreaks if physical distancing measures are relaxed prematurely. Interpretation: It is imperative that test results are interpreted with caution due to high false-negative rates and that contact tracing is used in combination with physical distancing measures. If the risks associated with imperfect test sensitivity are mitigated, we find that contact tracing can facilitate control when the reproduction number with physical distancing, Rs, is less than 15.", "title": "An imperfect tool: COVID-19 'test & trace' success relies on minimising the impact of false negatives and continuation of physical distancing.", "pid": "7f9c4j5m", "bm25_score": 215.11416625976562}, {"text": "Background The outbreak of the novel coronavirus disease in 2019 (COVID-19) caused a major public health crisis worldwide and challenged healthcare systems across the six continents. The high infectivity of the disease led many governments to adopt strict regulations and measures with the aim of containing its spread. The purpose of this study is to assess the incidence, severity, and territorial expansion of COVID-19. Methods Data from the World Health Organization was screened, and COVID-19 situation reports were extracted from January 21 up till March 14 (inclusive). Our data included the total number of cases, total number of new cases, total number of cured cases, and total number of related deaths. Percentage change of cases over the days of our study were calculated using the Joinpoint regression, with a significance level set at greater than 0.05. Results The total number of COVID-19 cases reached 156,622, with 5,845 subsequent deaths. China, Italy, and Iran have the highest number of cases worldwide. During the first 22 days, the incidence rate of COVID-19 increased significantly to reach 1.81 cases per million persons (p<0.001). That was followed by a significant decrease over the next 11 days (p<0.001) to reach 0.071 cases per million persons. A steady rise then followed, which saw a significant increase in incidence rate to 1.429 cases per million persons (p<0.001). Percentages of death and cured cases varied across the different countries; nevertheless, death percentages have generally been decreasing since the start of the crisis. Conclusion Adopting precautionary regulations such as social isolation, increasing sanitation, and employing strict quarantine measures have proved to be beneficial in containing the virus. Further research needs to be conducted to help discover therapeutic modalities and improve outcomes.", "title": "An Epidemiological Study on COVID-19: A Rapidly Spreading Disease", "pid": "52c7myio", "bm25_score": 215.1099090576172}, {"text": "We develop a simple analytical method to estimate the fraction of unreported infections in epidemics with a known epicenter and estimate the number of unreported COVID-19 infections in the US during the first half of March 2020. Our method utilizes the covariation in initial reported infections across US regions and the number of travelers to these regions from the epicenter, along with the results of a randomized testing study in Iceland. We estimate that 4%-14% (1.5%-10%) of actual infections had been reported in US up to March 16, accounting for an assumed reporting lag of 8 (5) days.", "title": "Estimating the Fraction of Unreported Infections in Epidemics with a Known Epicenter: an Application to COVID-19", "pid": "pv9risbr", "bm25_score": 215.1026153564453}, {"text": "Approximately 90 days of the SARS-CoV-2 (COVID-19) spreading originally from Wuhan, China, and across the globe has led to a widespread chain of events with imminent threats to the fragile relationship between community health and economic health. Despite near hourly reporting on this crisis, there has been no regular, updated, or accurate reporting of hospitalizations for COVID-19. It is known that many test-positive individuals may not develop symptoms or have a mild self-limited viral syndrome consisting of fever, malaise, dry cough, and constitutional symptoms. However some individuals develop a more fulminant syndrome including viral pneumonia, respiratory failure requiring oxygen, acute respiratory distress syndrome requiring mechanical ventilation, and in substantial fractions leading to death attributable to COVID-19. The pandemic is evolving in a clustered, non-inform fashion resulting in many hospitals with preparedness but few or no cases, and others that are completely overwhelmed. Thus, a considerable risk of spread when personal protection equipment becomes exhausted and a large fraction of mortality in those not offered mechanical ventilation are both attributable to a crisis due to maldistribution of resources. The pandemic is amenable to self-reporting through a mobile phone application that could obtain critical information on suspected cases and report on the results of self testing and actions taken. The only method to understand the clustering and the immediate hospital resource needs is mandatory, uniform, daily reporting of hospital censuses of COVID-19 cases admitted to hospital wards and intensive care units. Current reports of hospitalizations are delayed, uncertain, and wholly inadequate. This paper urges all the relevant stakeholders to take up self-reporting and reporting of hospitalizations of COVID-19 as an urgent task in combating this devastating pandemic.", "title": "Urgent need for individual mobile phone and institutional reporting of at home, hospitalized, and intensive care unit cases of SARS-CoV-2 (COVID-19) infection", "pid": "03tzip4q", "bm25_score": 215.10182189941406}, {"text": "Pandemics have a profound impact on our world, causing loss of life, affecting our culture and historically shaping our genetics. The response to a pandemic requires both resilience and imagination. It has been clearly documented that obtaining an accurate estimate and trends of the actual infection rate and mortality risk are very important for policy makers and medical professionals. One cannot estimate mortality rates without an accurate assessment of the number of infected individuals in the population. This need is also aligned with identifying the infected individuals so they can be properly treated, monitored and tracked. However, accurate estimation of the infection rate, locally, geographically and nationally is important independently. These infection rate estimates can guide policy makers at both state, national or world level to achieve a better management of risk to society. The decisions facing policy makers are very different during early stages of an emerging epidemic where the infection rate is low, middle stages where the rate is rapidly climbing, and later stages where the epidemic curve has flattened to a low and relatively sustainable rate. In this paper we provide relatively efficient pooling methods to both estimate infection rates and identify infected individuals for populations with low infection rates. These estimates may provide significant cost reductions for testing in rural communities, third world countries and other situations where the cost of testing is expensive or testing is not widely available. As we prepare for the second wave of the pandemic this line of work may provide new solutions for both the biomedical community and policy makers at all levels.", "title": "Rate Estimation and Identification of COVID-19 Infections: Towards Rational Policy Making During Early and Late Stages of Epidemics", "pid": "47a4pu27", "bm25_score": 215.09202575683594}, {"text": "Detection of SARS-CoV-2 infections to date has relied on RT-PCR testing. However, a failure to identify early cases imported to a country, bottlenecks in RT-PCR testing, and the existence of infections which are asymptomatic, sub-clinical, or with an alternative presentation than the standard cough and fever have resulted in an under-counting of the true prevalence of SARS-CoV-2. Here, we show how publicly available CDC influenza-like illness (ILI) outpatient surveillance data can be repurposed to estimate the detection rate of symptomatic SARS-CoV-2 infections. We find a surge of non-influenza ILI above the seasonal average and show that this surge is correlated with COVID case counts across states. By quantifying the number of excess ILI patients in March relative to previous years and comparing excess ILI to confirmed COVID case counts, we estimate the syndromic case detection rate of SARS-CoV-2 in the US to be less than 13%. If only 1/3 of patients infected with SARS-CoV-2 sought care, the ILI surge would correspond to more than 8.7 million new SARS-CoV-2 infections across the US during the three week period from March 8 to March 28. Combining excess ILI counts with the date of onset of community transmission in the US, we also show that the early epidemic in the US was unlikely to be doubling slower than every 4 days. Together these results suggest a conceptual model for the COVID epidemic in the US in which rapid spread across the US are combined with a large population of infected patients with presumably mild-to-moderate clinical symptoms. We emphasize the importance of testing these findings with seroprevalence data, and discuss the broader potential to use syndromic time series for early detection and understanding of emerging infectious diseases.", "title": "Using ILI surveillance to estimate state-specific case detection rates and forecast SARS-CoV-2 spread in the United States", "pid": "17oac3bg", "bm25_score": 215.07635498046875}, {"text": "The gold standard for COVID-19 diagnosis is detection of viral RNA in a reverse transcription PCR test. Due to global limitations in testing capacity, effective prioritization of individuals for testing is essential. Here, we devised a model that estimates the probability of an individual to test positive for COVID-19 based on answers to 9 simple questions regarding age, gender, presence of prior medical conditions, general feeling, and the symptoms fever, cough, shortness of breath, sore throat and loss of taste or smell, all of which have been associated with COVID-19 infection. Our model was devised from a subsample of a national symptom survey that was answered over 2 million times in Israel over the past 2 months and a targeted survey distributed to all residents of several cities in Israel. Overall, 43,752 adults were included, from which 498 self-reported as being COVID-19 positive. The model provides statistically significant predictions on held-out individuals and achieves a positive predictive value (PPV) of 46.3% at a 10% sensitivity. As our tool can be used online and without the need of exposure to suspected patients, it may have worldwide utility in combating COVID-19 by better directing the limited testing resources through prioritization of individuals for testing, thereby increasing the rate at which positive individuals can be identified and isolated.", "title": "Who should we test for COVID-19?A triage model built from national symptom surveys", "pid": "ryibszjm", "bm25_score": 215.0726776123047}, {"text": "In the early months of the pandemic, most reported cases and deaths due to COVID-19 occurred in high-income countries. However, insufficient testing could have led to an underestimation of true infections in many low- and middle-income countries. As confirmed cases increase, the ultimate impact of the pandemic on individuals and communities in low- and middle-income countries is uncertain. We therefore propose research in three broad areas as urgently needed to inform responses in low- and middle-income countries: transmission patterns of SARS-CoV-2, the clinical characteristics of the disease, and the impact of pandemic prevention and response measures. Answering these questions will require a multidisciplinary approach led by local investigators and in some cases additional resources. Targeted research activities should be done to help mitigate the potential burden of COVID-19 in low- and middle-income countries without diverting the limited human resources, funding, or medical supplies from response activities.", "title": "The need for COVID-19 research in low- and middle-income countries", "pid": "uzrxtgrg", "bm25_score": 215.07260131835938}, {"text": "Comparison of COVID-19 case numbers over time and between locations is complicated by limits to virologic testing confirm SARS-CoV-2 infection, leading to under-reporting of incidence, and by variations in testing capacity between locations and over time. The proportion of tested individuals who have tested positive (test positive proportion, TPP) can potentially be used to qualitatively assess the testing capacity of a location; a high TPP could provide evidence that too few people are tested, leading to more under-reporting. In this study we propose a simple model for testing in a population experiencing an epidemic of COVID-19, and derive an expression for TPP in terms of well-defined parameters in the model, related to testing and presence of other pathogens causing COVID-19 like symptoms. We use simulations to show situations in which the TPP is higher or lower than we expect based on these parameters, and the effect of testing strategies on the TPP. In our simulations, we find in the absence of dramatic shifts of testing practices in time or between spatial locations, the TPP is positively correlated with the incidence of infection. As a corollary, the TPP can be used to distinguish between a decline in confirmed cases due to decline in incidence (in which case TPP should decline) and a decline in confirmed cases due to testing constraints (in which case TPP should remain constant). We show that the proportion of tested individuals who present COVID-19 like symptoms (test symptomatic proportion, TSP) encodes similar information to the TPP but has different relationships with the testing parameters, and can thus provide additional information regarding dynamic changes in TPP and incidence. Finally, we compare data on confirmed cases and TPP from US states. We conjecture why states may have higher or lower TPP than average. We suggest that collection of symptom status and age/risk category of tested individuals can aid interpretation of changes in TPP and increase the utility of TPP in assessing the state of the pandemic in different locations and times.", "title": "The usefulness of SARS-CoV-2 test positive proportion as a surveillance tool", "pid": "ole70vk0", "bm25_score": 215.05758666992188}, {"text": "A key challenge in estimating the infection fatality rate (IFR) of COVID-19 is determining the total number of cases. The total number of cases is not known because not everyone is tested but also, more importantly, because tested individuals are not representative of the population at large. We refer to the phenomenon whereby infected individuals are more likely to be tested than non-infected individuals, as\"preferential testing.\"An open question is whether or not it is possible to reliably estimate the IFR without any specific knowledge about the degree to which the data are biased by preferential testing. In this paper we take a partial identifiability approach, formulating clearly where deliberate prior assumptions can be made and presenting a Bayesian model, which pools information from different samples. Results suggest that when limited knowledge is available about the magnitude of preferential testing, reliable estimation of the IFR is still possible so long as there is sufficient\"heterogeneity of bias\"across samples.", "title": "Bayesian adjustment for preferential testing in estimating the COVID-19 infection fatality rate: Theory and methods", "pid": "tnr625zk", "bm25_score": 215.05418395996094}, {"text": "", "title": "Covid-19: Lack of testing in Brazil is a \"major failure,\" says MSF", "pid": "rb5o20j2", "bm25_score": 215.0459747314453}, {"text": "The exact risk of dying from COVID-19 has remained elusive and a topic of debate. The observed case fatality rates of 46 different countries are hypothesized to be dependent on their testing rates. An analytical test to this hypothesis suggests that the case fatality rate of COVID-19 could be consistent to a certain degree across all countries and states. The current global fatality rate is estimated to be around 1% and expected to converge between 1-3% when the pandemic ends. This model can be helpful to estimate the true infection rate for individual countries.", "title": "The true case fatality of COVID19: An analytical solution", "pid": "2zf9rmbf", "bm25_score": 215.04537963867188}, {"text": "Given the low Covid-19 testing coverage in the country, this study tested whether the daily change in the number of new Covid-19 cases is due to increase (or decrease) in the number of tests done daily. We performed Granger causality test based on vector autoregressive models on Bangladesh case and test numbers between 8 March and 5 June 2020, using publicly available data. The test results show that the daily number of tests Granger-cause the number of new cases (p <0.001), meaning the daily number of new cases is perhaps due to an increase in test capacity rather than a change in the infection rates. From the results of this test we can infer that if the number of daily tests does not increase substantially, data on new infections will not give much information for understanding covid-19 infection dynamics in Bangladesh.", "title": "Is tracking and modeling Covid-19 infection dynamics for Bangladesh using daily data feasible?", "pid": "ettclw13", "bm25_score": 215.0418701171875}, {"text": "Population density, behaviour and cultural habits strongly influence the spread of pathogens. Consequently, key epidemiological parameters may vary from country to country. Many estimates of SARS-CoV-2 and COVID-19 strongly depend on testing frequency and case definitions. The fatal cases due to SARS-CoV2 could be a more reliable parameter, since missing of deaths is less likely. We analysed the dynamics of new infection and death cases to estimate the daily reproduction numbers (Rt) and the effectiveness of control measures in the most affected European Countries and the US. In summary, calculating Rt based on the daily number of deaths as well as of new infections may lead to more reliable estimates than those based on infection cases alone, as death based Rt are expected to be less susceptible to testing bias or limited capacities.", "title": "Modest effects of contact reduction measures on the reproduction number of SARS-CoV-2 in the most affected European countries and the US", "pid": "phn90fon", "bm25_score": 215.03756713867188}, {"text": "Background Intensive screening and testing for COVID-19 could facilitate early detection and isolation of infected persons and thereby control the size of the epidemic. It could also facilitate earlier and more targeted therapy. These factors could plausibly reduce attributable mortality which was the hypothesis tested in this study. Methods Linear regression was used to assess the country-level association between COVID-19 attributable mortality per 100 000 inhabitants (mortality/capita) and COVID-19 tests/capita (number of tests/100 000 inhabitants) controlling for the cumulative number of COVID-19 infections/100 000 inhabitants (cases/capita), the age of the epidemic (number of days between first case reported and 8 April), national health expenditure per capita and WHO world region. Results The COVID-19 mortality rate varied between 0.3 and 3110 deaths/100 000 inhabitants (median 30, IQR 8-105). The intensity of testing per 100 000 also varied considerably (median 21,970, IQR 2,735-89,095) as did the number of COVID-19 cases per 100 000 (median 1,600, IQR 340-4,760 cases/100 000). In the multivariate model, the COVID-19 mortality rate was negatively associated with tests/capita (Coef. -0.036, 95% CI -0.047- -0.025) and positively associated with cases/capita (Coef. 0.093, 95% CI 0.819- 1.034). Conclusions The results are compatible with the hypothesis that intensive testing and isolation could play a role in reducing COVID-10 mortality rates.", "title": "Intensive COVID-19 testing associated with reduced mortality - an ecological analysis of 108 countries", "pid": "pps56i3b", "bm25_score": 215.03634643554688}, {"text": "Confirmed cases in Australia notified up to 10 May 2020: notifications = 6,971; deaths = 98. The incidence of new cases of COVID-19 has reduced dramatically since a peak in mid-March. The reduction in international travel, social distancing measures and public health action have likely been effective in slowing the spread of the disease, in the Australian community. Cases of COVID-19 continue to be notified by jurisdictions, albeit at a slowed rate. Testing rates over the past week have increased markedly, with a very low proportion of people testing positive. These low rates of detection are indicative of low levels of COVID-19 transmission. It is important that testing rates and community adherence to public health measures remain high to support the continued suppression of the virus, particularly in vulnerable high-risk groups and settings. In the past reporting week new cases in Australia are mostly considered to be locally acquired, consistent with the drop in international travel. Most locally-acquired cases can be linked back to a known case or cluster. Although the proportion of locally-acquired cases has increased, the overall rate of cases, regardless of place of acquisition, continues to decrease. The crude case fatality rate in Australia remains low (1.4%), compared with the WHO reported global rate (6.9%). The low case fatality rate is likely reflective of high case detection and high quality of health care services in Australia. Deaths from COVID-19 in Australia have occurred predominantly among the elderly and those with comorbidities, with no deaths occurring in those under 40 years. The highest rate of COVID-19 continues to be among people aged 60-79 years, with a third of these cases associated with several outbreaks linked to cruise ships. The lowest rate of disease is in young children, a pattern reflected in international reports. Internationally, cases continue to increase, with some areas such as Brazil and India showing a dramatic rise in reported cases. Although some low-income countries have currently reported few cases, it is possible that this is due to limited diagnostic and public health capacity, and may not be reflective of disease occurrence.", "title": "COVID-19, Australia: Epidemiology Report 15 (Reporting week to 23:59 AEST 10 May 2020)", "pid": "qus2pjns", "bm25_score": 215.02821350097656}, {"text": "The reported number of new cases underestimates the real spread of COVID-19 pandemic because of non-tested asymptomatic people and limited global access to reliable diagnostic tests. In this context, COVID-19 mortality with confirmed diagnosis becomes an attractive source of information to be included in the analysis of perspectives and proposals. Objective data are required to calculate the capacity of resources provided by health systems. New strategies are needed to stabilize or minimize the mortality surge. However, we will not afford this goal until more alternatives were available. We still need an effective treatment, an affordable vaccine, or a collective achievement of sufficient immunity (reaching up to 70% of the whole population). At any time, the arriving waves of the pandemic are testing the capacity of governments. The health services struggle to keep the plateau in a steady-state below 100 deaths per million inhabitants. Therefore, it is necessary to increase the alternatives and supplies based on the current and near-future expected demands imposed by the number of deaths by COVID-19. Estimating COVID-19 mortality in various scenarios with the gradual release of social constraints will help predict the magnitude of those arriving waves.", "title": "COVID-19 Waves: Importance of Accumulative Mortality per Million Inhabitants", "pid": "acceu3l5", "bm25_score": 215.0237579345703}, {"text": "Since the beginning of 2020, the coronavirus disease 2019 (COVID-19) has spread rapidly in the city of Wuhan, P.R. China, and subsequently, across the world. The swift spread of the virus is largely attributed to its stealth transmissions in which infected patients may be asymptomatic. Undetected transmissions present a remarkable challenge for the containment of the virus and pose an appalling threat to the public. An urgent question that has been asked by the public is\"Should I be tested for COVID-19 if I am sick?\". While different regions established their own criteria for screening infected cases, the screening criteria have been modified based on new evidence and understanding of the virus as well as the availability of resources. The shortage of test kits and medical personnel has considerably limited our ability to do as many tests as possible. Public health officials and clinicians are facing a dilemma of balancing the limited resources and unlimited demands. On one hand, they are striving to achieve the best outcome by optimizing the usage of the scant resources. On the other hand, they are challenged by the patients' frustrations and anxieties, stemming from the concerns of not being tested for COVID-19 for not meeting the definition of PUI (person under investigation). In this paper, we evaluate the situation from the statistical viewpoint by factoring into the considerations of the uncertainty and inaccuracy of the test, an issue that is often overlooked by the general public. We aim to shed light on the tough situation by providing evidence-based reasoning from the statistical angle, and we expect this examination will help the general public understand and assess the situation rationally. Most importantly, the development offers recommendations for physicians to make sensible evaluations to optimally use the limited resources for the best medical outcome.", "title": "COVID-19: Should We Test Everyone?", "pid": "1mfize6h", "bm25_score": 215.0223388671875}]}
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"zcmywbrs": 0, "4i1djfn9": 0, "zcza30uj": 0, "zh2yqhc1": 0, "zhdjtv4j": 0, "zi98dq1v": 0, "zifccdqm": 0, "zio8yhuy": 0, "n056dtxr": 0, "68qqc64r": 0, "zmdoz3oz": 0, "zndtddty": 0, "znm5ibc1": 1, "zo78x4u8": 0, "zp4oddrt": 2, "zr34wsae": 0, "zrtfyz8s": 0, "zso922ae": 0, "v0v0ahjh": 0, "zwh1xj5u": 0, "zwhavf4h": 0, "ciiqqyne": 0, "zys414e3": 0, "zysy9izi": 1, "zzkqb0u2": 0, "zzp6cj76": 0, "zzvmj5qy": 1}, "bm25_results": [{"text": "Background: The SARS-CoV-2 disease 2019 (COVID-19) pandemic has spread across the world with varying impact on health systems and outcomes. We assessed how the type and timing of public- health interventions impacted the course of the outbreak in Alberta and other Canadian provinces. Methods: We used publicly-available data to summarize rates of laboratory data and mortality in relation to measures implemented to contain the outbreak and testing strategy. We estimated the transmission potential of SARS-CoV-2 before the state of emergency declaration for each province (R0) and at the study end date (Rt). Results: The first cases were confirmed in Ontario (January 25) and British Columbia (January 28). All provinces implemented the same health-policy measures between March 12 and March 30. Alberta had a higher percentage of the population tested (3.8%) and a lower mortality rate (3/100,000) than Ontario (2.6%; 11/100,000) or Quebec (3.1%; 31/100,000). British Columbia tested fewer people (1.7%) and had similar mortality as Alberta. Data on provincial testing strategies were insufficient to inform further analyses. Mortality rates increased with increasing rates of lab- confirmed cases in Ontario and Quebec, but not in Alberta. R0 was similar across all provinces, but varied widely from 2.6 (95% confidence intervals 1.9-3.4) to 6.4 (4.3-8.5), depending on the assumed time interval between onset of symptoms in a primary and a secondary case (serial interval). The outbreak is currently under control in Alberta, British Columbia and Nova Scotia (Rt <1). Interpretation: COVID-19-related health outcomes varied by province despite rapid implementation of similar health-policy interventions across Canada. Insufficient information about provincial testing strategies and a lack of primary data on serial interval are major limitations of existing data on the Canadian COVID-19 outbreak.", "title": "The Coronavirus 2019 pandemic in Canada: the impact of public health interventions on the course of the outbreak in Alberta and other provinces", "pid": "v346cpkl", "bm25_score": 216.36587524414062}, {"text": "", "title": "Canada and COVID-19: learning from SARS", "pid": "c7cd91pg", "bm25_score": 215.8143310546875}, {"text": "Background: The global spread of coronavirus disease 2019 (COVID-19) continues in several jurisdictions, causing significant strain to healthcare systems. The purpose of our study is to predict the impact of the COVID-19 pandemic on patient outcomes and the healthcare system in Ontario, Canada. Methods: We developed an individual-level simulation to model the flow of COVID-19 patients through the Ontario healthcare system. We simulated different combined scenarios of epidemic trajectory and healthcare capacity. Outcomes include numbers of patients needing admission to the ward, Intensive Care Unit (ICU), and requiring ventilation; days to resource depletion; and numbers of patients awaiting resources and deaths associated with limited access to resources. Findings: We demonstrate that with effective early public health measures system resources need not be depleted. For scenarios considering late or ineffective implementation of physical distancing, health system resources would be depleted within 14-26 days. Resource depletion was also avoided or delayed with aggressive measures to rapidly increase ICU, ventilator, and acute care hospital capacity. Interpretation: We found that without aggressive physical distancing measures the Ontario healthcare system would have been inadequately equipped to manage the expected number of patients with COVID-19, despite the rapid capacity increase. This overall lack of resources would have led to an increase in mortality. By slowing the spread of the disease via ongoing public health measures and having increased healthcare capacity, Ontario may have avoided catastrophic stresses to its health care system.", "title": "Potential magnitude of COVID-19-induced healthcare resource depletion in Ontario, Canada", "pid": "u2upcaod", "bm25_score": 215.81370544433594}, {"text": "BACKGROUND: Literature indicates that cardiovascular disease (CVD, including stroke), older age, and availability of healthcare resources impact COVID-19 case fatality rates (CFR). The cumulative effect of COVID-19 CFR in global CVD populations and the extrapolated impact on access to healthcare services in the CVD population in Canada are not fully known. This study explored the relationships of factors that may impact COVID-19 CFR and estimated the potential indirect impact of COVID-19 on Canadian healthcare resources. METHODS: Country-level epidemiological data were analyzed to study the correlation, main effect, and interaction between COVID-19 CFR and: a) proportion of the population with CVD, b) proportion of the population ≥ 65 years, and c) availability of essential health services as defined by the World Health Organization Universal Health Coverage (UHC) index. For indirect implications on healthcare resources, estimates of the volume of postponed coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI) and valve surgeries in Ontario were calculated. RESULTS: Positive correlations were found between COVID-19 CFR and a) proportion of the population with CVD (ρ=0.40, p=0.001), b) proportion of the population ≥ 65 years (ρ=0.43, p=0.0005) and c) UHC index (ρ=0.27, p=0.03). For every 1% increase in proportion of the population ≥ 65 years or proportion of the population with CVD, COVID-19 CFR was 9% and 19% higher, respectively. Approximately 1,252 procedures would be postponed monthly in Ontario due to current public health measures. CONCLUSIONS: Countries with more prevalent CVD reported higher COVID-19 CFR. Strain on healthcare resources is likely in Canada.", "title": "COVID-19 Pandemic: Global Impact and Potential Implications for Cardiovascular Disease in Canada", "pid": "el11o2cg", "bm25_score": 215.7608642578125}, {"text": "COVID-19 has spread with unequal efficiency in various parts of the world. In several European countries including Italy, the increase in the number of COVID-19 cases has followed a consistent, exponential pattern of spread. However, some countries, notably Taiwan and Hong Kong, have achieved a different outcome and have managed to bring the COVID-19 outbreak in their countries rapidly under control, without entering the exponential pattern and with very few cases. They have used several different approaches to COVID-19 outbreak control, including the innovative use of smartphone technology and the widespread use of surgical face masks. We show through our models, that Canada has followed the same, consistent COVID-19 exponential growth pattern that is seen in Italy. Both nationally and in its most heavily affected provinces, there is exponential growth of COVID-19 cases, making it possible to make predictions for the future, if no further interventions are made in public health policy. In particular, we argue for the urgent introduction of surgical face masks in health care and other settings and the harnessing of the power of smartphone technology on a national scale.", "title": "COVID-19 in Canada: Predictions for the future and control lessons from Asia", "pid": "ieobv7q8", "bm25_score": 215.64175415039062}, {"text": "", "title": "Canada and coronavirus: could have done better", "pid": "gz70hd7d", "bm25_score": 215.56768798828125}, {"text": "", "title": "Canada’s Covid-19 response: navigating national and global solidarity", "pid": "h5cc0poe", "bm25_score": 215.1945037841797}, {"text": "The world is confronted by the current pandemic of Corona Virus Disease (COVID-19), which is a wake-up call for all nations irrespective of their development status or geographical location. Since the start of the century we have seen five big infectious outbreaks which proved that epidemics are no more regarded as historic and geographically confined threats. The Canadian government underlined that these infectious disease outbreaks are threats to global health security and disrupt societal wellbeing and development. In this context, the Public Health Agency of Canada is proactive and has shown its preparedness for outbreaks of emerging and epidemic-prone diseases, and in dealing with these pathogens. Even before the declaration of pandemic, Canada has proved its global health leadership by ensuring collective action and multisectoral coordination which still remains a serious challenge especially for low and middle- income countries with existing poor health systems. In this article we discuss how Canada is addressing the global challenges posed by the COVID-19 pandemic through its leadership and practice of global health diplomacy.", "title": "Canada’s role in strengthening global health security during the COVID-19 pandemic", "pid": "qy66ih4m", "bm25_score": 215.1798858642578}, {"text": "Older people are especially vulnerable to COVID-19, including and especially people living in long-term care facilities. In this Perspective, we discuss the impact of the COVID-19 pandemic on long-term care policy in Canada. More specifically, we use the example of recent developments in Quebec, where a tragedy in a specific facility is acting as a dramatic \"focusing event\". It draws attention to the problems facing long-term care facilities, considering existing policy legacies and the opening of a \"policy window\" that may facilitate comprehensive reforms in the wake of the COVID-19 pandemic.", "title": "COVID-19 and Long-Term Care Policy for Older People in Canada", "pid": "ulav1vcf", "bm25_score": 215.15223693847656}, {"text": "Older people are especially vulnerable to COVID-19, including and especially people living in long-term care facilities. In this Perspective, we discuss the impact of the COVID-19 pandemic on long-term care policy in Canada. More specifically, we use the example of recent developments in Quebec, where a tragedy in a specific facility is acting as a dramatic \"focusing event\". It draws attention to the problems facing long-term care facilities, considering existing policy legacies and the opening of a \"policy window\" that may facilitate comprehensive reforms in the wake of the COVID-19 pandemic.", "title": "COVOID-19 and Long-Term Care Policy for Older People in Canada.", "pid": "scjui91o", "bm25_score": 215.14743041992188}, {"text": "The current COVID-19 crisis is unprecedented in recent history. On April 1, 2020, the Secretary-General of the United Nations, Antonio Guterres, warned that the world was facing the most challenging crisis since World War II (Associated Press, 2020). With the pandemic taking on an unprecedented magnitude in the twenty-first century, it quickly monopolized media attention. As of early April, Radar+'s large dataset showed that about 65 per cent of headlines on major Canadian media websites were related to the COVID-19 pandemic.", "title": "(Un)Covering the COVID-19 Pandemic: Framing Analysis of the Crisis in Canada", "pid": "irkroegh", "bm25_score": 215.14547729492188}, {"text": "BACKGROUND: The global spread of coronavirus disease 2019 (COVID-19) continues in several jurisdictions, causing substantial strain to health care systems. The purpose of our study was to predict the effect of the COVID-19 pandemic on patient outcomes and use of hospital resources in Ontario, Canada. METHODS: We developed an individual-level simulation to model the flow of patients with COVID-19 through the hospital system in Ontario. We simulated different combined scenarios of epidemic trajectory and hospital health care capacity. Our outcomes included the number of patients who needed admission to the ward or to the intensive care unit (ICU) with or without the need for mechanical ventilation, number of days to resource depletion, number of patients awaiting resources and number of deaths. RESULTS: We found that with effective early public health measures, hospital system resources would not be depleted. For scenarios with late or ineffective implementation of physical distancing, hospital resources would be depleted within 14-26 days, and in the worst case scenario, 13 321 patients would die while waiting for needed resources. Resource depletion would be avoided or delayed with aggressive measures to increase ICU, ventilator and acute care hospital capacities. INTERPRETATION: We found that without aggressive physical distancing measures, the Ontario hospital system would have been inadequately equipped to manage the expected number of patients with COVID-19 despite a rapid increase in capacity. This lack of hospital resources would have led to an increase in mortality. By slowing the spread of the disease using public health measures and by increasing hospital capacity, Ontario may have avoided catastrophic stresses to its hospitals.", "title": "Estimation of COVID-19-induced depletion of hospital resources in Ontario, Canada", "pid": "h6g65f9w", "bm25_score": 215.0690460205078}, {"text": "The novel coronavirus reached the United States and Canada almost at the same time. The first reported American case was January 20, 2020, and in Canada it was January 15, 2020 (Canada, 2020; Holshue et al., 2020). Yet, the response to this crisis has been different in the two countries. In the US, President Donald Trump, prominent Republicans, and conservative media initially dismissed the dangers of COVID-19 (Stecula, 2020). The pandemic became politicized from the early days, and even though Trump and Republicans have walked back many of their initial claims, there continue to be media reports of partisan differences in public opinion shaped by that early response. At the same time, the response in Canada has been mostly characterized by across-the-board partisan consensus among political elites (Merkley et al., 2020).", "title": "Novel Coronavirus, Old Partisanship: COVID-19 Attitudes and Behaviours in the United States and Canada", "pid": "4v3d86h3", "bm25_score": 215.0343017578125}, {"text": "BACKGROUND The risk of experiencing adverse outcomes from the coronavirus disease 2019 (COVID-19), such as hospitalization, admission to intensive care units and death, is elevated for older individuals and those with certain underlying health conditions including diabetes, chronic conditions affecting lungs, heart or kidneys, and a compromised immune system. DATA AND METHODS Data collected between March 29 and April 3, 2020 from the Canadian Perspectives Survey Series 1: Impacts of COVID-19 (n=4,627) were used to estimate the prevalence of underlying health conditions, health concerns and precautionary behaviours among Canadians aged 15 or older living in the provinces. Multivariate analyses examined associations between these variables after accounting for age, sex and education. RESULTS Close to 1 in 4 Canadians (24%) had an underlying health condition that increased their risk of adverse outcomes from COVID-19. Overall, 36% of the population were very or extremely concerned about the impact of COVID-19 on their own health. Individuals with underlying health conditions had higher odds (odds ratio: 2.0, 95% confidence interval: 1.6 to 2.5) of being highly concerned than those without these conditions, after adjustment for demographic characteristics. High percentages of Canadians took precautions to reduce the risk of infection regardless of whether or not they had underlying health conditions. DISCUSSION Health status was associated with higher levels of concern for one's own health in the early period of the COVID-19 pandemic. Most Canadians were taking precautions recommended by public health authorities to protect themselves and others.", "title": "Health-related concerns and precautions during the COVID-19 pandemic: A comparison of Canadians with and without underlying health conditions.", "pid": "06v5bf01", "bm25_score": 215.02655029296875}, {"text": "BACKGROUND: The risk of experiencing adverse outcomes from the coronavirus disease 2019 (COVID-19), such as hospitalization, admission to intensive care units and death, is elevated for older individuals and those with certain underlying health conditions including diabetes, chronic conditions affecting lungs, heart or kidneys, and a compromised immune system. DATA AND METHODS: Data collected between March 29 and April 3, 2020 from the Canadian Perspectives Survey Series 1: Impacts of COVID-19 (n=4,627) were used to estimate the prevalence of underlying health conditions, health concerns and precautionary behaviours among Canadians aged 15 or older living in the provinces. Multivariate analyses examined associations between these variables after accounting for age, sex and education. RESULTS: Close to 1 in 4 Canadians (24%) had an underlying health condition that increased their risk of adverse outcomes from COVID-19. Overall, 36% of the population were very or extremely concerned about the impact of COVID-19 on their own health. Individuals with underlying health conditions had higher odds (odds ratio: 2.0, 95% confidence interval: 1.6 to 2.5) of being highly concerned than those without these conditions, after adjustment for demographic characteristics. High percentages of Canadians took precautions to reduce the risk of infection regardless of whether or not they had underlying health conditions. DISCUSSION: Health status was associated with higher levels of concern for one's own health in the early period of the COVID-19 pandemic. Most Canadians were taking precautions recommended by public health authorities to protect themselves and others.", "title": "Health-related concerns and precautions during the COVID-19 pandemic: A comparison of Canadians with and without underlying health conditions", "pid": "in2edn29", "bm25_score": 215.00054931640625}, {"text": "Background: The burden of COVID-19 in Canada is unequally distributed geographically, with the largest number of cases and fatalities recorded in Quebec and Ontario while other provinces experienced limited outbreaks. To date, however, no study has assessed how provincial epidemics have unfolded in a comparative perspective. This is essential to calibrate projections of the future course of the epidemic and plan health care resources for the second wave of infections. Methods: Using newly released individual-level data collected by the Public Health Agency of Canada, we assess COVID-19-related morbidity and mortality across age and gender groups at the provincial level through a combination of demographic and survival analyses. Results: Quebec has the highest absolute and per capita number of COVID-19 confirmed positive cases, hospitalizations and fatalities in all age groups. In each province, a higher number of women than men test positive for the disease, especially above age 80. Yet consistently across age groups, infected men are more likely to be hospitalized and enter intensive care than women do. These gender differences in hospitalisation rates account for the higher case fatality risk due to COVID-19 among men compared to women. Interpretation: Although health care capacity across provinces has been sufficient to treat severe cases, we find that the main factor accounting for gender differences in COVID-19-related mortality is the need for hospitalization and intensive care, especially above age 80. This suggests a selection effect of severe cases requiring to be treated in a hospital setting that needs to be further investigated.", "title": "Assessing the burden of COVID-19 in Canada", "pid": "54obt430", "bm25_score": 214.99380493164062}, {"text": "A global pandemic caused by the novel coronavirus (COVID-19) resulted in restrictions to daily living for Canadians, including social distancing and closure of city and provincial recreation facilities, national parks and playgrounds. The objective of this study was to assess how these preemptive measures impacted physical activity behaviour and well-being of Canadians. An online survey was utilized to measure participant physical activity behavior, nature exposure, well-being and anxiety levels. Results indicate that while 40.5% of inactive individuals became less active, only 22.4% of active individuals became less active. Comparatively, 33% of inactive individuals became more active while 40.3% of active individuals became more active. There were significant differences in well-being outcomes in the inactive population between those who were more active, the same or less active (p < 0.001) but this was not seen in the active population. Inactive participants who spent more time engaged in outdoor physical activity had lower anxiety than those who spent less time in outdoor physical activity. Public health measures differentially affected Canadians who were active and inactive and physical activity was strongly associated with well-being outcomes in inactive individuals. This suggests that health promoting measures directed towards inactive individuals may be essential to improving well-being.", "title": "The Impact of COVID-19 on Physical Activity Behavior and Well-Being of Canadians", "pid": "4v0qgfat", "bm25_score": 214.96072387695312}, {"text": "", "title": "Effect of COVID-19 on the mental health care of older people in Canada", "pid": "zlpz435d", "bm25_score": 214.95901489257812}, {"text": "The global pandemic of coronavirus disease 2019 (COVID-19) has resulted in massive societal, economic, and environmental impacts that have both short- and long-term mental health influences. This commentary serves to tie existing literature on mental health and COVID-19 to the clinical experiences of a psychologist working in the Canadian hospital sector. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "A population mental health perspective on the impact of COVID-19.", "pid": "4q1j6g44", "bm25_score": 214.92703247070312}, {"text": "BACKGROUND The global spread of coronavirus disease 2019 (COVID-19) continues in several jurisdictions, causing substantial strain to health care systems. The purpose of our study was to predict the effect of the COVID-19 pandemic on patient outcomes and use of hospital resources in Ontario, Canada. METHODS We developed an individuallevel simulation to model the flow of patients with COVID-19 through the hospital system in Ontario. We simulated different combined scenarios of epidemic trajectory and hospital health care capacity. Our outcomes included the number of patients who needed admission to the ward or to the intensive care unit (ICU) with or without the need for mechanical ventilation, number of days to resource depletion, number of patients awaiting resources and number of deaths. RESULTS We found that with effective early public health measures, hospital system resources would not be depleted. For scenarios with late or ineffective implementation of physical distancing, hospital resources would be depleted within 14-26 days, and in the worst case scenario, 13 321 patients would die while waiting for needed resources. Resource depletion would be avoided or delayed with aggressive measures to increase ICU, ventilator and acute care hospital capacities. INTERPRETATION We found that without aggressive physical distancing measures, the Ontario hospital system would have been inadequately equipped to manage the expected number of patients with COVID-19 despite a rapid increase in capacity. This lack of hospital resources would have led to an increase in mortality. By slowing the spread of the disease using public health measures and by increasing hospital capacity, Ontario may have avoided catastrophic stresses to its hospitals.", "title": "Estimation of COVID-19-induced depletion of hospital resources in Ontario, Canada.", "pid": "gpxxdebo", "bm25_score": 214.91795349121094}, {"text": "The global epidemic of severe acute respiratory syndrome (SARS) indirectly has affected all health care facilities in affected nations and has unaffected nations on alert. Health care practitioners need to be aware of infection control measures to prevent the spread of SARS. This article looks at this new disease and how it has affected the delivery of health care in Canada.", "title": "Severe acute respiratory syndrome and its effects on health care: how Canada has dealt with this ordeal.", "pid": "xm9y4ovl", "bm25_score": 214.9050750732422}, {"text": "BACKGROUND While the physical health implications of the COVID-19 pandemic are regularly publicly available, the mental health toll on Canadians is unknown. This article examines the self-perceived mental health of Canadians during the COVID-19 pandemic and explores associations with various concerns after accounting for socioeconomic and health factors. DATA The cross-sectional Canadian Perspectives Survey Series 1 collected information related to COVID-19 in late March and early April 2020 concerning labour market participation, behaviours, and health for the Canadian population 15 years and older living in the 10 provinces. METHODS Socioeconomic and health characteristics of respondents as well as concerns about the impact of COVID-19 were examined to determine differences in experiencing excellent or very good compared to good, fair or poor perceived mental health. RESULTS Just over half of Canadians aged 15 and older (54%) reported excellent or very good mental health during the COVID-19 pandemic. Several concerns were also associated with mental health. Notably, after considering the effects of socioeconomic and health characteristics, women, youth, individuals with a physical health condition and those who were very or extremely concerned with family stress from confinement were less likely to report excellent or very good mental health. DISCUSSION These findings point to particular risks for lower perceived mental health during the COVID-19 pandemic. Results highlight various concerns of Canadians which may be associated with mental health, in particular, family stress in the home.", "title": "Understanding the Perceived Mental Health of Canadians During the COVID-19 Pandemic.", "pid": "lf5xg8p3", "bm25_score": 214.87583923339844}, {"text": "Abstract On March 11, 2020, the World Health Organization declared that COVID-19 was a pandemic. 1 At that time, only 118,000 cases had been reported globally, 90% of which had occurred in 4 countries. 1 Since then, the world landscape has changed dramatically. As of March 31, 2020, there are now nearly 800,000 cases, with truly global involvement. 2 Countries that were previously unaffected are currently experiencing mounting rates of the novel coronavirus infection with associated increases in COVID-19–related deaths. At present, Canada has more than 8000 cases of COVID-19, with considerable variation in rates of infection among provinces and territories. 3 Amid concerns over growing resource constraints, cardiac surgeons from across Canada have been forced to make drastic changes to their clinical practices. From prioritizing and delaying elective cases to altering therapeutic strategies in high-risk patients, cardiac surgeons, along with their heart teams, are having to reconsider how best to manage their patients. It is with this in mind that the Canadian Society of Cardiac Surgeons (CSCS) and its Board of Directors have come together to formulate a series of guiding statements. With strong representation from across the country and the support of the Canadian Cardiovascular Society, the authors have attempted to provide guidance to their colleagues on the subjects of leadership roles that cardiac surgeons may assume during this pandemic: patient assessment and triage, risk reduction, and real-time sharing of expertise and experiences. A visual abstract of the main principles underlying our recommended approach is provided in Figure 1.", "title": "Cardiac Surgery in Canada During the COVID-19 Pandemic: A Guidance Statement From the Canadian Society of Cardiac Surgeons", "pid": "n8omnki4", "bm25_score": 214.8508758544922}, {"text": "BACKGROUND: While the physical health implications of the COVID-19 pandemic are regularly publicly available, the mental health toll on Canadians is unknown. This article examines the self-perceived mental health of Canadians during the COVID-19 pandemic and explores associations with various concerns after accounting for socioeconomic and health factors. DATA: The cross-sectional Canadian Perspectives Survey Series 1 collected information related to COVID-19 in late March and early April 2020 concerning labour market participation, behaviours, and health for the Canadian population 15 years and older living in the 10 provinces. METHODS: Socioeconomic and health characteristics of respondents as well as concerns about the impact of COVID-19 were examined to determine differences in experiencing excellent or very good compared to good, fair or poor perceived mental health. RESULTS: Just over half of Canadians aged 15 and older (54%) reported excellent or very good mental health during the COVID-19 pandemic. Several concerns were also associated with mental health. Notably, after considering the effects of socioeconomic and health characteristics, women, youth, individuals with a physical health condition and those who were very or extremely concerned with family stress from confinement were less likely to report excellent or very good mental health. DISCUSSION: These findings point to particular risks for lower perceived mental health during the COVID-19 pandemic. Results highlight various concerns of Canadians which may be associated with mental health, in particular, family stress in the home.", "title": "Understanding the Perceived Mental Health of Canadians During the COVID-19 Pandemic", "pid": "90t0jmwf", "bm25_score": 214.84576416015625}, {"text": "BACKGROUND: After the declaration of COVID-19 pandemic on March 11th(,) 2020, local transmission chains starting in different countries including Canada are forcing governments to take decisions on public health interventions to mitigate the spread of the epidemic. METHODS: We conduct data-driven and model-free estimations for the growth rates of the COVID-19 epidemics in Italy and Canada, by fitting an exponential curve to the daily reported cases. We use these estimates to predict epidemic trends in Canada under different scenarios of public health interventions. RESULTS: In Italy, the initial growth rate (0.22) has reduced to 0.1 two weeks after the lockdown of the country on March 8th(,) 2020. This corresponds to an increase of the doubling time from about 3.15 to almost 7 days. In comparison, the growth rate in Canada has increased from 0.13 between March 1st and 13th, to 0.25 between March 13th to 22nd. This current growth rate corresponds to a doubling time of 2.7 days, and therefore, unless further public health interventions are escalated in Canada, we project 15,000 cases by March 31st. However, the case number may be reduced to 4000 if escalated public health interventions could instantly reduce the growth rate to 0.1, the same level achieved in Italy. INTERPRETATION: Prompt and farsighted interventions are critical to counteract the very rapid initial growth of the COVID-19 epidemic in Canada. Mitigation plans must take into account the delayed effect of interventions by up to 2-weeks and the short doubling time of 3–4 days.", "title": "Canada needs to rapidly escalate public health interventions for its COVID-19 mitigation strategies", "pid": "vwwt70mo", "bm25_score": 214.83035278320312}, {"text": "The global pandemic of coronavirus disease 2019 (COVID-19) has resulted in massive societal, economic, and environmental impacts that have both short- and long-term mental health influences. This commentary serves to tie existing literature on mental health and COVID-19 to the clinical experiences of a psychologist working in the Canadian hospital sector. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "A population mental health perspective on the impact of COVID-19", "pid": "6ngsyo8o", "bm25_score": 214.80889892578125}, {"text": "", "title": "COVID-19 in Canada and the use of Personal Protective Equipment", "pid": "nclq3sm0", "bm25_score": 214.79718017578125}, {"text": "In 2019, Canada's gross subnational debt to GDP was well over 40 per cent, easily the highest in the world (see Figure 1). This level will only grow as the provinces grapple with the pandemic and its fiscal effects. Some believe surging provincial debts have brought Canadian federalism to a critical juncture: they have greatly increased the odds of federal measures to stabilize provincial finances. This article assesses this claim. The cleanest and most balanced path to fiscal sustainability is a combination of enhanced federal transfers, which would bolster provincial fiscal capacity, and national fiscal rules, which would constrain provincial borrowing. But the former is unlikely to restore sustainability on its own, and the latter would require a severe provincial debt crisis, which Canada's existing fiscal federal structures can avoid. COVID-19 has increased the odds of certain reforms, and it is difficult to predict their long-run effects. But any obvious paths to fiscal sustainability remain hidden.", "title": "COVID-19, Fiscal Federalism and Provincial Debt: Have We Reached a Critical Juncture?", "pid": "mrwo4my7", "bm25_score": 214.79635620117188}, {"text": "On March 11, 2020, the World Health Organization declared that COVID-19 was a pandemic.1 At that time, only 118,000 cases had been reported globally, 90% of which had occurred in 4 countries.1 Since then, the world landscape has changed dramatically. As of March 31, 2020, there are now nearly 800,000 cases, with truly global involvement.2 Countries that were previously unaffected are currently experiencing mounting rates of the novel coronavirus infection with associated increases in COVID-19-related deaths. At present, Canada has more than 8000 cases of COVID-19, with considerable variation in rates of infection among provinces and territories.3 Amid concerns over growing resource constraints, cardiac surgeons from across Canada have been forced to make drastic changes to their clinical practices. From prioritizing and delaying elective cases to altering therapeutic strategies in high-risk patients, cardiac surgeons, along with their heart teams, are having to reconsider how best to manage their patients. It is with this in mind that the Canadian Society of Cardiac Surgeons (CSCS) and its Board of Directors have come together to formulate a series of guiding statements. With strong representation from across the country and the support of the Canadian Cardiovascular Society, the authors have attempted to provide guidance to their colleagues on the subjects of leadership roles that cardiac surgeons may assume during this pandemic: patient assessment and triage, risk reduction, and real-time sharing of expertise and experiences.", "title": "Cardiac Surgery in Canada During the COVID-19 Pandemic: A Guidance Statement From the Canadian Society of Cardiac Surgeons", "pid": "mzaxgbtc", "bm25_score": 214.7848663330078}, {"text": "In this paper, I explore the potential effects of the COVID‐19 pandemic on Canadian food processors. First, COVID‐19 may have an impact on food processing economic activities because of supply and demand shocks. Second, the impact of COVID‐19 on food processing may depend on the type of products and the size of the processors. The effects of measures taken by the government to flatten the epidemiological curve on the economic activities of the food processing sector are uncertain.", "title": "Economic thoughts on COVID‐19 for Canadian food processors", "pid": "qunw5hhy", "bm25_score": 214.7515869140625}, {"text": "COVID‐19 has imposed a series of unique challenges on the food retail and food service sectors in Canada. Almost overnight, the roughly 30% of the food dollar that Canadians have been spending on food away from home has shifted to retail.", "title": "The impact of COVID‐19 on food retail and food service in Canada: Preliminary assessment", "pid": "lz0chxab", "bm25_score": 214.7430877685547}, {"text": "", "title": "The Impact of COVID-19 on Diabetes Research in Canada", "pid": "woylyufz", "bm25_score": 214.63894653320312}, {"text": "OBJECTIVES: There are limited reports of the impact of the coronavirus disease 2019 pandemic focused on U.S. and Canadian PICUs. This hypothesis-generating report aims to identify the United States and Canadian trends of coronavirus disease 2019 in PICUs. DESIGN AND SETTING: To better understand how the coronavirus disease 2019 pandemic was affecting U.S. and Canadian PICUs, an open voluntary daily data collection process of Canadian and U.S. PICUs was initiated by Virtual Pediatric Systems, LLC (Los Angeles, CA; http://www.myvps.org) in mid-March 2020. Information was made available online to all PICUs wishing to participate. A secondary data collection was performed to follow-up on patients discharged from those PICUs reporting coronavirus disease 2019 positive patients. MEASUREMENTS AND MAIN RESULTS: To date, over 180 PICUs have responded detailing 530 PICU admissions requiring over 3,467 days of PICU care with 30 deaths. The preponderance of cases was in the eastern regions. Twenty-four percent of the patients admitted to the PICUs were over 18 years old. Fourteen percent of admissions were under 2 years old. Nearly 60% of children had comorbidities at admission with the average length of stay increasing by age and by severity of comorbidity. Advanced respiratory support was necessary during 67% of the current days of care, with 69% being conventional mechanical ventilation. CONCLUSIONS: PICUs have been significantly impacted by the pandemic. They have provided care not only for children but also adults. Patients with coronavirus disease 2019 have a high frequency of comorbidities, require longer stays, more ventilatory support than usual PICU admissions. These data suggest several avenues for further exploration.", "title": "The Impact of Coronavirus Disease 2019 Pandemic on U.S. and Canadian PICUs", "pid": "nd1gecxg", "bm25_score": 214.55902099609375}, {"text": "As SARS-CoV-2 threatens to overwhelm health systems in Canada, it is imperative that provinces are able to plan and manage an effective and reduced risk response. For this response to be most effective, it must reflect an evidence-based, pan-Canadian response. We designed four different prototypical patients with a combination of common COVID-19 symptoms and opportunities for exposure who were made to self-assess using the 10 provincial COVID-19 self-assessment tools on 1 April. These tools were developed to allow individuals to self-triage, allowing health systems direct capacity to testing and care. We assessed the consistency of the self-assessment tools and of the guidance provided to the patients. While the tools generally screen in three areas, the scope of included COVID-19 associated symptoms as well as the opportunities for exposure, and therefore transmission, vary between provinces such that no two provinces screened in the same way. This was, in turn, reflected in the inconsistency in guidance found. A patient with cough who had travelled abroad or had close contact with a confirmed case within 14 days received the most consistent guidance, with remaining patients receiving guidance ranging from mandatory quarantine or self-isolation to being told they did not have COVID-19 symptoms, guidance at odds with medical evidence. Thus, there is not a single, evidence-based Canadian standard of care simply for self-assessment. Without consistency in public health guidance, Canadians cannot appropriately self-isolate to mitigate community transmission, nor can the necessary valid and reliable data be collected to inform critical epidemiological models that help guide pandemic response. If federal and provincial governments are unable to coordinate a response, Parliament must use its available jurisdiction to legislate a duty on both to follow national standards, so as to improve coordination on COVID-19 in coming months.", "title": "Lack of coordination and medical disinformation in Canadian self-assessment tools for COVID-19", "pid": "idg60ids", "bm25_score": 214.5135040283203}, {"text": "COVID-19 has infected millions of people, with an estimated total dead in the hundreds of thousands. This has significantly impacted health care, including who is delivering it, how it is delivered, and how it is taught. This article describes challenges of the COVID-19 pandemic from the perspective of a Canadian nuclear medicine resident, including new risks with nuclear imaging, navigating new and sometimes challenging guidelines, as well as working and living within the confines of social distancing.", "title": "It’s a small world after all: A Canadian resident’s perspective on COVID-19", "pid": "4crdebgq", "bm25_score": 214.5062255859375}, {"text": "The COVID‐19 pandemic has prompted Canada and several other countries to impose an economic shutdown to prevent a deadly public health crisis from becoming much deadlier. In the agriculture and food sector, several hundred thousand restaurant workers have lost their jobs. The rise in unemployment, the closing of restaurants and schools, and social distancing have triggered demand reductions for certain commodities and foods and demand increases for others, bringing along changes in demand for inputs including labour. Canadian employers of temporary foreign workers (TFWs) are facing delays and additional constraints in recruiting, but so have US and European employers of TFWs. Rising food security concerns are making protectionist trade policies popular. Domestic and foreign firms may export less and do more foreign direct investment, inducing trade in jobs. This article is protected by copyright. All rights reserved", "title": "Labour issues and COVID‐19", "pid": "y1gfz1ub", "bm25_score": 214.4920654296875}, {"text": "On March 11 th 2020, World Health Organization (WHO) declared the 2019 novel corona virus as global pandemic. Corona virus, also known as COVID-19 was first originated in Wuhan, Hubei province in China around December 2019 and spread out all over the world within few weeks. Based on the public datasets provided by John Hopkins university and Canadian health authority, we have developed a forecasting model of COVID-19 outbreak in Canada using state-of-the-art Deep Learning (DL) models. In this novel research, we evaluated the key features to predict the trends and possible stopping time of the current COVID-19 outbreak in Canada and around the world. In this paper we presented the Long short-term memory (LSTM) networks, a deep learning approach to forecast the future COVID-19 cases. Based on the results of our Long short-term memory (LSTM) network, we predicted the possible ending point of this outbreak will be around June 2020. In addition to that, we compared transmission rates of Canada with Italy and USA. Here we also presented the 2, 4, 6, 8, 10, 12 and 14 th day predictions for 2 successive days. Our forecasts in this paper is based on the available data until March 31, 2020. To the best of our knowledge, this of the few studies to use LSTM networks to forecast the infectious diseases.", "title": "Time Series Forecasting of COVID-19 transmission in Canada Using LSTM Networks", "pid": "h588i68g", "bm25_score": 214.4519805908203}, {"text": "The COVID-19 pandemic has necessarily affected the operation of Canada's Parliament and, thus, the activities of Members of Parliament (MPs) (Malloy, 2020; Rayment and VandenBeukel, 2020). Here, we explore how the pandemic has affected the representational activities of individual MPs.", "title": "Has the COVID-19 Pandemic Affected MPs’ Representational Activities?", "pid": "u8hogdyf", "bm25_score": 214.44586181640625}, {"text": "Abstract The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country’s earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world’s COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada’s first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.", "title": "Tracking the origin of early COVID-19 cases in Canada", "pid": "wmfcey6f", "bm25_score": 214.44235229492188}, {"text": "There are limited reports of the impact of the coronavirus disease 2019 pandemic focused on U.S. and Canadian PICUs. This hypothesis-generating report aims to identify the United States and Canadian trends of coronavirus disease 2019 in PICUs. DESIGN AND SETTING: To better understand how the coronavirus disease 2019 pandemic was affecting U.S. and Canadian PICUs, an open voluntary daily data collection process of Canadian and U.S. PICUs was initiated by Virtual Pediatric Systems, LLC (Los Angeles, CA; http://www.myvps.org) in mid-March 2020. Information was made available online to all PICUs wishing to participate. A secondary data collection was performed to follow-up on patients discharged from those PICUs reporting coronavirus disease 2019 positive patients. MEASUREMENTS AND MAIN RESULTS: To date, over 180 PICUs have responded detailing 530 PICU admissions requiring over 3,467 days of PICU care with 30 deaths. The preponderance of cases was in the eastern regions. Twenty-four percent of the patients admitted to the PICUs were over 18 years old. Fourteen percent of admissions were under 2 years old. Nearly 60% of children had comorbidities at admission with the average length of stay increasing by age and by severity of comorbidity. Advanced respiratory support was necessary during 67% of the current days of care, with 69% being conventional mechanical ventilation. CONCLUSIONS: PICUs have been significantly impacted by the pandemic. They have provided care not only for children but also adults. Patients with coronavirus disease 2019 have a high frequency of comorbidities, require longer stays, more ventilatory support than usual PICU admissions. These data suggest several avenues for further exploration.", "title": "The Impact of Coronavirus Disease 2019 Pandemic on U.S. and Canadian PICUs", "pid": "zysy9izi", "bm25_score": 214.4187774658203}, {"text": "Abstract On March 11 th 2020, World Health Organization (WHO) declared the 2019 novel corona virus as global pandemic. Corona virus, also known as COVID-19 was first originated in Wuhan, Hubei province in China around December 2019 and spread out all over the world within few weeks. Based on the public datasets provided by John Hopkins university and Canadian health authority, we have developed a forecasting model of COVID-19 outbreak in Canada using state-of-the-art Deep Learning (DL) models. In this novel research, we evaluated the key features to predict the trends and possible stopping time of the current COVID-19 outbreak in Canada and around the world. In this paper we presented the Long short-term memory (LSTM) networks, a deep learning approach to forecast the future COVID-19 cases. Based on the results of our Long short-term memory (LSTM) network, we predicted the possible ending point of this outbreak will be around June 2020. In addition to that, we compared transmission rates of Canada with Italy and USA. Here we also presented the 2, 4, 6, 8, 10, 12 and 14 th day predictions for 2 successive days. Our forecasts in this paper is based on the available data until March 31, 2020. To the best of our knowledge, this of the few studies to use LSTM networks to forecast the infectious diseases.", "title": "Time Series Forecasting of COVID-19 transmission in Canada Using LSTM Networks", "pid": "eo887olu", "bm25_score": 214.4179229736328}, {"text": "", "title": "First imported case of 2019 novel coronavirus in Canada, presenting as mild pneumonia (vol 395, pg 734, 2020)", "pid": "wb35wm6k", "bm25_score": 214.41693115234375}, {"text": "The original coronavirus disease (COVID-19) outbreak in Wuhan, China has become a global pandemic. By tracking the earliest 118 COVID-19 cases in Canada, we produced a Voronoi treemap to show the travel origins of the country's earliest COVID-19 cases. By March 11, 2020, even though the majority (64.1%) of the world's COVID-19 confirmed cases still had their origin in China, only 7.6% of Canada's first 118 COVID-19 cases arose due in travelers to China. The most commonly reported travel history among the 118 cases originated from the Middle East, the United States, and Europe. Thus, in retrospect, broadening of early screening tools and travel restrictions to countries and regions outside China may help control global COVID-19 spread.", "title": "Tracking the origin of early COVID-19 cases in Canada", "pid": "kgifmjvb", "bm25_score": 214.40927124023438}, {"text": "", "title": "Is Canada ready for the second wave of COVID-19?", "pid": "6cg7u1lu", "bm25_score": 214.40151977539062}, {"text": "Social media is a rich source where we can learn about people's reactions to social issues. As COVID-19 has significantly impacted on people's lives, it is essential to capture how people react to public health interventions and understand their concerns. In this paper, we aim to investigate people's reactions and concerns about COVID-19 in North America, especially focusing on Canada. We analyze COVID-19 related tweets using topic modeling and aspect-based sentiment analysis, and interpret the results with public health experts. We compare timeline of topics discussed with timing of implementation of public health interventions for COVID-19. We also examine people's sentiment about COVID-19 related issues. We discuss how the results can be helpful for public health agencies when designing a policy for new interventions. Our work shows how Natural Language Processing (NLP) techniques could be applied to public health questions with domain expert involvement.", "title": "Exploratory Analysis of COVID-19 Related Tweets in North America to Inform Public Health Institutes", "pid": "yuv2ki4o", "bm25_score": 214.39215087890625}, {"text": "BACKGROUND: Healthy childhood development is fostered through sufficient physical activity (PA; including time outdoors), limiting sedentary behaviours (SB), and adequate sleep; collectively known as movement behaviours. Though the COVID-19 virus outbreak has changed the daily lives of children and youth, it is unknown to what extent related restrictions may compromise the ability to play and meet movement behaviour recommendations. This secondary data analysis examined the immediate impacts of COVID-19 restrictions on movement and play behaviours in children and youth. METHODS: A national sample of Canadian parents (n = 1472) of children (5–11 years) or youth (12–17 years) (54% girls) completed an online survey that assessed immediate changes in child movement and play behaviours during the COVID-19 outbreak. Behaviours included PA and play, SB, and sleep. Family demographics and parental factors that may influence movement behaviours were assessed. Correlations between behaviours and demographic and parental factors were determined. For open-ended questions, word frequency distributions were reported. RESULTS: Only 4.8% (2.8% girls, 6.5% boys) of children and 0.6% (0.8% girls, 0.5% boys) of youth were meeting combined movement behaviour guidelines during COVID-19 restrictions. Children and youth had lower PA levels, less outside time, higher SB (including leisure screen time), and more sleep during the outbreak. Parental encouragement and support, parental engagement in PA, and family dog ownership were positively associated with healthy movement behaviours. Although families spent less time in PA and more time in SB, several parents reported adopting new hobbies or accessing new resources. CONCLUSIONS: This study provides evidence of immediate collateral consequences of the COVID-19 outbreak, demonstrating an adverse impact on the movement and play behaviours of Canadian children and youth. These findings can guide efforts to preserve and promote child health during the COVID-19 outbreak and crisis recovery period, and to inform strategies to mitigate potential harm during future pandemics.", "title": "Impact of the COVID-19 virus outbreak on movement and play behaviours of Canadian children and youth: a national survey", "pid": "czcx5xwb", "bm25_score": 214.3914337158203}, {"text": "Understanding the epidemiology of COVID-19 among children and youth in Canada will help to inform public health measures in settings where children gather. As of April 27, 2020, provinces and territories provided the Public Health Agency of Canada with detailed information on 24,079 cases, of which 3.9% (n=938) were younger than 20 years of age. The detection rate per 100,000 population was lower in this age group (11.9 per 100,000), compared with those aged 20-59 years (72.4 per 100,000) and 60 and older (113.6 per 100,000). The median age among those younger than 20 years of age was 13 years, and cases were distributed equally across male and female genders. Among provinces and territories with more than 100 cases, 1.6% to 9.8% of cases were younger than 20 years of age. Cases in this age group were more likely to be asymptomatic: 10.7% compared with 2.4% in those aged 20-59 years and 4.1% in those aged 60 and older. Children and youth experienced severe outcomes less often, but 2.2% (n=15/672) of cases within this age group were severe enough to require hospitalization. Based on available exposure information, 11.3% (n=59/520) of cases aged younger than 20 years had no known contact with a case. Canadian findings align with those of other countries.", "title": "Laboratory-confirmed COVID-19 in children and youth in Canada, January 15-April 27, 2020.", "pid": "xzoleks8", "bm25_score": 214.3815155029297}, {"text": "COVID-19 has infected millions of people, with an estimated total dead in the hundreds of thousands. This has significantly impacted health care, including who is delivering it, how it is delivered, and how it is taught. This article describes challenges of the COVID-19 pandemic from the perspective of a Canadian nuclear medicine resident, including new risks with nuclear imaging, navigating new and sometimes challenging guidelines, as well as working and living within the confines of social distancing.", "title": "It's a small world after all: A Canadian resident's perspective on COVID-19", "pid": "js77ymx4", "bm25_score": 214.36602783203125}, {"text": "Evidence from the past 50 years suggests that changes in Canadian farmland values are influenced by farming returns, real interest rates, and exchange rates. Residential and commercial development also affects the value of farmland close to major urban centers. The COVID-19 economic shutdown is expected to reduce crop and livestock returns, which will put downward pressure on farmland values. The magnitude of this downward pressure will depend on the extent and the length of the recession. The evolution of interest rates over the next months and years could have a significant impact on farmland values. Historically, low real interest rates have coincided with higher farmland values, whereas high real interest rates have caused significant reductions in farmland values. The development value of farmland close to major cities could be negatively impacted by a sharp downturn in residential and commercial property markets.", "title": "Potential impacts of COVID-19 on Canadian farmland markets", "pid": "m6rj7h6u", "bm25_score": 214.3524169921875}, {"text": "Understanding the epidemiology of COVID-19 among children and youth in Canada will help to inform public health measures in settings where children gather. As of April 27, 2020, provinces and territories provided the Public Health Agency of Canada with detailed information on 24,079 cases, of which 3.9% (n=938) were younger than 20 years of age. The detection rate per 100,000 population was lower in this age group (11.9 per 100,000), compared with those aged 20-59 years (72.4 per 100,000) and 60 and older (113.6 per 100,000). The median age among those younger than 20 years of age was 13 years, and cases were distributed equally across male and female genders. Among provinces and territories with more than 100 cases, 1.6% to 9.8% of cases were younger than 20 years of age. Cases in this age group were more likely to be asymptomatic: 10.7% compared with 2.4% in those aged 20-59 years and 4.1% in those aged 60 and older. Children and youth experienced severe outcomes less often, but 2.2% (n=15/672) of cases within this age group were severe enough to require hospitalization. Based on available exposure information, 11.3% (n=59/520) of cases aged younger than 20 years had no known contact with a case. Canadian findings align with those of other countries.", "title": "Laboratory-confirmed COVID-19 in children and youth in Canada, January 15-April 27, 2020", "pid": "bvujapf5", "bm25_score": 214.3253173828125}, {"text": "Canadian fruit and vegetable markets were significantly impacted by the spread of the novel coronavirus SARS‐CoV‐2 (and COVID‐19 disease), beginning in March 2020. Due to the closure of restaurants, bars, and schools, produce growers and distributors were forced to shift supplies almost entirely from the foodservice to the retail channel. Shippers reported labor and logistical constraints in making the change, but the fresh produce supply chain remained robust. In the long term, we expect lasting changes in consumers’ online food‐purchasing habits, heightened constraints on immigrant labor markets, and tighter concentration in fresh produce distribution and perhaps retailing.", "title": "COVID‐19 impact on fruit and vegetable markets", "pid": "scbteel5", "bm25_score": 214.28335571289062}, {"text": "", "title": "Risk for COVID-19 Resurgence Related to Duration and Effectiveness of Physical Distancing in Ontario, Canada", "pid": "281pj442", "bm25_score": 214.27716064453125}, {"text": "Introduction: Efforts to mitigate the global spread of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have largely relied on broad compliance with public health recommendations, yet navigating the high volume of evolving information and misinformation related to SARS-CoV-2 can be challenging. We assessed national public perceptions (e.g., severity, concerns, health), knowledge (e.g., transmission, information sources), and behaviors (e.g., physical distancing) related to COVID-19 in Canada to understand public perspectives and inform future public health initiatives. Methods: We administered a national online survey with the goal of obtaining responses from 2000 adults residing in Canada. Respondent sampling was stratified by age, sex, and region. We used descriptive statistics to summarize respondent characteristics and tested for significant overall regional differences using chi-squared tests and t-tests, as appropriate. Results: We collected 1,996 eligible questionnaires between April 26th and May 1st, 2020. One-fifth (20%) of respondents knew someone diagnosed with COVID-19, but few had tested positive themselves (0.6%). Negative impacts of pandemic conditions were evidenced in several areas, including concerns about healthcare (e.g. sufficient equipment, 52%), pandemic stress (45%), and worsening social (49%) and mental/emotional (39%) health. Most respondents (88%) felt they had good to excellent knowledge of virus transmission, and predominantly accessed (74%) and trusted (60%) Canadian news television, newspapers/magazines, or non-government news websites for COVID-19 information. We found high compliance with distancing measures (80% either self-isolating or always physical distancing). We identified regional differences in perceptions, knowledge, and behaviors related to COVID-19. Discussion: We found that knowledge about COVID-19 is largely acquired through domestic news sources, which may explain high self-reported compliance with prevention measures. The results highlight the broader impact of a pandemic on the general public's overall health and wellbeing, outside of personal infection. The study findings should be used to inform public health communications during COVID-19 and future pandemics.", "title": "A national cross-sectional survey of public perceptions, knowledge, and behaviors during the COVID-19 pandemic", "pid": "2pmpa7n0", "bm25_score": 214.25106811523438}, {"text": "Background: The covid-19 pandemic has presented unprecedented professional and personal challenges for the oncology community. Under the auspices of the Canadian Association of Medical Oncologists, we conducted an online national survey to better understand the impact of the pandemic on the medical oncology community in Canada. Methods: An English-language multiple-choice survey, including questions about demographics, covid-19 risk, use of personal protective equipment (ppe), personal challenges, and chemotherapy management was distributed to Canadian medical oncologists. The survey was open from 30 March to 4 April 2020, and attracted 159 responses. Results: More than 70% of medical oncologists expressed moderate-to-extreme concern about personally contracting covid-19 and about family members or patients (or both) contracting covid-19 from them. Despite that high level of concern, considerable variability in the use of ppe in direct cancer care was reported at the time of this survey, with 33% of respondents indicating no routine ppe use at their institutions and 69% indicating uncertainty about access to adequate ppe. Of the respondents, 54% were experiencing feelings of nervousness or anxiety on most days, and 52% were having feelings of depression or hopelessness on at least some days. Concern about aging parents or family and individual wellness represented the top personal challenges identified. The management of cancer patients has been affected, with adoption of telemedicine reported by 82% of respondents, and cessation of clinical trial accrual reported by 54%. The 3 factors deemed most important for treatment decision-making were■cancer prognosis and anticipated benefit from treatment,■risk of treatment toxicity during scarce health care access, and■patient risk of contracting covid-19. Conclusions: This report describes the results of the first national survey assessing the impact of the covid-19 on Canadian medical oncologists and how they deliver systemic anticancer therapies. We hope that these data will provide a framework to address the challenges identified.", "title": "Impact of COVID-19 on Canadian medical oncologists and cancer care: Canadian Association of Medical Oncologists survey report", "pid": "y8ntig41", "bm25_score": 214.21475219726562}, {"text": "Canadian legislatures’ responses to the COVID-19 pandemic have raised questions about whether and how parliaments should continue to meet during the pandemic (Reid, 2020; Thomas, 2020a). The purpose of this research note is twofold: (1) to document how Canadian legislatures have changed in response to the COVID-19 pandemic and (2) to assess the effect of these responses on legislatures’ ability to fulfill their core functions. Through an analysis of parliamentary records from all elected federal, provincial and territorial legislatures in Canada, we find that the role of parliaments as sites of citizen representation has suffered the most, whereas the scrutinizing and legislative functions of parliaments have tended to be preserved, albeit in a significantly truncated form. We argue that patterns in legislatures' varied responses to the pandemic reveal which aspects of parliamentary functioning these bodies de facto prioritize and which are at risk of being eroded.", "title": "Pandemic Parliaments: Canadian Legislatures in a Time of Crisis", "pid": "hxn46xnn", "bm25_score": 214.2067108154297}, {"text": "Federal and provincial policy responses to the COVID-19 pandemic raise a host of constitutional issues that decision makers must pay heed to or risk serious violations of individual rights under the Charter of Rights and Freedoms. This research note will examine a number of policy challenges as they relate to mobility rights (s. 6), legal rights (ss. 7 through 14), and equality rights (s. 15) and will articulate the factors that policy makers should consider in design and implementation. Other important constitutional questions, such as those relating to the division of powers, emergency powers and the relationship between the executive and Parliament, have also emerged in Canada but are beyond the scope of this note.", "title": "Public Policy and Constitutional Rights in Times of Crisis", "pid": "miadomgn", "bm25_score": 214.19627380371094}, {"text": "Background The covid-19 pandemic has presented unprecedented professional and personal challenges for the oncology community. Under the auspices of the Canadian Association of Medical Oncologists, we conducted an online national survey to better understand the impact of the pandemic on the medical oncology community in Canada. Methods An English-language multiple-choice survey, including questions about demographics, covid-19 risk, use of personal protective equipment (ppe), personal challenges, and chemotherapy management was distributed to Canadian medical oncologists. The survey was open from 30 March to 4 April 2020, and attracted 159 responses. Results More than 70% of medical oncologists expressed moderate-to-extreme concern about personally contracting covid-19 and about family members or patients (or both) contracting covid-19 from them. Despite that high level of concern, considerable variability in the use of ppe in direct cancer care was reported at the time of this survey, with 33% of respondents indicating no routine ppe use at their institutions and 69% indicating uncertainty about access to adequate ppe. Of the respondents, 54% were experiencing feelings of nervousness or anxiety on most days, and 52% were having feelings of depression or hopelessness on at least some days. Concern about aging parents or family and individual wellness represented the top personal challenges identified. The management of cancer patients has been affected, with adoption of telemedicine reported by 82% of respondents, and cessation of clinical trial accrual reported by 54%. The 3 factors deemed most important for treatment decision-making were■ cancer prognosis and anticipated benefit from treatment,■ risk of treatment toxicity during scarce health care access, and■ patient risk of contracting covid-19. Conclusions This report describes the results of the first national survey assessing the impact of the covid-19 on Canadian medical oncologists and how they deliver systemic anticancer therapies. We hope that these data will provide a framework to address the challenges identified.", "title": "Impact of COVID-19 on Canadian medical oncologists and cancer care: Canadian Association of Medical Oncologists survey report.", "pid": "ux0kjt9l", "bm25_score": 214.1764678955078}, {"text": "The dumping of milk, the offering of hospitality size goods in grocery stores, and the closure of processing facilities are examples of the disruptions caused by the pandemic to the dairy, poultry, and egg sectors. These supply management sectors, however, are more resilient to the impacts of COVID‐19 than other sectors as producers are generally more financially stable, losses are pooled, and production/marketing efforts are coordinated.", "title": "Economic thoughts on the potential implications of COVID‐19 on the Canadian dairy and poultry sectors", "pid": "gd8217va", "bm25_score": 214.16905212402344}, {"text": "", "title": "Canadian Geriatrics in the Time of COVID-19", "pid": "jjjf9te0", "bm25_score": 214.16845703125}, {"text": "OBJECTIVES: To investigate the effect of the COVID-19 pandemic on the frequency of various crime types (property, violent, and mischief) in Vancouver, Canada. METHODS: Crime data representing residential burglary, commercial burglary, theft of vehicle, theft from vehicle, theft, violence, and mischief are analysed at the city level using interrupted time series techniques. RESULTS: While COVID-19 has not had an impact on all crime types, statistically significant change has been identified in a number of cases. Depending on the crime type, the magnitude and direction of the change in frequency varies. It is argued that (mandated) social restrictions, shifted activity patterns and opportunity structures which are responsible for these findings. CONCLUSIONS: We find support for changes in the frequency of particular crime types during the COVID-19 pandemic. This is important for criminal justice and social service practitioners when operating within an extraordinary event.", "title": "Show me a man or a woman alone and I'll show you a saint: Changes in the frequency of criminal incidents during the COVID-19 pandemic", "pid": "ssv1arr1", "bm25_score": 214.16217041015625}, {"text": "Macroeconomic indicators, notably unemployment, are significant moderators of suicide. We projected the number of excess suicides in Canada as a consequence of the impact of COVID-19 on unemployment. Annual suicide mortality (2000-2018) and unemployment (2000-2019) data were derived from Statistics Canada. Time-trend regression models were used to evaluate and predict the number of excess suicides in 2020 and 2021 for two possible projection scenarios following the COVID-19 pandemic: 1) an increase in unemployment of 1.6% in 2020, 1.2% in 2021, or 2) an increase in unemployment of 10.7% in 2020, 8.9% in 2021. A percentage point increase in unemployment was associated with a 1.0% increase in suicide between 2000-2018. In the first scenario, the rise in unemployment rates resulted in a projected total of 418 excess suicides in 2020-2021 (suicide rate per 100,000: 11.6 in 2020). In the second scenario, the projected suicide rates per 100,000 increased to 14.0 in 2020 and 13.6 in 2021, resulting in 2,114 excess suicides in 2020-2021. These results indicate that suicide prevention in the context of COVID-19-related unemployment is a critical priority. Furthermore, timely access to mental healthcare, financial provisions and social/labour support programs, as well as optimal treatment for mental disorders is urgently needed.", "title": "Projected Increases in Suicide in Canada as a Consequence of COVID-19", "pid": "mvo2k2jt", "bm25_score": 214.12686157226562}, {"text": "Canada's cattle/beef sector has already weathered a shock after a 2003 case of BSE resulted in closed borders and industry restructuring. Now the sector has to adjust to similar shocks due to COVID‐19. This paper examines the supply chain from the consumer up to the cow‐calf producer by considering consumer reactions, labour market constraints, and supply response. A quarterly market model of North American cattle and beef markets is used to examine price and revenue impacts associated with the market disruptions. Depending on the scenario, there is considerable price and revenue suppression at all levels of the market. This article is protected by copyright. All rights reserved", "title": "COVID‐19 and the Canadian cattle/beef sector: Some preliminary analysis", "pid": "owl5qy0x", "bm25_score": 214.10769653320312}, {"text": "We assessed the impact of the coronavirus disease 19 (COVID-19) pandemic on code stroke activations in the emergency department, stroke unit admissions, and referrals to the stroke prevention clinic at London's regional stroke center, serving a population of 1.8 million in Ontario, Canada. We found a 20% drop in the number of code strokes in 2020 compared to 2019, immediately after the first cases of COVID-19 were officially confirmed. There were no changes in the number of stroke admissions and there was a 22% decrease in the number of clinic referrals, only after the provincial lockdown. Our findings suggest that the decrease in code strokes was mainly driven by patient-related factors such as fear to be exposed to the SARS-CoV-2, while the reduction in clinic referrals was largely explained by hospital policies and the Government lockdown.", "title": "COVID-19: Stroke Admissions, Emergency Department Visits, and Prevention Clinic Referrals", "pid": "oek9ud99", "bm25_score": 214.10357666015625}, {"text": "Objectives: To provide the first known comprehensive analysis of COVID-19 outcomes in a federal penitentiary system. We examined the following COVID-19 outcomes within federal penitentiaries and contrasted them with the overall population in the penitentiaries' respective provincial jurisdictions: testing, prevalence, the proportion recovered, and fatality. Methods: Data for prisons were obtained from the Correctional Service of Canada and, for the general population, from COVID-19 Esri Canadian Outbreak Tracking Hub. Data were retrieved between March 30 and April 21, 2020, and are accurate to this date. Penitentiary-, province- and sex-specific frequency statistics for each outcome were calculated. Results: Data on 50 of 51 penitentiaries (98%) were available. Of these, 72% of penitentiaries reported fewer tests per 1000 population than the Canadian general population average (16 tests/1000 population), and 24% of penitentiaries reported zero tests. Penitentiaries with high levels of testing were those that already had elevated COVID-19 prevalence. Five penitentiaries reported an outbreak (at least one case). Hardest hit penitentiaries were those in Quebec and British Columbia, with some prisons reporting COVID-19 prevalence of 30% to 40%. Of these, two were women's prisons. Female prisoners were over-represented among cases (31% of cases overall, despite representing 5% of the total prison population). Conclusion: Increased sentinel or universal testing may be appropriate given the confined nature of prison populations. This, along with rigorous infection prevention control practices and the potential release of prisoners, will be needed to curb current outbreaks and those likely to come.", "title": "Testing lags and emerging COVID-19 outbreaks in federal penitentiaries in Canada", "pid": "qrywrn7m", "bm25_score": 214.09613037109375}, {"text": "Macroeconomic indicators, notably unemployment, are significant moderators of suicide. We projected the number of excess suicides in Canada as a consequence of the impact of COVID-19 on unemployment. Annual suicide mortality (2000-2018) and unemployment (2000-2019) data were derived from Statistics Canada. Time-trend regression models were used to evaluate and predict the number of excess suicides in 2020 and 2021 for two possible projection scenarios following the COVID-19 pandemic: 1) an increase in unemployment of 1.6% in 2020, 1.2% in 2021, or 2) an increase in unemployment of 10.7% in 2020, 8.9% in 2021. A percentage point increase in unemployment was associated with a 1.0% increase in suicide between 2000 and 2018. In the first scenario, the rise in unemployment rates resulted in a projected total of 418 excess suicides in 2020-2021 (suicide rate per 100,000: 11.6 in 2020). In the second scenario, the projected suicide rates per 100,000 increased to 14.0 in 2020 and 13.6 in 2021, resulting in 2114 excess suicides in 2020-2021. These results indicate that suicide prevention in the context of COVID-19-related unemployment is a critical priority. Furthermore, timely access to mental healthcare, financial provisions and social/labour support programs, as well as optimal treatment for mental disorders is urgently needed.", "title": "Projected increases in suicide in Canada as a consequence of COVID-19", "pid": "03fir7ct", "bm25_score": 214.08956909179688}, {"text": "", "title": "First imported case of 2019 novel coronavirus in Canada, presenting as mild pneumonia", "pid": "cietpenq", "bm25_score": 214.08226013183594}, {"text": "Background: Our objectives were to describe and compare healthcare worker (HCW) and non-HCW COVID-19 cases in Ontario, as well as the frequency of COVID-19 among HCWs household members. Methods: Using reportable disease data at Public Health Ontario which captures COVID-19 cases in Ontario, we conducted a cross-sectional study comparing demographic, exposure, and clinical variables between HCWs and non-HCWs with COVID-19 as of 14 May 2020. We calculated rates of infections over time and determined the frequency of within household transmissions using natural language processing. Results: There were 4,230 (17.5%) HCW COVID-19 cases in Ontario, of whom 20.2% were nurses, 2.3% were physicians, and the remaining 77.4% other specialties. HCWs were more likely to be between 30-60 years of age and female. HCWs were more likely to present asymptomatically (8.1% versus 7.0%, p=0.010) or with atypical symptoms (17.8% versus 10.5%, p<0.001). The mortality among HCWs was 0.2% compared to 10.5% of non-HCWs. HCWs commonly had exposures to a confirmed case or outbreak (74.1%), however only 3.1% were confirmed to be nosocomial. The rate of new infections was 5.5 times higher in HCWs than non-HCWs, but mirrored the epidemic curve. We identified 391 (9.8%) probable secondary household transmissions. Interpretation: HCWs represent a disproportionate number of COVID-19 cases in Ontario but with low confirmed numbers of nosocomial transmission. The data support substantial testing bias and under-ascertainment of general population cases. Protecting HCWs through appropriate personal protective equipment and physician distancing from colleagues is paramount.", "title": "Healthcare Worker COVID-19 Cases in Ontario, Canada: A Cross-sectional Study", "pid": "4rutnzbu", "bm25_score": 214.07235717773438}, {"text": "With the deep recession now forecast for the world economy, trade can be expected to fall even more steeply. Agricultural trade will be less significantly affected, being insulated by its relatively low income elasticities of demand. However, a drop in the range of 12 to 20 percent in real trade value should be expected. Canada can be expected to share in this, but, within agricultural exports, cereals will be least affected. This minimal expected impact to cereals stems from the risk of wheat export bans by Russia and Kazakhstan, due to the resulting increase in wheat prices. Livestock, pulses, and horticulture can be expected to face a larger decline in trade prospects and revenues. An equally large threat to falling incomes in our trade partners is their policy responses, particularly the potential increase in import restrictions. These may take the form of more costly inspections, tightened SPS and food safety regulations, and protectionist measures from competing domestic producers. This article is protected by copyright. All rights reserved", "title": "The COVID‐19 Pandemic: Anticipating its Effects on Canada's Agricultural Trade", "pid": "p7ig5rw2", "bm25_score": 214.0699920654297}, {"text": "The COVID-19 pandemic and subsequent state of public emergency have significantly affected older adults in Canada and worldwide. It is imperative that the gerontological response be efficient and effective. In this statement, the board members of the Canadian Association on Gerontology/L'Association canadienne de gérontologie (CAG/ACG) and the Canadian Journal on Aging/La revue canadienne du vieillissement (CJA/RCV) acknowledge the contributions of CAG/ACG members and CJA/RCV readers. We also profile the complex ways that COVID-19 is affecting older adults, from individual to population levels, and advocate for the adoption of multidisciplinary collaborative teams to bring together different perspectives, areas of expertise, and methods of evaluation in the COVID-19 response.", "title": "Interdisciplinary and Collaborative Approaches Needed to Determine Impact of COVID-19 on Older Adults and Aging: CAG/ACG and CJA/RCV Joint Statement", "pid": "fbq90100", "bm25_score": 214.0530242919922}, {"text": "The COVID-19 pandemic and subsequent state of public emergency have significantly affected older adults in Canada and worldwide. It is imperative that the gerontological response be efficient and effective. In this statement, the board members of the Canadian Association on Gerontology/L’Association canadienne de gérontologie (CAG/ACG) and the Canadian Journal on Aging/La revue canadienne du vieillissement (CJA/RCV) acknowledge the contributions of CAG/ACG members and CJA/RCV readers. We also profile the complex ways that COVID-19 is affecting older adults, from individual to population levels, and advocate for the adoption of multidisciplinary collaborative teams to bring together different perspectives, areas of expertise, and methods of evaluation in the COVID-19 response.", "title": "Interdisciplinary and Collaborative Approaches Needed to Determine Impact of COVID-19 on Older Adults and Aging: CAG/ACG and CJA/RCV Joint Statement", "pid": "4kojv5pv", "bm25_score": 214.05259704589844}, {"text": "BACKGROUND: There have been significant efforts to respond to the two public health emergencies of coronavirus disease 2019 (COVID-19) and overdose in British Columbia (BC), Canada. The purpose of this study was to quantify the prevalence of known risk factors associated with mortality due to COVID-19 for persons who have had a non-fatal overdose during 2015-2017 in comparison to persons who have not had an overdose. METHODS: Data were extracted from the BC Provincial Overdose Cohort which includes a 20 % random sample of BC residents and persons who have had a non-fatal overdose in BC from January 2015 to December 2017. Chi-square tests and logistic regression were used to compare risk factors by overdose history. RESULTS: Persons who had a non-fatal overdose were significantly more likely to have three (chronic pulmonary disease, diabetes, coronary heart disease) of the four known chronic conditions associated with the development of severe illness due to COVID-19 compared to persons who did not have a previous non-fatal overdose event. CONCLUSION: Persons who had an overdose were more likely to have several chronic conditions associated with the development of severe illness due to COVID-19. The increased likelihood of having these risk factors is reflective of the social and health inequities experienced by persons who have a history of overdose.", "title": "Overdose and risk factors for coronavirus disease 2019", "pid": "tppr087n", "bm25_score": 214.02554321289062}, {"text": "We assessed the impact of the coronavirus disease 19 (COVID-19) pandemic on code stroke activations in the emergency department, stroke unit admissions, and referrals to the stroke prevention clinic at London’s regional stroke center, serving a population of 1.8 million in Ontario, Canada. We found a 20% drop in the number of code strokes in 2020 compared to 2019, immediately after the first cases of COVID-19 were officially confirmed. There were no changes in the number of stroke admissions and there was a 22% decrease in the number of clinic referrals, only after the provincial lockdown. Our findings suggest that the decrease in code strokes was mainly driven by patient-related factors such as fear to be exposed to the SARS-CoV-2, while the reduction in clinic referrals was largely explained by hospital policies and the Government lockdown.", "title": "COVID-19: Stroke Admissions, Emergency Department Visits, and Prevention Clinic Referrals", "pid": "7g2kg2tz", "bm25_score": 214.01675415039062}, {"text": "", "title": "Continuing care and COVID-19: a Canadian tragedy that must not be allowed to happen again.", "pid": "k9gajt4l", "bm25_score": 214.00331115722656}, {"text": "This paper aims at providing the summary of the Global Data Science Project (GDSC) for COVID-19. as on May 31 2020. COVID-19 has largely impacted on our societies through both direct and indirect effects transmitted by the policy measures to counter the spread of viruses. We quantitatively analysed the multifaceted impacts of the COVID-19 pandemic on our societies including people's mobility, health, and social behaviour changes. People's mobility has changed significantly due to the implementation of travel restriction and quarantine measurements. Indeed, the physical distance has widened at international (cross-border), national and regional level. At international level, due to the travel restrictions, the number of international flights has plunged overall at around 88 percent during March. In particular, the number of flights connecting Europe dropped drastically in mid of March after the United States announced travel restrictions to Europe and the EU and participating countries agreed to close borders, at 84 percent decline compared to March 10th. Similarly, we examined the impacts of quarantine measures in the major city: Tokyo (Japan), New York City (the United States), and Barcelona (Spain). Within all three cities, we found the significant decline in traffic volume. We also identified the increased concern for mental health through the analysis of posts on social networking services such as Twitter and Instagram. Notably, in the beginning of April 2020, the number of post with #depression on Instagram doubled, which might reflect the rise in mental health awareness among Instagram users. Besides, we identified the changes in a wide range of people's social behaviors, as well as economic impacts through the analysis of Instagram data and primary survey data.", "title": "Global Data Science Project for COVID-19 Summary Report", "pid": "ltbvpv8b", "bm25_score": 214.00311279296875}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic has caused enormous psychological impact worldwide. We conducted a systematic review and meta-analysis on the psychological and mental impact of COVID-19 among healthcare workers, the general population, and patients with higher COVID-19 risk published between 1 Nov 2019 to 25 May 2020. We conducted literature researching used Embase, PubMed, Google scholar and WHO COVID-19 databases. Among the initial search of 9207 studies, 62 studies with 162,639 participants from 17 countries were included in the review. The pooled prevalence of anxiety and depression was 33% (95% confidence interval: 28%-38%) and 28% (23%-32%), respectively. The prevalence of anxiety and depression was the highest among patients with pre-existing conditions and COVID-19 infection (56% [39%-73%] and 55% [48%-62%]), and it was similar between healthcare workers and the general public. Studies from China, Italy, Turkey, Spain and Iran reported higher-than-pooled prevalence among healthcare workers and the general public. Common risk factors included being women, being nurses, having lower socioeconomic status, having high risks of contracting COVID-19, and social isolation. Protective factors included having sufficient medical resources, up-to-date and accurate information, and taking precautionary measures. In conclusion, psychological interventions targeting high-risk populations with heavy psychological distress are in urgent need.", "title": "The Psychological and Mental Impact of Coronavirus Disease 2019 (COVID-19) on Medical Staff and General Public – A Systematic Review and Meta-analysis", "pid": "hl3tvivk", "bm25_score": 214.0020751953125}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic has caused enormous psychological impact worldwide. We conducted a systematic review and meta-analysis on the psychological and mental impact of COVID-19 among healthcare workers, the general population, and patients with higher COVID-19 risk published between 1 Nov 2019 to 25 May 2020. We conducted literature research using Embase, PubMed, Google scholar and WHO COVID-19 databases. Among the initial search of 9207 studies, 62 studies with 162,639 participants from 17 countries were included in the review. The pooled prevalence of anxiety and depression was 33% (95% confidence interval: 28%-38%) and 28% (23%-32%), respectively. The prevalence of anxiety and depression was the highest among patients with pre-existing conditions and COVID-19 infection (56% [39%-73%] and 55% [48%-62%]), and it was similar between healthcare workers and the general public. Studies from China, Italy, Turkey, Spain and Iran reported higher-than-pooled prevalence among healthcare workers and the general public. Common risk factors included being women, being nurses, having lower socioeconomic status, having high risks of contracting COVID-19, and social isolation. Protective factors included having sufficient medical resources, up-to-date and accurate information, and taking precautionary measures. In conclusion, psychological interventions targeting high-risk populations with heavy psychological distress are in urgent need.", "title": "The psychological and mental impact of coronavirus disease 2019 (COVID-19) on medical staff and general public - A systematic review and meta-analysis", "pid": "3xzhi7gh", "bm25_score": 214.0020294189453}, {"text": "", "title": "The impact of COVID-19 on Canadian urology residents", "pid": "bo6ngxot", "bm25_score": 214.0019073486328}, {"text": "The Canadian banking system is among the best in the world. Amid the COVID-19 pandemic, the world is challenged and banks are expected to rescue society. Businesses are revising, repurposing, and reinventing their products and services to address people’s needs. In this context, this article seeks to understand how Canada’s banks are supporting their clients and communities, during the current health crisis. Content analysis was conducted to analyse Canada’s ten largest banks’ supporting actions towards the pandemic, leading to 125 documents and 19 different actions consulted. Based on the data, a combination of hierarchical clustering and multidimensional scaling was conducted. Following a CSR approach, three clusters of banks are identified: sweeping actions, cautious actions, and wait & see, highlighting that while most banks are doing little to help their stakeholders, three of them have a proactive and strong commitment to their clients and communities in these times of need.", "title": "Canadian banks’ responses to COVID-19: a strategic positioning analysis", "pid": "r0ach2jn", "bm25_score": 213.99945068359375}, {"text": "PURPOSE: Accurately forecasting the occurrence of future covid-19-related cases across relaxed (Sweden) and stringent (USA and Canada) policy contexts has a renewed sense of urgency. Moreover, there is a need for a multidimensional county-level approach to monitor the second wave of covid-19 in the USA. METHOD: We use an artificial intelligence framework based on timeline of policy interventions that triangulated results based on the three approaches-Bayesian susceptible-infected-recovered (SIR), Kalman filter, and machine learning. RESULTS: Our findings suggest three important insights. First, the effective growth rate of covid-19 infections dropped in response to the approximate dates of key policy interventions. We find that the change points for spreading rates approximately coincide with the timelines of policy interventions across respective countries. Second, forecasted trend until mid-June in the USA was downward trending, stable, and linear. Sweden is likely to be heading in the other direction. That is, Sweden's forecasted trend until mid-June appears to be non-linear and upward trending. Canada appears to fall somewhere in the middle-the trend for the same period is flat. Third, a Kalman filter based robustness check indicates that by mid-June the USA will likely have close to two million virus cases, while Sweden will likely have over 44,000 covid-19 cases. CONCLUSION: We show that drop in effective growth rate of covid-19 infections was sharper in the case of stringent policies (USA and Canada) but was more gradual in the case of relaxed policy (Sweden). Our study exhorts policy makers to take these results into account as they consider the implications of relaxing lockdown measures.", "title": "Risk of a second wave of Covid-19 infections: using artificial intelligence to investigate stringency of physical distancing policies in North America", "pid": "pqoe4vdi", "bm25_score": 213.98907470703125}, {"text": "The outbreak of SARS-CoV-2 in China has spread around the world, infecting millions and causing governments to implement strict policies to counteract the spread of the disease. One of the most effective strategies in reducing the severity of the pandemic is social distancing, where members of the population systematically reduce their interactions with others to limit the transmission rate of the virus. However, the implementation of social distancing can be difficult and costly, making it imperative that both policy makers and the citizenry understand the potential benefits if done correctly and the risks if not. In this work, a mathematical model is developed to study the effects of social distancing on the spread of the SARS-CoV-2 virus in Canada. The model is based upon a standard epidemiological SEIRD model that has been stratified to directly incorporate the proportion of individuals who are following social distancing protocols. The model parameters characterizing the disease are estimated from current epidemiological data on COVID-19 using machine learning techniques. The results of the model show that social distancing policies in Canada have already saved thousands of lives and that the prolonged adherence to social distancing guidelines could save thousands more. Importantly, our model indicates that social distancing can significantly delay the onset of infection peaks, allowing more time for the production of a vaccine or additional medical resources. Furthermore, our results stress the importance of easing social distancing restrictions gradually, rather than all at once, in order to prevent a second wave of infections. Model results are compared to the current capacity of the Canadian healthcare system by examining the current and future number of ventilators available for use, emphasizing the need for the increased production of additional medical resources.", "title": "Mathematical modeling of COVID-19 containment strategies with considerations for limited medical resources", "pid": "51g3vhcx", "bm25_score": 213.97406005859375}, {"text": "PURPOSE: The novel coronavirus disease (COVID-19) pandemic has swept the globe, with a domino effect on medical education and training. In this study, we surveyed Canadian radiology residents to understand the impact of the pandemic on their residency training, strategies utilized by the residency programs in mitigating those impacts, and factors important to residents in the selection of educational resources on COVID-19. METHODS: A 10-item questionnaire was distributed to 460 resident members of the Canadian Association of Radiologists. The survey was open for 2 weeks, with a reminder sent at half-way mark. RESULTS: We received 96 responses (response rate: 20.9%). The 4 highest affected domains of training were daytime case volumes (92.4%), daytime schedules (87.4%), internal and external assessments (86.5%), and vacation/travel (83.3%). Virtual teaching rounds (91.7%), change in schedules to allow staying home (78.1%), and virtual/phone readouts (72.9%) were the most utilized strategies by the Canadian radiology residency programs. Overall stress of exposure to the disease was moderate to low (86.5%). A minority of the residents were redeployed (6.2%), although most (68.8%) were on standby for redeployment. Residents preferred published society guidelines (92.3%), review papers (79.3%), video lectures (79.3%), and web tools (76.9%) for learning about COVID-19 imaging manifestations. CONCLUSION: The COVID-19 pandemic has had a significant impact on various domains of the Canadian radiology residency programs, which has been mitigated by several strategies employed by the training programs.", "title": "Impact of COVID-19 on Canadian Radiology Residency Training Programs", "pid": "12eny1vl", "bm25_score": 213.9728240966797}, {"text": "In April 2020, a nationally representative sample of 4, 240 Canadians age 18 years and older were polled about COVID experience in March, early in the epidemic. We examined determinants of COVID symptoms, defined as fever plus difficulty breathing/shortness of breath, dry cough so severe that it disrupts sleep, and/or loss of sense of smell; and testing for SARS-CoV-2 by respondents and/or household members. About 8% of Canadians reported that they and/or one or more household members experienced COVID symptoms. Symptoms were more common in younger than older adults, and among visible minorities. Overall, 3% of respondents and/or household members had been tested for SARS-CoV-2. Being tested was associated with having COVID symptoms, being of Indigenous identity, and living in Quebec. Periodic nationally representative surveys, including high-risk older populations, of symptoms, as well as SARS-CoV-2 antibodies, are needed to understand the course of the Canadian epidemic and prepare for the future.", "title": "Determinants of self-reported symptoms and testing for COVID-19 in Canada using a nationally representative survey", "pid": "u54kja4g", "bm25_score": 213.96812438964844}, {"text": "We explored the impact of physical distancing measures on COVID-19 transmission in the population of Ontario, Canada using a previously described age- and health-status stratified transmission model. The model was fit to confirmed cases occupying intensive care unit (ICU) beds and mortality among hospitalized COVID-19 cases for the time period 19 March to 26 April 2020. We projected that mortality would have been 4.6-fold what was observed had physical distancing measures not been implemented in the province. Relaxation of physical distancing measures without compensatory increases in case detection, isolation, and/or contact tracing was projected to result in resurgence of disease activity. Return to normal or near-normal levels of contact would rapidly result in cases exceeding ICU capacity. Maintaining physical distancing for a longer period of time, allowing for the initial wave of infections to subside, delayed this resurgence, but the level of contacts post-restrictive distancing was the major factor determining how quickly ICU capacity was expected to be overwhelmed. Using a model, we demonstrate the marked impact strong public health measures had in reducing ICU admissions and mortality in Ontario. We also show that this hard-earned success is tenuous: relaxation of physical distancing measures in the near-term is projected to result in a rapid resurgence of disease activity.", "title": "Reduced COVID-19-Related Critical Illness and Death, and High Risk of Epidemic Resurgence, After Physical Distancing in Ontario, Canada", "pid": "bp2ilntr", "bm25_score": 213.96107482910156}, {"text": "Public health interventions have been implemented to mitigate the spread of coronavirus disease 2019 (COVID-19) in Ontario, Canada; however, the quantification of their effectiveness remains to be done and is important to determine if some of the social distancing measures can be relaxed without resulting in a second wave. We aim to equip local public health decision- and policy-makers with mathematical model-based quantification of implemented public health measures and estimation of the trend of COVID-19 in Ontario to inform future actions in terms of outbreak control and de-escalation of social distancing. Our estimates confirm that (1) social distancing measures have helped mitigate transmission by reducing daily infection contact rate, but the disease transmission probability per contact remains as high as 0.145 and case detection rate was so low that the effective reproduction number remained higher than the threshold for disease control until the closure of non-essential business in the Province; (2) improvement in case detection rate and closure of non-essential business had resulted in further reduction of the effective control number to under the threshold. We predict the number of confirmed cases according to different control efficacies including a combination of reducing further contact rates and transmission probability per contact. We show that improved case detection rate plays a decisive role to reduce the effective reproduction number, and there is still much room in terms of improving personal protection measures to compensate for the strict social distancing measures.", "title": "Quantifying the role of social distancing, personal protection and case detection in mitigating COVID-19 outbreak in Ontario, Canada", "pid": "952a4n71", "bm25_score": 213.9557342529297}, {"text": "Coronovirus disease 2019 (COVID-19) first broke out in Wuhan, Hubei Province, China in 2019, and now it spreads in more than 100 countries around the world. On January 30th, the World Health Organization (WHO) declared COVID-19 a public health emergency (PHEIC) of international concern. It was classified as a pandemic by (WHO) of the World Health Organization on March 11, 2020. With the increase in the number of cases reported by various countries every day, the COVID-19 pandemic has attracted more and more attention around the world. At the same time, this public health emergency has caused a variety of psychological problems, such as panic disorder, anxiety and depression. In addition, the Wuhan Mental Health Center's analysis of 2144 calls from the psychological hotline from February 4 to February 20, 2020 showed that general public accounted for 70%, medical workers accounted for 2.2%, patients with mental disorders accounted for 19.5%, and other personnel accounted for 8.3% (https://mp.weixin.qq.com/s/kmff1vnaLsT2d9xQkK5pwg). Therefore, while controlling the pandemic, the government should also pay attention to the mental health of the general public, medical workers and patients with mental disorders. Community mental health service system, online mental health service, telemedicine and other measures for patients with mental disorders may play a vital role during the pandemic.", "title": "Psychological influence of Coronovirus disease 2019 (COVID-19) pandemic on the general public, medical workers and patients with mental disorders and its countermeasures", "pid": "k1dkbg32", "bm25_score": 213.94290161132812}, {"text": "Abstract In late 2019, a novel coronavirus was identified as the cause of a cluster of atypical pneumonia cases in Wuhan, China. It subsequently spread throughout China and around the world, quickly becoming a public health emergency. In March 2020, the World Health Organization declared coronavirus disease 2019 a pandemic. This article explores the preparation and early experiences of a large Canadian critical care transport program during the coronavirus disease 2019 pandemic focused on 6 broad strategic objectives centered around staff welfare, regular and transparent communication, networking, evidenced-based approach to personal protective equipment, agile mission planning, and an expedited approach to clinical practice and policy updates and future state modeling.", "title": "Large-Scale Air Medical Operations in the Age of Coronavirus Disease 2019: Early Leadership Lessons From the Front Lines of British Columbia", "pid": "o4uusbix", "bm25_score": 213.93011474609375}, {"text": "As of January 22, 2020, \"disease caused by a novel coronavirus\" became a reportable disease of public health significance in Ontario. Public health units were provided with guidance on the entry of patients tested for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the virus causing 2019 coronavirus disease (COVID-19), into the provincial public health information system. Between January 22 and February 22, 2020, there were 359 individuals who had a negative test result recorded and three confirmed cases of COVID-19. Of those who tested negative, 51% were female and 71% were under 50 years of age. The most common symptoms reported were cough (55%), fever (37%) and sore throat (35%). The majority were tested within three days of symptom onset, but over one-quarter tested more than seven days after symptom onset. Over the first month of reportability, reported travel history shifted from China to an increasing proportion with travel outside of China.", "title": "Surveillance of persons-who tested negative for COVID-19 in Ontario, January 22-February 22, 2020.", "pid": "z2zt4fs2", "bm25_score": 213.90374755859375}, {"text": "PURPOSE Accurately forecasting the occurrence of future covid-19-related cases across relaxed (Sweden) and stringent (USA and Canada) policy contexts has a renewed sense of urgency. Moreover, there is a need for a multidimensional county-level approach to monitor the second wave of covid-19 in the USA. METHOD We use an artificial intelligence framework based on timeline of policy interventions that triangulated results based on the three approaches-Bayesian susceptible-infected-recovered (SIR), Kalman filter, and machine learning. RESULTS Our findings suggest three important insights. First, the effective growth rate of covid-19 infections dropped in response to the approximate dates of key policy interventions. We find that the change points for spreading rates approximately coincide with the timelines of policy interventions across respective countries. Second, forecasted trend until mid-June in the USA was downward trending, stable, and linear. Sweden is likely to be heading in the other direction. That is, Sweden's forecasted trend until mid-June appears to be non-linear and upward trending. Canada appears to fall somewhere in the middle-the trend for the same period is flat. Third, a Kalman filter based robustness check indicates that by mid-June the USA will likely have close to two million virus cases, while Sweden will likely have over 44,000 covid-19 cases. CONCLUSION We show that drop in effective growth rate of covid-19 infections was sharper in the case of stringent policies (USA and Canada) but was more gradual in the case of relaxed policy (Sweden). Our study exhorts policy makers to take these results into account as they consider the implications of relaxing lockdown measures.", "title": "Risk of a second wave of Covid-19 infections: using artificial intelligence to investigate stringency of physical distancing policies in North America.", "pid": "6ar58ea6", "bm25_score": 213.90048217773438}, {"text": "Abstract The coronavirus disease 2019 (COVID-19) has had a profound global impact. Its rapid transmissibility has forced whole countries to adopt strict measures to contain its spread. As part of necessary pandemic planning, the majority of Canadian cardiac surgical programs have prioritized and delayed elective procedures in an effort to reduce the burden on the health care system and to mobilize resources in the event of a pandemic surge. While the number of COVID-19 cases continue to increase worldwide, new cases have begun to decline in many jurisdictions. This “flattening of the curve” has inevitably prompted discussions around re-opening of the economy, relaxing some public health restrictions and resuming non-urgent health care delivery.", "title": "Ramping Up the Delivery of Cardiac Surgery During the COVID-19 Pandemic: A Guidance Statement from the Canadian Society of Cardiac Surgeons", "pid": "xtudcufl", "bm25_score": 213.89224243164062}, {"text": "During the COVID-19 pandemic, the dental education community faced unprecedented challenges. In this commentary, we share the perspectives of faculty clinicians, residents and students in academic dental institutions in the United States and Canada. We discuss COVID-19's impact on various aspects of academic dentistry including patient care, education, research and raise key concerns regarding the future of dental education post-pandemic.", "title": "The impact of COVID-19 on dental education in North America-Where do we go next?", "pid": "nj4vpgky", "bm25_score": 213.88638305664062}, {"text": "", "title": "Continuing care and COVID-19: a Canadian tragedy that must not be allowed to happen again", "pid": "yu8tgoc6", "bm25_score": 213.88340759277344}, {"text": "", "title": "COVID-19 and Wound Care – A Canadian Perspective", "pid": "x9axoi9w", "bm25_score": 213.88284301757812}, {"text": "The COVID-19 pandemic has necessitated public health measures that have impacted the provision of care for people living with dementia and their families. Additionally, the isolation that results from social distancing may be harming well-being for families, as formal and informal supports become less accessible. For those with living with dementia and experiencing agitation, social distancing may be even harder to maintain, or social distancing could potentially aggravate dementia-related neuropsychiatric symptoms. To understand the lived experience of social and physical distancing during the COVID-19 pandemic in Canada we remotely interviewed 21 participants who normally attend a dementia specialty clinic in Calgary, Alberta, during a period where essential businesses were closed and healthcare had abruptly transitioned to telemedicine. The impacts of the public health measures in response to the pandemic emerged in three main categories of experience: 1) personal; 2) health services; and 3) health status (of both person living with dementia and care partner). This in-depth understanding of the needs and experiences of the pandemic for people living with dementia suggests that innovative means are urgently needed to facilitate provision of remote medicine and also social interaction and integration.", "title": "Understanding the impact of the COVID-19 pandemic on well-being and virtual care for people living with dementia and care partners living in the community", "pid": "pzmo4hja", "bm25_score": 213.879150390625}, {"text": "BACKGROUND: The detection of coronavirus disease 2019 (COVID-19) cases remains a huge challenge. As of April 22, 2020, the COVID-19 pandemic continues to take its toll, with >2.6 million confirmed infections and >183,000 deaths. Dire projections are surfacing almost every day, and policymakers worldwide are using projections for critical decisions. Given this background, we modeled unobserved infections to examine the extent to which we might be grossly underestimating COVID-19 infections in North America. METHODS: We developed a machine-learning model to uncover hidden patterns based on reported cases and to predict potential infections. First, our model relied on dimensionality reduction to identify parameters that were key to uncovering hidden patterns. Next, our predictive analysis used an unbiased hierarchical Bayesian estimator approach to infer past infections from current fatalities. RESULTS: Our analysis indicates that, when we assumed a 13-day lag time from infection to death, the United States, as of April 22, 2020, likely had at least 1.3 million undetected infections. With a longer lag time-for example, 23 days-there could have been at least 1.7 million undetected infections. Given these assumptions, the number of undetected infections in Canada could have ranged from 60,000 to 80,000. Duarte's elegant unbiased estimator approach suggested that, as of April 22, 2020, the United States had up to >1.6 million undetected infections and Canada had at least 60,000 to 86,000 undetected infections. However, the Johns Hopkins University Center for Systems Science and Engineering data feed on April 22, 2020, reported only 840,476 and 41,650 confirmed cases for the United States and Canada, respectively. CONCLUSIONS: We have identified 2 key findings: (1) as of April 22, 2020, the United States may have had 1.5 to 2.029 times the number of reported infections and Canada may have had 1.44 to 2.06 times the number of reported infections and (2) even if we assume that the fatality and growth rates in the unobservable population (undetected infections) are similar to those in the observable population (confirmed infections), the number of undetected infections may be within ranges similar to those described above. In summary, 2 different approaches indicated similar ranges of undetected infections in North America. LEVEL OF EVIDENCE: Prognostic Level V. See Instructions for Authors for a complete description of levels of evidence.", "title": "Using Machine Learning to Estimate Unobserved COVID-19 Infections in North America", "pid": "mdt11ba5", "bm25_score": 213.86582946777344}, {"text": "", "title": "Understanding heterogeneity to inform the public health response to COVID-19 in Canada.", "pid": "2sct0c3p", "bm25_score": 213.853515625}, {"text": "", "title": "Refugees, asylum seekers and COVID-19: Canada needs to do more to protect at-risk refugees during the current pandemic", "pid": "w0e1rqlo", "bm25_score": 213.84722900390625}, {"text": "BACKGROUND: Public health emergencies like epidemics put enormous pressure on health care systems while revealing deep structural and functional problems in the organization of care. The current coronavirus disease (COVID-19) pandemic illustrates this at a global level. The sudden increased demand on delivery systems puts unique pressures on pre-established care pathways. These extraordinary times require efficient tools for smart governance and resource allocation. OBJECTIVE: The aim of this study is to develop an innovative web-based solution addressing the seemingly insurmountable challenges of triaging, monitoring, and delivering nonhospital services unleashed by the COVID-19 pandemic. METHODS: An adaptable crisis management digital platform was envisioned and designed with the goal of improving the system's response on the basis of the literature; an existing shared health record platform; and discussions between health care providers, decision makers, academia, and the private sector in response to the COVID 19 epidemic. RESULTS: The Crisis Management Platform was developed and offered to health authorities in Ontario on a nonprofit basis. It has the capability to dramatically streamline patient intake, triage, monitoring, referral, and delivery of nonhospital services. It decentralizes the provision of services (by moving them online) and centralizes data gathering and analysis, maximizing the use of existing human resources, facilitating evidence-based decision making, and minimizing the risk to both users and providers. It has unlimited scale-up possibilities (only constrained by human health risk resource availability) with minimal marginal cost. Similar web-based solutions have the potential to fill an urgent gap in resource allocation, becoming a unique asset for health systems governance and management during critical times. They highlight the potential effectiveness of web-based solutions if built on an outcome-driven architecture. CONCLUSIONS: Data and web-based approaches in response to a public health crisis are key to evidence-driven oversight and management of public health emergencies.", "title": "Emergency Response to COVID-19 in Canada: Platform Development and Implementation for eHealth in Crisis Management", "pid": "bh48s29v", "bm25_score": 213.84637451171875}, {"text": "BACKGROUND: Public health emergencies like epidemics put enormous pressure on health care systems while revealing deep structural and functional problems in the organization of care. The current coronavirus disease (COVID-19) pandemic illustrates this at a global level. The sudden increased demand on delivery systems puts unique pressures on pre-established care pathways. These extraordinary times require efficient tools for smart governance and resource allocation. OBJECTIVE: The aim of this study is to develop an innovative web-based solution addressing the seemingly insurmountable challenges of triaging, monitoring, and delivering nonhospital services unleashed by the COVID-19 pandemic. METHODS: An adaptable crisis management digital platform was envisioned and designed with the goal of improving the system’s response on the basis of the literature; an existing shared health record platform; and discussions between health care providers, decision makers, academia, and the private sector in response to the COVID 19 epidemic. RESULTS: The Crisis Management Platform was developed and offered to health authorities in Ontario on a nonprofit basis. It has the capability to dramatically streamline patient intake, triage, monitoring, referral, and delivery of nonhospital services. It decentralizes the provision of services (by moving them online) and centralizes data gathering and analysis, maximizing the use of existing human resources, facilitating evidence-based decision making, and minimizing the risk to both users and providers. It has unlimited scale-up possibilities (only constrained by human health risk resource availability) with minimal marginal cost. Similar web-based solutions have the potential to fill an urgent gap in resource allocation, becoming a unique asset for health systems governance and management during critical times. They highlight the potential effectiveness of web-based solutions if built on an outcome-driven architecture. CONCLUSIONS: Data and web-based approaches in response to a public health crisis are key to evidence-driven oversight and management of public health emergencies.", "title": "Emergency Response to COVID-19 in Canada: Platform Development and Implementation for eHealth in Crisis Management", "pid": "lcwxn3vq", "bm25_score": 213.8463592529297}, {"text": "We report diagnosis and management of the first laboratory-confirmed case of coronavirus disease 2019 (COVID-19) hospitalized in Toronto, Canada. No healthcare-associated transmission occurred. In the face of a potential pandemic of COVID-19, we suggest sustainable and scalable control measures developed based on lessons learned from SARS.", "title": "Diagnosis and Management of First Case of COVID-19 in Canada: Lessons applied from SARS", "pid": "vx5rd8hs", "bm25_score": 213.84268188476562}, {"text": "This paper evaluated the unique challenges of Australians in relation to the global novel coronavirus (COVID-19) pandemic. The 2019-2020 bushfires and COVID-19 outbreak have increased rates of anxiety and distress in Australia. On the contrary, unprecedented spending by the Australian Government on health care, employment, and housing has potentially lowered anxiety and stress for some Australians. Research is required to monitor the potential long-term mental health consequences of COVID-19 in Australia. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "The COVID-19 pandemic in Australia: Lessons learnt", "pid": "3qlmxcww", "bm25_score": 213.83297729492188}]}
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In this work we analyze the effect of current social distancing measures in the United States. We quantify the reduction in doubling rate, by state, that is associated with social distancing. We find that social distancing is associated with a statistically-significant reduction in the doubling rate for all but three states. At the same time, we do not find significant evidence that social distancing has resulted in a reduction in the number of daily confirmed cases. Instead, social distancing has merely stabilized the spread of the disease. We provide an illustration of our findings for each state, including point estimates of the effective reproduction number, R, both with and without social distancing. We also discuss the policy implications of our findings.", "title": "Social Distancing Has Merely Stabilized COVID-19 in the US", "pid": "all7ocnd", "bm25_score": 219.89207458496094}, {"text": "OBJECTIVE. To analyze the effectiveness of social distancing in the United States (U.S.). METHODS. A novel cell-phone ping data was used to quantify the measures of social distancing by all U.S. counties. RESULTS. Using a difference-in-difference approach results show that social distancing has been effective in slowing the spread of COVID-19. CONCLUSIONS. As policymakers face the very difficult question of the necessity and effectiveness of social distancing across the U.S., counties where the policies have been imposed have effectively increased social distancing and have seen slowing the spread of COVID-19. These results might help policymakers to make the public understand the risks and benefits of the lockdown.", "title": "U.S. county level analysis to determine If social distancing slowed the spread of COVID-19", "pid": "pn02p843", "bm25_score": 219.36451721191406}, {"text": "In March of 2020, many U.S. state governments encouraged or mandated restrictions on social interactions to slow the spread of COVID-19, the disease caused by the novel coronavirus SARS-CoV-2 that has spread to nearly 180 countries. Estimating the effectiveness of these social-distancing strategies is challenging because surveillance of COVID-19 has been limited, with tests generally being prioritized for high-risk or hospitalized cases according to temporally and regionally varying criteria. Here we show that reductions in mobility across U.S. counties with at least 100 confirmed cases of COVID-19 led to reductions in fever incidences, as captured by smart thermometers, after a mean lag of 6.5 days ($90\\%$ within 3--10 days) that is consistent with the incubation period of COVID-19. Furthermore, counties with larger decreases in mobility subsequently achieved greater reductions in fevers ($p<0.01$), with the notable exception of New York City and its immediate vicinity. These results indicate that social distancing has reduced the transmission of influenza like illnesses, including COVID 19, and support social distancing as an effective strategy for slowing the spread of COVID-19.", "title": "Fever and mobility data indicate social distancing has reduced incidence of communicable disease in the United States", "pid": "cb5ebiiv", "bm25_score": 219.27499389648438}, {"text": "The emergence of SARS-CoV-2 and the coronavirus infectious disease (COVID-19) has become a pandemic. Social (physical) distancing is a key non-pharmacologic control measure to reduce the transmission rate of SARS-COV-2, but high-level adherence is needed. Using daily travel distance and stay-at-home time derived from large-scale anonymous mobile phone location data provided by Descartes Labs and SafeGraph, we quantify the degree to which social distancing mandates have been followed in the U.S. and its effect on growth of COVID-19 cases. The correlation between the COVID-19 growth rate and travel distance decay rate and dwell time at home change rate was -0.586 (95% CI: -0.742 ~ -0.370) and 0.526 (95% CI: 0.293 ~ 0.700), respectively. Increases in state-specific doubling time of total cases ranged from 1.04 ~ 6.86 days to 3.66 ~ 30.29 days after social distancing orders were put in place, consistent with mechanistic epidemic prediction models. Social distancing mandates reduce the spread of COVID-19 when they are followed.", "title": "Mobile phone location data reveal the effect and geographic variation of social distancing on the spread of the COVID-19 epidemic", "pid": "esa5700v", "bm25_score": 219.07969665527344}, {"text": "From the end of 2019, an unprecedented novel coronavirus, which was named COVID-19 by the World Health Organization (WHO) emerged from Wuhan city, China. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 has continued to rise, with over 4 million confirmed-cases and over 300,000 deaths worldwide until mid-May. This study aims to present the effect of the promulgation of social distancing measures on the spread of COVID-19 in the cases of 10 highly infected countries. The authors focus on the statistics of the COVID-19 confirmed-cases and deaths in 10 highly infected countries, including The U.S., Spain, Italy, The U.K., France, Germany, Russia, Turkey, Iran and China, and the response to the pandemic of these countries in the period from January 11 to May 2, 2020. The relationships between the social distancing measures and the statistics of COVID-19 confirmed-cases and deaths were analyzed in order to elucidate the effectiveness of the social distancing measures on the spread of COVID-19 in 10 highly infected countries. The results showed it took1-4 weeks since the highest level of social distancing measures promulgation until the daily confirmed-cases and deaths showed signs of decreasing. The effectiveness of the social distancing measures on the spread of COVID-19 was different between the 10 focused countries. This variation is due to the difference in the levels of promulgated social distancing measures, as well as the difference in the COVID-19 spread situation at the time of promulgation between the countries.", "title": "Effect of the social distancing measures on the spread of COVID-19 in 10 highly infected countries", "pid": "1r8dhqi5", "bm25_score": 218.89117431640625}, {"text": "Abstract From the end of 2019, an unprecedented novel coronavirus, which was named COVID-19 by the World Health Organization (WHO) emerged from Wuhan city, China. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 has continued to rise, with over 4 million confirmed-cases and over 300,000 deaths worldwide until mid-May. This study aims to present the effect of the promulgation of social distancing measures on the spread of COVID-19 in the cases of 10 highly infected countries. The authors focus on the statistics of the COVID-19 confirmed-cases and deaths in 10 highly infected countries, including The U.S., Spain, Italy, The U.K., France, Germany, Russia, Turkey, Iran and China, and the response to the pandemic of these countries in the period from January 11 to May 2, 2020. The relationships between the social distancing measures and the statistics of COVID-19 confirmed-cases and deaths were analyzed in order to elucidate the effectiveness of the social distancing measures on the spread of COVID-19 in 10 highly infected countries. The results showed it took1–4 weeks since the highest level of social distancing measures promulgation until the daily confirmed-cases and deaths showed signs of decreasing. The effectiveness of the social distancing measures on the spread of COVID-19 was different between the 10 focused countries. This variation is due to the difference in the levels of promulgated social distancing measures, as well as the difference in the COVID-19 spread situation at the time of promulgation between the countries.", "title": "Effect of the social distancing measures on the spread of COVID-19 in 10 highly infected countries", "pid": "mhmno6vb", "bm25_score": 218.83213806152344}, {"text": "The outbreak the SARS-CoV-2 (CoV-2) virus has resulted in over 2.5 million cases of COVID19, greatly stressing global healthcare infrastructure. Lacking medical prophylactic measures to combat disease spread, many nations have adopted social distancing policies in order to mitigate transmission of CoV-2. While mathematical models have suggested the efficacy of social distancing to curb the spread of CoV-2, there is a lack of systematic studies to quantify the real-world efficacy of these approaches. Here, we quantify the spread rate of COVID19 before and after national social distancing measures were implemented in 26 nations and compare this to the changes in COVID19 spread rate over equivalent time periods in 27 nations that did not enact social distancing policies. We find that social distancing policies significantly reduced the COVID19 spread rate. Using mixed linear regression models we estimate that social distancing policies reduced the spread of COVID19 by 66%. These data suggest that social distancing policies may be a powerful tool to prevent spread of COVID19 in real-world scenarios.", "title": "Enacting national social distancing policies corresponds with dramatic reduction in COVID19 infection rates", "pid": "vdrd74nz", "bm25_score": 218.7276611328125}, {"text": "COVID-19 is present in every state and over 90 percent of all counties in the United States. Decentralized government efforts to reduce spread, combined with the complex dynamics of human mobility and the variable intensity of local outbreaks makes assessing the effect of large-scale social distancing on COVID-19 transmission in the U.S. is a challenge. We generate a novel metric to represent social distancing behavior derived from mobile phone data, and examine its relationship with COVID-19 case reports at the county level. Our analysis reveals that social distancing is strongly correlated with decreased COVID-19 case growth rates for the 25 most affected counties in the United States, with a lag period consistent with the incubation time of SARS-CoV-2. We also demonstrate evidence that social distancing was already under way in many U.S. counties before county and state-level policies were implemented. This study strongly supports social distancing as an effective way to mitigate COVID-19 transmission in the United States.", "title": "Social Distancing is Effective at Mitigating COVID-19 Transmission in the United States", "pid": "noyx53ej", "bm25_score": 218.6866455078125}, {"text": "State and local governments imposed social distancing measures in March and April of 2020 to contain the spread of novel coronavirus disease 2019 (COVID-19). These included large event bans, school closures, closures of entertainment venues, gyms, bars, and restaurant dining areas, and shelter-in-place orders (SIPOs). We evaluated the impact of these measures on the growth rate of confirmed COVID-19 cases across US counties between March 1, 2020 and April 27, 2020. An event-study design allowed each policy's impact on COVID-19 case growth to evolve over time. Adoption of government-imposed social distancing measures reduced the daily growth rate by 5.4 percentage points after 1-5 days, 6.8 after 6-10 days, 8.2 after 11-15 days, and 9.1 after 16-20 days. Holding the amount of voluntary social distancing constant, these results imply 10 times greater spread by April 27 without SIPOs (10 million cases) and more than 35 times greater spread without any of the four measures (35 million). Our paper illustrates the potential danger of exponential spread in the absence of interventions, providing relevant information to strategies for restarting economic activity. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "title": "Strong Social Distancing Measures In The United States Reduced The COVID-19 Growth Rate.", "pid": "ereh4ub8", "bm25_score": 218.67572021484375}, {"text": "State and local governments imposed social distancing measures in March and April of 2020 to contain the spread of novel coronavirus disease 2019 (COVID-19). These included large event bans, school closures, closures of entertainment venues, gyms, bars, and restaurant dining areas, and shelter-in-place orders (SIPOs). We evaluated the impact of these measures on the growth rate of confirmed COVID-19 cases across US counties between March 1, 2020 and April 27, 2020. An event-study design allowed each policy's impact on COVID-19 case growth to evolve over time. Adoption of government-imposed social distancing measures reduced the daily growth rate by 5.4 percentage points after 1-5 days, 6.8 after 6-10 days, 8.2 after 11-15 days, and 9.1 after 16-20 days. Holding the amount of voluntary social distancing constant, these results imply 10 times greater spread by April 27 without SIPOs (10 million cases) and more than 35 times greater spread without any of the four measures (35 million). Our paper illustrates the potential danger of exponential spread in the absence of interventions, providing relevant information to strategies for restarting economic activity. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "title": "Strong Social Distancing Measures In The United States Reduced The COVID-19 Growth Rate", "pid": "h6ngg7ea", "bm25_score": 218.58856201171875}, {"text": "Cities across China implemented stringent social distancing measures in early 2020 to curb coronavirus disease outbreaks. We estimated the speed with which these measures contained transmission in cities. A 1-day delay in implementing social distancing resulted in a containment delay of 2.41 (95% CI 0.97-3.86) days.", "title": "Effects of Proactive Social Distancing on COVID-19 Outbreaks in 58 Cities, China.", "pid": "maxvppn8", "bm25_score": 218.56248474121094}, {"text": "The coronavirus disease (COVID-19) affecting across the globe. The government of different countries has adopted various policies to contain this epidemic and the most common were social distancing and lockdown. We use a simple log-linear model with intercept and trend break to evaluate whether the measures are effective preventing/slowing down the spread of the disease in Turkey. We estimate the model parameters from the Johns Hopkins University (2020) epidemic data between 15th March and 16th April 2020. Our analysis revealed that the measures can slow down the outbreak. We can reduce the epidemic size and prolong the time to arrive at the epidemic peak by seriously following the measures suggested by the authorities.", "title": "Evaluation of Turkish social distancing measures on the spread of COVID-19", "pid": "uwix8ftr", "bm25_score": 218.53274536132812}, {"text": "A better understanding of how the COVID-19 epidemic responds to social distancing efforts is required for the control of future outbreaks and to calibrate partial lock-downs. We present quantitative relationships between key parameters characterizing the COVID-19 epidemiology and social distancing efforts of nine selected European countries. Epidemiological parameters were extracted from the number of daily deaths data, while mitigation efforts are estimated from mobile phone tracking data. The decrease of the basic reproductive number (R0) as well as the duration of the initial exponential expansion phase of the epidemic strongly correlates with the magnitude of mobility reduction. Utilizing these relationships we decipher the relative impact of the timing and the extent of social distancing on the total death burden of the epidemic.", "title": "Effects of social distancing on the spreading of COVID-19 inferred from mobile phone data", "pid": "gz18sxzc", "bm25_score": 218.5283660888672}, {"text": "Following the introduction of unprecedented \"stay-at-home\" national policies, the COVID-19 pandemic recently started declining in Europe. Our research aims were to characterize the changepoint in the flow of the COVID-19 epidemic in each European country and to evaluate the association of the level of social distancing with the observed decline in the national epidemics. Interrupted time series analyses were conducted in 28 European countries. Social distance index was calculated based on Google Community Mobility Reports. Changepoints were estimated by threshold regression, national findings were analyzed by Poisson regression, and the effect of social distancing in mixed effects Poisson regression model. Our findings identified the most probable changepoints in 28 European countries. Before changepoint, incidence of new COVID-19 cases grew by 24% per day on average. From the changepoint, this growth rate was reduced to 0.9%, 0.3% increase, and to 0.7% and 1.7% decrease by increasing social distancing quartiles. The beneficial effect of higher social distance quartiles (i.e., turning the increase into decline) was statistically significant for the fourth quartile. Notably, many countries in lower quartiles also achieved a flat epidemic curve. In these countries, other plausible COVID-19 containment measures could contribute to controlling the first wave of the disease. The association of social distance quartiles with viral spread could also be hindered by local bottlenecks in infection control. Our results allow for moderate optimism related to the gradual lifting of social distance measures in the general population, and call for specific attention to the protection of focal micro-societies enriching high-risk elderly subjects, including nursing homes and chronic care facilities.", "title": "The effect of social distance measures on COVID-19 epidemics in Europe: an interrupted time series analysis", "pid": "4z3r8hoe", "bm25_score": 218.50967407226562}, {"text": "Background: Social distancing measures to address the U.S. COVID-19 epidemic may have significant health, social, and economic impacts. Objective: To estimate the mean change in state-level COVID-19 epidemic growth before versus after the implementation of statewide social distancing measures. Design: Interrupted time-series analysis. Setting: United States. Measurements: Our primary exposure was time in relation to implementation of the first statewide social distancing measure. The pre-implementation period began 14 days prior to implementation and included up to 3 days after implementation to account for incubation. Post-implementation began 4 days after, up to and including March 30. Our primary outcome was the COVID-19 growth rate, calculated as the log of daily COVID-19 cases minus the log of daily COVID-19 cases on the prior day. Results: All states applied some form of statewide social distancing between March 10-27. The mean daily COVID-19 growth rate decreased beginning four days after implementation of the first statewide social distancing measures, by an additional 0.8% per day; 95% CI, -1.4% to -0.2%; P=0.002). This reduction corresponds to an increase in doubling time of the epidemic from 3.3 days (before) to 5.0 days (at 14 days after implementation). Limitations: Potential bias due to the aggregate nature of the ecological data, potential confounding by contemporaneous changes (e.g., increases in testing), and potential underestimation of social distancing due to spillovers across neighboring states. Conclusion: Statewide social distancing measures were associated with a decrease in U.S. COVID-19 epidemic growth. Based on the size of the epidemic at the time of implementation in each state, social distancing measures were associated with a decrease of 3,090 cases at 7 days, and 68,255 cases at 14 days, after implementation.", "title": "Social distancing to slow the U.S. COVID-19 epidemic: an interrupted time-series analysis", "pid": "ls408b2b", "bm25_score": 218.4893798828125}, {"text": "Cities across China implemented stringent social distancing measures in early 2020 to curb coronavirus disease outbreaks. We estimated the speed with which these measures contained transmission in cities. A 1-day delay in implementing social distancing resulted in a containment delay of 2.41 (95% CI 0.97-3.86) days.", "title": "Effects of Proactive Social Distancing on COVID-19 Outbreaks in 58 Cities, China", "pid": "kdbw5k7w", "bm25_score": 218.4877166748047}, {"text": "We combine COVID-19 case data with demographic and mobility data to estimate a modified susceptible-infected-recovered (SIR) model for the spread of this disease in the United States. We find that the incidence of infectious COVID-19 individuals has a concave effect on contagion, as would be expected if people have inter-related social networks. We also demonstrate that social distancing and population density have large effects on the rate of contagion. The social distancing in late March and April substantially reduced the number of COVID-19 cases. However, the concave contagion pattern means that when social distancing measures are lifted, the growth rate is considerable but will not be exponential as predicted by standard SIR models. Furthermore, counties with the lowest population density could likely avoid high levels of contagion even with no social distancing. We forecast rates of new cases for COVID-19 under different social distancing norms and find that if social distancing is eliminated there will be a massive increase in the cases of COVID-19, about double what would occur if the US only restored to 50% of the way to normalcy.", "title": "Forecasting the Spread of COVID-19 under Different Reopening Strategies", "pid": "icituitn", "bm25_score": 218.48728942871094}, {"text": "Following the introduction of unprecedented “stay-at-home” national policies, the COVID-19 pandemic recently started declining in Europe. Our research aims were to characterize the changepoint in the flow of the COVID-19 epidemic in each European country and to evaluate the association of the level of social distancing with the observed decline in the national epidemics. Interrupted time series analyses were conducted in 28 European countries. Social distance index was calculated based on Google Community Mobility Reports. Changepoints were estimated by threshold regression, national findings were analyzed by Poisson regression, and the effect of social distancing in mixed effects Poisson regression model. Our findings identified the most probable changepoints in 28 European countries. Before changepoint, incidence of new COVID-19 cases grew by 24% per day on average. From the changepoint, this growth rate was reduced to 0.9%, 0.3% increase, and to 0.7% and 1.7% decrease by increasing social distancing quartiles. The beneficial effect of higher social distance quartiles (i.e., turning the increase into decline) was statistically significant for the fourth quartile. Notably, many countries in lower quartiles also achieved a flat epidemic curve. In these countries, other plausible COVID-19 containment measures could contribute to controlling the first wave of the disease. The association of social distance quartiles with viral spread could also be hindered by local bottlenecks in infection control. Our results allow for moderate optimism related to the gradual lifting of social distance measures in the general population, and call for specific attention to the protection of focal micro-societies enriching high-risk elderly subjects, including nursing homes and chronic care facilities.", "title": "The effect of social distance measures on COVID-19 epidemics in Europe: an interrupted time series analysis", "pid": "1abupl36", "bm25_score": 218.47665405273438}, {"text": "In early 2020, cities across China enacted strict social distancing measures to contain emerging coronavirus (COVID-19) outbreaks. We estimated the speed with which these measures contained community transmission in each of 58 Chinese cities. On average, containment was achieved 7.83 days (SD 6.79 days) after the implementation of social distancing interventions, with an average reduction in the reproduction number (R(t)) of 54.3% (SD 17.6%) over that time period. A single day delay in the implementation of social distancing led to a 2.41 (95% CI: 0.97, 3.86) day delay in containment. Swift social distancing interventions may thus achieve rapid containment of newly emerging COVID-19 outbreaks.", "title": "Proactive social distancing mitigates COVID-19 outbreaks within a month across 58 mainland China cities", "pid": "43w659t1", "bm25_score": 218.47238159179688}, {"text": "The novel coronavirus (COVID-19) pandemic continues to be a global health problem whose impact has been significantly felt in South Africa. Social distancing has been touted as the best form of response in managing a rapid increase in the number of infected cases. In this paper, we present a deterministic model to model the impact of social distancing on the transmission dynamics of COVID-19 in South Africa. The model is fitted to the currently available data on the cumulative number of infected cases and a scenario analysis on different levels of social distancing are presented. The results show a continued rise in the number of cases in the lock down period with the current levels of social distancing albeit at a lower rate. The model shows that the number of cases will rise to above 4000 cases by the end of the lockdown. The model also looks at the impact of relaxing the social distancing measures after the initial announcement of the lock down measures. A relaxation of the social distancing by 2% can result in a 23% rise in the number of cumulative cases while on the other hand increasing the levels of social distancing by 2% would reduce the number of cumulative cases by about 18%. These results have implications on the management and policy direction in the early phases of the epidemic.", "title": "Modelling the potential impact of social distancing on the COVID-19 epidemic in South Africa", "pid": "q5xc4m3j", "bm25_score": 218.43807983398438}, {"text": "By April 2, 2020, >1 million persons worldwide were infected with severe acute respiratory syndrome coronavirus 2. We used a mathematical model to investigate the effectiveness of social distancing interventions in a mid-sized city. Interventions reduced contacts of adults >60 years of age, adults 20-59 years of age, and children <19 years of age for 6 weeks. Our results suggest interventions started earlier in the epidemic delay the epidemic curve and interventions started later flatten the epidemic curve. We noted that, while social distancing interventions were in place, 20% of new cases and most hospitalizations and deaths were averted, even with modest reductions in contact among adults. However, when interventions ended, the epidemic rebounded. Our models suggest that social distancing can provide crucial time to increase healthcare capacity but must occur in conjunction with testing and contact tracing of all suspected cases to mitigate virus transmission.", "title": "Evaluating the Effectiveness of Social Distancing Interventions to Delay or Flatten the Epidemic Curve of Coronavirus Disease", "pid": "3mk5a5u6", "bm25_score": 218.29116821289062}, {"text": "Social distancing has been adopted as a non-pharmaceutical intervention to prevent the COVID-19 pandemic from overwhelming the medical resources across the United States (US). The catastrophic socio-economic impacts of this intervention could outweigh its benefits if the timing and duration of implementation are left uncontrolled and ill-strategized. Here we investigate the dynamics of social distancing on age-stratified US population and benchmark its effectiveness in reducing the burden on hospital and ICU beds. Our findings highlight the diminishing marginal benefit of social distancing, characterized by a linear decrease in medical demands against an exponentially increasing social distancing duration. We determine an optimal intermittent social-to-no-distancing ratio of 5:1 corresponding to ~80% reduction in healthcare demands; beyond this ratio, benefit of social distancing diminishes to a negligible level. COVID-19 Medical Forecast: https://eece.wustl.edu/chakrabarty-group/covid/", "title": "Diminishing Marginal Benefit of Social Distancing in Balancing COVID-19 Medical Demand-to-Supply", "pid": "rzh7ja6a", "bm25_score": 218.27867126464844}, {"text": "COVID-19 continues to spread across the country and around the world. Current strategies for managing the spread of COVID-19 include social distancing. We present VERA, an interactive AI tool, that first enables users to specify conceptual models of the impact of social distancing on the spread of COVID-19. Then, VERA automatically spawns agent-based simulations from the conceptual models, and, given a data set, automatically fills in the values of the simulation parameters from the data. Next, the user can view the simulation results, and, if needed, revise the simulation parameters and run another experimental trial, or build an alternative conceptual model. We describe the use VERA to develop a SIR model for the spread of COVID-19 and its relationship with healthcare capacity.", "title": "Using VERA to explain the impact of social distancing on the spread of COVID-19", "pid": "p1jeiljo", "bm25_score": 218.26766967773438}, {"text": "Background: To date, no study has examined the effectiveness of social distancing, while controlling for social mobility and social distancing restrictions in the United States. We utilize the quasi-experimental setting created by the nationwide protests precipitated by George Floyd's tragic death on May 25, 2020, to assess the causal impact of social distancing on the spread of SARS-CoV-2. Methods: Our sample period spans from January 22, 2020, to June 20, 2020, and consists of 474,422 county-days representing 3,142 counties from all 50 states and the District of Columbia. To assess the change in COVID-19 case counts following the protests, we employ a differences in differences estimation strategy in a multivariate setting, in which we control for social distancing restrictions and social mobility across counties. We also control for covariates that may influence COVID-19 transmission, and implement placebo tests using a Monte Carlo simulation. Findings: We document a country wide increase of over 3.06 cases per day, per 100,000 population, following the onset of the protests (95%CI: 2.47-3.65), and a further increase of 1.73 cases per day, per 100,000 population, in the counties in which the protests took place (95%CI: 0.59- 2.87). Relative to the week preceding the onset of the protests, this represents a 61.2% country wide increase in COVID-19 cases, and a further 34.6% increase in the protest counties. Interpretation: Our study documents a significant increase in COVID-19 case counts in counties that experienced a protest, and we conclude that social distancing practices causally impact the spread of SARS-CoV-2. The observed effect cannot be explained by changes in social distancing restrictions and social mobility, and placebo tests rule out the possibility that this finding is attributable to chance.", "title": "Social Distancing Causally Impacts the Spread of SARS-CoV-2: A U.S. Nationwide Event Study", "pid": "s74jgknw", "bm25_score": 218.24679565429688}, {"text": "Abstract The spread of the COVID-19 virus has resulted in unprecedented measures restricting travel and activity participation in many countries. Social distancing, i.e., reducing interactions between individuals in order to slow down the spread of the virus, has become the new norm. In this viewpoint I will discuss the potential implications of social distancing on daily travel patterns. Avoiding social contact might completely change the number and types of out-of-home activities people perform, and how people reach these activities. It can be expected that the demand for travel will reduce and that people will travel less by public transport. Social distancing might negatively affect subjective well-being and health status, as it might result in social isolation and limited physical activity. As a result, walking and cycling, recreationally or utilitarian, can be important ways to maintain satisfactory levels of health and well-being. Policymakers and planners should consequently try to encourage active travel, while public transport operators should focus on creating ways to safely use public transport.", "title": "The effect of COVID-19 and subsequent social distancing on travel behavior", "pid": "ocwetgv6", "bm25_score": 218.24302673339844}, {"text": "By April 2, 2020, >1 million persons worldwide were infected with severe acute respiratory syndrome coronavirus 2. We used a mathematical model to investigate the effectiveness of social distancing interventions in a mid-sized city. Interventions reduced contacts of adults >60 years of age, adults 20-59 years of age, and children <19 years of age for 6 weeks. Our results suggest interventions started earlier in the epidemic delay the epidemic curve and interventions started later flatten the epidemic curve. We noted that, while social distancing interventions were in place, 20% of new cases and most hospitalizations and deaths were averted, even with modest reductions in contact among adults. However, when interventions ended, the epidemic rebounded. Our models suggest that social distancing can provide crucial time to increase healthcare capacity but must occur in conjunction with testing and contact tracing of all suspected cases to mitigate virus transmission.", "title": "Evaluating the Effectiveness of Social Distancing Interventions to Delay or Flatten the Epidemic Curve of Coronavirus Disease.", "pid": "x9zg7ulr", "bm25_score": 218.1806182861328}, {"text": "Mandated social distancing has been globally applied to limit the spread of corona virus disease 2019 (COVID-19) from highly pathogenic severe acute respiratory syndrome (SARS) -associated coronavirus 2 (SARS-CoV-2). The benefit of this community-based intervention in limiting COVID-19 has not been proven nor quantified. We examined the effect of timing of mandated social distancing on the rate of COVID-19 in 119 geographic regions derived from 41 states within United States and 78 countries. We found that highest number of new COVID-19 cases per day per million persons was significantly associated with total number of COVID-19 cases per million persons on the day before mandated social distancing (Beta;=0.66, p<0.0001). Our findings suggest that the initiation of mandated social distancing for each doubling in number of existing COVID-19 cases would result in eventual peak with 58% higher number of COVID-19 infections per day. Subgroup analysis on those regions where the highest number of new COVID-19 cases per day have peaked increased Beta to .85 (p<0.0001). We demonstrate that initiating mandated social distancing at a 10 times smaller number of COVID-19 cases will reduce the number of daily new COVID-19 cases at peak by 80% highlighting the importance of this community-based intervention.", "title": "Early Mandated Social Distancing is a Strong Predictor of Reduction in Highest Number of New COVID-19 cases per Day within Various Geographic Regions", "pid": "xcxjc3po", "bm25_score": 218.14064025878906}, {"text": "Non-pharmaceutical intervention measures, such as social distancing, have so far been the only means to slow the spread of COVID19. In the United States, strict social distancing has resulted in different types infection dynamics. In some states, such as New York, extensive infection spread was followed by a pronounced decline of infection levels. In other states, such as California, less infection spread occurred before strict social distancing, and a different pattern was observed. Instead of a pronounced infection decline, a long-lasting plateau is evident, characterized by similar daily new infection levels. While these plateau dynamics cannot be readily reproduced with standard SIR infection models, we show that network models, in which individuals and their social contacts are explicitly tracked, can reproduce the plateau if network connections are cut due to social distancing measures. The reason is that in networks characterized by a degree of 2D spatial structure, infection tends to spread quadratically with time, but as edges are randomly removed, the infection spreads along nearly one-dimensional infection \"corridors\", resulting in plateau dynamics. Interestingly, the plateau dynamics are predicted to eventually transition into an infection decline phase without any further increase in social distancing measures. Additionally, the models suggest that a potential second wave becomes significantly less pronounced if social distancing is only relaxed once the dynamics have transitioned to the decline phase. The network models analyzed here allow us to interpret and reconcile different infection dynamics during social distancing observed in various US states.", "title": "Modeling the dynamics of COVID19 spread during and after social distancing", "pid": "0b6dsdct", "bm25_score": 218.13912963867188}, {"text": "BACKGROUND: Across the U.S., various social distancing measures were implemented to control COVID-19 pandemic. However, there is uncertainty in the effectiveness of such measures for specific regions with varying population demographics and different levels of adherence to social distancing. The objective of this paper is to determine the impact of social distancing measures in unique regions. METHODS: We developed COVid-19 Agent-based simulation Model (COVAM), an agent-based simulation model (ABM) that represents the social network and interactions among the people in a region considering population demographics, limited testing availability, imported infections from outside of the region, asymptomatic disease transmission, and adherence to social distancing measures. We adopted COVAM to represent COVID-19-associated events in Dane County, Wisconsin, Milwaukee metropolitan area, and New York City (NYC). We used COVAM to evaluate the impact of three different aspects of social distancing: 1) Adherence to social distancing measures; 2) timing of implementing social distancing; and 3) timing of easing social distancing. RESULTS: We found that the timing of social distancing and adherence level had a major effect on COVID-19 occurrence. For example, in NYC, implementing social distancing measures on March 5, 2020 instead of March 12, 2020 would have reduced the total number of confirmed cases from 191,984 to 43,968 as of May 30, whereas a 1-week delay in implementing such measures could have increased the number of confirmed cases to 1,299,420. Easing social distancing measures on June 1, 2020 instead of June 15, 2020 in NYC would increase the total number of confirmed cases from 275,587 to 379,858 as of July 31. CONCLUSION: The timing of implementing social distancing measures, adherence to the measures, and timing of their easing have major effects on the number of COVID-19 cases. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases Institute", "title": "Impact of Timing of and Adherence to Social Distancing Measures on COVID-19 Burden in the US: A Simulation Modeling Approach", "pid": "aiah8kkn", "bm25_score": 218.13645935058594}, {"text": "Abstract Background: The ability of countries to contain and control COVID-19 virus transmission via social distancing is critical in the absence of a vaccine. Early activation of robust measures has been shown to control the daily infection rate, and consequential pressure on the health care system. As countries begin to control COVID-19 spread an understanding of how to ease social distancing measures to prevent a rebound in cases and deaths is required. Methods: Using COVID-19 transmission data from the outbreak source in Hubei Province, China prior to activation of containment measures, we adapted an established individual-based simulation model of the city of Newcastle, Australia. Simulation of virus transmission in this model, with and without, social distancing measures activated permitted us to quantify social distancing effectiveness. Optimal strategies for relaxing social distancing were determined under two settings: with high numbers of daily cases, as in New York; and where early social distancing activation resulted in limited ongoing transmission, as in Perth, Australia. Findings: In countries where strong social distancing measures were activated after the COVID-19 virus had spread widely, our study found these measures are required to be maintained for significant periods before being eased, to return to a situation where daily case numbers become low. In countries where early responses to the COVID-19 pandemic have been highly successful, as in Australia, we show that a staged relaxation of social distancing prevents a rebound in cases. Interpretation: Modelling studies and direct observation have shown that robust and timely social distancing have the most effect in containing the spread of the COVID-19 virus. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society and economic activity. This study demonstrates the necessity of holding robust social distancing in place until COVID-19 virus transmission has significantly decreased, and how they may then be safely eased.", "title": "A Modelling Analysis of Strategies for Relaxing COVID-19 Social Distancing", "pid": "t7p2j504", "bm25_score": 218.1224822998047}, {"text": "The outbreak of the novel coronavirus, COVID-19, has been declared a pandemic by the WHO. The structures of social contact critically determine the spread of the infection and, in the absence of vaccines, the control of these structures through large-scale social distancing measures appears to be the most effective means of mitigation. Here we use an age-structured SIR model with social contact matrices obtained from surveys and Bayesian imputation to study the progress of the COVID-19 epidemic in India. The basic reproductive ratio R0 and its time-dependent generalization are computed based on case data, age distribution and social contact structure. The impact of social distancing measures - workplace non-attendance, school closure, lockdown - and their efficacy with durations are then investigated. A three-week lockdown is found insufficient to prevent a resurgence and, instead, protocols of sustained lockdown with periodic relaxation are suggested. Forecasts are provided for the reduction in age-structured morbidity and mortality as a result of these measures. Our study underlines the importance of age and social contact structures in assessing the country-specific impact of mitigatory social distancing.", "title": "Age-structured impact of social distancing on the COVID-19 epidemic in India", "pid": "xbuypaf6", "bm25_score": 218.11972045898438}, {"text": "Social distancing and isolation have been introduced widely to counter the COVID-19 pandemic. However, more moderate contact reduction policies become desirable owing to adverse social, psychological, and economic consequences of a complete or near-complete lockdown. Adopting a social network approach, we evaluate the effectiveness of three targeted distancing strategies designed to 'keep the curve flat' and aid compliance in a post-lockdown world. These are limiting interaction to a few repeated contacts, seeking similarity across contacts, and strengthening communities via triadic strategies. We simulate stochastic infection curves that incorporate core elements from infection models, ideal-type social network models, and statistical relational event models. We demonstrate that strategic reduction of contact can strongly increase the efficiency of social distancing measures, introducing the possibility of allowing some social contact while keeping risks low. This approach provides nuanced insights to policy makers for effective social distancing that can mitigate negative consequences of social isolation.", "title": "Social network-based distancing strategies to flatten the COVID 19 curve in a post-lockdown world", "pid": "o8k66pes", "bm25_score": 218.0894317626953}, {"text": "On January 20, 2020, the first COVID-19 case was confirmed in South Korea. After a rapid outbreak, the number of incident cases has been consistently decreasing since early March; this decrease has been widely attributed to its intensive testing. We report here on the likely role of social distancing in reducing transmission in South Korea. Our analysis suggests that transmission may still be persisting in some regions.", "title": "Potential roles of social distancing in mitigating the spread of coronavirus disease 2019 (COVID-19) in South Korea", "pid": "7t3ci8tl", "bm25_score": 218.06204223632812}, {"text": "This paper questions various claims from the paper \"Social distancing strategies for curbing the COVID-19 epidemic\" by Kissler, Tedijanto, Lipsitch, and Grad: most importantly, the claim that China's \"intense\" distancing measures achieved only a 60% reduction in R0.", "title": "Further analysis of the impact of distancing upon the COVID-19 pandemic", "pid": "qjf23a7e", "bm25_score": 218.05520629882812}, {"text": "Physical distancing measures are intended to mitigate the spread of COVID-19. However, the impact these measures have on social contact and disease transmission patterns remains unclear. We ran the first comparative contact survey (N=53,708) across eight countries (Belgium, France, Germany, Italy, Netherlands, Spain, United Kingdom, United States) for the period March 13 - April 13, 2020. Our results show that social contact numbers mainly decreased after governments issued physical distancing guidelines rather than after announcing national lockdown measures. Compared to pre-COVID levels, social contact numbers decreased by 48% - 85% across countries. Except in Italy, these reductions were smaller than those observed in Wuhan (China). However, they sufficed to bring the R0 below one in almost every context considered. Finally, in all countries studied, the numbers of contacts decreased more rapidly among older people than among younger people, indicating higher levels of protection for groups at greater risk.", "title": "The differential impact of physical distancing strategies on social contacts relevant for the spread of COVID-19", "pid": "u9fmokcf", "bm25_score": 218.0493927001953}, {"text": "State and local governments imposed social distancing measures in March and April 2020 to contain the spread of the novel coronavirus disease (COVID-19). These measures included bans on large social gatherings; school closures; closures of entertainment venues, gyms, bars, and restaurant dining areas; and shelter-in-place orders. We evaluated the impact of these measures on the growth rate of confirmed COVID-19 cases across US counties between March 1, 2020, and April 27, 2020. An event study design allowed each policy's impact on COVID-19 case growth to evolve over time. Adoption of government-imposed social distancing measures reduced the daily growth rate of confirmed COVID-19 cases by 5.4 percentage points after one to five days, 6.8 percentage points after six to ten days, 8.2 percentage points after eleven to fifteen days, and 9.1 percentage points after sixteen to twenty days. Holding the amount of voluntary social distancing constant, these results imply that there would have been ten times greater spread of COVID-19 by April 27 without shelter-in-place orders (ten million cases) and more than thirty-five times greater spread without any of the four measures (thirty-five million cases). Our article illustrates the potential danger of exponential spread in the absence of interventions, providing information relevant to strategies for restarting economic activity.", "title": "Strong Social Distancing Measures In The United States Reduced The COVID-19 Growth Rate", "pid": "h62xj47p", "bm25_score": 218.0480194091797}, {"text": "Social distancing is one of the non-pharmacological measures to contain the infection of COVID-19. At this point in time, no vaccine is available to prevent the infection, no effective drugs are available to prevent and treat the disease, and none of the communities have acquired herd immunity. Various models have shown positive impact of social distancing, provided its implementation on vast majority of the population over a long period of time. Its effect is manifold. Besides flattening the curve, it impacts the political, fiscal, social, economic aspects of the society, along with socially vulnerable and economically underprivileged population. It becomes obsolete after the population develops herd immunity subsequent to widespread infection in the community, or after effective mass immunisation or specific drugs for its control, cure and prevention are available widely.", "title": "Social distancing: A non-pharmacological intervention for COVID-19.", "pid": "3cke9x69", "bm25_score": 218.0457763671875}, {"text": "The most effective way to stem the spread of a pandemic such as coronavirus disease 2019 (COVID-19) is social distancing, but the introduction of such measures is hampered by the fact that a sizeable part of the population fails to see their need. Three studies conducted during the mass spreading of the virus in the United States toward the end of March 2020 show that this results partially from people's misperception of the virus's exponential growth in linear terms and that overcoming this bias increases support for social distancing. Study 1 shows that American participants mistakenly perceive the virus's exponential growth in linear terms (conservatives more so than liberals). Studies 2 and 3 show that instructing people to avoid the exponential growth bias significantly increases perceptions of the virus's growth and thereby increases support for social distancing. Together, these results show the importance of statistical literacy to recruit support for fighting pandemics such as the coronavirus.", "title": "Correcting misperceptions of exponential coronavirus growth increases support for social distancing.", "pid": "c84lpxrn", "bm25_score": 218.02774047851562}, {"text": "Social distancing and isolation have been widely introduced to counter the COVID-19 pandemic. Adverse social, psychological and economic consequences of a complete or near-complete lockdown demand the development of more moderate contact-reduction policies. Adopting a social network approach, we evaluate the effectiveness of three distancing strategies designed to keep the curve flat and aid compliance in a post-lockdown world. These are: limiting interaction to a few repeated contacts akin to forming social bubbles; seeking similarity across contacts; and strengthening communities via triadic strategies. We simulate stochastic infection curves incorporating core elements from infection models, ideal-type social network models and statistical relational event models. We demonstrate that a strategic social network-based reduction of contact strongly enhances the effectiveness of social distancing measures while keeping risks lower. We provide scientific evidence for effective social distancing that can be applied in public health messaging and that can mitigate negative consequences of social isolation.", "title": "Social network-based distancing strategies to flatten the COVID-19 curve in a post-lockdown world.", "pid": "qpzg8lam", "bm25_score": 218.026123046875}, {"text": "This paper evaluates the dynamic impact of various policies, such as school, business, and restaurant closures, adopted by the US states on the growth rates of confirmed Covid-19 cases and social distancing behavior measured by Google Mobility Reports, where we take into consideration of people's voluntarily behavioral response to new information of transmission risks. Using the US state-level data, our analysis finds that both policies and information on transmission risks are important determinants of people's social distancing behavior, and shows that a change in policies explains a large fraction of observed changes in social distancing behavior. Our counterfactual experiments indicate that removing all policies on April 1st of 2020 would have lead to 30 to 200 times more additional cases by late May. Removing only the non-essential businesses closures (while maintaining restrictions on movie theaters and restaurants) would have increased the weekly growth rate of cases between -0.02 and 0.06 and would have lead to -10% to 40% more cases by late May. Finally, nationally mandating face masks for employees on April 1st would have reduced the case growth rate by 0.1-0.25. This leads to 30% to 57% fewer reported cases by late May, which translates into, roughly, 30-57 thousand saved lives.", "title": "Causal Impact of Masks, Policies, Behavior on Early Covid-19 Pandemic in the U.S.", "pid": "2fokjcjr", "bm25_score": 218.00924682617188}, {"text": "Social distancing is one of the non-pharmacological measures to contain the infection of COVID-19. At this point in time, no vaccine is available to prevent the infection, no effective drugs are available to prevent and treat the disease, and none of the communities have acquired herd immunity. Various models have shown positive impact of social distancing, provided its implementation on vast majority of the population over a long period of time. Its effect is manifold. Besides flattening the curve, it impacts the political, fiscal, social, economic aspects of the society, along with socially vulnerable and economically underprivileged population. It becomes obsolete after the population develops herd immunity subsequent to widespread infection in the community, or after effective mass immunisation or specific drugs for its control, cure and prevention are available widely.", "title": "Social distancing: A non-pharmacological intervention for COVID-19", "pid": "omygp8bu", "bm25_score": 218.00918579101562}, {"text": "The many variations on a graphic illustrating the impact of non-pharmaceutical measures to mitigate pandemic influenza that have appeared in recent news reports about COVID-19 suggest a need to better explain the mechanism by which social distancing reduces the spread of infectious diseases. And some reports understate one benefit of reducing the frequency or proximity of interpersonal encounters, a reduction in the total number of infections. In hopes that understanding will increase compliance, we describe how social distancing (a) reduces the peak incidence of infections, (b) delays the occurrence of this peak, and (c) reduces the total number of infections during epidemics. In view of the extraordinary efforts underway to identify existing medications that are active against SARS-CoV-2 and to develop new antiviral drugs, vaccines and antibody therapies, any of which may have community-level effects, we also describe how pharmaceutical interventions affect transmission.", "title": "On the benefits of flattening the curve: A perspective", "pid": "883y61q5", "bm25_score": 217.96743774414062}, {"text": "How does social distancing affect the reach of an epidemic in social networks? We present Monte Carlo simulation results of a Susceptible- Infected-Removed (SIR) model on a network, where individuals are limited in the number of other people they can interact with. While increased social distancing always reduces the spread of an infectious disease, the magnitude varies greatly depending on the topology of the social network. Our results also reveal the importance of coordination at the global level. In particular, the public health benefits from social distancing to a group (e.g., a country) may be completely undone if that group maintains connections with outside groups that are not social distancing.", "title": "The Effect of Social Distancing on the Reach of an Epidemic in Social Networks", "pid": "k208rpth", "bm25_score": 217.9559783935547}, {"text": "Social distancing and isolation have been widely introduced to counter the COVID-19 pandemic. Adverse social, psychological and economic consequences of a complete or near-complete lockdown demand the development of more moderate contact-reduction policies. Adopting a social network approach, we evaluate the effectiveness of three distancing strategies designed to keep the curve flat and aid compliance in a post-lockdown world. These are: limiting interaction to a few repeated contacts akin to forming social bubbles; seeking similarity across contacts; and strengthening communities via triadic strategies. We simulate stochastic infection curves incorporating core elements from infection models, ideal-type social network models and statistical relational event models. We demonstrate that a strategic social network-based reduction of contact strongly enhances the effectiveness of social distancing measures while keeping risks lower. We provide scientific evidence for effective social distancing that can be applied in public health messaging and that can mitigate negative consequences of social isolation.", "title": "Social network-based distancing strategies to flatten the COVID-19 curve in a post-lockdown world", "pid": "c5lankxq", "bm25_score": 217.93263244628906}, {"text": "The most effective way to stem the spread of a pandemic such as coronavirus disease 2019 (COVID-19) is social distancing, but the introduction of such measures is hampered by the fact that a sizeable part of the population fails to see their need. Three studies conducted during the mass spreading of the virus in the United States toward the end of March 2020 show that this results partially from people's misperception of the virus's exponential growth in linear terms and that overcoming this bias increases support for social distancing. Study 1 shows that American participants mistakenly perceive the virus's exponential growth in linear terms (conservatives more so than liberals). Studies 2 and 3 show that instructing people to avoid the exponential growth bias significantly increases perceptions of the virus's growth and thereby increases support for social distancing. Together, these results show the importance of statistical literacy to recruit support for fighting pandemics such as the coronavirus.", "title": "Correcting misperceptions of exponential coronavirus growth increases support for social distancing", "pid": "7t8yzbr7", "bm25_score": 217.9226531982422}, {"text": "In the absence of pharmaceutical interventions, social distancing is being used worldwide to curb the spread of COVID-19. The impact of these measures has been inconsistent, with some regions rapidly nearing disease elimination and others seeing delayed peaks or nearly flat epidemic curves. Here we build a stochastic epidemic model to examine the effects of COVID-19 clinical progression and transmission network structure on the outcomes of social distancing interventions. We find that the strength of within-household transmission is a critical determinant of success, governing the timing and size of the epidemic peak, the rate of decline, individual risks of infection, and the success of partial relaxation measures. The structure of residual external connections, driven by workforce participation and essential businesses, interacts to determine outcomes. These findings can improve future predictions of the timescale and efficacy of interventions needed to control similar outbreaks, and highlight the need for better quantification and control of household transmission.", "title": "Dynamics of COVID-19 under social distancing measures are driven by transmission network structure", "pid": "v941u1t1", "bm25_score": 217.91635131835938}, {"text": "SARS-CoV-2 has infected over 140,000 people as of March 14, 2020. We use a mathematical model to investigate the effectiveness of social distancing interventions lasting six weeks in a middle-sized city in the US. We explore four social distancing strategies by reducing the contacts of adults over 60 years old, adults over 60 years old and children, all adults (25, 75 or 95% compliance), and everyone in the population. Our results suggest that social distancing interventions can avert cases by 20% and hospitalizations and deaths by 90% even with modest compliance within adults as long as the intervention is kept in place, but the epidemic is set to rebound once the intervention is lifted. Our models suggest that social distancing interventions will buy crucial time but need to occur in conjunction with testing and contact tracing of all suspected cases to mitigate transmission of SARS-CoV-2.", "title": "Evaluating the effectiveness of social distancing interventions against COVID-19", "pid": "0a49okho", "bm25_score": 217.89669799804688}, {"text": "AIM: COVID-19 has spread rapidly worldwide since it began, greatly affecting peoples' lives, social economies and medical systems. At present, little is known about the disease, and vaccines are still under development. Therefore, in the face of severe outbreaks, previous effective experience can help people better protect themselves and their families. The aim of this article is to discuss the social distancing measures for COVID-19. SUBJECTS AND METHODS: Literature and document search. RESULTS: Recent research and a novel coronavirus pneumonia prediction model revealed social distancing measures and wearing masks are required to mitigate hospital system overload and prevent pathogen exposure. After a series of social distancing measures, there are 309 cities with zero cases and 34 cities with confirmed cases in China as of April 13, 2020. CONCLUSION: From China's experience with novel coronavirus pneumonia, we know that social distancing is the most effective measure at present. We need to win more time to allow limited medical resources to save lives.", "title": "COVID-19 and social distancing", "pid": "5tx03o6h", "bm25_score": 217.87228393554688}, {"text": "BACKGROUND: In the absence of a cure in the time of a pandemic, social distancing measures seem to be the most effective intervention to slow the spread of disease. Various simulation-based studies have been conducted to investigate the effectiveness of these measures. While those studies unanimously confirm the mitigating effect of social distancing on disease spread, the reported effectiveness varies from 10% to more than 90% reduction in the number of infections. This level of uncertainty is mostly due to the complex dynamics of epidemics and their time-variant parameters. However, real transactional data can reduce uncertainty and provide a less noisy picture of the effectiveness of social distancing. OBJECTIVE: The aim of this paper was to integrate multiple transactional data sets (GPS mobility data from Google and Apple as well as disease statistics from the European Centre for Disease Prevention and Control) to study the role of social distancing policies in 26 countries and analyze the transmission rate of the coronavirus disease (COVID-19) pandemic over the course of 5 weeks. METHODS: Relying on the susceptible-infected-recovered (SIR) model and official COVID-19 reports, we first calculated the weekly transmission rate (ß) of COVID-19 in 26 countries for 5 consecutive weeks. Then, we integrated these data with the Google and Apple mobility data sets for the same time frame and used a machine learning approach to investigate the relationship between the mobility factors and ß values. RESULTS: Gradient boosted trees regression analysis showed that changes in mobility patterns resulting from social distancing policies explain approximately 47% of the variation in the disease transmission rates. CONCLUSIONS: Consistent with simulation-based studies, real cross-national transactional data confirms the effectiveness of social distancing interventions in slowing the spread of COVID-19. In addition to providing less noisy and more generalizable support for the idea of social distancing, we provide specific insights for public health policy makers regarding locations that should be given higher priority for enforcing social distancing measures.", "title": "No Place Like Home: Cross-National Data Analysis of the Efficacy of Social Distancing During the COVID-19 Pandemic", "pid": "qekxxsfy", "bm25_score": 217.87197875976562}, {"text": "Understanding the number of individuals who have been infected with the novel coronavirus SARS-CoV-2, and the extent to which social distancing policies have been effective at limiting its spread, are critical for effective policy going forward. Here we present estimates of the extent to which confirmed cases in the United States undercount the true number of infections, and analyze how effective social distancing measures have been at mitigating or suppressing the virus. Our analysis uses a Bayesian model of COVID-19 fatalities with a likelihood based on an underlying differential equation model of the epidemic. We provide analysis for four states with significant epidemics: California, Florida, New York, and Washington. Our short-term forecasts suggest that these states may be following somewhat different trajectories for growth of the number of cases and fatalities.", "title": "Estimating the number of SARS-CoV-2 infections and the impact of social distancing in the United States", "pid": "df64x2eu", "bm25_score": 217.85910034179688}, {"text": "The many variations on a graphic illustrating the impact of non-pharmaceutical measures to mitigate pandemic influenza that have appeared in recent news reports about COVID-19 suggest a need to better explain the mechanism by which social distancing reduces the spread of infectious diseases. And some reports understate one benefit of reducing the frequency or proximity of interpersonal encounters, a reduction in the total number of infections. In hopes that understanding will increase compliance, we describe how social distancing a) reduces the peak incidence of infections, b) delays the occurrence of this peak, and c) reduces the total number of infections during epidemics. In view of the extraordinary efforts underway to identify existing medications that are active against SARS-CoV-2 and to develop new antiviral drugs, vaccines and antibody therapies, any of which may have community-level effects, we also describe how pharmaceutical interventions affect transmission.", "title": "On the benefits of flattening the curve: A perspective()", "pid": "zukjh1hr", "bm25_score": 217.83413696289062}, {"text": "In the absence of any pharmacological intervention, one approach to slowing the COVID-19 pandemic is reducing the contact rate in the population through social distancing. Governments the world over have instituted different measures to increase social distancing but information on their effectiveness in reducing mobility is lacking. We analyzed the mobility data from 41 cities to look at the effect of these interventions. The median mobility across cities on March 2, 2020 was 100% (IQR: 94%, 107%), which decreased to a median of 10% (IQR: 7%, 17%) on March 26, 2020. We found that the mobility decreased on average by 3.4% (95%CI: 3.3%, 3.6%) per day from March 2 through March 26. Social distancing measures decreased the mobility by an additional 23% (95%CI: 20%, 27%). Our study provides initial evidence for the reduction in mobility in cities instituting social distancing measures.", "title": "COVID-19 related social distancing measures and reduction in city mobility", "pid": "71b6ai77", "bm25_score": 217.813232421875}, {"text": "The SARS-CoV-2 pandemic is straining healthcare resources worldwide, prompting social distancing measures to reduce transmission intensity. The amount of social distancing needed to curb the SARS-CoV-2 epidemic in the context of seasonally varying transmission remains unclear. Using a mathematical model, we assessed that one-time interventions will be insufficient to maintain COVID-19 prevalence within the critical care capacity of the United States. Seasonal variation in transmission will facilitate epidemic control during the summer months but could lead to an intense resurgence in the autumn. Intermittent distancing measures can maintain control of the epidemic, but without other interventions, these measures may be necessary into 2022. Increasing critical care capacity could reduce the duration of the SARS-CoV-2 epidemic while ensuring that critically ill patients receive appropriate care.", "title": "Social distancing strategies for curbing the COVID-19 epidemic", "pid": "nzat41wu", "bm25_score": 217.80419921875}, {"text": "The infectious diseases are spreading due to human interactions enabled by various social networks. Therefore, when a new pathogen such as SARS-CoV-2 causes an outbreak, the non-pharmaceutical isolation strategies (e.g., social distancing) are the only possible response to disrupt its spreading. To this end, we introduce the new epidemic model (SICARS) and compare the centralized (C), decentralized (D), and combined (C+D) social distancing strategies, and analyze their efficiency to control the dynamics of COVID-19 on heterogeneous complex networks. Our analysis shows that the centralized social distancing is necessary to minimize the pandemic spreading. The decentralized strategy is insufficient when used alone, but offers the best results when combined with the centralized one. Indeed, the (C+D) is the most efficient isolation strategy at mitigating the network superspreaders and reducing the highest node degrees to less than 10% of their initial values. Our results also indicate that stronger social distancing, e.g., cutting 75% of social ties, can reduce the outbreak by 75% for the C isolation, by 33% for the D isolation, and by 87% for the (C+D) isolation strategy. Finally, we study the impact of proactive versus reactive isolation strategies, as well as their delayed enforcement. We find that the reactive response to the pandemic is less efficient, and delaying the adoption of isolation measures by over one month (since the outbreak onset in a region) can have alarming effects; thus, our study contributes to an understanding of the COVID-19 pandemic both in space and time. We believe our investigations have a high social relevance as they provide insights into understanding how different degrees of social distancing can reduce the peak infection ratio substantially; this can make the COVID-19 pandemic easier to understand and control over an extended period of time.", "title": "Centralized and decentralized isolation strategies and their impact on the COVID-19 pandemic dynamics", "pid": "ts3ra09u", "bm25_score": 217.77099609375}, {"text": "BACKGROUND: Social distancing and stringent hygiene seem effective in reducing the number of transmitted virus particles, and therefore the infectivity, of coronavirus disease 2019 (COVID-19) and could alter the mode of transmission of the disease. However, it is not known if such practices can change the clinical course in infected individuals. METHODS: We prospectively studied an outbreak of COVID-19 in Switzerland among a population of 508 predominantly male soldiers with a median age of 21 years. We followed the number of infections in two spatially separated cohorts with almost identical baseline characteristics with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before and after implementation of stringent social distancing. RESULTS: Of the 354 soldiers infected prior to the implementation of social distancing, 30% fell ill from COVID-19. While no soldier in a group of 154, in which infections appeared after implementation of social distancing, developed COVID-19 despite the detection of viral RNA in the nose and virus-specific antibodies within this group. CONCLUSIONS: Social distancing not only can slow the spread of SARS-CoV-2 in a cohort of young, healthy adults but can also prevent the outbreak of COVID-19 while still inducing an immune response and colonizing nasal passages. Viral inoculum during infection or mode of transmission may be key factors determining the clinical course of COVID-19.", "title": "Social distancing alters the clinical course of COVID-19 in young adults: A comparative cohort study", "pid": "trn2deod", "bm25_score": 217.7642059326172}, {"text": "In the absence of a vaccine and effective antiviral medications, most of the non-pharmaceutical interventions focus on reducing social contact rates through different social distancing policies. However, the effectiveness of different policies and their relative impact vis-a-vis that of mechanisms driven by public awareness and voluntary actions have not been studied. This is crucial since in most places we observe significant reductions in social interaction before any policy was implemented. Variations in types and effective dates of different social distancing policies across different states in the US create a natural experiment to study the causal impact of each policy during the early stage of the outbreak. Using these policy variations and the aggregate human mobility and location trends published by Google for the month of March 2020, we employ a quasi-experimental approach to measure the impact of six common policies on people's presence at home and their mobility in different types of public places. Our results rank six common social distancing policies based on the magnitude and significance of their impact, beyond what has already been achieved through voluntary actions. They show that while strong policies such as statewide stay home mandate and non-essential business closure have strong causal impacts on reducing social interactions, most of the expected impact of more lenient policies (such as large gathering ban and school closure mandates) are already reaped from non-policy mechanisms such as voluntary actions and public awareness.", "title": "The Immediate Effect of COVID-19 Policies on Social Distancing Behavior in the United States", "pid": "2jd7aa2d", "bm25_score": 217.73934936523438}, {"text": "For preventing the spread of epidemics such as the coronavirus disease COVID-19, social distancing and the isolation of infected persons are crucial. However, existing reaction-diffusion equations for epidemic spreading are incapable of describing these effects. We present an extended model for disease spread based on combining an SIR model with a dynamical density functional theory where social distancing and isolation of infected persons are explicitly taken into account. The model shows interesting nonequilibrium phase separation associated with a reduction of the number of infections, and allows for new insights into the control of pandemics.", "title": "Effects of social distancing and isolation on epidemic spreading: a dynamical density functional theory model", "pid": "apjwnwky", "bm25_score": 217.65896606445312}, {"text": "We investigate the effects of social distancing in controlling the impact of the COVID-19 epidemic using a simple susceptible-infected-removed epidemic model. We show that an alternative or complementary approach based on targeted isolation of the vulnerable sub-population may provide a more efficient and robust strategy at a lower economic and social cost within a shorter timeframe resulting in a collectively immune population.", "title": "Targeted adaptive isolation strategy for COVID-19 pandemic", "pid": "qpufvt3o", "bm25_score": 217.64096069335938}, {"text": "We investigate the effects of social distancing in controlling the impact of the COVID-19 epidemic using a simple susceptible-infected-removed epidemic model. We show that an alternative or complementary approach based on targeted isolation of the vulnerable sub-population may provide a more efficient and robust strategy at a lower economic and social cost within a shorter timeframe resulting in a collectively immune population.", "title": "Targeted adaptive isolation strategy for Covid-19 pandemic", "pid": "80d9p4j8", "bm25_score": 217.64096069335938}, {"text": "", "title": "COVID-19: Getting ahead of the epidemic curve by early implementation of social distancing.", "pid": "yv3x3g4u", "bm25_score": 217.63499450683594}, {"text": "This paper is the first to examine the role of the cultural dimension in practising social distancing across the world. By drawing the data from the Google COVID-19 community mobility reports and the Hofstede cultural factors for 58 countries over the period from 16 February to 29 March 2020, we find that countries with higher ‘Uncertainty Avoidance Index’ predict the lower proportion of people gathering in public such as retail and recreation, grocery and pharmacy, parks, transit stations, workplaces. However, we do not find any predictive factor in having a relationship with the percentage of citizens staying in their residential areas. Our results are robust by adding the control variable as the wealth status, GDP per capita. Hence, this paper suggests some effective communications to contain the COVID-19 pandemic by emphasizing the role of uncertainties.", "title": "Does culture matter social distancing under the COVID-19 pandemic?", "pid": "rmoroqrv", "bm25_score": 217.61923217773438}, {"text": "", "title": "Social Distancing in the Covid-19 Pandemic", "pid": "f0sc3vmp", "bm25_score": 217.5968017578125}, {"text": "Social distancing policies were implemented in most US states as a containment strategy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The effectiveness of these policy interventions on morbidity and mortality remains unknown. Our analysis examined the associations between statewide policies and objective measures of social distancing, and objective social distancing and COVID-19 incidence and mortality. We used nationwide, de-identified smartphone GPS data to estimate county-level social distancing. COVID-19 incidence and mortality data were from the Johns Hopkins Coronavirus Resource Center. Generalized linear mixed models were used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between objective social distancing and COVID-19 incidence and mortality. Stay-at-home orders were associated with a 35% increase in social distancing. Higher social distancing was associated with a 29% reduction in COVID-19 incidence (adjusted IRR 0.71; 95% CI 0.57–0.87) and a 35% reduction in COVID-19 mortality (adjusted IRR 0.65; 95% CI 0.55–0.76). These findings provide evidence to inform ongoing national discussions on the effectiveness of these public health measures and the potential implications of returning to normal social activity.", "title": "Effect of social distancing on COVID-19 incidence and mortality in the US", "pid": "z82gogvs", "bm25_score": 217.5823974609375}, {"text": "In this article the mortality data from four European countries arising from the Covid-19 pandemic is modelled using logistic functions. The countries chosen for examination are Spain, Italy, France and the UK. They have been selected because in each the pandemic is advanced, mortality high and any prospect of containment has passed. They have also been selected because in each social distancing has been used in an attempt to reduce peak daily mortality with relatively strict enforcement following a defined date. The choices of data set and model type is justified. The impact, if any, of social distancing is examined.", "title": "The Impact of Social Distancing on TheCourse of The Covid-19 Pandemic in FourEuropean Countries", "pid": "ld435hiv", "bm25_score": 217.57461547851562}, {"text": "We examine the net benefits of social distancing to slow the spread of COVID-19 in USA. Social distancing saves lives but imposes large costs on society due to reduced economic activity. We use epidemiological and economic forecasting to perform a rapid benefit–cost analysis of controlling the COVID-19 outbreak. Assuming that social distancing measures can substantially reduce contacts among individuals, we find net benefits of about $5.2 trillion in our benchmark case. We examine the magnitude of the critical parameters that might imply negative net benefits, including the value of statistical life and the discount rate. A key unknown factor is the speed of economic recovery with and without social distancing measures in place. A series of robustness checks also highlight the key role of the value of mortality risk reductions and discounting in the analysis and point to a need for effective economic stimulus when the outbreak has passed.", "title": "The Benefits and Costs of Using Social Distancing to Flatten the Curve for COVID-19", "pid": "vfnpeuzr", "bm25_score": 217.5629425048828}, {"text": "The purpose of this article is to reach all those who find it difficult to become well informed about the repercussions of a lockdown strategy to tackle the COVID-19 pandemic and to spark discussion and thought. Here we use simple stochastic simulations to evaluate different approaches taken to tackle the crisis, along with the efficiency they will hold and the number of casualties they may incur. It is clear that the less strict the social distancing the more time it will take for life to return to normal, and the more lives will be at risk. This is shown through simulations formed by an open sourced code, which allows evaluation of the outcomes from different intervention scenarios or conditions.", "title": "COVID-19 Modelling: the Effects of Social Distancing", "pid": "cc05jqb6", "bm25_score": 217.55113220214844}, {"text": "Intense non-pharmaceutical interventions were put in place in China to stop transmission of the novel coronavirus disease (COVID-19). As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact surveys data for Wuhan and Shanghai before and during the outbreak and contact tracing information from Hunan Province. Daily contacts were reduced 7-8-fold during the COVID-19 social distancing period, with most interactions restricted to the household. We find that children 0-14 years are less susceptible to SARS-CoV-2 infection than adults 15-64 years of age (odd ratio 0.34, 95%CI 0.24-0.49), while in contrast, individuals over 65 years are more susceptible to infection (odd ratio 1.47, 95%CI: 1.12-1.92). Based on these data, we build a transmission model to study the impact of social distancing and school closure on transmission. We find that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. While proactive school closures cannot interrupt transmission on their own, they can reduce peak incidence by 40-60% and delay the epidemic.", "title": "Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China", "pid": "f1ckv4bk", "bm25_score": 217.54180908203125}, {"text": "One of the primary strategies of slowing down the COVID-19 pandemic has been the establishment of social distancing rules that recommend keeping a buffer distance between individuals, and this has proven effective in helping in reducing the basic reproduction number [R 0] . However, social distancing rules have put the use of public spaces in densely populated places under strain, and this is especially important as some of the most virulent outbreaks of the COVID-19 pandemic have been in compact cities. It is therefore fundamental to take into account each neighbourhood's morphological characteristics and the potential population densities each street, square or park can accommodate under such new regulations in order to effectively enforce social distancing rules. Otherwise, certain areas may be rapidly overwhelmed by crowds with citizens unable to maintain the minimum safe distance between individuals. In this paper, we develop a method to identify the potential public space accessibility if social distancing rules are followed and we apply it to three global and highly affected by COVID-19 cities. Our research finds that, at micro level there are important inequalities between neighbourhoods, so people will struggle to comply with social distancing rules and consequently it will make controlling infection rates more difficult.", "title": "Lack of sufficient public space can limit the effectiveness of COVID-19's social distancing measures", "pid": "qh96bfi6", "bm25_score": 217.54095458984375}, {"text": "Currently there are many attempts around the world to use computers, smartphones, tablets and other electronic devices in order to stop the spread of COVID-19. Most of these attempts focus on collecting information about infected people, in order to help healthy people avoid contact with them. However, social distancing decisions are still taken by the governments empirically. That is, the authorities do not have an automated tool to recommend which decisions to make in order to maximize social distancing and to minimize the impact for the economy. In this paper we address the aforementioned problem and we design an algorithm that provides social distancing methods (i.e., what schools, shops, factories, etc. to close) that are efficient (i.e., that help reduce the spread of the virus) and have low impact on the economy. On short: a) we propose several models (i.e., combinatorial optimization problems); b) we show some theoretical results regarding the computational complexity of the formulated problems; c) we give an algorithm for the most complex of the previously formulated problems; d) we implement and test our algorithm; and e) we show an integer linear program formulation for our problem.", "title": "A decision support system for optimizing the cost of social distancing in order to stop the spread of COVID-19", "pid": "axymuyev", "bm25_score": 217.5255126953125}, {"text": "The research team has utilized an integrated dataset, consisting of anonymized location data, COVID-19 case data, and census population information, to study the impact of COVID-19 on human mobility. The study revealed that statistics related to social distancing, namely trip rate, miles traveled per person, and percentage of population staying at home have all showed an unexpected trend, which we named social distancing inertia. The trends showed that as soon as COVID-19 cases were observed, the statistics started improving, regardless of government actions. This suggests that a portion of population who could and were willing to practice social distancing voluntarily and naturally reacted to the emergence of COVID-19 cases. However, after about two weeks, the statistics saturated and stopped improving, despite the continuous rise in COVID-19 cases. The study suggests that there is a natural behavior inertia toward social distancing, which puts a limit on the extent of improvement in the social-distancing-related statistics. The national data showed that the inertia phenomenon is universal, happening in all the U.S. states and for all the studied statistics. The U.S. states showed a synchronized trend, regardless of the timeline of their statewide COVID-19 case spreads or government orders.", "title": "Observed mobility behavior data reveal social distancing inertia", "pid": "hb1r2aw7", "bm25_score": 217.52218627929688}, {"text": "Social distancing has emerged as the primary mitigation strategy to combat the COVID-19 pandemic in the United States. However, large-scale evaluation of the public's response to social distancing campaigns has been lacking. We used anonymized and aggregated mobility data from Google Location History users to estimate the impact of social distancing recommendations on bulk mobility among users who have opted into this service. We found that state-of-emergency declarations resulted in approximately a 10% reduction in time spent away from places of residence. Implementation of one or more social distancing policies resulted in an additional 25% reduction in mobility the following week. Subsequent shelter-in-place mandates provided an additional 29% reduction. Our findings provide evidence that state-wide mandates are effective in promoting social distancing within this study group.", "title": "Impacts of State-Level Policies on Social Distancing in the United States Using Aggregated Mobility Data during the COVID-19 Pandemic", "pid": "f6rx4h3r", "bm25_score": 217.514892578125}, {"text": "Background Social distancing has led to a flattening of the curve in many states across the U.S. This is part of a novel, massive, global social experiment which has served to mitigate the pandemic in the absence of a vaccine or effective anti-viral drugs. Hence it is important to be able to forecast hospitalizations reasonably accurately. Methods We propose on phenomenological grounds a generalized diffusion equation which in- corporates the effect of social distancing to forecast the temporal evolution of the probability of having a given number of hospitalizations. The probability density function is log-normal in the number of hospitalizations, which is useful in describing pandemics where the number of hospital- izations is very high. Findings We used this insight and data to make forecasts for states using Monte Carlo methods. Back testing validates our approach, which yields good results about a week into the future. States are beginning to reopen at the time of publication and our forecasts indicate possible precursors of increased hospitalizations. Additionally we studied the reproducibility Ro in New York (Italian strain) and California (Wuhan strain). We find that even if there is a difference in the transmission of the two strains, social distancing has been able to control the progression of COVID 19. Funding None.", "title": "Dynamical model for social distancing in the U.S. during the COVID-19 epidemic", "pid": "gkkvu8d5", "bm25_score": 217.48171997070312}, {"text": "The COVID-19 outbreak has posed significant threats to international health and the economy. In the absence of treatment for this virus, public health officials asked the public to practice social distancing to reduce the number of physical contacts. However, quantifying social distancing is a challenging task and current methods are based on human movements. We propose a time and cost-effective approach to measure how people practice social distancing. This study proposes a new method based on utilizing the frequency of hashtags supporting and encouraging social distancing for measuring social distancing. We have identified 18 related hashtags and tracked their trends between Jan and May 2020. Our evaluation results show that there is a strong correlation (P<0.05) between our findings and the Google social distancing report.", "title": "Social Media and COVID-19: Can Social Distancing be Quantified without Measuring Human Movements?", "pid": "k574jppq", "bm25_score": 217.48159790039062}, {"text": "BACKGROUND In the absence of a cure in the time of pandemics, social distancing measures seem to be the most effective intervention to slow down the spread of disease. Various simulation-based studies have been conducted in the past to investigate the effectiveness of such measures. While those studies unanimously confirm the mitigating effect of social distancing on the disease spread, the reported effectiveness varies from 10% to more than 90% reduction in the number of infections. This level of uncertainty is mostly due to the complex dynamics of epidemics and their time-variant parameters. A real transactional data, however, can reduce the uncertainty and provide a less noisy picture of social distancing effectiveness. OBJECTIVE In this paper, we integrate multiple transactional data sets (GPS mobility data from Google and Apple as well as disease statistics data from ECDC) to study the role of social distancing policies in 26 countries wherein the transmission rate of the COVID-19 pandemic is analyzed over the course of five weeks. METHODS Relying on the SIR model and official COVID-19 reports, we first calculated the weekly transmission rate (β) of the coronavirus disease in 26 countries for five consecutive weeks. Then we integrated that with the Google's and Apple's mobility data sets for the same time frame and used a machine learning approach to investigate the relationship between mobility factors and β values. RESULTS Gradient Boosted Trees (GBT) regression analysis showed that changes in mobility patterns, resulted from social distancing policies, explain around 47% of the variation in the disease transmission rate. CONCLUSIONS Consistent with simulation-based studies, real cross-national transactional data confirms the effectiveness of social distancing interventions in slowing down the spread of the disease. Apart from providing less noisy and more generalizable support for the whole social distancing idea, we provide specific insights for public health policy-makers as to what locations should be given a higher priority for enforcing social distancing measures. CLINICALTRIAL", "title": "No Place Like Home: A Cross-National Assessment of the Efficacy of Social Distancing during the COVID-19 Pandemic.", "pid": "3nanf73b", "bm25_score": 217.46754455566406}, {"text": "", "title": "COVID-19 and social distancing", "pid": "0ufwlw87", "bm25_score": 217.46426391601562}, {"text": "Recent experiences during a variety of disease outbreaks, ranging from Ebola to influenza, have underscored the potential for epidemics to have an impact on daily life, even for those who are not themselves infected.1,2 In severe situations, epidemics or pandemics can even affect overall community functioning. For example, a rapidly expanding pandemic can result in shuttered schools, cancelled events, food insecurity, and social distrust in communities. (Am J Public Health. Published online ahead of print May 21, 2020: e1-e2. doi:10.2105/AJPH.2020.305740).", "title": "Supporting Social Distancing for COVID-19 Mitigation Through Community-Based Volunteer Networks.", "pid": "ftlwzeg3", "bm25_score": 217.45994567871094}, {"text": "The COVID-19 pandemic has challenged researchers and policy makers to identify public safety measures forpreventing the collapse of healthcare systems and reducingdeaths. This narrative review summarizes the available evidence on the impact of social distancing measures on the epidemic and discusses the implementation of these measures in Brazil. Articles on the effect of social distancing on COVID-19 were selected from the PubMed, medRXiv and bioRvix databases. Federal and state legislation was analyzed to summarize the strategies implemented in Brazil. Social distancing measures adopted by the population appear effective, particularly when implemented in conjunction with the isolation of cases and quarantining of contacts. Therefore, social distancing measures, and social protection policies to guarantee the sustainability of these measures, should be implemented. To control COVID-19 in Brazil, it is also crucial that epidemiological monitoring is strengthened at all three levels of the Brazilian National Health System (SUS). This includes evaluating and usingsupplementary indicators to monitor the progression of the pandemic and the effect of the control measures, increasing testing capacity, and making disaggregated notificationsand testing resultstransparentand broadly available.", "title": "Social distancing measures to control the COVID-19 pandemic: potential impacts and challenges in Brazil.", "pid": "fex8sd1t", "bm25_score": 217.44544982910156}, {"text": "Brazil's continental dimension poses a challenge to the control of the spread of COVID-19. Due to the country specific scenario of high social and demographic heterogeneity, combined with limited testing capacity, lack of reliable data, under-reporting of cases, and restricted testing policy, the focus of this study is twofold: (i) to develop a generalized SEIRD model that implicitly takes into account the quarantine measures, and (ii) to estimate the response of the COVID-19 spread dynamics to perturbations/uncertainties. By investigating the projections of cumulative numbers of confirmed and death cases, as well as the effective reproduction number, we show that the model parameter related to social distancing measures is one of the most influential along all stages of the disease spread and the most influential after the infection peak. Due to such importance in the outcomes, different relaxation strategies of social distancing measures are investigated in order to determine which strategies are viable and less hazardous to the population. The results highlight the need of keeping social distancing policies to control the disease spread. Specifically, the considered scenario of abrupt social distancing relaxation implemented after the occurrence of the peak of positively diagnosed cases can prolong the epidemic, with a significant increase of the projected numbers of confirmed and death cases. An even worse scenario could occur if the quarantine relaxation policy is implemented before evidence of the epidemiological control, indicating the importance of the proper choice of when to start relaxing social distancing measures.", "title": "Spreading of COVID-19 in Brazil: Impacts and uncertainties in social distancing strategies", "pid": "31jzsl2y", "bm25_score": 217.43719482421875}, {"text": "", "title": "COVID-19: Getting ahead of the epidemic curve by early implementation of social distancing", "pid": "kk38cfli", "bm25_score": 217.4291534423828}, {"text": "The outbreak of SARS-CoV-2 in China has spread around the world, infecting millions and causing governments to implement strict policies to counteract the spread of the disease. One of the most effective strategies in reducing the severity of the pandemic is social distancing, where members of the population systematically reduce their interactions with others to limit the transmission rate of the virus. However, the implementation of social distancing can be difficult and costly, making it imperative that both policy makers and the citizenry understand the potential benefits if done correctly and the risks if not. In this work, a mathematical model is developed to study the effects of social distancing on the spread of the SARS-CoV-2 virus in Canada. The model is based upon a standard epidemiological SEIRD model that has been stratified to directly incorporate the proportion of individuals who are following social distancing protocols. The model parameters characterizing the disease are estimated from current epidemiological data on COVID-19 using machine learning techniques. The results of the model show that social distancing policies in Canada have already saved thousands of lives and that the prolonged adherence to social distancing guidelines could save thousands more. Importantly, our model indicates that social distancing can significantly delay the onset of infection peaks, allowing more time for the production of a vaccine or additional medical resources. Furthermore, our results stress the importance of easing social distancing restrictions gradually, rather than all at once, in order to prevent a second wave of infections. Model results are compared to the current capacity of the Canadian healthcare system by examining the current and future number of ventilators available for use, emphasizing the need for the increased production of additional medical resources.", "title": "Mathematical modeling of COVID-19 containment strategies with considerations for limited medical resources", "pid": "51g3vhcx", "bm25_score": 217.41015625}, {"text": "Background The Novel Coronavirus that originated in Wuhan, Hubei, China, has raised global concerns and has been declared a pandemic. The infection shows the primary symptoms of pneumonia and has an incubation period, with the majority of people showing symptoms within 14 days. Online Social Networks are the closest simulations of real-world networks and have similar topology characteristics. This article simulates the spread and control of the nCoV-19 using the SIQR-t model to highlight the importance of self-quarantine and exercise of proper health care as a method to prevent the spread of the virus. Method The article uses the Susceptible-Infected-Quarantined-Recovered model with modification, introducing 14 different Infected states depending on the number of days the host has been carrying the infection. We simulate the spread of 2019-nCoV on human interaction similar graph taken from Online Social Network Epinions, of about 75000 nodes, similar to a small town or settlement. The infection rates depend on the sanitation and cleanliness these people exercise. Results When people practice self-quarantine and hygiene, aided by the governmental efforts of testing and quarantine, the cumulative number of affected people fall drastically. The decrease is apparent in time-based simulations of the spread received from the study. Conclusion The 2019-nCoV is a highly infectious zoonotic virus. It has spread like a pandemic, and governments across the world have launched quarantines. The results of the SIQR-t model indicate that hygiene and social-distancing can reduce its impact and sharply decrease the infection scale. Individual efforts are key to the control.", "title": "Importance of Social Distancing: Modeling the spread of 2019-nCoV using Susceptible-Infected-Quarantined-Recovered-t model", "pid": "lp4vhwsz", "bm25_score": 217.3912811279297}, {"text": "COVID-19 pandemic has affected over 100 countries in a matter of weeks. People's response toward social distancing in the emerging pandemic is uncertain. In this study, we evaluated the influence of information (formal and informal) sources on situational awareness of the public for adopting health-protective behaviors such as social distancing. For this purpose, a questionnaire-based survey was conducted. The hypothesis proposed suggests that adoption of social distancing practices is an outcome of situational awareness which is achieved by the information sources. Results suggest that information sources, formal (P = .001) and informal (P = 0.007) were found to be significantly related to perceived understanding. Findings also indicate that social distancing is significantly influenced by situational awareness, P = .000. It can, therefore, be concluded that an increase in situational awareness in times of public health crisis using formal information sources can significantly increase the adoption of protective health behavior and in turn contain the spread of infectious diseases.", "title": "Analyzing situational awareness through public opinion to predict adoption of social distancing amid pandemic COVID-19", "pid": "e8gga4oh", "bm25_score": 217.37884521484375}, {"text": "Motivated by the current COVID-19 epidemic, this work introduces an epidemiological model in which separate compartments are used for susceptible and asymptomatic \"socially distant\" populations. Distancing directives are represented by rates of flow into these compartments, as well as by a reduction in contacts that lessens disease transmission. The dynamical behavior of this system is analyzed, under various different rate control strategies, and the sensitivity of the basic reproduction number to various parameters is studied. One of the striking features of this model is the existence of a critical implementation delay in issuing separation mandates: while a delay of about four weeks does not have an appreciable effect, issuing mandates after this critical time results in a far greater incidence of infection. In other words, there is a nontrivial but tight \"window of opportunity\" for commencing social distancing. Different relaxation strategies are also simulated, with surprising results. Periodic relaxation policies suggest a schedule which may significantly inhibit peak infective load, but that this schedule is very sensitive to parameter values and the schedule's frequency. Further, we considered the impact of steadily reducing social distancing measures over time. We find that a too-sudden reopening of society may negate the progress achieved under initial distancing guidelines, if not carefully designed.", "title": "A novel COVID-19 epidemiological model with explicit susceptible and asymptomatic isolation compartments reveals unexpected consequences of timing social distancing", "pid": "x9d7g5kb", "bm25_score": 217.3739471435547}, {"text": "Governments have implemented social distancing measures to address the ongoing COVID-19 pandemic. The measures include instructions that individuals maintain social distance when in public, school closures, limitations on gatherings and business operations, and instructions to remain at home. Social distancing may have an impact on the volume and distribution of crime. Crimes such as residential burglary may decrease as a byproduct of increased guardianship over personal space and property. Crimes such as domestic violence may increase because of extended periods of contact between potential offenders and victims. Understanding the impact of social distancing on crime is critical for ensuring the safety of police and government capacity to deal with the evolving crisis. Understanding how social distancing policies impact crime may also provide insights into whether people are complying with public health measures. Examination of the most recently available data from both Los Angeles, CA, and Indianapolis, IN, shows that social distancing has had a statistically significant impact on a few specific crime types. However, the overall effect is notably less than might be expected given the scale of the disruption to social and economic life.", "title": "Impact of social distancing during COVID-19 pandemic on crime in Los Angeles and Indianapolis", "pid": "po2c65nb", "bm25_score": 217.35845947265625}, {"text": "Background The novel coronavirus COVID19 has been classified by the World Health Organisation as a pandemic due to its worldwide spread. The ability of countries to contain and control transmission is critical in the absence of a vaccine. We evaluated a range of social distancing measures to determine which strategies are most effective in reducing the peak daily infection rate, and consequential pressure on the health care system. Methods Using COVID19 transmission data from the outbreak source in Hubei Province, China, collected prior to activation of containment measures, we adapted an established individual based simulation model of the city of Newcastle, Australia, population 272,409. Simulation of virus transmission in this community model without interventions provided a baseline from which to compare alternative social distancing strategies. The infection history of each individual was determined, as was the time infected. From this model generated data, the rate of growth in cases, the magnitude of the epidemic peak, and the outbreak duration were obtained. Findings The application of all four social distancing interventions: school closure, workplace non-attendance, increased case isolation, and community contact reduction is highly effective in flattening the epidemic curve, reducing the maximum daily case numbers, and lengthening outbreak duration. These were also found to be effective even after 10 weeks delay from index case arrivals. The most effective single intervention was found to be increasing case isolation, to 100 percent of children and 90 percent of adults. Interpretation As strong social distancing intervention strategies had the most effect in reducing the epidemic peak, this strategy may be considered when weaker strategies are first tried and found to be less effective. Questions arise as to the duration of strong social distancing measures, given they are highly disruptive to society. Tradeoffs may need to be made between the effectiveness of social distancing strategies and population willingness to adhere to them.", "title": "The Effectiveness of Social Distancing in Mitigating COVID-19 Spread: a modelling analysis", "pid": "qqsefagq", "bm25_score": 217.34158325195312}, {"text": "Objective: In absence of any vaccine, the Corona Virus Disease 2019 (COVID-19) pandemic is being contained through a non-pharmaceutical measure termed Social Distancing (SD). However, whether SD alone is enough to flatten the epidemic curve is debatable. Using a Stochastic Computational Simulation Model, we investigated the impact of increasing SD, hospital beds and COVID-19 detection rates in preventing COVID-19 cases and fatalities. Research Design and Methods: The Stochastic Simulation Model was built using the EpiModel package in R. As a proof of concept study, we ran the simulation on Kasaragod, the most affected district in Kerala. We added 3 compartments to the SEIR model to obtain a SEIQHRF (Susceptible-Exposed-Infectious-Quarantined-Hospitalised-Recovered-Fatal) model. Results: Implementing SD only delayed the appearance of peak prevalence of COVID-19 cases. Doubling of hospital beds could not reduce the fatal cases probably due to its overwhelming number compared to the hospital beds. Increasing detection rates could significantly flatten the curve and reduce the peak prevalence of cases (increasing detection rate by 5 times could reduce case number to half). Conclusions: An effective strategy to contain the epidemic spread of COVID-19 in India is to increase detection rates in combination with SD measures and increase in hospital beds.", "title": "Increased Detection coupled with Social Distancing and Health Capacity Planning Reduce the Burden of COVID-19 Cases and Fatalities: A Proof of Concept Study using a Stochastic Computational Simulation Model", "pid": "01f5mvsc", "bm25_score": 217.32489013671875}, {"text": "COVID-19 is a global epidemic. Till now, there is no remedy for this epidemic. However, isolation and social distancing are seemed to be effective to control this pandemic. In this paper, we provide an analytical model on the effectiveness of the sustainable lockdown policy that accommodates both isolation and social distancing features of the individuals. To promote social distancing, we analyze a noncooperative game environment that provides an incentive for maintaining social distancing. Furthermore, the sustainability of the lockdown policy is also interpreted with the help of a game-theoretic incentive model for maintaining social distancing. Finally, an extensive numerical analysis is provided to study the impact of maintaining a social-distancing measure to prevent the Covid-19 outbreak. Numerical results show that the individual incentive increases more than 85% with an increasing percentage of home isolation from 25% to 100% for all considered scenarios. The numerical results also demonstrate that in a particular percentage of home isolation, the individual incentive decreases with an increasing number of individuals.", "title": "A Noncooperative Game Analysis for Controlling COVID-19 Outbreak", "pid": "dtb2nza1", "bm25_score": 217.3186492919922}, {"text": "COVID-19, caused by the SARS-CoV-2 virus, has quickly spread throughout the world, necessitating assessment of the most effective containment methods. Very little research exists on the effects of social distancing measures on this pandemic. The purpose of this study was to examine the effects of government implemented social distancing measures on the cumulative incidence rates of COVID-19 in the United States on a state level, and in the 25 most populated cities, while adjusting for socio-demographic risk factors. The social distancing variables assessed in this study were: days to closing of non-essential business; days to stay home orders; days to restrictions on gathering, days to restaurant closings and days to school closing. Using negative binomial regression, adjusted rate ratios and 95% confidence intervals were calculated comparing two levels of a binary variable: above median value, and median value and below for days to implementing a social distancing measure. For city level data, the effects of these social distancing variables were also assessed in high (above median value) vs low (median value and below) population density cities. For the state level analysis, days to school closing was associated with cumulative incidence, with an adjusted rate ratio of 1.59 (95% CI:1.03,2.44), p=0.04 at 35 days. Some results were counterintuitive, including inverse associations between cumulative incidence and days to closure of non-essential business and restrictions on gatherings. This finding is likely due to reverse causality, where locations with slower growth rates initially chose not to implement measures, and later implemented measures when they absolutely needed to respond to increasing rates of infection. Effects of social distancing measures seemed to vary by population density in cities. Our results suggest that the effect of social distancing measures may differ between states and cities and between locations with different population densities. States and cities need individual approaches to containment of an epidemic, with an awareness of their own structure in terms of crowding and socio-economic variables. In an effort to reduce infection rates, cities may want to implement social distancing in advance of state mandates.", "title": "Effects of Government Mandated Social Distancing Measures on Cumulative Incidence of COVID-19 in the United States and its Most Populated Cities", "pid": "in3pyyue", "bm25_score": 217.31439208984375}, {"text": "In the absence of pharmaceutical interventions to curb the spread of COVID-19, countries relied on a number of nonpharmaceutical interventions to fight the first wave of the pandemic. The most prevalent one has been stay-at-home orders, whose the goal is to limit the physical contact between people, which consequently will reduce the number of secondary infections generated. In this work, we use a detailed set of mobility data to evaluate the impact that these interventions had on alleviating the spread of the virus in the US as measured through the COVID-19-related deaths. To establish this impact, we use the notion of Granger causality between two time-series. We show that there is a unidirectional Granger causality, from the median percentage of time spent daily at home to the daily number of COVID-19-related deaths with a lag of 2 weeks. We further analyze the mobility patterns at the census block level to identify which parts of the population might encounter difficulties in adhering and complying with social distancing measures. This information is important, since it can consequently drive interventions that aim at helping these parts of the population.", "title": "Effectiveness and Compliance to Social Distancing During COVID-19", "pid": "ibrrr546", "bm25_score": 217.30679321289062}, {"text": "The new coronavirus disease 2019 (COVID-19) has required the implementation of severe mobility restrictions and social distancing measures worldwide. While these measures have been proven effective in abating the epidemic in several countries, it is important to estimate the effectiveness of testing and tracing strategies to avoid a potential second wave of the COVID-19 epidemic. We integrate highly detailed (anonymized, privacy-enhanced) mobility data from mobile devices, with census and demographic data to build a detailed agent-based model to describe the transmission dynamics of SARS-CoV-2 in the Boston metropolitan area. We find that enforcing strict social distancing followed by a policy based on a robust level of testing, contact-tracing and household quarantine, could keep the disease at a level that does not exceed the capacity of the health care system. Assuming the identification of 50% of the symptomatic infections, and the tracing of 40% of their contacts and households, which corresponds to about 9% of individuals quarantined, the ensuing reduction in transmission allows the reopening of economic activities while attaining a manageable impact on the health care system. Our results show that a response system based on enhanced testing and contact tracing can play a major role in relaxing social distancing interventions in the absence of herd immunity against SARS-CoV-2.", "title": "Modeling the impact of social distancing, testing, contact tracing and household quarantine on second-wave scenarios of the COVID-19 epidemic", "pid": "nek58pxo", "bm25_score": 217.29547119140625}, {"text": "As COVID-19 has plagued our world, the term \"social distancing\" has been widely used with the aim to encourage the general population to physically distance themselves from others in order to reduce the spread of the virus. However, this term can have unintended but detrimental effects, as it evokes negative feelings of being ignored, unwelcome, left alone with one's own fears, and even excluded from society. These feelings may be stronger in people with mental illnesses and in socio-economically disadvantaged groups, such as stigmatized minorities, migrants, and homeless persons [1], many of them also having high risk for suicidal behaviors [2]. Mental health disorders are pervasive worldwide; the global burden accounting for approximately 21.2-32.4% of years lived with disability-more than any other group of illnesses [3]. So, the vulnerable group of people with mental health disorders represents a considerable share of the total global population.", "title": "The term \"physical distancing\" is recommended rather than \"social distancing\" during the COVID-19 pandemic for reducing feelings of rejection among people with mental health problems", "pid": "ztm3m9fs", "bm25_score": 217.28680419921875}, {"text": "How to avoid a second wave of COVID-19 after reopening the economy is a pressing question. The extremely high basic reproductive number $R_0$ (5.7 to 6.4, shown in new studies) of SARS-CoV-2 further complicates the challenge. Here we assess effects of Social distancing 2.0, i.e. proximity alert (to maintain inter-personal distance) plus privacy-preserving contact tracing. To solve the dual task, we develop an open source mobile app. The app uses a Bluetooth-based, decentralized contact tracing platform over which the anonymous user ID cannot be linked by the government or a third party. Modeling results show that a 50\\% adoption rate of Social distancing 2.0, with privacy-preserving contact tracing, would suffice to decrease the $R_0$ to less than 1 and prevent the resurgence of COVID-19 epidemic.", "title": "Social Distancing 2.0 with Privacy-Preserving Contact Tracing to Avoid a Second Wave of COVID-19", "pid": "7dj7dnjk", "bm25_score": 217.2855987548828}, {"text": "Intense nonpharmaceutical interventions were put in place in China to stop transmission of the novel coronavirus disease 2019 (COVID-19). As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact survey data for Wuhan and Shanghai before and during the outbreak and contact-tracing information from Hunan province. Daily contacts were reduced seven- to eightfold during the COVID-19 social distancing period, with most interactions restricted to the household. We find that children 0 to 14 years of age are less susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than adults 15 to 64 years of age (odds ratio 0.34, 95% confidence interval 0.24 to 0.49), whereas individuals more than 65 years of age are more susceptible to infection (odds ratio 1.47, 95% confidence interval 1.12 to 1.92). Based on these data, we built a transmission model to study the impact of social distancing and school closure on transmission. We find that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. Although proactive school closures cannot interrupt transmission on their own, they can reduce peak incidence by 40 to 60% and delay the epidemic.", "title": "Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China", "pid": "g9flwm6w", "bm25_score": 217.28280639648438}, {"text": "We demonstrate that the epidemic renormalisation group approach to pandemics provides an effective and simple way to investigate the dynamics of disease transmission and spreading across different regions of the world. The framework also allows for reliable projections on the impact of travel limitations and social distancing measures on global epidemic spread. We test and calibrate it on reported cases while unveiling the mechanism that governs the delay in the relative peaks of newly infected cases among different regions of the globe. We discover that social distancing measures are more effective than travel limitations across borders in delaying the epidemic peak. We further provide the link to compartmental models such as the simplistic and time-honoured SIR-like models. We also show how to generalise the framework to account for the interactions across several regions of the world, replacing or complementing large scale simulations.", "title": "Interplay of social distancing and border restrictions for pandemics (COVID-19) via the epidemic Renormalisation Group framework", "pid": "c9w6235b", "bm25_score": 217.2816162109375}, {"text": "As COVID-19 has plagued our world, the term “social distancing” has been widely used with the aim to encourage the general population to physically distance themselves from others in order to reduce the spread of the virus. However, this term can have unintended but detrimental effects, as it evokes negative feelings of being ignored, unwelcome, left alone with one's own fears, and even excluded from society. These feelings may be stronger in people with mental illnesses and in socio-economically disadvantaged groups, such as stigmatized minorities, migrants, and homeless persons [1], many of them also having high risk for suicidal behaviors [2]. Mental health disorders are pervasive worldwide; the global burden accounting for approximately 21.2–32.4% of years lived with disability—more than any other group of illnesses [3]. So, the vulnerable group of people with mental health disorders represents a considerable share of the total global population.", "title": "The term “physical distancing” is recommended rather than “social distancing” during the COVID-19 pandemic for reducing feelings of rejection among people with mental health problems", "pid": "j8voj68w", "bm25_score": 217.2218017578125}, {"text": "Abstract Introduction: Social distancing measures (SDMs) protect public health from the outbreak of coronavirus disease 2019 (COVID-19). However, the impact of SDMs has been inconsistent and unclear. This study aims to assess the effects of SDMs (e.g. isolation, quarantine) for reducing the transmission of COVID-19. Methods and analysis: We will conduct a systematic review meta-analysis research of both randomised controlled trials and non-randomised controlled trials. We will search MEDLINE, EMBASE, Allied & Complementary Medicine, COVID-19 Research and WHO database on COVID-19 for primary studies assessing the enablers and barriers associated with SDMs, and will be reported in accordance with PRISMA statement. The PRISMA-P checklist will be used while preparing this protocol. We will use Joanna Briggs Institute guidelines (JBI Critical Appraisal Checklists) to assess the methodological qualities and synthesised performing thematic analysis. Two reviewers will independently screen the papers and extracted data. If sufficient data are available, the random-effects model for meta-analysis will be performed to measure the effect size of SDMs or the strengths of relationships. To assess the heterogeneity of effects, I2 together with the observed effects (Q-value, with degrees of freedom) will be used to provide the true effects in the analysis. Ethics and dissemination: Ethics approval and consent will not be required for this systematic review of the literature as it does not involve human participation. We will be able to disseminate the study findings using the following strategies: we will be publishing at least one paper in peer-reviewed journals, and an abstract will be presented at suitable national/international conferences or workshops. We will also share important information with public health authorities as well as with the World Health Organization.", "title": "Impact of social distancing measures for preventing coronavirus disease 2019 : A systematic review and meta-analysis protocol", "pid": "3mwx9s5x", "bm25_score": 217.21414184570312}, {"text": "The U.S. is the epicenter of the coronavirus disease 2019 (COVID-19) pandemic. In response, governments have implemented measures to slow transmission through \"social distancing.\" However, the practice of social distancing may depend on prevailing socioeconomic conditions and beliefs. Using 15-17 million anonymized cell phone records, we find that lower per capita income and greater Republican orientation were associated with significantly reduced social distancing among U.S. counties. These associations persisted after adjusting for county-level sociodemographic and labor market characteristics as well as state fixed effects. These results may help policymakers and health professionals identify communities that are most vulnerable to transmission and direct resources and communications accordingly.", "title": "Association of County-Level Socioeconomic and Political Characteristics with Engagement in Social Distancing for COVID-19", "pid": "lb0fd7ig", "bm25_score": 217.21182250976562}, {"text": "The exponential character of the recent Covid-19 outbreak requires a change in strategy from containment to mitigation. Meanwhile, most countries apply social distancing with the objective to keep the number of critical cases below the capabilities of the health care system. Due to the novelty and rapid spread of the virus, an a priori assessment of this strategy was not possible. In this study, we present a model-based systems analysis to assess the effectiveness of social distancing measures in terms of intensity and duration of application. Results show a super-linear scaling between intensity (percent contact reduction) and required duration of application to have an added value (lower fatality rate). This holds true for an effective reproduction of R > 1 and is reverted for R < 1. If R is not reduced below 1, secondary effects of required long-term isolation are likely to unravel the added value of disease mitigation. We recommend an extinction strategy implemented by intense countermeasures.", "title": "Investigating duration and intensity of Covid-19 social-distancing strategies", "pid": "b8f4a7o3", "bm25_score": 217.21070861816406}, {"text": "Social distancing at its various levels has been a key measure to mitigate the transmission of COVID-19. The implementation of strict measures for social distancing is challenging, including in the Kingdom of Saudi Arabia (KSA) due to its level of urbanization, its social and religious norms and its annual hosting of high visibility international religious mass gatherings. KSA started introducing decisive social distancing measures early before the first case of COVID-19 was confirmed in the Kingdom. These ranged from suspension or cancelations of religious, entertainment and sporting mass gatherings and events such as the Umrah, temporary closure of educational establishments and mosques and postponing all non-essential gatherings, to imposing a curfew. These measures were taken in spite of their socio-economic, political and religious challenges in the interest of public and global health. The effect of these actions on the epidemic curve of the Kingdom and on the global fight against COVID-19 remains to be seen. However, given the current COVID-19 situation, further bold and probably unpopular measures are likely to be introduced in the future.", "title": "COVID-19 social distancing in the Kingdom of Saudi Arabia: Bold measures in the face of political, economic, social and religious challenges", "pid": "zyd0njyk", "bm25_score": 217.20802307128906}, {"text": "Community mitigation activities (also referred to as nonpharmaceutical interventions) are actions that persons and communities can take to slow the spread of infectious diseases. Mitigation strategies include personal protective measures (e.g., handwashing, cough etiquette, and face coverings) that persons can use at home or while in community settings; social distancing (e.g., maintaining physical distance between persons in community settings and staying at home); and environmental surface cleaning at home and in community settings, such as schools or workplaces. Actions such as social distancing are especially critical when medical countermeasures such as vaccines or therapeutics are not available. Although voluntary adoption of social distancing by the public and community organizations is possible, public policy can enhance implementation. The CDC Community Mitigation Framework (1) recommends a phased approach to implementation at the community level, as evidence of community spread of disease increases or begins to decrease and according to severity. This report presents initial data from the metropolitan areas of San Francisco, California; Seattle, Washington; New Orleans, Louisiana; and New York City, New York* to describe the relationship between timing of public policy measures, community mobility (a proxy measure for social distancing), and temporal trends in reported coronavirus disease 2019 (COVID-19) cases. Community mobility in all four locations declined from February 26, 2020 to April 1, 2020, decreasing with each policy issued and as case counts increased. This report suggests that public policy measures are an important tool to support social distancing and provides some very early indications that these measures might help slow the spread of COVID-19.", "title": "Timing of Community Mitigation and Changes in Reported COVID-19 and Community Mobility - Four U.S. Metropolitan Areas, February 26-April 1, 2020", "pid": "41d7343o", "bm25_score": 217.19227600097656}]}
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The majority of patients will experience mild disease, but others will develop a severe respiratory infection that requires hospitalisation. This is causing a significant strain on health services. Patients are presenting at emergency departments with symptoms of dyspnoea, dry cough and fever with varying severity. The appropriate triaging of patients will assist in preventing health services becoming overwhelmed during the pandemic. This is assisted through clinical assessment and various imaging and laboratory investigations, including chest X-ray, blood analysis and identification of viral infection with SARS-CoV-2. Here, a succinct triaging pathway that aims to be fast, reliable and affordable is presented. The hope is that such a pathway will assist health services in appropriately combating the pandemic.", "title": "Simple, fast and affordable triaging pathway for COVID-19.", "pid": "ba5x3ysq", "bm25_score": 217.5846405029297}, {"text": "Coronavirus disease 2019 has caused a global pandemic. The majority of patients will experience mild disease, but others will develop a severe respiratory infection that requires hospitalisation. This is causing a significant strain on health services. Patients are presenting at emergency departments with symptoms of dyspnoea, dry cough and fever with varying severity. The appropriate triaging of patients will assist in preventing health services becoming overwhelmed during the pandemic. This is assisted through clinical assessment and various imaging and laboratory investigations, including chest X-ray, blood analysis and identification of viral infection with SARS-CoV-2. Here, a succinct triaging pathway that aims to be fast, reliable and affordable is presented. The hope is that such a pathway will assist health services in appropriately combating the pandemic.", "title": "Simple, fast and affordable triaging pathway for COVID-19", "pid": "h1z8rg9p", "bm25_score": 217.4496612548828}, {"text": "In the end of 2019, the epidemic of a new coronavirus (SARS-CoV-2) occurred in Wuhan and spread rapidly. Changsha, a city located south to the epicenter, was soon impacted. To control the transmission of the coronavirus and avoid nosocomial infection, triage procedures based on epidemiology were implemented in a local hospital of the city. This retrospective study analyzed the data collected during the triage period and found that COVID-19 patients were enriched seven folds into the Section A designated for rapid detection and quarantine. On the other side, roughly triple amounts of visits were received at the Section B for patients without obvious epidemiological history. Eight COVID-19 cases were spotted out of 247 suspected patients. More than 50% of the suspected patients were submitted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection. Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as a COVID-19 case. Of the eight COVID-19 patients, three were confirmed only after multiple rounds of nucleic acid analysis. Besides comorbidities, delayed sharing of epidemiological history added another layer of complexity to the diagnosis in practice. While SARS-CoV-2 epidemic is being alerted in many countries, our report will be helpful to other colleagues in rapid identification of COVID-19 cases and controlling the transmission of the disease.", "title": "Triaging patients in the outbreak of the 2019 novel coronavirus", "pid": "tof0so67", "bm25_score": 217.39132690429688}, {"text": "In this Commentary, we would like to comment on the article titled “A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)” as a featured article in Military Medical Research. In the guideline, except for “confirmed cases”, “suspected cases”, “close contact” and “suspicious exposure” were defined by clinical perspective based on epidemiological risk, clinical symptoms and auxiliary examination. Combined with our experience, we introduced a simple scoring proposal additionally based on not only CT imaging as strongly recommended by the guideline but also blood routine test, especially for primary screening of such patients in the out-patient department.", "title": "Primary stratification and identification of suspected Corona virus disease 2019 (COVID-19) from clinical perspective by a simple scoring proposal", "pid": "leysxvf2", "bm25_score": 216.8001708984375}, {"text": "In this Commentary, we would like to comment on the article titled \"A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)\" as a featured article in Military Medical Research. In the guideline, except for \"confirmed cases\", \"suspected cases\", \"close contact\" and \"suspicious exposure\" were defined by clinical perspective based on epidemiological risk, clinical symptoms and auxiliary examination. Combined with our experience, we introduced a simple scoring proposal additionally based on not only CT imaging as strongly recommended by the guideline but also blood routine test, especially for primary screening of such patients in the out-patient department.", "title": "Primary stratification and identification of suspected Corona virus disease 2019 (COVID-19) from clinical perspective by a simple scoring proposal", "pid": "lfxne39o", "bm25_score": 216.71499633789062}, {"text": "A global health emergency has been declared by the World Health Organization as the 2019-nCoV outbreak spreads across the world, with confirmed patients in Canada. Patients infected with 2019-nCoV are at risk for developing respiratory failure and requiring admission to critical care units. While providing optimal treatment for these patients, careful execution of infection control measures is necessary to prevent nosocomial transmission to other patients and to healthcare workers providing care. Although the exact mechanisms of transmission are currently unclear, human-to-human transmission can occur, and the risk of airborne spread during aerosol-generating medical procedures remains a concern in specific circumstances. This paper summarizes important considerations regarding patient screening, environmental controls, personal protective equipment, resuscitation measures (including intubation), and critical care unit operations planning as we prepare for the possibility of new imported cases or local outbreaks of 2019-nCoV. Although understanding of the 2019-nCoV virus is evolving, lessons learned from prior infectious disease challenges such as Severe Acute Respiratory Syndrome will hopefully improve our state of readiness regardless of the number of cases we eventually manage in Canada.", "title": "Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients", "pid": "8f2r1d14", "bm25_score": 216.22325134277344}, {"text": "OBJECTIVE: To prevent and control public health emergencies, we set up a prescreening and triage workflow and analyzed the effects on coronavirus disease 2019 (COVID-19). METHODS: In accordance with the requirements of the level 1 emergency response of public health emergencies in Shaanxi Province, China, a triage process for COVID-19 was established to guide patients through a 4-level triage process during their hospital visits. The diagnosis of COVID-19 was based on positive COVID-19 nucleic acid testing according to the unified triage standards of the Guidelines for the Diagnosis and Treatment of Novel Coronavirus Pneumonia (Trial version 4),4 issued by the National Health Commission of the People's Republic of China. RESULTS: The screened rate of suspected COVID-19 was 1.63% (4 of 246) in the general fever outpatient clinic and 8.28% (13 of 157) in the COVID-19 outpatient clinic, and they showed a significant difference (P = .00). CONCLUSIONS: The triage procedure effectively screened the patients and identified the high-risk population.", "title": "The role of triage in the prevention and control of COVID-19", "pid": "jv3xx09f", "bm25_score": 216.13229370117188}, {"text": "OBJECTIVE: To prevent and control public health emergencies, we set up a prescreening and triage workflow and analyzed the effects on coronavirus disease 2019 (COVID-19). METHODS: In accordance with the requirements of the level 1 emergency response of public health emergencies in Shaanxi Province, China, a triage process for COVID-19 was established to guide patients through a 4-level triage process during their hospital visits. The diagnosis of COVID-19 was based on positive COVID-19 nucleic acid testing according to the unified triage standards of the Guidelines for the Diagnosis and Treatment of Novel Coronavirus Pneumonia (Trial version 4),(4) issued by the National Health Commission of the People’s Republic of China. RESULTS: The screened rate of suspected COVID-19 was 1.63% (4 of 246) in the general fever outpatient clinic and 8.28% (13 of 157) in the COVID-19 outpatient clinic, and they showed a significant difference (P = .00). CONCLUSIONS: The triage procedure effectively screened the patients and identified the high-risk population.", "title": "The role of triage in the prevention and control of COVID-19", "pid": "4jag7lzb", "bm25_score": 216.083984375}, {"text": "OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world's healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. \"First come, first served\" is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.", "title": "Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival", "pid": "mu0g857x", "bm25_score": 216.02752685546875}, {"text": "INTRODUCTION: The COVID-19 pandemic presents a significant infection prevention and control challenge. The admission of large numbers of patients with suspected COVID-19 disease risks overwhelming the capacity to protect other patients from exposure. The delay between clinical suspicion and confirmatory testing adds to the complexity of the problem. METHODS: We implemented a triage tool aimed at minimising hospital acquired COVID-19 particularly to patients at risk of severe disease. Patients were allocated to triage categories defined by likelihood of COVID-19 and risk of a poor outcome. Category A (low-likelihood; high-risk), B (high-likelihood; high-risk), C (high-likelihood; low-risk) and D (low-likelihood; low-risk). This determined the order of priority for isolation in single-occupancy rooms with Category A the highest. Patients in other groups were cohorted when isolation capacity was limited with additional interventions to reduce transmission. RESULTS: 93 patients were evaluated with 79 (85%) receiving a COVID-19 diagnosis during their admission. Of those without a COVID-19 diagnosis: 10 were initially triaged to Category A; 0 to B; 1 to C and 4 to D. All high risk patients requiring isolation were, therefore, admitted to single-occupancy rooms and protected from exposure. 28 (30%) suspected COVID-19 patients were evaluated to be low risk (groups C & D) and eligible for cohorting. No symptomatic hospital acquired infections were detected in the cohorted patients. DISCUSSION: Application of a clinical triage tool to guide isolation and cohorting decisions may reduce the risk of hospital acquired transmission of COVID-19 especially to individuals at the greatest of risk of severe disease.", "title": "A Novel Cohorting and Isolation Strategy for Suspected COVID-19 Cases during a Pandemic", "pid": "sglgo6hy", "bm25_score": 215.897216796875}, {"text": "OBJECTIVES: Coronavirus disease 2019 patients are currently overwhelming the world’s healthcare systems. This article provides practical guidance to front-line physicians forced to make critical rationing decisions. DATA SOURCES: PubMed and Medline search for scientific literature, reviews, and guidance documents related to epidemic ICU triage including from professional bodies. STUDY SELECTION: Clinical studies, reviews, and guidelines were selected and reviewed by all authors and discussed by internet conference and email. DATA EXTRACTION: References and data were based on relevance and author consensus. DATA SYNTHESIS: We review key challenges of resource-driven triage and data from affected ICUs. We recommend that once available resources are maximally extended, triage is justified utilizing a strategy that provides the greatest good for the greatest number of patients. A triage algorithm based on clinical estimations of the incremental survival benefit (saving the most life-years) provided by ICU care is proposed. “First come, first served” is used to choose between individuals with equal priorities and benefits. The algorithm provides practical guidance, is easy to follow, rapidly implementable and flexible. It has four prioritization categories: performance score, ASA score, number of organ failures, and predicted survival. Individual units can readily adapt the algorithm to meet local requirements for the evolving pandemic. Although the algorithm improves consistency and provides practical and psychologic support to those performing triage, the final decision remains a clinical one. Depending on country and operational circumstances, triage decisions may be made by a triage team or individual doctors. However, an experienced critical care specialist physician should be ultimately responsible for the triage decision. Cautious discharge criteria are proposed acknowledging the difficulties to facilitate the admission of queuing patients. CONCLUSIONS: Individual institutions may use this guidance to develop prospective protocols that assist the implementation of triage decisions to ensure fairness, enhance consistency, and decrease provider moral distress.", "title": "Adult ICU Triage During the Coronavirus Disease 2019 Pandemic: Who Will Live and Who Will Die? Recommendations to Improve Survival", "pid": "x0me00m0", "bm25_score": 215.88436889648438}, {"text": "BACKGROUND: The emerging infection of the 2019 novel coronavirus (2019-nCoV) in late December, 2019 in Wuhan, China, has caused an extreme health concern, with many patients having progressed to acute respiratory disease or other complications in a short period. Meanwhile, the risk factors associated with the disease progression still remain elusive. METHODS: A cohort of 17 patients with laboratory-confirmed 2019-nCoV infections who were admitted to the Ninth Hospital of Nanchang between January 28 and February 6, 2020, were enrolled in this study. All the patients received standardized treatment. The disease progression was evaluated every 7 days after admission. The clinical, radiologic, and laboratory characteristics were retrospectively analyzed, and the factors associated with the disease progression were screened by binary logistic regression analysis. RESULTS: The cohort comprised 11 women (64.7%) and 6 men (35.3%) between the ages of 18 to 70 years old. All patients had a reported history of contact with infection-confirmed patients. Fever (11/64.7%) and cough (8/47.1%) were the most common symptoms, whereas dyspnea (2/11.8%) and fatigue (3/17.6%) were rare, and there was no patient with diarrhea symptoms. There were 5 patients with aggravated disease at the first disease progression evaluation, and no patient received mechanical ventilation, transferred to the intensive care unit (ICU), or progressed to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, coagulation dysfunction, or death. Based on the disease progression, patients were divided into the non-aggravation group (12 cases) and the aggravation group (5 cases). There were no significant differences between the 2 groups with respect to their clinical characteristics. Chest computed tomography (CT) on admission revealed there were 8 patients (47.1%) with invasive lesions found bilaterally on the lungs on multiple lobes, 4 patients (23.5%) with invasive lesions on 1 lobe, and 5 patients (29.4%) with normal chest CT. The aggravation group had1 patient (20.0%) with invasive lesions on one lobe, 3 (60.0%) with invasive lesions on multiple lobes, bilaterally, and 1 (20.0%) with normal chest CT; meanwhile, the nonaggravation group had 3 patients (25.0%) with invasive lesions on one lobe, 5 (41.7%) with invasive lesions on multiple lobes, bilaterally, and 4 (33.3%) with normal chest CT. No significant difference was found between the 2 groups. In the aggravation group, the total lymphocyte counts significantly decreased in comparison to that in the non-aggravation group. Further analysis showed that the CD4+ T cell count but not the CD8+ T cell count of the aggravation group was significantly lower than that of the non-aggravation group. Correlation analysis indicated total lymphocyte count was positively correlated with CD4+ T cell count, and no significant differences were found between the 2 groups in other laboratory measurements, including those of white blood cell (WBC) count, C-reactive protein (CRP), albumin, lactate dehydrogenase (LDH), and D-dimer. Finally, a binary logistic regression model was used to identify the factors associated with the disease progression. It was found that total lymphocyte count was a risk factor associated with disease progression in patients infected with 2019-nCoV. CONCLUSIONS: A higher cell count of total lymphocytes may indicate a better outcome of the disease, and immune response may be a vital factor for directing disease progression in the early stage of 2019-nCoV infection.", "title": "Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus", "pid": "ijtz50ut", "bm25_score": 215.84426879882812}, {"text": "INTRODUCTION Data about optimal initial assessment in patients with suspicion for COVID19-infection or already confirmed infection are sparse. Especially, in preparation for expected mass casualty incident it is necessary to distinguish early and efficiently between outpatient and inpatient treatment including the need for intensive care therapy. METHODS We present a model for a safe and efficient triage, which is established and used in the university hospital of Essen, Germany. It is intended for a non-disaster situation. This model is a combination of clinical assessment by using vital parameters and Manchester triage scale (MTS). Possible additional parameters are POCT (point-of-care-testing) values, electrocardiogram, CT pulmonary angiography, SARS-Cov2-PCR as well as detailed diagnostic of laboratory values. The model was validated by 100 consecutive patients. We demonstrate three patients to illustrate this model. RESULTS During the first two weeks after implementing this model in our normal operation at the emergency department, we had an efficient selectivity between need for inpatient and outpatient treatment. 16 patients were classified as \"inpatients\" according to initial assessment. Among 84 patients who were initially classified as \"outpatients\", 7 patients returned to our emergency department within 14 days. Three of these patients returned due to complaints other than COVID19. One female patient had to be admitted due to progressive dyspnea. CONCLUSIONS This introduced triage-model seems to be an efficient concept. Adjustment might be necessary after further experience and after a growing number of patients.", "title": "[COVID-19 Triage: Who is an inpatient? The Essen triage model].", "pid": "hrqwt37s", "bm25_score": 215.83734130859375}, {"text": "In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named \"2019 novel coronavirus (2019-nCoV)\" by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world's attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.", "title": "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "pid": "1e49nyb5", "bm25_score": 215.82913208007812}, {"text": "", "title": "Triage of patients with COVID-19.", "pid": "ir1ukbzy", "bm25_score": 215.80650329589844}, {"text": "", "title": "Triage of patients with COVID-19", "pid": "tkxsvybh", "bm25_score": 215.788330078125}, {"text": "Abstract Background Coronavirus OC43 infection causes severe pneumonia in patients presenting with comorbidities, but clinical signs alone do not allow for viral identification. Objectives To analyze acute manifestations of Coronavirus OC43 infections and outcomes of patients admitted to an intensive care unit (ICU). Patients and methods Retrospective and monocentric study performed during a Coronavirus OC43 outbreak. We used multiplex PCR to detect an OC43 outbreak in Reunion Island during the 2016 Southern Hemisphere's winter: seven admissions to the ICU. Results Mean age of patients was 71 [67;76] years, SAPS II was 42 [28;53], pneumonia severity index 159 [139;182] vs 73 [40.5;107] for patients in medical wards, and 43% required mechanical ventilation. Comorbidities were diabetes mellitus (87%), chronic respiratory failure (57%), and chronic renal failure (29%). One patient died from Haemophilus influenzae co-infection. Conclusion As for MERS Co-V infections, underlying comorbidities impacted the clinical outcomes of OC43 infections.", "title": "Intensive care admission for Coronavirus OC43 respiratory tract infections", "pid": "vrcul1t5", "bm25_score": 215.78189086914062}, {"text": "INTRODUCTION: Data about optimal initial assessment in patients with suspicion for COVID19-infection or already confirmed infection are sparse. Especially, in preparation for expected mass casualty incident it is necessary to distinguish early and efficiently between outpatient and inpatient treatment including the need for intensive care therapy. METHODS: We present a model for a safe and efficient triage, which is established and used in the university hospital of Essen, Germany. It is intended for a non-disaster situation. This model is a combination of clinical assessment by using vital parameters and Manchester triage scale (MTS). Possible additional parameters are POCT (point-of-care-testing) values, electrocardiogram, CT pulmonary angiography, SARS-Cov2-PCR as well as detailed diagnostic of laboratory values. The model was validated by 100 consecutive patients. We demonstrate three patients to illustrate this model. RESULTS: During the first two weeks after implementing this model in our normal operation at the emergency department, we had an efficient selectivity between need for inpatient and outpatient treatment. 16 patients were classified as \"inpatients\" according to initial assessment. Among 84 patients who were initially classified as \"outpatients\", 7 patients returned to our emergency department within 14 days. Three of these patients returned due to complaints other than COVID19. One female patient had to be admitted due to progressive dyspnea. CONCLUSIONS: This introduced triage-model seems to be an efficient concept. Adjustment might be necessary after further experience and after a growing number of patients.", "title": "COVID-19-Triage: Wer bleibt stationär? Das Modell Essen./ [COVID-19 Triage: Who is an inpatient? The Essen triage model]", "pid": "w4zrux2e", "bm25_score": 215.7611083984375}, {"text": "Objectives: To report our experiences screening and managing patients with suspected or confirmed novel coronavirus (COVID-19) disease using a hospital-specific protocol. Design: Longitudinal cohort study. Setting: A 1,200 bed tertiary care teaching hospital in Chengdu, Sichuan, China. Participants: 802 adults presenting to hospital with concerns of having COVID-19, 1,246 inpatients and 2,531 hospital visitors. Interventions: Screening and management of patients using a hospital-specific protocol, which included fever triage, monitoring visitors and patients, emergency response, personnel training for healthcare team members, health education for patients and family, medical materials management, disinfection and wastes disposal protocols. Results: Between 23 January and 28 February 2020, 73 people were identified as having fever plus respiratory signs with/without a history of exposure and were tested for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by our hospital lab using RT PCR. Forty-five of these 73 people were subsequently excluded based on one negative RT PCR result plus positive results to quick screening tests for flu or other respiratory viruses. The remaining 28 people received a second RT PCR test 24 h later. Three people were confirmed positive for COVID-19 based on two consecutive positive RT PCR tests whilst 25 people were excluded based on two consecutive negative tests. The three COVID-19 confirmed cases received non-critical care. There were no new infections of medical staff or new infections of other hospital inpatients. Conclusions: All three cases were detected as a result of vigilant monitoring of hospital visitors. Whilst screening out-patients presenting to a fever clinic remains important, monitoring visitors must not be overlooked.", "title": "Screening and managing of suspected or confirmed novel coronavirus (COVID-19) patients: experiences from a tertiary hospital outside Hubei province", "pid": "nz02frdm", "bm25_score": 215.74681091308594}, {"text": "BACKGROUND The emerging infection of the 2019 novel coronavirus (2019-nCoV) in late December, 2019 in Wuhan, China, has caused an extreme health concern, with many patients having progressed to acute respiratory disease or other complications in a short period. Meanwhile, the risk factors associated with the disease progression still remain elusive. METHODS A cohort of 17 patients with laboratory-confirmed 2019-nCoV infections who were admitted to the Ninth Hospital of Nanchang between January 28 and February 6, 2020, were enrolled in this study. All the patients received standardized treatment. The disease progression was evaluated every 7 days after admission. The clinical, radiologic, and laboratory characteristics were retrospectively analyzed, and the factors associated with the disease progression were screened by binary logistic regression analysis. RESULTS The cohort comprised 11 women (64.7%) and 6 men (35.3%) between the ages of 18 to 70 years old. All patients had a reported history of contact with infection-confirmed patients. Fever (11/64.7%) and cough (8/47.1%) were the most common symptoms, whereas dyspnea (2/11.8%) and fatigue (3/17.6%) were rare, and there was no patient with diarrhea symptoms. There were 5 patients with aggravated disease at the first disease progression evaluation, and no patient received mechanical ventilation, transferred to the intensive care unit (ICU), or progressed to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, coagulation dysfunction, or death. Based on the disease progression, patients were divided into the non-aggravation group (12 cases) and the aggravation group (5 cases). There were no significant differences between the 2 groups with respect to their clinical characteristics. Chest computed tomography (CT) on admission revealed there were 8 patients (47.1%) with invasive lesions found bilaterally on the lungs on multiple lobes, 4 patients (23.5%) with invasive lesions on 1 lobe, and 5 patients (29.4%) with normal chest CT. The aggravation group had1 patient (20.0%) with invasive lesions on one lobe, 3 (60.0%) with invasive lesions on multiple lobes, bilaterally, and 1 (20.0%) with normal chest CT; meanwhile, the nonaggravation group had 3 patients (25.0%) with invasive lesions on one lobe, 5 (41.7%) with invasive lesions on multiple lobes, bilaterally, and 4 (33.3%) with normal chest CT. No significant difference was found between the 2 groups. In the aggravation group, the total lymphocyte counts significantly decreased in comparison to that in the non-aggravation group. Further analysis showed that the CD4+ T cell count but not the CD8+ T cell count of the aggravation group was significantly lower than that of the non-aggravation group. Correlation analysis indicated total lymphocyte count was positively correlated with CD4+ T cell count, and no significant differences were found between the 2 groups in other laboratory measurements, including those of white blood cell (WBC) count, C-reactive protein (CRP), albumin, lactate dehydrogenase (LDH), and D-dimer. Finally, a binary logistic regression model was used to identify the factors associated with the disease progression. It was found that total lymphocyte count was a risk factor associated with disease progression in patients infected with 2019-nCoV. CONCLUSIONS A higher cell count of total lymphocytes may indicate a better outcome of the disease, and immune response may be a vital factor for directing disease progression in the early stage of 2019-nCoV infection.", "title": "Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus.", "pid": "z3rpoqao", "bm25_score": 215.69578552246094}, {"text": "In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.", "title": "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "pid": "hmy8fs3g", "bm25_score": 215.68649291992188}, {"text": "OBJECTIVES Since the beginning of the novel coronavirus outbreak, different strategies have been explored to stem the spread of the disease and appropriately manage patient flow. Triage, an effective solution proposed in disaster medicine, also works well to manage Emergency Department (ED) flow. The aim of this study was to describe the role of an ED Triage Center for patients with suspected novel coronavirus disease (Covid-19) and characterize the patient flow. Methods. In March 2020, we established a Covid-19 triage center close to the Liège University EDs. From March 2 to March 23, we planned to analyze the specific flow of patients admitted to this triage zone and their characteristics in terms of inner specificities, work-up and management. During this period, all patients presented to the ED with symptoms suggestive of Covid-19 were included in the study. RESULTS A total amount of 1071 patients presented to the triage center during the study period. 41.50% of the patients presented with flu-like symptoms. In 82.00% of the cases, no risk factor of virus transmission was found. The SARS-Cov2 positive patients represented 29.26% of the screened patients. 83.00% of patients were discharged home while 17.00% were admitted to the hospital. CONCLUSION Our experience suggests that triage centers for the assessment and management of Covid-19 suspected patients is an essential key strategy to prevent the spread of the disease among non-symptomatic patients who present to the EDs for care. This allows for a disease-centered work-up and safer diversion of Covid-19 patients to specific hospital units.", "title": "Immersion in an emergency department triage center during the Covid-19 outbreak: first report of the Liège University hospital experience.", "pid": "gyghpk64", "bm25_score": 215.67269897460938}, {"text": "OBJECTIVES: Since the beginning of the novel coronavirus outbreak, different strategies have been explored to stem the spread of the disease and appropriately manage patient flow. Triage, an effective solution proposed in disaster medicine, also works well to manage Emergency Department (ED) flow. The aim of this study was to describe the role of an ED Triage Center for patients with suspected novel coronavirus disease (Covid-19) and characterize the patient flow. METHODS: In March 2020, we established a Covid-19 triage center close to the Liège University EDs. From March 2 to March 23, we planned to analyze the specific flow of patients admitted to this triage zone and their characteristics in terms of inner specificities, work-up and management. During this period, all patients presented to the ED with symptoms suggestive of Covid-19 were included in the study. RESULTS: A total amount of 1071 patients presented to the triage center during the study period. 41.50% of the patients presented with flu-like symptoms. In 82.00% of the cases, no risk factor of virus transmission was found. The SARS-Cov2 positive patients represented 29.26% of the screened patients. 83.00% of patients were discharged home while 17.00% were admitted to the hospital. CONCLUSION: Our experience suggests that triage centers for the assessment and management of Covid-19 suspected patients is an essential key strategy to prevent the spread of the disease among non-symptomatic patients who present to the EDs for care. This allows for a disease-centered work-up and safer diversion of Covid-19 patients to specific hospital units.", "title": "Immersion in an emergency department triage center during the Covid-19 outbreak: first report of the Liège University hospital experience", "pid": "9tlk02y6", "bm25_score": 215.64808654785156}, {"text": "Objectives The novel coronavirus disease 19 (COVID-19), caused by SARS-CoV-2, spreads rapidly across the world. The exponential increase in the number of cases has resulted in overcrowding of emergency departments (ED). Detection of SARS-CoV-2 is based on an RT-PCR of nasopharyngeal swab material. However, RT-PCR testing is time-consuming and many hospitals deal with a shortage of testing materials. Therefore, we aimed to develop an algorithm to rapidly evaluate an individual's risk of SARS-CoV-2 infection at the ED. Methods In this multicenter retrospective study, routine laboratory parameters (C-reactive protein, lactate dehydrogenase, ferritin, absolute neutrophil and lymphocyte counts), demographic data and the chest X-ray/CT result from 967 patients entering the ED with respiratory symptoms were collected. Using these parameters, an easy-to-use point-based algorithm, called the corona-score, was developed to discriminate between patients that tested positive for SARS-CoV-2 by RT-PCR and those testing negative. Computational sampling was used to optimize the corona-score. Validation of the model was performed using data from 592 patients. Results The corona-score model yielded an area under the receiver operating characteristic curve of 0.91 in the validation population. Patients testing negative for SARS-CoV-2 showed a median corona-score of 3 vs. 11 (scale 0-14) in patients testing positive for SARS-CoV-2 (p<0.001). Using cut-off values of 4 and 11 the model has a sensitivity and specificity of 96 and 95%, respectively. Conclusions The corona-score effectively predicts SARS-CoV-2 RT-PCR outcome based on routine parameters. This algorithm provides the means for medical professionals to rapidly evaluate SARS-CoV-2 infection status of patients presenting at the ED with respiratory symptoms.", "title": "Rapid identification of SARS-CoV-2-infected patients at the emergency department using routine testing", "pid": "1cew6vn5", "bm25_score": 215.6278076171875}, {"text": "Objectives The novel coronavirus disease 19 (COVID-19), caused by SARS-CoV-2, spreads rapidly across the world. The exponential increase in the number of cases has resulted in overcrowding of emergency departments (ED). Detection of SARS-CoV-2 is based on an RT-PCR of nasopharyngeal swab material. However, RT-PCR testing is time-consuming and many hospitals deal with a shortage of testing materials. Therefore, we aimed to develop an algorithm to rapidly evaluate an individual's risk of SARS-CoV-2 infection at the ED. Methods In this multicenter retrospective study, routine laboratory parameters (C-reactive protein, lactate dehydrogenase, ferritin, absolute neutrophil and lymphocyte counts), demographic data and the chest X-ray/CT result from 967 patients entering the ED with respiratory symptoms were collected. Using these parameters, an easy-to-use point-based algorithm, called the corona-score, was developed to discriminate between patients that tested positive for SARS-CoV-2 by RT-PCR and those testing negative. Computational sampling was used to optimize the corona-score. Validation of the model was performed using data from 592 patients. Results The corona-score model yielded an area under the receiver operating characteristic curve of 0.91 in the validation population. Patients testing negative for SARS-CoV-2 showed a median corona-score of 3 vs. 11 (scale 0-14) in patients testing positive for SARS-CoV-2 (p<0.001). Using cut-off values of 4 and 11 the model has a sensitivity and specificity of 96 and 95%, respectively. Conclusions The corona-score effectively predicts SARS-CoV-2 RT-PCR outcome based on routine parameters. This algorithm provides the means for medical professionals to rapidly evaluate SARS-CoV-2 infection status of patients presenting at the ED with respiratory symptoms.", "title": "Rapid identification of SARS-CoV-2-infected patients at the emergency department using routine testing.", "pid": "fnmztcol", "bm25_score": 215.61485290527344}, {"text": "The coronavirus epidemic that is spreading around our world poses a number of challenges for healthcare workers. The virus is spread by droplet infection and has a high virulence, so any intervention that generates airway aerosol formation potentially endangers the health of those involved in care. Severe forms of coronavirus infection are associated with progressive respiratory failure, for the treatment of which early endotracheal intubation and invasive mechanical ventilation are essential. There is an increased risk of airway aerosol formation during intubation, resulting in a high risk of infection for care personnel. In addition to the above, difficult airway insurance is relatively common in these patients. The aim of our article is to provide a practice-oriented overview of the specialties of airway insurance in patients infected with coronavirus, with particular reference to aspects of infection control and patient safety. Orv Hetil. 2020; 161 (17): 696-703.", "title": "[Respiratory insurance in coronavirus-infected patients].", "pid": "rkmwe5mj", "bm25_score": 215.5991668701172}, {"text": "Since December 2019, China has been experiencing an outbreak of new infectious disease caused by 2019 novel coronavirus (2019-nCoV). The clinical features include fever, coughing, shortness of breath, and inflammatory pulmonary infiltration revealed by X ray. China rapidly identified 2019-nCoV-related pneumonia a statutory infectious disease. To standardize the diagnosis and treatment of this new infectious disease, operational guidelines for the diagnosis and management of 2019-nCoV infection is accomplished by Peking Union Medical College Hospital.", "title": "[Diagnosis and clinical management of 2019 novel coronavirus infection: an operational recommendation of Peking Union Medical College Hospital (V2.0)].", "pid": "s9vecqv9", "bm25_score": 215.592529296875}, {"text": "First reported in China, the 2019 novel coronavirus has been spreading across the globe. Till 26 March, 2020, 416,686 cases have been diagnosed and 18,589 have died the world over. The coronavirus disease mainly starts with a respiratory illness and about 5-16% require intensive care management for acute respiratory distress syndrome (ARDS) and multi-organ dysfunction. Children account for about 1-2% of the total cases, and 6% of these fall under severe or critical category requiring pediatric intensive care unit (PICU) care. Diagnosis involves a combination of clinical and epidemiological features with laboratory confirmation. Preparedness strategies for managing this pandemic are the need of the hour, and involve setting up cohort ICUs with isolation rooms. Re-allocation of resources in managing this crisis involves careful planning, halting elective surgeries and training of healthcare workers. Strict adherence to infection control like personal protective equipment and disinfection is the key to contain the disease transmission. Although many therapies have been tried in various regions, there is a lack of strong evidence to recommend anti-virals or immunomodulatory drugs.", "title": "Novel Coronavirus 2019 (2019-nCoV) Infection: Part I - Preparedness and Management in the Pediatric Intensive Care Unit in Resource-limited Settings", "pid": "tirmcptc", "bm25_score": 215.56935119628906}, {"text": "Since December 2019, China has been experiencing an outbreak of new infectious disease caused by 2019 novel coronavirus (2019-nCoV). The clinical features include fever, coughing, shortness of breath, and inflammatory pulmonary infiltration revealed by X ray. China rapidly identified 2019-nCoV-related pneumonia a statutory infectious disease. To standardize the diagnosis and treatment of this new infectious disease, operational guidelines for the diagnosis and management of 2019-nCoV infection is accomplished by Peking Union Medical College Hospital.", "title": "[Diagnosis and clinical management of 2019 novel coronavirus infection: an operational recommendation of Peking Union Medical College Hospital (V2.0)]", "pid": "beldeyux", "bm25_score": 215.5692138671875}, {"text": "Coronavirus Disease-2019 (COVID-19) originated in the Wuhan, Hubei Province, China in November 2019 and has since been declared a pandemic by the WHO. COVID-19 is an acute infectious disease, primarily affecting the respiratory system. Currently, real-time reverse transcription polymerase chain reaction (RT-PCR) performed on respiratory specimens is considered the reference by which to diagnose COVID-19. However, the limitations of RT-PCR, specifically, the fact that it is time-consuming and inadequate for the assessment of disease severity, have affected the process of epidemiological disease containment and has taken a toll on the healthcare management chain. As the risk of infection for other patients and personnel must be kept to a minimum, the indications for imaging have to be carefully considered. Imaging is primarily performed in patients with a negative RT-PCR, but a high clinical suspicion of COVID-19, or, in patients with diagnosed COVID-19 who are suffering from moderate to severe symptoms. In this article, we review the typical imaging findings in COVID-19, the differential diagnoses, and common complications.", "title": "Imaging in corona virus disease 2019 (COVID-19)-A scoping review", "pid": "aura0th0", "bm25_score": 215.5447998046875}, {"text": "Background: The novel coronavirus disease 19 (COVID-19), caused by SARS-CoV-2, spreads rapidly across the world. The exponential increase in the number of cases has resulted in overcrowding of emergency departments (ED). Detection of SARS-CoV-2 is based on an RT-PCR of nasopharyngeal swab material. However, RT-PCR testing is time-consuming and many hospitals deal with a shortage of testing materials. Therefore, we aimed to develop an algorithm to rapidly evaluate an individual′s risk of SARS-CoV-2 infection at the ED. Methods: In this multicenter retrospective study, routine laboratory parameters (C-reactive protein, lactate dehydrogenase, ferritin, absolute neutrophil and lymphocyte counts), demographic data and the chest X-ray/CT result from 967 patients entering the ED with respiratory symptoms were gathered. Using these parameters, an easy-to-use point-based algorithm, called the corona-score, was developed to discriminate between patients that tested positive for SARS-CoV-2 by RT-PCR and those testing negative. Computational sampling was used to optimize the corona-score. Validation of the model was performed using data from 592 patients. Results: The corona-score model yielded an area under the receiver operating characteristic curve of 0.91 in the validation population. Patients testing negative for SARS-CoV-2 showed a median corona-score of 3 versus 11 (scale 0-14) in patients testing positive for SARS-CoV-2 (p<0.001). Using cut-off values of 4 and 11 the model has a sensitivity and specificity of 96% and 95%, respectively. Conclusion: The corona-score effectively predicts SARS-CoV-2 RT-PCR outcome based on routine parameters. This algorithm provides the means for medical professionals to rapidly evaluate SARS-CoV-2 infection status of patients presenting at the ED with respiratory symptoms.", "title": "Rapid identification of SARS-CoV-2-infected patients at the emergency department using routine testing", "pid": "mjxnd3az", "bm25_score": 215.5424041748047}, {"text": "A global health emergency has been declared by the World Health Organization as the 2019-nCoV outbreak spreads across the world, with confirmed patients in Canada. Patients infected with 2019-nCoV are at risk for developing respiratory failure and requiring admission to critical care units. While providing optimal treatment for these patients, careful execution of infection control measures is necessary to prevent nosocomial transmission to other patients and to healthcare workers providing care. Although the exact mechanisms of transmission are currently unclear, human-to-human transmission can occur, and the risk of airborne spread during aerosol-generating medical procedures remains a concern in specific circumstances. This paper summarizes important considerations regarding patient screening, environmental controls, personal protective equipment, resuscitation measures (including intubation), and critical care unit operations planning as we prepare for the possibility of new imported cases or local outbreaks of 2019-nCoV. Although understanding of the 2019-nCoV virus is evolving, lessons learned from prior infectious disease challenges such as Severe Acute Respiratory Syndrome will hopefully improve our state of readiness regardless of the number of cases we eventually manage in Canada.", "title": "Directives concrètes à l'intention des équipes de soins intensifs et d'anesthésiologie prenant soin de patients atteints du coronavirus 2019-nCoV./ Practical recommendations for critical care and anesthesiology teams caring for novel coronavirus (2019-nCoV) patients", "pid": "j9jub8al", "bm25_score": 215.5201416015625}, {"text": "Since December 2019, the outbreak of novel coronavirus disease 2019 became a major epidemic threat in China and later spread worldwide. During the coronavirus disease 2019 outbreak in mainland China, the Chinese Obstetricians and Gynecologists Association distributed guidelines regarding the care of gynecologic patients. These guidelines were developed by the Department of Obstetrics and Gynecology at the Peking Union Medical College Hospital and represent an effort to integrate infection control strategy and promote professionalism in medical practice. The guidelines represent collaboration with experts from 31 provinces and autonomous regions of mainland China over 2 weeks' time. With the implementation of these guidelines, no nosocomial infections of coronavirus disease 2019 have been identified at the Peking Union Medical College Hospital. We think these guidelines might be helpful to departments of obstetrics and gynecology internationally during these unprecedented times. In our guidelines, we describe basic infection precaution principles, an epidemiologic screening tool, prioritization of surgical procedures, and operating room requirements. Using these principles, we then review the management of gynecologic patients during the coronavirus disease 2019 epidemic in the outpatient and operative and nonoperative inpatient settings and in clinical trials.", "title": "Management of gynecology patients during the coronavirus disease 2019 pandemic: Chinese expert consensus", "pid": "qe46tqwi", "bm25_score": 215.519775390625}, {"text": "A recent epidemic of pneumonia cases in Wuhan China was caused by a novel coronavirus with strong infectivity, the 2019 novel coronavirus (2019-nCoV). The article provides the pulmonary rehabilitation (PR) methods in the principle of 4S (simple, safe, satisfy, save) for patients with pneumonia caused by the novel coronavirus, shows how to establish a ventilative and convectional PR environment to prevent the spread of virus through droplets, how to guide the patients to carry out PR, how to carry out respiratory muscle training, effective cough, expectoration, sneeze, general exercise, digestive function rehabilitation and psychological rehabilitation, and how to clean and disinfect the PR environment.", "title": "[Pulmonary rehabilitation guidelines in the principle of 4S for patients infected with 2019 novel coronavirus (2019-nCoV)]", "pid": "91j5ozws", "bm25_score": 215.51820373535156}, {"text": "OBJECTIVES: Spain has been one of the countries most severely affected by the coronavirus disease 2019. This study aims to describe a series of children admitted to a PICU due to coronavirus disease 2019 infection. DESIGN: Prospective observational study. SETTING: Tertiary hospital in Madrid, Spain. PATIENTS: Children admitted to the PICU with severe acute respiratory syndrome coronavirus 2 (severe acute respiratory syndrome coronavirus 2) infection, from March 1, 2020, to April 15, 2020. INTERVENTIONS: Observational study. MEASUREMENTS AND MAIN RESULTS: Epidemiologic data, previous clinical characteristics, support therapy needed, imaging tests, laboratory observations on admission, and pharmacologic therapy. Eleven children were admitted to the PICU, with suspected coronavirus disease 2019; the polymerase chain reaction test was positive in seven. The median age was 100.7 months (range, 0.5-162). Five were admitted from the emergency department and two from the ward. The Pediatric Sequential Organ Failure Assessment score was 3 (range, 0-9), and Pediatric Risk of Mortality II score was 4 (range, 0-16). All children were previously healthy except one (allogeneic hematopoietic stem cell transplantation). Respiratory symptoms and fever were prevalent. A chest radiograph led to a pneumonia diagnosis. Not all patients presented with lymphopenia on admission. D-Dimer and ferritin were elevated. All patients needed oxygen therapy through a nasal cannula; five patients received high-flow nasal cannula therapy, which was later substituted with noninvasive ventilation in four. Mechanical ventilation was necessary in two patients on the first day of PICU admission. Two children required mechanical ventilation and inotropic support. Tocilizumab was applied in two intubated children. Also, four children received heparin. No patients died. CONCLUSIONS: On the whole, the children were previously healthy and are more than 1 year old. Respiratory symptoms were the leading cause of PICU admission, making respiratory support the principal therapy. Patients requiring mechanical ventilation showed deterioration on the first day of admission. These children seemed to require close monitoring, and multicenter studies are necessary.", "title": "Children in Critical Care Due to Severe Acute Respiratory Syndrome Coronavirus 2 Infection: Experience in a Spanish Hospital", "pid": "mbr8ogli", "bm25_score": 215.51300048828125}, {"text": "Coronavirus Disease-2019 (COVID-19) originated in the Wuhan, Hubei Province, China in November 2019 and has since been declared a pandemic by the WHO. COVID-19 is an acute infectious disease, primarily affecting the respiratory system. Currently, real-time reverse transcription polymerase chain reaction (RT-PCR) performed on respiratory specimens is considered the reference by which to diagnose COVID-19. However, the limitations of RT-PCR, specifically, the fact that it is time-consuming and inadequate for the assessment of disease severity, have affected the process of epidemiological disease containment and has taken a toll on the healthcare management chain. As the risk of infection for other patients and personnel must be kept to a minimum, the indications for imaging have to be carefully considered. Imaging is primarily performed in patients with a negative RT-PCR, but a high clinical suspicion of COVID-19, or, in patients with diagnosed COVID-19 who are suffering from moderate to severe symptoms. In this article, we review the typical imaging findings in COVID-19, the differential diagnoses, and common complications.", "title": "Imaging in corona virus disease 2019 (COVID-19)—A scoping review", "pid": "v9ftmdlv", "bm25_score": 215.5118408203125}, {"text": "A recent epidemic of pneumonia cases in Wuhan China was caused by a novel coronavirus with strong infectivity, the 2019 novel coronavirus (2019-nCoV). The article provides the pulmonary rehabilitation (PR) methods in the principle of 4S (simple, safe, satisfy, save) for patients with pneumonia caused by the novel coronavirus, shows how to establish a ventilative and convectional PR environment to prevent the spread of virus through droplets, how to guide the patients to carry out PR, how to carry out respiratory muscle training, effective cough, expectoration, sneeze, general exercise, digestive function rehabilitation and psychological rehabilitation, and how to clean and disinfect the PR environment.", "title": "[Pulmonary rehabilitation guidelines in the principle of 4S for patients infected with 2019 novel coronavirus (2019-nCoV)].", "pid": "4067srwc", "bm25_score": 215.5006866455078}, {"text": "BACKGROUND: The rapid spread of coronavirus disease (COVID-19) is affecting many countries. While healthcare systems need to cope with the need to treat a large number of people with different degrees of respiratory failure, actions to preserve aliquots of the healthcare system to guarantee treatment to patients are mandatory. METHODS: In order to protect the Fondazione IRCCS-Istituto Nazionale dei Tumori di Milano from the spread of COVID-19, a number of to-hospital and within-hospital filters were applied. Among others, a triage process to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity in patients with cancer was developed consisting of high-resolution low-dose computed tomography (CT) scan followed by reverse transcription polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 in nose-throat swabs whenever CT was suggestive of lung infection. To serve symptomatic patients who were already admitted to the hospital or in need of hospitalization while waiting for RT-PCR laboratory confirmation of infection, a COVID-19 surveillance zone was set up. RESULTS: A total of 301 patients were screened between March 6 and April 3, 2020. Of these, 47 were hospitalized, 53 needed a differential diagnosis to continue with their cancer treatment, and 201 were about to undergo surgery. RT-PCR was positive in 13 of 40 hospitalized patients (32%), 14 of 52 day hospital patients (27%), and 6 of 201 surgical patients (3%). CONCLUSION: Applying filters to protect our comprehensive cancer center from COVID-19 spread contributed to guaranteeing cancer care during the COVID-19 crisis in Milan. A surveillance area and surgical triage allowed us to protect the hospital from as many as 33 patients infected with SARS-CoV-2.", "title": "Response of a comprehensive cancer center to the COVID-19 pandemic: the experience of the Fondazione IRCCS-Istituto Nazionale dei Tumori di Milano", "pid": "pifk9j8a", "bm25_score": 215.4894561767578}, {"text": "IMPORTANCE: Recent reports identify that among hospitalized coronavirus disease 2019 patients, 30% require ICU care. Understanding ICU resource needs remains an essential component of meeting current and projected needs of critically ill coronavirus disease 2019 patients. OBJECTIVES: This study queried U.S. ICU clinician perspectives on challenging aspects of care in managing coronavirus disease 2019 patients, current and anticipated resource demands, and personal stress. DESIGN, SETTING, AND PARTICIPANTS: Using a descriptive survey methodology, an anonymous web-based survey was administered from April 7, 2020, to April 22, 2020 (email and newsletter) to query members of U.S. national critical care organizations. MEASUREMENTS AND MAIN RESULTS: Through a 16-item descriptive questionnaire, ICU clinician perceptions were assessed regarding current and emerging critical ICU needs in managing the severe acute respiratory syndrome coronavirus 2 infected patients, resource levels, concerns about being exposed to severe acute respiratory syndrome coronavirus 2, and perceived level of personal stress. A total of 9,120 ICU clinicians responded to the survey, representing all 50 U.S. states, with 4,106 (56.9%) working in states with 20,000 or more coronavirus disease 2019 cases. The 7,317 respondents who indicated their profession included ICU nurses (n = 6,731, 91.3%), advanced practice providers (nurse practitioners and physician assistants; n = 334, 4.5%), physicians (n = 212, 2.9%), respiratory therapists (n = 31, 0.4%), and pharmacists (n = 30, 0.4%). A majority (n = 6,510, 88%) reported having cared for a patient with presumed or confirmed coronavirus disease 2019. The most critical ICU needs identified were personal protective equipment, specifically N95 respirator availability, and ICU staffing. Minimizing healthcare worker virus exposure during care was believed to be the most challenging aspect of coronavirus disease 2019 patient care (n = 2,323, 30.9%). Nurses report a high level of concern about exposing family members to severe acute respiratory syndrome coronavirus 2 (median score of 10 on 0-10 scale). Similarly, the level of concern reached the maximum score of 10 in ICU clinicians who had provided care to coronavirus disease 2019 patients. CONCLUSIONS: This national ICU clinician survey identifies continued concerns regarding personal protective equipment supplies with the chief issue being N95 respirator availability. As the pandemic continues, ICU clinicians anticipate a number of limited resources that may impact ICU care including personnel, capacity, and surge potential, as well as staff and subsequent family members exposure to severe acute respiratory syndrome coronavirus 2. These persistent concerns greatly magnify personal stress, offering a therapeutic target for professional organization and facility intervention efforts.", "title": "Coronavirus Disease 2019 Pandemic Measures: Reports From a National Survey of 9,120 ICU Clinicians", "pid": "ec53qp93", "bm25_score": 215.4808807373047}, {"text": "2019 Novel Coronavirus (2019-nCoV) is an emerging infectious disease closely related to MERS-CoV and SARS-CoV that was first reported in Wuhan City, Hubei Province, China in December 2019. As of January 2020, cases of 2019-nCoV are continuing to be reported in other Eastern Asian countries as well as in the United States, Europe, Australia, and numerous other countries. An unusually high volume of domestic and international travel corresponding to the beginning of the 2020 Chinese New Year complicated initial identification and containment of infected persons. Due to the rapidly rising number of cases and reported deaths, all countries should be considered at risk of imported 2019-nCoV. Therefore, it is essential for prehospital, clinic, and emergency department personnel to be able to rapidly assess 2019-nCoV risk and take immediate actions if indicated. The Identify-Isolate-Inform (3I) Tool, originally conceived for the initial detection and management of Ebola virus and later adjusted for other infectious agents, can be adapted for any emerging infectious disease. This paper reports a modification of the 3I Tool for use in the initial detection and management of patients under investigation for 2019-nCoV. After initial assessment for symptoms and epidemiological risk factors, including travel to affected areas and exposure to confirmed 2019-nCoV patients within 14 days, patients are classified in a risk-stratified system. Upon confirmation of a suspected 2019-nCoV case, affected persons must immediately be placed in airborne infection isolation and the appropriate public health agencies notified. This modified 3I Tool will assist emergency and primary care clinicians, as well as out-of-hospital providers, in effectively managing persons with suspected or confirmed 2019-nCoV.", "title": "2019-nCoV: The Identify-Isolate-Inform (3I) Tool Applied to a Novel Emerging Coronavirus", "pid": "dixdgfbe", "bm25_score": 215.47259521484375}, {"text": "The new coronavirus pneumonia has been listed as one of the Class B infectious disease but is managed as Class A infectious disease. To prevent and control its spread in hospitals, the outpatient department is the first key gate. Based on the relevant diagnosis and treatment strategies of the National Health Commission of the People's Republic of China, combined with the actual situation of the hospital's epidemic prevention and control work, this article formulated comprehensive prevention and control strategies from the perspective of the patients and staffs. From the aspects of organization and leadership, medical epidemic prevention, pre-screening and screening, process formulation, admission management, cleaning and disinfection, epidemic report, prevention and control supervision, personnel and material deployment, patient education, comprehensive management, personnel management and psychological support and so on, advice and guidance on prevention and control of this infectious disease in outpatient department of hospital were provided.", "title": "Prevention and control strategies of new coronavirus pneumonia in general hospitals/ 重庆医学", "pid": "2qjy26ae", "bm25_score": 215.45294189453125}, {"text": "OBJECTIVE During an influenza or COVID-19 pandemic that results in acute respiratory distress, available ventilators will not meet demand. In 2007, the NYS Task Force on Life and the Law and Department of Health released draft Guidelines for ethical allocation of ventilators for adults. In 2015, updated guidelines were released to ensure that: (1) revisions reflect the public's values and (2) the triage protocol is substantiated by evidence-based clinical data. We summarize the development and content of the 2015 Guidelines compared to the 2007 version, emphasizing new/revised aspects of the ethical considerations and clinical protocol. METHODS We compared the 2007 and 2015 guidelines, with particular emphasis on the ethical issues and clinical protocols. RESULTS The 2015 Guidelines retained much of the ethical and clinical framework of the 2007 draft. The triage protocol was revised using evidence-based clinical data. Patients with the highest likelihood of short-term survival with ventilator therapy have priority access. Protocol consists of exclusion criteria, the sequential organ failure assessment (SOFA) score, and periodic clinical assessments. Guidance is provided on secondary triage criteria. Other forms of medical intervention/palliative care and review of triage decisions are discussed. CONCLUSIONS The 2015 Guidelines reflect advances in medicine and societal values and provide an evidenced-based framework to save the most lives. The framework could be adapted in other emergencies, such as the COVID-19 pandemic, that require ventilators.", "title": "Clinical and Ethical Considerations in Allocation of Ventilators in an Influenza Pandemic or Other Public Health Disaster: A Comparison of the 2007 and 2015 New York State Ventilator Allocation Guidelines.", "pid": "fgnrujsf", "bm25_score": 215.426025390625}, {"text": "INTRODUCTION Efficient identification and isolation of patients with communicable diseases limits exposure to health care workers, other patients, and visitors. In August 2014, our team developed and implemented an algorithm to triage suspected cases of Ebola virus disease in a midwestern United States emergency department and outpatient clinics based on patient travel history and symptoms. Here, we present the lessons learned and modifications to update the tool. METHODS Two strategies were developed and utilized to properly identify, isolate, and inform on patients with suspected highly hazardous communicable diseases: 1) a robust electronic symptom and travel screen with decision support tools in the electronic medical record, and 2) the availability of workflow protocols for Ebola virus disease, Middle East Respiratory Syndrome (MERS), and coronavirus 2019 (COVID-19) once a person under investigation is identified. After action reports provided opportunities to modify the algorithm and improve the identification and isolation processes. RESULTS Since our screening and travel electronic medical record inception 5 years ago, modifications changed iteratively to further enhance the screening process. Since 2018, staff have identified 5 patients at risk for MERS; in all cases, identification occurred during the check-in process. Exposure investigations in the emergency department decreased significantly after algorithm implementation in January 2019, from 30 in 2018 to 0 in 2019. DISCUSSION Although highly hazardous communicable diseases like Ebola virus disease and MERS are of concern due to their mortality rates and limited treatment options, these same concepts may be applied to the early identification and isolation of patients suspected of having more common communicable diseases like measles and influenza, emphasizing the importance of protocol-based screening in the healthcare environment.", "title": "Can You Catch It? Lessons Learned and Modification of ED Triage Symptom- and Travel-Screening Strategy", "pid": "e8jmyfkm", "bm25_score": 215.4168701171875}, {"text": "INTRODUCTION: Rapid worldwide spread of Coronavirus Disease 2019 (COVID-19) has resulted in a global pandemic. OBJECTIVE: This review article provides emergency physicians with an overview of the most current understanding of COVID-19 and recommendations on the evaluation and management of patients with suspected COVID-19. DISCUSSION: Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for causing COVID-19, is primarily transmitted from person-to-person through close contact (approximately 6 ft) by respiratory droplets. Symptoms of COVID-19 are similar to other viral upper respiratory illnesses. Three major trajectories include mild disease with upper respiratory symptoms, non-severe pneumonia, and severe pneumonia complicated by acute respiratory distress syndrome (ARDS). Emergency physicians should focus on identifying patients at risk, isolating suspected patients, and informing hospital infection prevention and public health authorities. Patients with suspected COVID-19 should be asked to wear a facemask. Respiratory etiquette, hand washing, and personal protective equipment are recommended for all healthcare personnel caring for suspected cases. Disposition depends on patient symptoms, hemodynamic status, and patient ability to self-quarantine. CONCLUSION: This narrative review provides clinicians with an updated approach to the evaluation and management of patients presenting to the emergency department with suspected COVID-19.", "title": "Coronavirus Disease (COVID-19): A primer for emergency physicians", "pid": "s91sz7c0", "bm25_score": 215.40142822265625}, {"text": "Background: Since December 2019, a number of patients infected with COVID-19 (SARS-CoV-2) have been identified in Wuhan, Hubei, China. As the epidemic has spread, similar cases have also been found in other parts of mainland China and abroad. The main reason for this spread is the highly contagious nature of the virus and the fact that children can also become infected during its incubation period. This has made the virus a substantial challenge for the outpatient triage staff of children's hospitals outside the epidemic area of the Hubei Province. It is very important for the preview and triage personnel to accurately grasp the epidemiology of the virus and identify children's symptoms in the fever clinic. Methods: We performed an analysis of our early preview and triage of suspected COVID-19 in 36 children presenting at fever clinics. Two specialists either excluded suspected cases or referred cases to the isolation ward for new nucleic acid testing. Results: All 14 children who were transferred to the isolation ward had a fever, and 71.43% of them had a cough. Their nucleic acid testing results were negative. The suspected cases and excluded suspected cases had similar epidemiology history as well as complete blood count results. With reference to the diagnostic criteria in existing pediatric guidelines, we have further improved the triage screening questionnaire for children with fever in our hospital. Conclusions: According to the situation in our city and hospital, an evaluation questionnaire that is suitable for use with children in our hospital has been formulated to achieve the goals of early detection, isolation, diagnosis, and treatment. We provided an important basis for the next step in developing accurate preview and triage screening standards and appropriate guidelines for pediatric patients.", "title": "Analysis and suggestions for the preview and triage screening of children with suspected COVID-19 outside the epidemic area of Hubei Province", "pid": "macqp9k1", "bm25_score": 215.39833068847656}, {"text": "Recent reports identify that among hospitalized coronavirus disease 2019 patients, 30% require ICU care. Understanding ICU resource needs remains an essential component of meeting current and projected needs of critically ill coronavirus disease 2019 patients. OBJECTIVES: This study queried U.S. ICU clinician perspectives on challenging aspects of care in managing coronavirus disease 2019 patients, current and anticipated resource demands, and personal stress. DESIGN, SETTING, AND PARTICIPANTS: Using a descriptive survey methodology, an anonymous web-based survey was administered from April 7, 2020, to April 22, 2020 (email and newsletter) to query members of U.S. national critical care organizations. MEASUREMENTS AND MAIN RESULTS: Through a 16-item descriptive questionnaire, ICU clinician perceptions were assessed regarding current and emerging critical ICU needs in managing the severe acute respiratory syndrome coronavirus 2 infected patients, resource levels, concerns about being exposed to severe acute respiratory syndrome coronavirus 2, and perceived level of personal stress. A total of 9,120 ICU clinicians responded to the survey, representing all 50 U.S. states, with 4,106 (56.9%) working in states with 20,000 or more coronavirus disease 2019 cases. The 7,317 respondents who indicated their profession included ICU nurses (n = 6,731, 91.3%), advanced practice providers (nurse practitioners and physician assistants; n = 334, 4.5%), physicians (n = 212, 2.9%), respiratory therapists (n = 31, 0.4%), and pharmacists (n = 30, 0.4%). A majority (n = 6,510, 88%) reported having cared for a patient with presumed or confirmed coronavirus disease 2019. The most critical ICU needs identified were personal protective equipment, specifically N95 respirator availability, and ICU staffing. Minimizing healthcare worker virus exposure during care was believed to be the most challenging aspect of coronavirus disease 2019 patient care (n = 2,323, 30.9%). Nurses report a high level of concern about exposing family members to severe acute respiratory syndrome coronavirus 2 (median score of 10 on 0–10 scale). Similarly, the level of concern reached the maximum score of 10 in ICU clinicians who had provided care to coronavirus disease 2019 patients. CONCLUSIONS: This national ICU clinician survey identifies continued concerns regarding personal protective equipment supplies with the chief issue being N95 respirator availability. As the pandemic continues, ICU clinicians anticipate a number of limited resources that may impact ICU care including personnel, capacity, and surge potential, as well as staff and subsequent family members exposure to severe acute respiratory syndrome coronavirus 2. These persistent concerns greatly magnify personal stress, offering a therapeutic target for professional organization and facility intervention efforts.", "title": "Coronavirus Disease 2019 Pandemic Measures: Reports From a National Survey of 9,120 ICU Clinicians", "pid": "4asttsy2", "bm25_score": 215.38400268554688}, {"text": "Objective@#To study the clinical characteristics of 2019 coronavirus (2019-nCoV) pneumonia patients and make a feasible screening process in fever clinic.@*Methods@#Epidemiologic features, clinical presentation, laboratory findings and image features of the screened patients were retrospectively collected and analyzed.@*Results@#Totally, 46 patients were screened, 9 of them were laboratory-confirmed 2019-nCoV infection, and others were defined as laboratory-excluded patients. Laboratory-confirmed patients had higher frequency of travelling or residence in Wuhan within two weeks of onset (P&lt;0.05), but there were no differences on age, sex, other epidemiologic features and comorbidities between the two groups (P&gt;0.05). The most common feature of the laboratory-confirmed patients was fever (100%), but the symptoms showed no differences between the two groups (P&gt;0.05). Laboratory-confirmed patients had lower white blood cell count than the laboratory-excluded patients (P&lt;0.05), and all of them had pneumonia in chest CT scan. None of the patients with normal chest CT had positive 2019-nCoV nucleic acid test.@*Conclusions@#No specific symptom was helpful in the diagnosis of 2019-nCoV infection. However, patients without chest CT scan changes had a very low risk of 2019-nCoV infection despite of the epidemiologic history and fever. We recommended a screening procedure that might be helpful to reduce the rate of miss diagnosis and improve screening efficiency.", "title": "Clinical features of 2019 novel coronavirus infection patients and a feasible screening procedure/ 中华急诊医学杂志", "pid": "8hlp6u58", "bm25_score": 215.38063049316406}, {"text": "Psychiatric patients are at high risk for contracting COVID-19, and inpatient psychiatric units face substantial risks of institutional outbreaks. Here, the authors describe an algorithm for testing and triage in a large psychiatric facility designed to prevent local COVID-19 transmission. The algorithm is based on expert opinion and clinical experience between March and April of 2020, during which the institution cared for 47 COVID-19 positive psychiatric inpatients. The implementation of the algorithm is designed to mitigate COVID-19 transmission, preserve the safest and least restrictive treatment environment for psychiatric inpatients, and provide a model adaptable to other institutional settings.", "title": "A COVID-19 testing and triage algorithm for psychiatric units: One hospital's response to the New York region's pandemic", "pid": "0nhxr2te", "bm25_score": 215.37930297851562}, {"text": "Coronavirus is an enveloped virus with positive-sense single-stranded RNA. Coronavirus infection in humans mainly affects the upper respiratory tract and to a lesser extent the gastrointestinal tract. Clinical symptoms of coronavirus infections can range from relatively mild (similar to the common cold) to severe (bronchitis, pneumonia, and renal involvement). The disease caused by the 2019 novel coronavirus (2019-nCoV) was called Covid-19 by the World Health Organization in February 2020. Face-to-face communication and consistent exposure to body fluids such as blood and saliva predispose dental care workers at serious risk for 2019-nCoV infection. As demonstrated by the recent coronavirus outbreak, information is not enough. During dental practice, blood and saliva can be scattered. Accordingly, dental practice can be a potential risk for dental staff, and there is a high risk of cross-infection. This article addresses all information collected to date on the virus, in accordance with the guidelines of international health care institutions, and provides a comprehensive protocol for managing possible exposure to patients or those suspected of having coronavirus.", "title": "Being a front-line dentist during the Covid-19 pandemic: a literature review", "pid": "gyvvcnuf", "bm25_score": 215.37237548828125}, {"text": "BACKGROUND: Coronavirus has serially overtaken our metropolitan hospitals. At peak, patients with acute respiratory distress syndrome may outnumber mechanical ventilators. In our Miami Hospital System, COVID‐19 cases have multiplied for 4 weeks and elective surgery has been suspended. METHODS: An Otolaryngologic Triage Committee was created to appropriately allocate resources to patients. Hospital ethicists provided support. Our tumor conference screened patients for nonsurgical options. Patients were tested twice for coronavirus before performing urgent contaminated operations. N95 masks and protective equipment were conserved when possible. Patients with low‐grade cancers were advised to delay surgery, and other difficult decisions were made. RESULTS: Hundreds of surgeries were canceled. Sixty‐five cases screened over 3 weeks are tabulated. Physicians and patients expressed discomfort regarding perceived deviations from standards, but risk of COVID‐19 exposure tempered these discussions. CONCLUSIONS: We describe the use of actively managed surgical triage to fairly balance our patient's health with public health concerns.", "title": "Ethical surgical triage of patients with head and neck cancer during the COVID‐19 pandemic", "pid": "sicjrsl4", "bm25_score": 215.3713836669922}, {"text": "The rapid emergence of COVID-19 (coronavirus disease 2019) has necessitated the implementation of diverse pandemic control strategies throughout the world. In order to effectively control the spread of this disease, it is essential that it be diagnosed at an early stage so that patients can be reliably quarantined such that disease spread will be slowed. At present, the diagnosis of this infectious form of coronavirus pneumonia is largely dependent upon a combination of laboratory testing and imaging analyses of variable diagnostic efficacy. In the present report, we reviewed prior literature pertaining to the diagnosis of different forms of pneumonia caused by coronaviruses (SARS, MERS, and SARS-CoV-2) and assessed two different potential diagnostic approaches. We ultimately found that computed tomography (CT) was associated with a higher rate of diagnostic accuracy than was a real-time quantitative polymerase chain reaction (qPCR)-based approach (P = 0.0041), and chest radiography (P = 0.0100). Even so, it is important that clinicians utilize a combination of laboratory and radiological testing where possible in order to ensure that this virus is reliably and quickly detected such that it may be treated and patients may be isolated in a timely fashion, thereby effectively curbing the further progression of this pandemic. This article is protected by copyright. All rights reserved.", "title": "The Diagnosis of SARS-CoV2 Pneumonia: A Review of Laboratory and Radiological Testing Results", "pid": "5toc1b8f", "bm25_score": 215.36766052246094}, {"text": "At the end of January 2020, a novel betacoronavirus, known as severe acute respiratory syndrome coronavirus 2, progressively spread in Italy. Patients with cancer are considered more prone to infections because of the immunosuppressive status due to both malignancy and anticancer treatments. From the first Italian government restrictions (23rd February), Modena Cancer Center adopted practical health vigilance recommendations to minimise the risk of exposure to the virus without overlooking cancer management. From 23rd February to 31st March 2020, 1257 patients on active anticancer treatment for oncological or haematological malignancies attended our institution. All the staff activities were rescheduled following our practical coronavirus disease 2019 (COVID-19) guideline. During this period, we have tallied 9 cases of COVID-19 infection (0.71%) in patients with cancer and 3 cases (1.66%) in health workers. The mortality rate of our patients with cancer was 22%, consistent with the data reported in the literature. In conclusion, following our practical health vigilance recommendations, physicians should be confident in maintaining life-saving anticancer treatment without exceedingly increasing the risk of nosocomial COVID-19 infection. The high rate of mortality suggested that all patients on active anticancer treatment with flu-like symptoms have to be carefully screened for COVID-19 infection.", "title": "Cancer treatment during the coronavirus disease 2019 pandemic: Do not postpone, do it!", "pid": "axk2ik3y", "bm25_score": 215.36398315429688}, {"text": "During the first two decades of the 21st century, there have been three coronavirus infection outbreaks raising global health concerns by severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV-2. Although the reported imaging findings of coronavirus infection are variable and non-specific, the most common initial chest radiograph (CXR) and CT findings are ground-glass opacities and consolidation with peripheral predominance and eventually spread to involve both lungs as the disease progresses. These findings can be explained by the immune pathogenesis of coronavirus infection causing diffuse alveolar damage. Although it is insensitive in mild or early coronavirus infection, the CXR remains as the first-line and the most commonly used imaging modality. That is because it is rapid and easily accessible and helpful for monitoring patient progress during treatment. CT is more sensitive to detect early parenchymal lung abnormalities and disease progression, and can provide an alternative diagnosis. In this pictorial review, various coronavirus infection cases are presented to provide imaging spectrums of coronavirus infection and present differences in imaging among them or from other viral infections, and to discuss the role of imaging in viral infection outbreaks.", "title": "Imaging findings in coronavirus infections: SARS-CoV, MERS-CoV, and SARS-CoV-2", "pid": "1r6jmnum", "bm25_score": 215.35983276367188}, {"text": "The 2019 novel coronavirus infection has brought a great challenge in prevention and control of the national epidemic of coronavirus disease 2019 (COVID-19) in China. During the fight against the epidemic of COVID-19, properly carrying out pre-examination and triage for patients with skin lesions and fever has been a practical problem encountered in hospitals for skin diseases as well as clinics of dermatology in general hospitals. Considering that certain skin diseases may have symptom of fever, and some of the carriers of 2019 novel coronavirus and patients with COVID-19 at their early stage may do not present any symptoms of COVID-19, to properly deal with the visitors to clinics of dermatology, the Chinese Society of Dermatology organized experts to formulate the principles and procedures for pre-examination and triage of visitors to clinics of dermatology during the epidemic of COVID-19.", "title": "Consensus on Pre-examination and Triage in Clinic of Dermatology During Outbreak of COVID-19 From Chinese Experts(#)", "pid": "h83aed9u", "bm25_score": 215.34292602539062}, {"text": "The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale (VELTAS) was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: 1) Venous thromboembolism (VTE), 2) Chronic Venous Disease (CVD), 3) Vascular anomalies, 4) Venous trauma 5) Venous compression and 6) Lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included 1) Medical Emergencies (requiring immediate attendance), example massive pulmonary embolism; 2) Urgent (to be seen as soon as possible), example deep vein thrombosis ; 3) Semi-urgent (to be attended to within 30-90 days), example highly symptomatic CVD, and 4) Discretionary/Non-urgent- (to be seen within 6-12 months), example chronic lymphoedema. VELTAS aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.", "title": "Triage of Patients with Venous and Lymphatic Diseases during the COVID-19 pandemic- the Venous and Lymphatic Triage and Acuity Scale (VELTAS)", "pid": "bx8q2gst", "bm25_score": 215.33847045898438}, {"text": "Coronavirus infection is a transmissible disease. It was first described in China in December, 2019. It has been said to have a person-to-person transmission after prolonged and unprotected exposure. Patients with a potential SARS-CoV-2 exposure present with symptoms of low-grade pyrexia, dry cough, or shortness of breath. People with these symptoms should contact health-care providers before seeking medical intervention so that appropriate preventive actions may be implemented. Health-care facilities should rapidly isolate suspected individuals and notify local health departments for support involved in performing laboratory tests and efforts in containment. The present article describes the nature of virus, method of detection, and its mode of transmission.", "title": "Coronavirus: An emergency for healthcare professionals", "pid": "yxmkaqo8", "bm25_score": 215.33645629882812}, {"text": "", "title": "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)", "pid": "kawnb75k", "bm25_score": 215.33340454101562}, {"text": "BACKGROUND: Coronavirus has serially overtaken our metropolitan hospitals. At peak, patients with acute respiratory distress syndrome may outnumber mechanical ventilators. In our Miami Hospital System, COVID-19 cases have multiplied for 4 weeks and elective surgery has been suspended. METHODS: An Otolaryngologic Triage Committee was created to appropriately allocate resources to patients. Hospital ethicists provided support. Our tumor conference screened patients for nonsurgical options. Patients were tested twice for coronavirus before performing urgent contaminated operations. N95 masks and protective equipment were conserved when possible. Patients with low-grade cancers were advised to delay surgery, and other difficult decisions were made. RESULTS: Hundreds of surgeries were canceled. Sixty-five cases screened over 3 weeks are tabulated. Physicians and patients expressed discomfort regarding perceived deviations from standards, but risk of COVID-19 exposure tempered these discussions. CONCLUSIONS: We describe the use of actively managed surgical triage to fairly balance our patient's health with public health concerns.", "title": "Ethical surgical triage of patients with head and neck cancer during the COVID-19 pandemic", "pid": "3qk0lwh0", "bm25_score": 215.33192443847656}, {"text": "Abstract Purpose An ongoing pandemic of COVID-19 that started in Hubei, China has resulted in massive strain on the healthcare infrastructure in Lombardy, Italy. The management of these patients is still evolving. Materials and methods This is a single-center observational cohort study of critically ill patients infected with COVID-19. Bedside clinicians abstracted daily patient data on history, treatment, and short-term course. We describe management and a proposed severity scale for treatment used in this hospital. Results 44 patients were enrolled; with incomplete information on 11. Of the 33 studied patients, 91% were male, median age 64; 88% were overweight or obese. 45% were hypertensive, 12% had been taking an ACE-inhibitor. Noninvasive ventilation was performed on 39% of patients for part or all or their ICU stay with no provider infection. Most patients received antibiotics for pneumonia. Patients also received lopinivir/ritonavir (82%), hydroxychloroquine (79%), and tocilizumab (12%) according to this treatment algorithm. Nine of 10 patients survived their ICU course and were transferred to the floor, with one dying in the ICU. Conclusions ICU patients with COVID-19 frequently have hypertension. Many could be managed with noninvasive ventilation, despite the risk of aerosolization. The use of a severity scale augmented clinician management.", "title": "Clinical presentation and initial management critically ill patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Brescia, Italy", "pid": "syr9av09", "bm25_score": 215.330322265625}, {"text": "The COVID-19 pandemic presents clinicians a unique set of challenges in managing breast cancer (BC) patients. As hospital resources and staff become more limited during the COVID-19 pandemic, it becomes critically important to define which BC patients require more urgent care and which patients can wait for treatment until the pandemic is over. In this Special Communication, we use expert opinion of representatives from multiple cancer care organizations to categorize BC patients into priority levels (A, B, C) for urgency of care across all specialties. Additionally, we provide treatment recommendations for each of these patient scenarios. Priority A patients have conditions that are immediately life threatening or symptomatic requiring urgent treatment. Priority B patients have conditions that do not require immediate treatment but should start treatment before the pandemic is over. Priority C patients have conditions that can be safely deferred until the pandemic is over. The implementation of these recommendations for patient triage, which are based on the highest level available evidence, must be adapted to current availability of hospital resources and severity of the COVID-19 pandemic in each region of the country. Additionally, the risk of disease progression and worse outcomes for patients need to be weighed against the risk of patient and staff exposure to SARS CoV-2 (virus associated with the COVID-19 pandemic). Physicians should use these recommendations to prioritize care for their BC patients and adapt treatment recommendations to the local context at their hospital.", "title": "Recommendations for prioritization, treatment, and triage of breast cancer patients during the COVID-19 pandemic. the COVID-19 pandemic breast cancer consortium", "pid": "m8iqens3", "bm25_score": 215.2894287109375}, {"text": "Public health emergencies have the potential to place enormous strain on health systems. The current pandemic of the novel 2019 coronavirus disease has required hospitals in numerous countries to expand their surge capacity to meet the needs of patients with critical illness. When even surge capacity is exceeded, however, principles of critical care triage may be needed as a means to allocate scarce resources, such as mechanical ventilators or key medications. The goal of a triage system is to direct limited resources towards patients most likely to benefit from them. Implementing a triage system requires careful coordination between clinicians, health systems, local and regional governments, and the public, with a goal of transparency to maintain trust. We discuss the principles of tertiary triage and methods for implementing such a system, emphasizing that these systems should serve only as a last resort. Even under triage, we must uphold our obligation to care for all patients as best possible under difficult circumstances.", "title": "Triage of Scarce Critical Care Resources in COVID-19 An Implementation Guide for Regional Allocation: An Expert Panel Report of the Task Force for Mass Critical Care and the American College of Chest Physicians", "pid": "hlwcr2uh", "bm25_score": 215.28726196289062}, {"text": "The rapid emergence of COVID‐19 (coronavirus disease 2019) has necessitated the implementation of diverse pandemic control strategies throughout the world. In order to effectively control the spread of this disease, it is essential that it be diagnosed at an early stage so that patients can be reliably quarantined such that disease spread will be slowed. At present, the diagnosis of this infectious form of coronavirus pneumonia is largely dependent upon a combination of laboratory testing and imaging analyses of variable diagnostic efficacy. In the present report, we reviewed prior literature pertaining to the diagnosis of different forms of pneumonia caused by coronaviruses (SARS, MERS, and SARS‐CoV‐2) and assessed two different potential diagnostic approaches. We ultimately found that computed tomography (CT) was associated with a higher rate of diagnostic accuracy than was a real‐time quantitative polymerase chain reaction (qPCR)‐based approach (P = 0.0041), and chest radiography (P = 0.0100). Even so, it is important that clinicians utilize a combination of laboratory and radiological testing where possible in order to ensure that this virus is reliably and quickly detected such that it may be treated and patients may be isolated in a timely fashion, thereby effectively curbing the further progression of this pandemic. This article is protected by copyright. All rights reserved.", "title": "The Diagnosis of SARS‐CoV2 Pneumonia: A Review of Laboratory and Radiological Testing Results", "pid": "kowo6dt4", "bm25_score": 215.28021240234375}, {"text": "BACKGROUND: The World Health Organization has highlighted the need for improved surveillance and understanding of the health burden imposed by non-influenza RNA respiratory viruses. Human coronaviruses (CoVs) are a major cause of respiratory and gastrointestinal tract infections with associated morbidity and mortality. OBJECTIVES: The objective of our study was to characterize the epidemiology of CoVs in our tertiary care centre, and identify clinical correlates of disease severity. STUDY DESIGN: A cross-sectional study was performed of 226 patients admitted with confirmed CoV respiratory tract infection between 2010 and 2016. Variables consistent with a severe disease burden were evaluated including symptoms, length of stay, intensive care unit (ICU) admission and mortality. RESULTS: CoVs represented 11.3% of all positive respiratory virus samples and OC43 was the most commonly identified CoV. The majority of infections were community-associated while 21.6% were considered nosocomial. The average length of stay was 11.8 days with 17.3% of patients requiring ICU admission and an all-cause mortality of 7%. In a multivariate model, female gender and smoking were associated with increased likelihood of admission to ICU or death. CONCLUSION: This study highlights the significant burden of CoVs and justifies the need for surveillance in the acute care setting.", "title": "Severity of coronavirus respiratory tract infections in adults admitted to acute care in Toronto, Ontario", "pid": "i8bw7ut9", "bm25_score": 215.27931213378906}, {"text": "BACKGROUND At present, the severity of patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a focal point. METHODS To assess the factors associated with severity and prognosis of patients infected with SARS-CoV-2, we retrospectively investigated the clinical, imaging, and laboratory characteristics of confirmed 280 cases of novel coronavirus disease (COVID-19) from January 20 to February 20, 2020. RESULTS The median age of patients in the mild group was 37.55 years old, while that in the severe group was 63.04 years old. The proportion of patients over 65 years old in the severe group was significantly higher than that of the mild group (59.04% vs. 10.15%, P < 0.05). 85.54% of severe patients had diabetes or cardiovascular diseases, which was significantly higher than that of the mild group (51.81% vs 7.11%, P = 0.025; 33.73% vs 3.05%, P = 0.042). Patients in the mild group experienced earlier initiation of antiviral treatment (1.19 ± 0.45 vs 2.65 ± 1.06 days in the severe group, P < 0.001). Our study showed that comorbidity, time from illness onset to antiviral, and age >=65 were three major risk factors for COVID-19 progression, while comorbidity and time from illness onset to antiviral were two major risk factors for COVID-19 recovery. CONCLUSIONS The elderly and patients with underlying diseases are more likely to experience a severe progression of COVID-19. It is recommended that timely antiviral treatment should be initiated to slow the disease progression and improve the prognosis.", "title": "Early antiviral treatment contributes to alleviate the severity and improve the prognosis of patients with novel coronavirus disease (COVID-19).", "pid": "w3i4h93b", "bm25_score": 215.27857971191406}, {"text": "Objective@#To investigate the principles of differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of novel coronavirus (2019-nCoV) by analyzing one case of lymphoma who presented pulmonary ground-glass opacities (GGO) after courses of chemotherapy.@*Methods@#Baseline demographics and clinicopathological data of eligible patients were retrieved from medical records. Information of clinical manifestations, history of epidemiology, lab tests and chest CT scan images of visiting patients from February 13 to February 28 were collected. Literatures about pulmonary infiltrates in cancer patients were searched from databases including PUBMED, EMBASE and CNKI.@*Results@#Among the 139 cancer patients underwent chest CT scans before chemotherapy, pulmonary infiltrates were identified in eight patients (5.8%), five of whom were characterized as GGOs in lungs. 2019-nCoV nuclear acid testing was performed in three patients and the results were negative. One case was a 66-year-old man diagnosed as non-Hodgkin lymphoma and underwent CHOP chemotherapy regimen. His chest CT scan image displayed multiple GGOs in lungs and the complete blood count showed decreased lymphocytes. This patient denied any contact with confirmed/suspected cases of 2019-nCoV infection and without fever and other respiratory symptoms. Considering the negative result of nuclear acid testing, this patient was presumptively diagnosed as viral pneumonia and an experiential anti-infection treatment had been prescribed for him.@*Conclusions@#The 2019 novel coronavirus disease (COVID-19) complicates the clinical scenario of pulmonary infiltrates in cancer patients. The epidemic history, clinical manifestation, CT scan image and lab test should be combined consideration. The 2019-nCoV nuclear acid testing might be applicated in more selected patients. Active anti-infection treatment and surveillance of patient condition should be initiated if infectious disease is considered.", "title": "The differential diagnosis of pulmonary infiltrates in cancer patients during the outbreak of the 2019 novel coronavirus disease/ 中华肿瘤杂志", "pid": "s5f1olt4", "bm25_score": 215.27783203125}, {"text": "BACKGROUND: The outbreak of the coronavirus disease 2019 (COVID-19) has globally strained medical resources and caused significant mortality. OBJECTIVE: To develop and validate machine-learning model based on clinical features for severity risk assessment and triage for COVID-19 patients at hospital admission. METHOD: 725 patients were used to train and validate the model including a retrospective cohort of 299 hospitalised COVID-19 patients at Wuhan, China, from December 23, 2019, to February 13, 2020, and five cohorts with 426 patients from eight centers in China, Italy, and Belgium, from February 20, 2020, to March 21, 2020. The main outcome was the onset of severe or critical illness during hospitalisation. Model performances were quantified using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion-matrix. RESULTS: The median age was 50.0†years and 137 (45.8%) were men in the retrospective cohort. The median age was 62.0†years and 236 (55.4%) were men in five cohorts. The model was prospectively validated on five cohorts yielding AUCs ranging from 0.84 to 0.89, with accuracies ranging from 74.4% to 87.5%, sensitivities ranging from 75.0% to 96.9%, and specificities ranging from 57.5% to 88.0%, all of which performed better than the pneumonia severity index. The cut-off values of the low, medium, and high-risk probabilities were 0.21 and 0.80. The online-calculators can be found at www.covid19risk.ai. CONCLUSION: The machine-learning model, nomogram, and online-calculator might be useful to access the onset of severe and critical illness among COVID-19 patients and triage at hospital admission.", "title": "Development of a Clinical Decision Support System for Severity Risk Prediction and Triage of COVID-19 Patients at Hospital Admission: an International Multicenter Study", "pid": "0lfjktq1", "bm25_score": 215.27471923828125}, {"text": "Objective: To investigate the clinical characteristics of medical staff with novel coronavirus pneumonia(NCP). Methods: 30 patients infected with novel coronavirus referred to jianghan university hospital between January 11, 2020 and January 3, 2020 were studied. The data reviewed included those of clinical manifestations, laboratory investigation and Radiographic features. Results: The patients consisted of 10 men and 20 women, including 22 doctors and 8 nurses,aged 21~59 years(mean 35±8 years).They were divided to 26 common type and 4 severe cases, all of whom had close(within 1m) contact with patients infected of novel coronavirus pneumonia. The average contact times were 12 (7,16) and the average cumulative contact time was 2 (1.5,2.7) h.Clinical symptoms of these patients were fever in 23 patients (76.67%) , headache in 16 petients (53.33%) , fatigue or myalgia in 21patients (70%) , nausea, vomiting or diarrhea in 9 petients (30%) , cough in 25 petients (83.33%) , and dyspnea in 14 petients (46.67%) .Routine blood test revealed WBC<4.0×10(9)/L in 8 petients (26.67%) , (4-10) ×10(9)/L in 22 petients (73.33%) , and WBC>4.0×10(9)/L in 4 petients (13.33%) during the disease.Lymphocyte count<1.0×10(9)/L occurred in 12 petients (40%),abnormal liver function in 7 petients (23.33%) ,myocardial damage in 5 petients(16.67%), elevated D-dimer (>0.5mg/l) in 5 patients (16.67%). Compared with normal patients, the average exposure times, cumulative exposure time, BMI, Fever time, white blood cell count, liver enzyme, LDH, myoenzyme and D-dimer were significantly increased in severe patients, while the lymphocyte count and albumin levels in peripheral blood were significantly decreased.Chest CT mainly showed patchy shadows and interstitial changes.According to imaging examination, 11 patients (36.67%) showed Unilateral pneumonia and 19 patients (63.33%) showed bilateral pneumonia,4 patients (13.33%) showed bilateral multiple mottling and ground-glass opacity.Compared with the patients infected in the protected period, the proportion of severe infection and bilateral pneumonia were both increased in the patients infected in unprotected period. Conclusion: Medical staffs are at higher risk of infection.Infection rates are associated with contact time, the amount of suction virus. Severe patients had BMI increased, heating time prolonged, white blood cell count, lymphocyte count, D-dimer and albumin level significantly changed and were prone to be complicated with liver damage and myocardial damage.Strict protection measures is important to prevent infection for medical workers.", "title": "[Clinical characteristics of 30 medical workers infected with new coronavirus pneumonia].", "pid": "j8cz0wx5", "bm25_score": 215.25448608398438}, {"text": "Objective: To investigate the clinical characteristics of medical staff with novel coronavirus pneumonia(NCP). Methods: 30 patients infected with novel coronavirus referred to jianghan university hospital between January 11, 2020 and January 3, 2020 were studied. The data reviewed included those of clinical manifestations, laboratory investigation and Radiographic features. Results: The patients consisted of 10 men and 20 women, including 22 doctors and 8 nurses,aged 21~59 years(mean 35±8 years).They were divided to 26 common type and 4 severe cases, all of whom had close(within 1m) contact with patients infected of novel coronavirus pneumonia. The average contact times were 12 (7,16) and the average cumulative contact time was 2 (1.5,2.7) h.Clinical symptoms of these patients were fever in 23 patients (76.67%) , headache in 16 petients (53.33%) , fatigue or myalgia in 21patients (70%) , nausea, vomiting or diarrhea in 9 petients (30%) , cough in 25 petients (83.33%) , and dyspnea in 14 petients (46.67%) .Routine blood test revealed WBC <4.0×10(9)/L in 8 petients (26.67%) , (4-10) ×10(9)/L in 22 petients (73.33%) , and WBC>4.0×10(9)/L in 4 petients (13.33%) during the disease.Lymphocyte count <1.0×10(9)/L occurred in 12 petients (40%),abnormal liver function in 7 petients (23.33%) ,myocardial damage in 5 petients(16.67%), elevated D-dimer (>0.5mg/l) in 5 patients (16.67%). Compared with normal patients, the average exposure times, cumulative exposure time, BMI, Fever time, white blood cell count, liver enzyme, LDH, myoenzyme and D-dimer were significantly increased in severe patients, while the lymphocyte count and albumin levels in peripheral blood were significantly decreased.Chest CT mainly showed patchy shadows and interstitial changes.According to imaging examination, 11 patients (36.67%) showed Unilateral pneumonia and 19 patients (63.33%) showed bilateral pneumonia,4 patients (13.33%) showed bilateral multiple mottling and ground-glass opacity.Compared with the patients infected in the protected period, the proportion of severe infection and bilateral pneumonia were both increased in the patients infected in unprotected period. Conclusion: Medical staffs are at higher risk of infection.Infection rates are associated with contact time, the amount of suction virus. Severe patients had BMI increased, heating time prolonged , white blood cell count, lymphocyte count, D-dimer and albumin level significantly changed and were prone to be complicated with liver damage and myocardial damage.Strict protection measures is important to prevent infection for medical workers.", "title": "[Clinical characteristics of 30 medical workers infected with new coronavirus pneumonia].", "pid": "a4fce66l", "bm25_score": 215.25448608398438}, {"text": "The outbreak of the new Coronavirus disease, COVID-19, has been involved in 77,262 cases in China as well as in 27 other countries as of February 24, 2020. Because the virus is novel to human beings, and there is no vaccine yet available, every individual is susceptible and can become infected. Healthcare workers are at high risk, and unfortunately, more than 3,000 healthcare workers in China have been infected. Anesthesiologists are among healthcare workers who are at an even higher risk of becoming infected because of their close contact with infected patients and high potential of exposure to respiratory droplets or aerosol from their patients' airways. In order to provide healthcare workers with updated recommendations on the management of patients in the perioperative setting as well as for emergency airway management outside of the operating room, the two largest anesthesia societies, the Chinese Society of Anesthesiology (CSA) and the Chinese Association of Anesthesiologists (CAA) have formed a task force to produce the recommendations. The task force hopes to help healthcare workers, particularly anesthesiologists, optimize the care of their patients and protect patients, healthcare workers, and the public from becoming infected. The recommendations were created mainly based on the practice and experience of anesthesiologists who provide care to patients in China. Therefore, adoption of these recommendations outside of China must be done with caution, and the local environment, culture, uniqueness of the healthcare system, and patients' needs should be considered. The task force will continuously update the recommendations and incorporate new information in future versions.", "title": "Perioperative Management of Patients Infected with the Novel Coronavirus: Recommendation from the Joint Task Force of the Chinese Society of Anesthesiology and the Chinese Association of Anesthesiologists", "pid": "vqdfu0t5", "bm25_score": 215.25279235839844}, {"text": "", "title": "Reply: Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the Coronavirus Disease 2019 (COVID-19) Pandemic: An ACC/SCAI Consensus Statement", "pid": "dn1nse7h", "bm25_score": 215.25259399414062}, {"text": "The Coronavirus Disease 2019 pandemic placed urologic surgeons, and especially urologic oncologists, in an unprecedented situation. Providers and healthcare systems were forced to rapidly create triage schemas in order to preserve resources and reduce potential viral transmission while continuing to provide care for patients. We reviewed United States and international triage proposals from professional societies, peer-reviewed publications, and publicly available institutional guidelines to identify common themes and critical differences. To date, there are varying levels of agreement on the optimal triaging of urologic oncology cases. As the need to preserve resources and prevent viral transmission grows, prioritizing only high priority surgical cases is paramount. A similar approach to prioritization will also be needed as nonemergent cases are allowed to proceed in the coming weeks. While these decisions will often be made on a case-by-case basis, more nuanced surgeon-driven consensus guidelines are needed for the near future.", "title": "Urologic oncology surgery during COVID-19: a rapid review of current triage guidance documents", "pid": "f7i85959", "bm25_score": 215.2486114501953}, {"text": "In December 2019, a series of patients with severe pneumonia were identified in Wuhan, Hubei province, China, who progressed to severe acute respiratory syndrome and acute respiratory distress syndrome. Subsequently, COVID-19 was attributed to a new betacoronavirus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Approximately 20% of patients diagnosed as COVID-19 develop severe forms of the disease, including acute hypoxemic respiratory failure, severe acute respiratory syndrome, acute respiratory distress syndrome and acute renal failure and require intensive care. There is no randomized controlled clinical trial addressing potential therapies for patients with confirmed COVID-19 infection at the time of publishing these treatment recommendations. Therefore, these recommendations are based predominantly on the opinion of experts (level C of recommendation).", "title": "Intensive support recommendations for critically-ill patients with suspected or confirmed COVID-19 infection", "pid": "mddnm7s3", "bm25_score": 215.24093627929688}, {"text": "During the first two decades of the 21st century, there have been three coronavirus infection outbreaks raising global health concerns by severe acute respiratory syndrome coronavirus (SARS-CoV), the Middle East respiratory syndrome coronavirus (MERS-CoV), and the SARS-CoV-2. Although the reported imaging findings of coronavirus infection are variable and nonspecific, the most common initial chest radiograph (CXR) and computed tomography (CT) findings are ground-glass opacities and consolidation with peripheral predominance and eventually spread to involve both lungs as the disease progresses. These findings can be explained by the immune pathogenesis of coronavirus infection causing diffuse alveolar damage. Although it is insensitive in mild or early coronavirus infection, the CXR remains as the first-line and the most commonly used imaging modality. That is because it is rapid and easily accessible and helpful for monitoring patient progress during treatment. CT is more sensitive to detect early parenchymal lung abnormalities and disease progression, and can provide an alternative diagnosis. In this pictorial review, various coronavirus infection cases are presented to provide imaging spectrums of coronavirus infection and present differences in imaging among them or from other viral infections, and to discuss the role of imaging in viral infection outbreaks.", "title": "Imaging findings in coronavirus infections: SARS-CoV, MERS-CoV, and SARS-CoV-2.", "pid": "nxoclojl", "bm25_score": 215.23944091796875}, {"text": "Abstract The current climate is one of uncertainty and immeasurable tragedy for people afflicted by the pandemic of SARS-CoV-2 virus infection. As professionals, we have a duty of care towards all patients especially the vulnerable and those suffering with life-threatening illnesses such as oral cancer. We present a safe & objective triaging method for afflicted with this disease in the prevailing morbid situation.", "title": "Triaging algorithm for Head & Neck oncology follow-up patients in COVID-19 climate", "pid": "qjd31m8l", "bm25_score": 215.23211669921875}, {"text": "BACKGROUND: Novel Coronavirus SARS-CoV-2 pandemic is spreading around the world. At the end of February, the outburst of the pandemic has hit hard on northern Italian's hospitals. As of today, no data have been published regarding the severity of respiratory failure of patients presenting to the Emergency Departments. Moreover, the outcome the patients forced to undergo Continuous Positive Airway Pressure (CPAP) or Non-Invasive Positive Pressure Ventilation (NIPPV) due to lack of Intensive Care resources is unknown. “Papa Giovanni XXIII” hospital (HPG23) of Bergamo is one of the largest hospitals in the Country, with an Emergency Department (ED) managing over 100,000 patients per year. METHODS: This is a retrospective observational study based on chart review of patients presenting to the Emergency Department of HPG23 from 29/02/2020 to 10/03/2020 with a clinical condition highly suspicious for COVID-19 infection. Registration of admission rates, severity of respiratory failure (ARDS classification), need of respiratory support, SARS-CoV-2 PCR test and outcome of patients treated with a ventilatory support were registered on 10th of May 2020. FINDINGS: From 29/02 to 10/03 611 patients with a suspected diagnosis of COVID-19 infection were evaluated in our ED; 320 (52%) met the criteria for hospital admission and 99 (31%) needed to be immediately started on ventilatory support (81% CPAP, 7% NIPPV, 12% Invasive Mechanical Ventilation). Eighty-five (86%) of the 99 patients needing a ventilatory support eventually had SARS-CoV-2 infection confirmed by PCR test on nasal-pharyngeal swab. Their median PO2/FiO2 ratio was 128 (IQR 85–168), with 23 patients (29.5%) classified as severe ARDS. Mortality rate as of 10th of May was 76.5%, ranging from 44.4% within patients <60 years old to 85% within those older than 60 years (p = 0.001). NIPPV/CPAP failure occurred in 91.5% of patients. INTERPRETATION: The population of patients suspected for COVID-19 infection presenting at our ED showed a very high rate of severe respiratory failure, with urgent need of a large amount of intensive care resources. Mortality rates of critically ill patients with confirmed COVID-19 (76.5%) are similar to previously reported studies with similar population. CPAP/NIPPV could be a valid strategy to treat severely hypoxic patients that cannot be intubated in the ED due to lack of intensive care resources. FUNDING: No funds were received for this research project.", "title": "Severity of respiratory failure and outcome of patients needing a ventilatory support in the Emergency Department during Italian novel coronavirus SARS-CoV2 outbreak: Preliminary data on the role of Helmet CPAP and Non-Invasive Positive Pressure Ventilation", "pid": "h6ihp1un", "bm25_score": 215.23129272460938}, {"text": "BACKGROUND: The outbreak of the coronavirus disease 2019 (COVID-19) has globally strained medical resources and caused significant mortality. OBJECTIVE: To develop and validate machine-learning model based on clinical features for severity risk assessment and triage for COVID-19 patients at hospital admission. METHOD: 725 patients were used to train and validate the model including a retrospective cohort of 299 hospitalised COVID-19 patients at Wuhan, China, from December 23, 2019, to February 13, 2020, and five cohorts with 426 patients from eight centers in China, Italy, and Belgium, from February 20, 2020, to March 21, 2020. The main outcome was the onset of severe or critical illness during hospitalisation. Model performances were quantified using the area under the receiver operating characteristic curve (AUC) and metrics derived from the confusion-matrix. RESULTS: The median age was 50.0 years and 137 (45.8%) were men in the retrospective cohort. The median age was 62.0 years and 236 (55.4%) were men in five cohorts. The model was prospectively validated on five cohorts yielding AUCs ranging from 0.84 to 0.89, with accuracies ranging from 74.4% to 87.5%, sensitivities ranging from 75.0% to 96.9%, and specificities ranging from 57.5% to 88.0%, all of which performed better than the pneumonia severity index. The cut-off values of the low, medium, and high-risk probabilities were 0.21 and 0.80. The online-calculators can be found at www.covid19risk.ai. CONCLUSION: The machine-learning model, nomogram, and online-calculator might be useful to access the onset of severe and critical illness among COVID-19 patients and triage at hospital admission.", "title": "Development of a Clinical Decision Support System for Severity Risk Prediction and Triage of COVID-19 Patients at Hospital Admission: an International Multicenter Study", "pid": "ahysay2l", "bm25_score": 215.22877502441406}, {"text": "The SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) was reported in Wuhan, Hubei Province, People's Republic of China, and, subsequently, in other provinces and regions across the People's Republic of China and >212 countries. COVID-19, the disease caused by this coronavirus, was declared a worldwide pandemic by the World Health Organization (WHO). The incidence of patients with fracture who are also positive for COVID-19 is on the rise. The diagnosis and management of such patients can be complicated as their clinical characteristics are heterogeneous. Furthermore, a surgical procedure can be particularly challenging given that the use of high-speed devices results in aerosol generation. In this study, we develop and propose globally applicable guidelines to fill this knowledge gap and we identify and propose the necessary protective strategies for medical personnel in an orthopaedic emergency department and in the inpatient wards. We also introduce diagnostic criteria, surgical complication management, and follow-up strategies for infected patients. These guidelines may be helpful to decrease the infection rate of orthopaedic trauma personnel and to provide diagnosis and treatment therapy for patients with fracture and COVID-19.", "title": "COVID-19 Orthopaedic Safe Care Toolset: Guidelines for the Diagnosis and Management of Patients with Fracture and COVID-19.", "pid": "n1em42tr", "bm25_score": 215.22251892089844}, {"text": "When preparing for the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the coronavirus infection disease (COVID-19) questions arose regarding various aspects concerning the anaesthetist. When reviewing the literature it became obvious that keeping up-to-date with all relevant publications is almost impossible. We searched for and summarised clinically relevant topics that could help making clinical decisions. This is a subjective analysis of literature concerning specific topics raised in our daily practice (e.g., clinical features of COVID-19 patients; ventilation of the critically ill COVID-19 patient; diagnostic of infection with SARS-CoV-2; stability of the virus; Covid-19 in specific patient populations, e.g., paediatrics, immunosuppressed patients, patients with hypertension, diabetes mellitus, kidney or liver disease; co-medication with non-steroidal anti-inflammatory drugs (NSAIDs); antiviral treatment) and we believe that these answers help colleagues in clinical decision-making. With ongoing treatment of severely ill COVID-19 patients other questions will come up. While respective guidelines on these topics will serve clinicians in clinical practice, regularly updating all guidelines concerning COVID-19 will be a necessary, although challenging task in the upcoming weeks and months. All recommendations during the current extremely rapid development of knowledge must be evaluated on a daily basis, as suggestions made today may be out-dated with the new evidence available tomorrow.", "title": "Update for Anaesthetists on Clinical Features of COVID-19 Patients and Relevant Management", "pid": "cfqfchk4", "bm25_score": 215.22024536132812}, {"text": "PURPOSE: The purpose of our research is to evaluate the usefulness of chest X-ray for triaging patients with suspected COVID-19 infection. METHODS: IRB approval was obtained to allow a retrospective review of adult patients who presented to the Emergency Department with a complaint of fever, cough, dyspnea or hypoxia and had a chest X-ray between 12 March 2020 and 26 March 2020. The initial chest X-ray was graded on a scale of 0-3 with grade 0 representing no alveolar opacities, grade 1: < 1/3 alveolar opacities of the lung, Grade 2: 1/3 to 2/3 lung with alveolar opacities and grade 3: > 2/3 alveolar opacities of the lung. Past medical history of diabetes and hypertension, initial oxygen saturation, COVID-19 testing results, intubation, and outcome were also collected. RESULTS: Four hundred ten patient chest X-rays were reviewed. Oxygen saturation and X-ray grade were both significantly associated with the length of stay in hospital, the hazard ratio (HR) of discharge was 1.05 (95% CI [1.01, 1.09], p = 0.017) and 0.61 (95% CI [0.51, 0.73], p < 0.001), respectively. In addition, oxygen saturation and X-ray grade were significant predictors of intubation (odds ratio (OR) of intubation is 0.88 (95% CI [0.81, 0.96], p = 0.004) and 3.69 (95% CI [2.25, 6.07], p < 0.001). CONCLUSIONS: Initial chest X-ray is a useful tool for triaging those subjects who might have poor outcomes with suspected COVID-19 infection and benefit most from hospitalization.", "title": "The role of initial chest X-ray in triaging patients with suspected COVID-19 during the pandemic", "pid": "v2pjvppf", "bm25_score": 215.2193603515625}, {"text": "The coronavirus disease-2019 (COVID-19) pandemic has strained health care resources around the world, causing many institutions to curtail or stop elective procedures. This has resulted in an inability to care for patients with valvular and structural heart disease in a timely fashion, potentially placing these patients at increased risk for adverse cardiovascular complications, including CHF and death. The effective triage of these patients has become challenging in the current environment as clinicians have had to weigh the risk of bringing susceptible patients into the hospital environment during the COVID-19 pandemic against the risk of delaying a needed procedure. In this document, the authors suggest guidelines for how to triage patients in need of structural heart disease interventions and provide a framework for how to decide when it may be appropriate to proceed with intervention despite the ongoing pandemic. In particular, the authors address the triage of patients in need of transcatheter aortic valve replacement and percutaneous mitral valve repair. The authors also address procedural issues and considerations for the function of structural heart disease teams during the COVID-19 pandemic.", "title": "Triage Considerations for Patients Referred for Structural Heart Disease Intervention During the COVID-19 Pandemic: An ACC/SCAI Position Statement", "pid": "hzi8zuyt", "bm25_score": 215.21726989746094}, {"text": "Aims To explore the epidemiological and clinical features of 2019 novel coronavirus(2019-nCoV)-infected patients with cardiac injury . Methods and results Data were collected from patients medical records, and we defined cardiac injury according to cardiac biomarker troponin I level > 0.03>ug/L. Among the 291 patients, 15 (5.2%) showed evidence of cardiac injury. Of 16 hospitalized patients with cardiac injury, the median age was 62 years, and 11/15 (73.3%) were men. Underlying cardiovascular diseases in some patients were hypertension (n=7, 46.6%), coronary heart disease (n=3, 20%) and diabetes (n=3, 20%). The most common symptoms at illness onset in patients with cardiac injury were fever (n=11, 73.3%), cough (n=7, 46.7%), headache or fatigue (n=5, 33.3%) and dyspnoea (n=4, 26.6%). These patients had higher systolic pressures, and lower lymphocyte counts and platelet counts, compared with patients without cardiac injury, respectively. Bilateral infiltrates on chest X-ray and elevated C-reactive protein occurred in all patients with cardiac injury. Compared with patients without cardiac injury, patients with cardiac injury were more likely to develop acute respiratory distress syndrome (73.3%), and receive mechanical ventilation (53.4%), continuous renal replacement therapy (33.3%), extracorporeal membrane oxygenation (26.7%) and vasopressor therapy (26.7%) and be admitted to the intensive care unit (73.3%). One patient died during the study. Conclusion Cardiac injury is a common condition among patients infected with 2019-nCoV.Compared with patients without cardiac injury, the clinical outcomes of patients with cardiac injury are relatively worse. Keywords: 2019-nCoV, Cardiac injury, Clinical features", "title": "Clinical features and outcomes of 2019 novel coronavirus-infected patients with cardiac injury", "pid": "qbxx6yae", "bm25_score": 215.21470642089844}, {"text": "Since December 2019, the corona virus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (2019-nCoV) has been reported in Wuhan, Hubei Province. Almost 70% of patients susceptible to 2019-nCoV are over age of 50 years, with extremely large proportion of critical illness and death of the elderly patients. Meanwhile, the elderly patients are at high risk of osteoporotic fractures especially osteoporotic vertebral compression fractures (OVCF). During the prevention and control of COVID-19 epidemic, orthopedists are confronted with the following difficulties including how to screen and protect OVCF patients, how to accurately diagnose and assess the condition of OVCF patients with suspected or confirmed COVID-19, and how to develop reasonable treatment plans and comprehensive protective measures in emergency and outpatient clinics. In order to standardize the diagnosis and treatment of patients with OVCF diagnosed with COVID-19, the authors jointly develop this expert consensus. The consensus systematically recommends the standardized emergency and outpatient screening and confirmation procedures for OVCF patients with suspected or confirmed COVID-19 and protective measures for emergency and outpatient clinics. Moreover, the consensus describes the grading and classification of OVCF patients diagnosed with COVID-19 according to the severity of illness and recommends different treatment plans and corresponding protective measures based on the different types and epidemic prevention and control requirements.", "title": "Consensus on standardized diagnosis and treatment for osteoporotic vertebral compression fracture patients during epidemic of corona virus disease 2019/ 中华创伤杂志", "pid": "7jjpnfay", "bm25_score": 215.21417236328125}, {"text": "BACKGROUND The rapid spread of coronavirus disease (COVID-19) is affecting many countries. While healthcare systems need to cope with the need to treat a large number of people with different degrees of respiratory failure, actions to preserve aliquots of the healthcare system to guarantee treatment to patients are mandatory. METHODS In order to protect the Fondazione IRCCS-Istituto Nazionale dei Tumori di Milano from the spread of COVID-19, a number of to-hospital and within-hospital filters were applied. Among others, a triage process to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positivity in patients with cancer was developed consisting of high-resolution low-dose computed tomography (CT) scan followed by reverse transcription polymerase chain reaction (RT-PCR) detection of SARS-CoV-2 in nose-throat swabs whenever CT was suggestive of lung infection. To serve symptomatic patients who were already admitted to the hospital or in need of hospitalization while waiting for RT-PCR laboratory confirmation of infection, a COVID-19 surveillance zone was set up. RESULTS A total of 301 patients were screened between March 6 and April 3, 2020. Of these, 47 were hospitalized, 53 needed a differential diagnosis to continue with their cancer treatment, and 201 were about to undergo surgery. RT-PCR was positive in 13 of 40 hospitalized patients (32%), 14 of 52 day hospital patients (27%), and 6 of 201 surgical patients (3%). CONCLUSION Applying filters to protect our comprehensive cancer center from COVID-19 spread contributed to guaranteeing cancer care during the COVID-19 crisis in Milan. A surveillance area and surgical triage allowed us to protect the hospital from as many as 33 patients infected with SARS-CoV-2.", "title": "Response of a comprehensive cancer center to the COVID-19 pandemic: the experience of the Fondazione IRCCS-Istituto Nazionale dei Tumori di Milano.", "pid": "r4r1a6fd", "bm25_score": 215.21185302734375}, {"text": "Abstract Background The World Health Organization has highlighted the need for improved surveillance and understanding of the health burden imposed by non-influenza RNA respiratory viruses. Human coronaviruses (CoVs) are a major cause of respiratory and gastrointestinal tract infections with associated morbidity and mortality. Objectives The objective of our study was to characterize the epidemiology of CoVs in our tertiary care centre, and identify clinical correlates of disease severity. Study design A cross-sectional study was performed of 226 patients admitted with confirmed CoV respiratory tract infection between 2010 and 2016. Variables consistent with a severe disease burden were evaluated including symptoms, length of stay, intensive care unit (ICU) admission and mortality. Results CoVs represented 11.3% of all positive respiratory virus samples and OC43 was the most commonly identified CoV. The majority of infections were community-associated while 21.6% were considered nosocomial. The average length of stay was 11.8 days with 17.3% of patients requiring ICU admission and an all-cause mortality of 7%. In a multivariate model, female gender and smoking were associated with increased likelihood of admission to ICU or death. Conclusion This study highlights the significant burden of CoVs and justifies the need for surveillance in the acute care setting.", "title": "Severity of coronavirus respiratory tract infections in adults admitted to acute care in Toronto, Ontario", "pid": "8li6xhbu", "bm25_score": 215.21165466308594}, {"text": "Worst case scenarios for pandemic influenza planning in the US involve over 700,000 patients requiring mechanical ventilation. UK planning predicts a 231% occupancy of current level 3 (intensive care unit) bed capacity. Critical care planners need to recognise that mortality is likely to be high and the risk to healthcare workers significant. Contingency planning should, therefore, be multi-faceted, involving a robust health command structure, the facility to expand critical care provision in terms of space, equipment and staff and cohorting of affected patients in the early stages. It should also be recognised that despite this expansion of critical care, demand will exceed supply and a process for triage needs to be developed that is valid, reproducible, transparent and consistent with distributive justice. We advocate the development and validation of physiological scores for use as a triage tool, coupled with candid public discussion of the process.", "title": "Clinical review: Mass casualty triage – pandemic influenza and critical care", "pid": "mzn448zk", "bm25_score": 215.20814514160156}, {"text": "Coronavirus outbreak has affected thousands of people in at least 186 countries which has affected the cancer care delivery system apart from affecting the overall health system. Cancer patients are more susceptible to coronavirus infection than individuals without cancer as they are in an immunosuppressive state because of the malignancy and anticancer treatment. Oncologists should be more attentive to detect coronavirus infection early, as any type of advanced cancer is at much higher risk for unfavorable outcomes. Oncology communities must ensure that cancer patients should spend more time at home and less time out in the community. Oncologists and other health care professionals involved in cancer care have a critical opportunity to communicate to their patients to pass on right information regarding practice modifications in view of COVID-19 outbreaks. Countries must isolate, test, treat and trace to control the coronavirus pandemic. There is a paucity of information on novel coronavirus infection and its impact on cancer patients and cancer care providers. To date, there is no scientific guideline regarding management of cancer patients in a background of coronavirus outbreak..", "title": "Cancer Care Delivery Challenges Amidst Coronavirus Disease - 19 (COVID-19) Outbreak: Specific Precautions for Cancer Patients and Cancer Care Providers to Prevent Spread.", "pid": "0sxlhww0", "bm25_score": 215.20623779296875}, {"text": "IMPORTANCE The outbreak of the coronavirus disease 2019 (COVID-19) has globally strained medical resources and caused significant mortality for severely and critically ill patients. However, the availability of validated nomograms and the machine-learning model to predict severity risk and triage of affected patients is limited. OBJECTIVE To develop and validate nomograms and machine-learning models for severity risk assessment and triage for COVID-19 patients at hospital admission. DESIGN, SETTING, AND PARTICIPANTS A retrospective cohort of 299 consecutively hospitalized COVID-19 patients at The Central Hospital of Wuhan, China, from December 23, 2019, to February 13, 2020, was used to train and validate the models. Six cohorts with 426 patients from eight centers in China, Italy, and Belgium, from February 20, 2020, to March 21, 2020, were used to prospectively validate the models. MAIN OUTCOME AND MEASURES The main outcome was the onset of severe or critical illness during hospitalization. Model performances were quantified using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. RESULTS Of the 299 hospitalized COVID-19 patients in the retrospective cohort, the median age was 50 years ((interquartile range, 35.5-63.0; range, 20-94 years) and 137 (45.8%) were men. Of the 426 hospitalized COVID-19 patients in the prospective cohorts, the median age was 62.0 years ((interquartile range, 50.0-72.0; range, 19-94 years) and 236 (55.4%) were men. The model was prospectively validated on six cohorts yielding AUCs ranging from 0.816 to 0.976, with accuracies ranging from 70.8% to 93.8%, sensitivities ranging from 83.7% to 100%, and specificities ranging from 41.0% to 95.7%. The cut-off values of the low, medium, and high-risk probabilities were 0.072 and 0.244. The developed online calculators can be found at www.predict19risk.ai. CONCLUSION AND RELEVANCE The machine learning models, nomograms, and online calculators might be useful for the prediction of onset of severe and critical illness among COVID-19 patients and triage at hospital admission. Further prospective research and clinical feedback are necessary to evaluate the clinical usefulness of this model and to determine whether these models can help optimize medical resources and reduce mortality rates compared with current clinical practices.", "title": "Development of a Clinical Decision Support System for Severity Risk Prediction and Triage of COVID-19 Patients at Hospital Admission: an International Multicenter Study", "pid": "blqpb9a1", "bm25_score": 215.20132446289062}, {"text": "In December 2019, several patients with pneumonia of an unknown cause were detected in Wuhan, China. On 7 January 2020, the causal organism was identified as a new coronavirus, later named as the 2019 novel coronavirus (2019-nCoV). Genome sequencing found the genetic sequence of 2019-nCoV homologous to that of severe acute respiratory syndrome-associated coronavirus. As of 29 January 2020, the virus had been diagnosed in more than 7000 patients in China and 77 patients in other countries. It is reported that both symptomatic and asymptomatic patients with 2019-nCoV can play a role in disease transmission via airborne and contact. This finding has caused a great concern about the prevention of illness spread. The clinical features of the infection are not specific and are often indistinguishable from those of other respiratory infections, making it difficult to diagnose. Given that the virus has a strong ability to spread between individuals, it is of top priority to identify potential or suspected patients as soon as possible-or the virus may cause a serious pandemic. Therefore, a precision medicine approach to managing this disease is urgently needed for detecting and controlling the spread of the virus. In this article, we present such an approach to managing 2019-nCoV-related pneumonia based on the unique traits of the virus recently revealed and on our experience with coronaviruses at West China Hospital in Chengdu, China.", "title": "A precision medicine approach to managing 2019 novel coronavirus pneumonia", "pid": "68nyjf64", "bm25_score": 215.20108032226562}, {"text": "The outbreak of the new Coronavirus disease, COVID-19, has been involved in 77,262 cases in China as well as in 27 other countries as of February 24, 2020. Because the virus is novel to human beings, and there is no vaccine yet available, every individual is susceptible and can become infected. Healthcare workers are at high risk, and unfortunately, more than 3,000 healthcare workers in China have been infected. Anesthesiologists are among healthcare workers who are at an even higher risk of becoming infected because of their close contact with infected patients and high potential of exposure to respiratory droplets or aerosol from their patients’ airways. In order to provide healthcare workers with updated recommendations on the management of patients in the perioperative setting as well as for emergency airway management outside of the operating room, the two largest anesthesia societies, the Chinese Society of Anesthesiology (CSA) and the Chinese Association of Anesthesiologists (CAA) have formed a task force to produce the recommendations. The task force hopes to help healthcare workers, particularly anesthesiologists, optimize the care of their patients and protect patients, healthcare workers, and the public from becoming infected. The recommendations were created mainly based on the practice and experience of anesthesiologists who provide care to patients in China. Therefore, adoption of these recommendations outside of China must be done with caution, and the local environment, culture, uniqueness of the healthcare system, and patients’ needs should be considered. The task force will continuously update the recommendations and incorporate new information in future versions.", "title": "Perioperative Management of Patients Infected with the Novel Coronavirus: Recommendation from the Joint Task Force of the Chinese Society of Anesthesiology and the Chinese Association of Anesthesiologists", "pid": "3vwi5myc", "bm25_score": 215.1942901611328}, {"text": "The SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) was reported in Wuhan, Hubei Province, People's Republic of China, and, subsequently, in other provinces and regions across the People's Republic of China and >212 countries. COVID-19, the disease caused by this coronavirus, was declared a worldwide pandemic by the World Health Organization (WHO). The incidence of patients with fracture who are also positive for COVID-19 is on the rise. The diagnosis and management of such patients can be complicated as their clinical characteristics are heterogeneous. Furthermore, a surgical procedure can be particularly challenging given that the use of high-speed devices results in aerosol generation. In this study, we develop and propose globally applicable guidelines to fill this knowledge gap and we identify and propose the necessary protective strategies for medical personnel in an orthopaedic emergency department and in the inpatient wards. We also introduce diagnostic criteria, surgical complication management, and follow-up strategies for infected patients. These guidelines may be helpful to decrease the infection rate of orthopaedic trauma personnel and to provide diagnosis and treatment therapy for patients with fracture and COVID-19.", "title": "COVID-19 Orthopaedic Safe Care Toolset: Guidelines for the Diagnosis and Management of Patients with Fracture and COVID-19", "pid": "mtizdkm0", "bm25_score": 215.194091796875}, {"text": "In the midst of the severe acute respiratory syndrome coronavirus 2 pandemic, which causes coronavirus disease 2019, there is a recognized need to expand critical care services and beds beyond the traditional boundaries. There is considerable concern that widespread infection will result in a surge of critically ill patients that will overwhelm our present adult ICU capacity. In this setting, one proposal to add “surge capacity” has been the use of PICU beds and physicians to care for these critically ill adults. DESIGN: Narrative review/perspective. SETTING: Not applicable. PATIENTS: Not applicable. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The virus’s high infectivity and prolonged asymptomatic shedding have resulted in an exponential growth in the number of cases in the United States within the past weeks with many (up to 6%) developing acute respiratory distress syndrome mandating critical care services. Coronavirus disease 2019 critical illness appears to be primarily occurring in adults. Although pediatric intensivists are well versed in the care of acute respiratory distress syndrome from viral pneumonia, the care of differing aged adult populations presents some unique challenges. In this statement, a team of adult and pediatric-trained critical care physicians provides guidance on common “adult” issues that may be encountered in the care of these patients and how they can best be managed in a PICU. CONCLUSIONS: This concise scientific statement includes references to the most recent and relevant guidelines and clinical trials that shape management decisions. The intention is to assist PICUs and intensivists in rapidly preparing for care of adult coronavirus disease 2019 patients should the need arise.", "title": "Caring for Critically Ill Adults With Coronavirus Disease 2019 in a PICU: Recommendations by Dual Trained Intensivists*", "pid": "pep4opiq", "bm25_score": 215.19285583496094}, {"text": "PURPOSE: The purpose of our research is to evaluate the usefulness of chest X-ray for triaging patients with suspected COVID-19 infection. METHODS: IRB approval was obtained to allow a retrospective review of adult patients who presented to the Emergency Department with a complaint of fever, cough, dyspnea or hypoxia and had a chest X-ray between 12 March 2020 and 26 March 2020. The initial chest X-ray was graded on a scale of 0–3 with grade 0 representing no alveolar opacities, grade 1: < 1/3 alveolar opacities of the lung, Grade 2: 1/3 to 2/3 lung with alveolar opacities and grade 3: > 2/3 alveolar opacities of the lung. Past medical history of diabetes and hypertension, initial oxygen saturation, COVID-19 testing results, intubation, and outcome were also collected. RESULTS: Four hundred ten patient chest X-rays were reviewed. Oxygen saturation and X-ray grade were both significantly associated with the length of stay in hospital, the hazard ratio (HR) of discharge was 1.05 (95% CI [1.01, 1.09], p = 0.017) and 0.61 (95% CI [0.51, 0.73], p < 0.001), respectively. In addition, oxygen saturation and X-ray grade were significant predictors of intubation (odds ratio (OR) of intubation is 0.88 (95% CI [0.81, 0.96], p = 0.004) and 3.69 (95% CI [2.25, 6.07], p < 0.001). CONCLUSIONS: Initial chest X-ray is a useful tool for triaging those subjects who might have poor outcomes with suspected COVID-19 infection and benefit most from hospitalization.", "title": "The role of initial chest X-ray in triaging patients with suspected COVID-19 during the pandemic", "pid": "t3zota2s", "bm25_score": 215.19082641601562}, {"text": "Abstract On March 11, 2020, the Director-General of the World Health Organization (WHO) declared the disease caused by SARS-CoV-2 (COVID-19) as a pandemic. The spread and evolution of the pandemic is overwhelming the healthcare systems of dozens of countries and has led to a myriad of opinion papers, contingency plans, case series and emerging trials. Covering all this literature is complex. Briefly and synthetically, in line with the previous recommendations of the Working Groups, the Spanish Society of Intensive, Critical Medicine and Coronary Units (SEMICYUC) has prepared this series of basic recommendations for patient care in the context of the pandemic.", "title": "Recommendations of the Working Groups from the Spanish Society of Intensive and Critical Care Medicine and Coronary Units (SEMICYUC) for the management of adult critically ill patients in the coronavirus disease (COVID-19)", "pid": "gg6ws986", "bm25_score": 215.18626403808594}, {"text": "Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and wildlife. A total of six species have been identified to cause disease in humans. They are known to infect the neurological, respiratory, enteric, and hepatic systems. The past few decades have seen endemic outbreaks in the form of Middle East respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome related coronavirus (SARS-CoV). Yet again, we see the emergence of another outbreak due to a new strain called the SARS-CoV-2 virus. The most recent outbreak initially presented as pneumonia of unknown etiology in a cluster of patients in Wuhan, China. The epicenter of infection was linked to seafood and exotic animal wholesale markets in the city. SARS-CoV-2 is highly contagious and has resulted in a rapid pandemic of COVID-19. As the number of cases continues to rise, it is clear that these viruses pose a threat to public health. This review will introduce a general overview of coronavirus and describe the clinical features, evaluation, and treatment of COVID-19 patients. It will also provide a means to raise awareness among primary and secondary healthcare providers during the current pandemic. Furthermore, our review focuses on the most up-to-date clinical information for the effective management, prevention, and counseling of patients worldwide.", "title": "Coronavirus (COVID-19): A Review of Clinical Features, Diagnosis, and Treatment", "pid": "aoz3j9rl", "bm25_score": 215.18521118164062}, {"text": "The novel coronavirus (nCoV-2019) outbreak in Wuhan, China has spread rapidly nationwide, with some cases occurring in other parts of the world. Although most patients present with mild febrile illness with patchy pulmonary inflammation, a significant portion develop severe acute respiratory distress syndrome (ARDS), with a current case fatality of 2.3-3%. Diagnosis is based on clinical history and laboratory and chest radiographic findings, but confirmation currently relies on nucleic acid-based assays. The latter are playing an important role in facilitating patient isolation, treatment and assessment of infectious activities. However, due to their limited capacity to handle an epidemic of the current scale and insufficient supply of assay kits, only a portion of suspected cases can be tested, leading to incompleteness and inaccuracy in updating new cases, as well as delayed diagnosis. Furthermore, there has not been enough time to assess specificity and sensitivity. Conventional serological assays, such as enzyme-linked immunoassay (ELISA) for specific IgM and IgG antibodies, should offer a high-throughput alternative, which allows for uniform tests for all suspected patients, and can facilitate more complete identification of infected cases and avoidance of unnecessary cross infection among unselected patients. This article is protected by copyright. All rights reserved.", "title": "Evolving status of the 2019 novel coronavirus infection: Proposal of conventional serologic assays for disease diagnosis and infection monitoring", "pid": "ewcv8m06", "bm25_score": 215.17367553710938}, {"text": "BACKGROUND Pandemics and disasters can result in large numbers of critically ill or injured patients who may overwhelm available resources despite implementing surge-response strategies. If this occurs, critical care triage, which includes both prioritizing patients for care and rationing scarce resources, will be required. The suggestions in this chapter are important for all who are involved in large-scale pandemics or disasters with multiple critically ill or injured patients, including front-line clinicians, hospital administrators, and public health or government officials. METHODS The Triage topic panel reviewed previous task force suggestions and the literature to identify 17 key questions for which specific literature searches were then conducted to identify studies upon which evidence-based recommendations could be made. No studies of sufficient quality were identified. Therefore, the panel developed expert opinion-based suggestions using a modified Delphi process. Suggestions from the previous task force that were not being updated were also included for validation by the expert panel. RESULTS The suggestions from the task force outline the key principles upon which critical care triage should be based as well as a path for the development of the plans, processes, and infrastructure required. This article provides 11 suggestions regarding the principles upon which critical care triage should be based and policies to guide critical care triage. CONCLUSIONS Ethical and efficient critical care triage is a complex process that requires significant planning and preparation. At present, the prognostic tools required to produce an effective decision support system (triage protocol) as well as the infrastructure, processes, legal protections, and training are largely lacking in most jurisdictions. Therefore, critical care triage should be a last resort after mass critical care surge strategies.", "title": "Triage Care of the Critically Ill and Injured During Pandemics and Disasters: CHEST Consensus Statement", "pid": "io7ozfpi", "bm25_score": 215.17318725585938}, {"text": "On 24 October 2012, a patient with acute respiratory distress syndrome of unknown origin and symptom onset on 5 October was transferred from Qatar to a specialist lung clinic in Germany. Late diagnosis on 20 November of an infection with the novel Coronavirus (NCoV) resulted in potential exposure of a considerable number of healthcare workers. Using a questionnaire we asked 123 identified contacts (120 hospital and three out-of-hospital contacts) about exposure to the patient. Eighty-five contacts provided blood for a serological test using a two-stage approach with an initial immunofluorescence assay as screening test, followed by recombinant immunofluorescence assays and a NCoV-specific serum neutralisation test. Of 123 identified contacts nine had performed aerosol-generating procedures within the third or fourth week of illness, using personal protective equipment rarely or never, and two of these developed acute respiratory illness. Serology was negative for all nine. Further 76 hospital contacts also tested negative, including two sera initially reactive in the screening test. The contact investigation ruled out transmission to contacts after illness day 20. Our two-stage approach for serological testing may be used as a template for similar situations.", "title": "Contact investigation of a case of human novel coronavirus infection treated in a German hospital, October-November 2012.", "pid": "t6brpjsy", "bm25_score": 215.17166137695312}, {"text": "OBJECTIVE: In the midst of the severe acute respiratory syndrome coronavirus 2 pandemic, which causes coronavirus disease 2019, there is a recognized need to expand critical care services and beds beyond the traditional boundaries. There is considerable concern that widespread infection will result in a surge of critically ill patients that will overwhelm our present adult ICU capacity. In this setting, one proposal to add \"surge capacity\" has been the use of PICU beds and physicians to care for these critically ill adults. DESIGN: Narrative review/perspective. SETTING: Not applicable. PATIENTS: Not applicable. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The virus's high infectivity and prolonged asymptomatic shedding have resulted in an exponential growth in the number of cases in the United States within the past weeks with many (up to 6%) developing acute respiratory distress syndrome mandating critical care services. Coronavirus disease 2019 critical illness appears to be primarily occurring in adults. Although pediatric intensivists are well versed in the care of acute respiratory distress syndrome from viral pneumonia, the care of differing aged adult populations presents some unique challenges. In this statement, a team of adult and pediatric-trained critical care physicians provides guidance on common \"adult\" issues that may be encountered in the care of these patients and how they can best be managed in a PICU. CONCLUSIONS: This concise scientific statement includes references to the most recent and relevant guidelines and clinical trials that shape management decisions. The intention is to assist PICUs and intensivists in rapidly preparing for care of adult coronavirus disease 2019 patients should the need arise.", "title": "Caring for Critically Ill Adults With Coronavirus Disease 2019 in a PICU: Recommendations by Dual Trained Intensivists", "pid": "fije7qyo", "bm25_score": 215.16375732421875}, {"text": "The novel coronavirus (CoV) pandemic is a serious threat for patients with cancer, who have an immunocompromised status and are considered at high risk of infections. Data on the novel CoV respiratory disease (coronavirus disease 2019 [COVID-19]) in patients with cancer are still limited. Unlike other common viruses, CoVs have not been shown to cause a more severe disease in immunocompromised subjects. Along with direct viral pathogenicity, in some individuals, CoV infection triggers an uncontrolled aberrant inflammatory response, leading to lung tissue damage. In patients with cancer treated with immunotherapy (e.g. immune checkpoint inhibitors), COVID-19 may therefore represent a serious threat. After a thorough review of the literature on CoV pathogenesis and cancer, we selected several shared features to define which patients can be considered at higher risk of COVID-19. We combined these clinical and laboratory variables, with the aim of developing a score to weight the risk of COVID-19 in patients with cancer.", "title": "Developing a risk assessment score for patients with cancer during the coronavirus disease 2019 pandemic", "pid": "ms2edvps", "bm25_score": 215.1570587158203}, {"text": "In December 2019, a novel coronavirus causing severe acute respiratory disease occurred in Wuhan, China. It is an emerging infectious disease with widespread and rapid infectiousness. The World Health Organization declared the coronavirus outbreak to be a public health emergency of international concern on 31 January 2020. Severe COVID-19 patients should be managed and treated in a critical care unit. Performing a chest X-ray/CT can judge the severity of the disease. The management of COVID-19 patients includes epidemiological risk and patient isolation; treatment entails general supportive care, respiratory support, symptomatic treatment, nutritional support, psychological intervention, etc. The prognosis of the patients depends upon the severity of the disease, the patient's age, the underlying diseases of the patients, and the patient's overall medical condition. The management of COVID-19 should focus on early diagnosis, immediate isolation, general and optimized supportive care, and infection prevention and control.", "title": "The management of coronavirus disease 2019 (COVID-19)", "pid": "nkkvumc0", "bm25_score": 215.1560821533203}]}
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hospitals are essential for COVID-19 contention.", "pid": "1fo24dq8", "bm25_score": 216.9678497314453}, {"text": "", "title": "Quarantine hospitals are essential for COVID-19 contention", "pid": "yo2zancp", "bm25_score": 216.72769165039062}, {"text": "Because nosocomial and zoonotic diseases are inherent and ever-present risks in veterinary hospitals, proactive policies should be in place to reduce the risk of sporadic cases and outbreaks. Policies should ideally be put in place before disease issues arise, and policies should be effectively conveyed to all relevant personnel. Written policies are required for practical and liability reasons and should be reviewed regularly. Although no infection control program can eliminate disease concerns, proper implementation of barrier precautions and isolation can reduce the exposure of hospitalized animals and hospital personnel to infectious agents. Appropriate personal hygiene, particularly hand hygiene, can assist in the prevention of disease transmission when pathogens bypass barriers and are able to contact personnel. Veterinary hospitals have moral, professional, and legal requirements to provide a safe workplace and to reduce the risks to hospitalized patients. Based on experience in the human medical field and on the continual emergence of new infectious diseases, infection control challenges can only be expected to increase in the future. Regular reassessment of protocols based on ongoing research and clinical experiences is required.", "title": "Barrier precautions, isolation protocols, and personal hygiene in veterinary hospitals", "pid": "2el9tx9v", "bm25_score": 216.7021026611328}, {"text": "BACKGROUND: Severe acute respiratory syndrome (SARS) was the first major novel infectious disease to hit the international community in the 21st century. While SARS was sweeping over almost 30 countries, most hospitals in Taiwan instituted mandatory quarantine measures, one of the most effective public health strategies for preventing disease transmission. We explored the anti-SARS quarantine experience of patients in a hospital-based fever screening station. METHODS: We conducted a phenomenologic, qualitative study using semistructured telephone interviews during the SARS outbreak in Taiwan. Seventeen patients with fever who were quarantined in the fever screening station of a hospital emergency department for at least 2 hours were recruited into this study. RESULTS: Data analysis using Collaizi's 9 steps revealed 2 categories—external burden and internal struggle—and 6 themes regarding patients' quarantine experience. External burden included 3 themes: (1) bearing the uncomfortable surroundings, (2) facing discrimination, and (3) lacking in-person family support. Internal struggle consisted of 3 themes: (1) struggle with being quarantined, (2) struggle with emotional turmoil, and (3) struggle with possible SARS diagnosis. CONCLUSION: These results will contribute to sensitizing health care professionals to empathize with quarantined persons while providing quality quarantine care and other infection control measures.", "title": "Lessons learned from the anti-SARS quarantine experience in a hospital-based fever screening station in Taiwan", "pid": "8tccbvxh", "bm25_score": 216.5626983642578}, {"text": "Responses to public health emergencies can entail difficult decisions about restricting individual liberties to prevent the spread of disease. The quintessential example is quarantine. While isolating sick patients tends not to provoke much concern, quarantine of healthy people who only might be infected often is controversial. In fact, as the experience with severe acute respiratory syndrome (SARS) shows, the vast majority of those placed under quarantine typically don't become ill. Efforts to enforce involuntary quarantine through military or police powers also can backfire, stoking both panic and disease spread. Yet quarantine is part of a limited arsenal of options when effective treatment or prophylaxis is not available, and some evidence suggests it can be effective, especially when it is voluntary, home-based and accompanied by extensive outreach, communication and education efforts. Even assuming that quarantine is medically effective, however, it still must be ethically justified because it creates harms for many of those affected. Moreover, ethical principles of reciprocity, transparency, non-discrimination and accountability should guide any implementation of quarantine.", "title": "Ethics and public health emergencies: restrictions on liberty.", "pid": "3rtx6fo3", "bm25_score": 216.20855712890625}, {"text": "Preparing for mass casualty incidents is essential to maximizing community resilience. Many US-based organizations and regions have developed stockpiles of medications, supplies, and equipment for mass casualty incident preparedness. The Centers for Disease Control and Prevention (CDC) assess and manage federally stockpiled materials, but hospitals, healthcare systems, and regional organizations are responsible for maintaining locally owned caches. The CDC has protocols for assessing and managing the Strategic National Stockpile, but no such guidance exists for local or geographical/regional stockpiles. This article outlines best practices and recommendations identified in the literature related to maintaining and sustaining a local or regional stockpile. Recommendations are provided on the timing and procedures for assessing, inventorying, storing, managing, tracking, and deploying materials stockpiled on site, in a trailer, or in a warehouse. In addition, alternative approaches for maintaining a local or regional cache, such as vendor- or user-managed inventory methods, are addressed. Management of local or regional caches requires an investment in infrastructure and training but is necessary to ensure the integrity of stockpiled medication and supplies and to enable rapid and appropriate activation during a mass casualty incident. Hospitals, healthcare systems, businesses, academic institutions, public health agencies, organizations, and regions can use the recommendations here to develop protocols or policies to properly manage their existing stockpiles, which should minimize costs related to damaged supplies.", "title": "Best Practices for Healthcare Facility and Regional Stockpile Maintenance and Sustainment: A Literature Review.", "pid": "e4sshkgk", "bm25_score": 216.1886444091797}, {"text": "A 1-day table-top exercise in San Diego, California, in December 2004 emphasized voluntary compliance with home quarantine to control an emerging infectious disease outbreak. The exercise heightened local civilian-military collaboration in public health emergency management. Addressing concerns about lost income by residents in quarantine was particularly challenging.", "title": "Quarantine Stressing Voluntary Compliance", "pid": "bu617h9z", "bm25_score": 216.14280700683594}, {"text": "Summary A report by the Hong Kong government noted that hospital infection control standards were inadequate, requiring audit, development and implementation. In addition, hospital staff needed training in infection control measures. We investigated infection control practices among 162 hospital health workers (109 nurses, 45 doctors and 8 therapists) and 44 support workers in one acute hospital and two rehabilitation hospitals using a non-blinded, observational design. We examined compliance with isolation precautions and infection control guidelines, including proper wearing of a mask, goggles/face shield, or gown; handling patient care equipment, linen, and laundry; routine and terminal cleaning; and terminal cleaning of an isolation room. One major breakdown in compliance was use of sleeveless disposable plastic aprons instead of long-sleeved gowns during procedures likely to generate splashes or sprays of blood and body fluids. In more than half of the observed episodes, participants failed to disinfect medical devices, such as stethoscopes, before re-use. Thorough cleansing of commodes between patients was also lacking. Overall compliance with local and international infection control guidelines was satisfactory, but several aspects required improvement.", "title": "Infection control practices among hospital health and support workers in Hong Kong", "pid": "c0c4rjfa", "bm25_score": 215.9824676513672}, {"text": "Hospital visitation restrictions have been widely implemented during the coronavirus disease 2019 pandemic as a means of decreasing the transmission of coronavirus. While decreasing transmission is an important goal, it is not the only goal that quality healthcare must aim to achieve. Severely restricted visitation policies undermine our ability to provide humane, family-centered care, particularly during critical illness and at the end of life. The enforcement of these policies consequently increases the risk of moral distress and injury for providers. Using our experience in a PICU, we survey the shortcomings of current visitation restrictions. We argue that hospital visitation restrictions can be implemented in ways that are nonmaleficent, but this requires unwavering acknowledgment of the value of social and familial support during illness and death. We advocate that visitation restriction policies be implemented by independent, medically knowledgeable decision-making bodies, with the informed participation of patients and their families.", "title": "Paved With Good Intentions: Hospital Visitation Restrictions in the Age of Coronavirus Disease 2019", "pid": "bp30zius", "bm25_score": 215.8935089111328}, {"text": "The outbreak of COVID-19 epidemic in December 2019 has highlighted issues with hospital biosafety capacitation in the People’s Republic of China, although the epidemic has been controlled now. This study examined the primary issues, including an absence of hospital emergency system, inadequate management and control of nosocomial infection, limited hospital laboratory capacity, and poor hospital admission capacity. Accordingly, the study put forward the following countermeasures and suggestions for hospitals to deal with future biosecurity events, such as a major epidemic: first, there is a need to build biosecurity management systems and emergency response mechanisms in hospitals; second, the investment and guarantee mechanisms for hospital biosecurity construction should be improved; third, the capacity building of biosecurity incident treatment needs attention in general hospitals; and fourth, comprehensive plans need to be developed for the integrated construction of medical treatment and prevention facilities through disease-control systems.", "title": "Hospital biosecurity capacitation: Analysis and recommendations from the prevention and control of COVID-19", "pid": "ohw0chbg", "bm25_score": 215.82077026367188}, {"text": "Coronavirus becomes officially a global pandemic due to the speed spreading off in various countries. An increasing number of infected with this disease causes the Inability problem to fully care in hospitals and afflict many doctors and nurses inside the hospitals. This paper proposes a smart health system that monitors the patients holding the Coronavirus remotely. Due to protect the lives of the health services members (like physicians and nurses) from infection. This smart system observes the people with this disease based on putting many sensors to record many features of their patients in every second. These parameters include measuring the patient's temperature, respiratory rate, pulse rate, blood pressure, and time. The proposed system saves lives and improves making decisions in dangerous cases. It proposes using artificial intelligence and Internet-of-things to make remotely quarantine and develop decisions in various situations. It provides monitoring patients remotely and guarantees giving patients medicines and getting complete health care without anyone getting sick with this disease. It targets two people's slides the most serious medical conditions and infection and the lowest serious medical conditions in their houses. Observing in hospitals for the most serious medical cases that cause infection in thousands of healthcare members so there is a big need to uses it. Other less serious patients slide, this system enables physicians to monitor patients and get the healthcare from patient's houses to save places for the critical cases in hospitals.", "title": "E-Quarantine: A Smart Health System for Monitoring Coronavirus Patients for Remotely Quarantine", "pid": "ql1tthyr", "bm25_score": 215.80108642578125}, {"text": "Psychiatric hospitals play an important role in supporting patients with mental illness to relieve symptoms and improve functioning in a physically and psychologically safe environment. However, these hospitals are also vulnerable to emerging infectious diseases. In early 2020, a psychiatric hospital and a psychiatric unit were reported to have nosocomial coronavirus disease 2019 (COVID-19) infection. A large number of patients and staff were severely impacted. This type of nosocomial infection threatens patient safety and quality of care. By learning from previous experiences of severe acute respiratory syndrome (SARS) and previous studies, psychiatric hospitals can provide safeguards to prevent nosocomial infection among patients and staff during an epidemic or biological disaster. These strategies include a series of actions such as following national guidelines for infection control, reserving adequate support for disinfection equipment, providing relevant and sufficient pro-service and in-service education and training, establishing regular surveillance of hand hygiene habits, proper communication and health education, and providing opportunities for vaccination if possible. Based on the harm reduction concept, staff division of office breaks and ward classification and shunting are recommended and should be further implemented.", "title": "Challenge and strategies of infection control in psychiatric hospitals during biological disasters-From SARS to COVID-19 in Taiwan", "pid": "6jivoj9l", "bm25_score": 215.80006408691406}, {"text": "Psychiatric hospitals play an important role in supporting patients with mental illness to relieve symptoms and improve functioning in a physically and psychologically safe environment. However, these hospitals are also vulnerable to emerging infectious diseases. In early 2020, a psychiatric hospital and a psychiatric unit were reported to have nosocomial coronavirus disease 2019 (COVID-19) infection. A large number of patients and staff were severely impacted. This type of nosocomial infection threatens patient safety and quality of care. By learning from previous experiences of severe acute respiratory syndrome (SARS) and previous studies, psychiatric hospitals can provide safeguards to prevent nosocomial infection among patients and staff during an epidemic or biological disaster. These strategies include a series of actions such as following national guidelines for infection control, reserving adequate support for disinfection equipment, providing relevant and sufficient pro-service and in-service education and training, establishing regular surveillance of hand hygiene habits, proper communication and health education, and providing opportunities for vaccination if possible. Based on the harm reduction concept, staff division of office breaks and ward classification and shunting are recommended and should be further implemented.", "title": "Challenge and strategies of infection control in psychiatric hospitals during biological disasters—From SARS to COVID-19 in Taiwan", "pid": "vyun75bu", "bm25_score": 215.78834533691406}, {"text": "The World Health Organization's recommended pandemic influenza interventions, based on limited data, vary by transmission pattern, pandemic phase, and illness severity and extent. In the pandemic alert period, recommendations include isolation of patients and quarantine of contacts, accompanied by antiviral therapy. During the pandemic period, the focus shifts to delaying spread and reducing effects through population-based measures. Ill persons should remain home when they first become symptomatic, but forced isolation and quarantine are ineffective and impractical. If the pandemic is severe, social distancing measures such as school closures should be considered. Nonessential domestic travel to affected areas should be deferred. Hand and respiratory hygiene should be routine; mask use should be based on setting and risk, and contaminated household surfaces should be disinfected. Additional research and field assessments during pandemics are essential to update recommendations. Legal authority and procedures for implementing interventions should be understood in advance and should respect cultural differences and human rights.", "title": "Nonpharmaceutical Interventions for Pandemic Influenza, National and Community Measures", "pid": "bb6lv6yg", "bm25_score": 215.73898315429688}, {"text": "Abstract: Evidence is accumulating for the role of cleaning in controlling hospital infections. Hospital pathogens such as meticillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), norovirus, multi-resistant Gram-negative bacilli and Clostridium difficile persist in the healthcare environment for considerable lengths of time. Cleaning with both detergent and disinfectant-based regimens help control these pathogens in both routine and outbreak situations. The most important transmission risk comes from organisms on frequently handled items because hand contact with a contaminated site could deliver a pathogen to a patient. Cleaning practices should be tailored to clinical risk, near-patient areas and hand-touch-sites and scientifically evaluated for all surfaces and equipment in today’s hospitals.", "title": "15 Cleaning and decontamination of the healthcare environment", "pid": "9rn8kzst", "bm25_score": 215.70973205566406}, {"text": "The guidelines in this article provide veterinarians, veterinary technicians, and veterinary health care workers with an overview of evidence-based recommendations for the best practices associated with environmental cleaning and disinfection of a veterinary clinic that deals with small animals. Hospital-associated infections and the control and prevention programs necessary to alleviate them are addressed from an environmental perspective. Measures of hospital cleaning and disinfection include understanding mechanisms and types of contamination in veterinary settings, recognizing areas of potential concern, addressing appropriate decontamination techniques and selection of disinfectants, the management of potentially contaminated equipment, laundry, and waste management, and environmental surveillance strategies.", "title": "Environmental Cleaning and Disinfection", "pid": "kjjis7hu", "bm25_score": 215.60354614257812}, {"text": "Quarantine is an important but often misused tool of public health. An effective quarantine requires a process that inspires trust in government, only punishes noncompliance, and promotes a culture of social responsibility. Accomplishing successful quarantine requires incentives and enabling factors, payments, job security, and a tiered enforcement plan. In this article, we examine the variation in state-level quarantine laws and assess the effectiveness of these laws and regulations. We find that most states allow for an individual to have a hearing (63%) and to have a voice in burial and cremation procedures (71%), yet are weak on all other individual rights measures. Only 20% of states have provisions to protect employment when an individual is under quarantine, and less than half have plans for safe and humane quarantines. Decision makers at the state and local levels must make a concerted effort to revise and update quarantine laws and regulations. Ideally, these laws and regulations should be harmonized so as to avoid confusion and disruption between states, and public health officials should work with populations to identify and address the factors that will support successful quarantines if they are ever required.", "title": "Raising the Yellow Flag: State Variation in Quarantine Laws.", "pid": "ivznlkhp", "bm25_score": 215.58827209472656}, {"text": "Countries worldwide face the threat of emerging infectious diseases. To understand the public's reaction to the use of widespread quarantine should such an outbreak occur, the Harvard School of Public Health, with the U.S. Centers for Disease Control and Prevention, undertook a survey of residents of Hong Kong, Taiwan, Singapore, and the United States. A sizable proportion of the public in each country opposed compulsory quarantine. Respondents were concerned about overcrowding, infection, and inability to communicate with family members while in quarantine. Officials will need specific plans to deal with the public's concerns about compulsory quarantine policies.", "title": "Attitudes toward the use of quarantine in a public health emergency in four countries.", "pid": "5eu59xps", "bm25_score": 215.58706665039062}, {"text": "", "title": "Home quarantine or centralized quarantine, which is more conducive to fighting COVID-19 pandemic?", "pid": "veckwubt", "bm25_score": 215.572021484375}, {"text": "Hospital-acquired infections (HAIs) are serious problems for healthcare systems, especially in developing countries where public health infrastructure and technology for infection preventions remain undeveloped. Here, we characterized how strategy and technology could be mobilized to improve the effectiveness of infection prevention and control in hospitals during the outbreaks of Ebola, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS) in Asia and West Africa. Published literature on the hospital-borne outbreaks of SARS, Ebola, and MERS in Asia and West Africa was comprehensively reviewed. The results showed that healthcare systems and hospital management in affected healthcare facilities had poor strategies and inadequate technologies and human resources for the prevention and control of HAIs, which led to increased morbidity, mortality, and unnecessary costs. We recommend that governments worldwide enforce disaster risk management, even when no outbreaks are imminent. Quarantine and ventilation functions should be taken into consideration in architectural design of hospitals and healthcare facilities. We also recommend that health authorities invest in training healthcare workers for disease outbreak response, as their preparedness is essential to reducing disaster risk.", "title": "Strategy and technology to prevent hospital-acquired infections: Lessons from SARS, Ebola, and MERS in Asia and West Africa", "pid": "hiw9unh3", "bm25_score": 215.5181884765625}, {"text": "Abstract Nursing homes are facing the rapid spread of COVID-19 among residents and staff and are at the centre of the public health emergency due to the COVID-19 pandemic. As policy changes and interventions designed to support nursing homes are put into place, there are barriers to implementing a fundamental, highly effective element of infection control, namely the isolation of suspected or confirmed cases. Many nursing home residents have dementia, associated with impairments in memory, language, insight and judgment that impact their ability to understand and appreciate the necessity of isolation and to voluntarily comply with isolation procedures. While there is a clear ethical and legal basis for the involuntary confinement of people with dementia, the potential for unintended harm with these interventions is high, and there is little guidance for nursing homes on how to isolate safely, while maintaining the human dignity and personhood of the individual with dementia. In this commentary, we discuss strategies for effective, safe and compassionate isolation care planning, and present a case vignette of a person with dementia who is placed in quarantine on a dementia unit.", "title": "Achieving Safe, Effective and Compassionate Quarantine or Isolation of Older Adults with Dementia in Nursing Homes.", "pid": "q03884i9", "bm25_score": 215.50137329101562}, {"text": "Background Hong Kong went through a battle with a new respiratory disease, severe acute respiratory syndrome (SARS), from March to June 2003. All clinical settings, including rehabilitative and infirmary setting, have actively involved in fighting against the infection. The intent of this paper was to reflect on the SARS precautionary measures that had been taken in a severe intellectual disabilities hospital in Hong Kong. Methods A review on six SARS precautionary measures were conducted. They were assessment of risk, formulation of operational guidelines, implementation of infection control measures, education and training of staff, conducting audits and carrying out environmental improvement work. Results Patients were at risk of getting infected from carers, visitors, volunteers, and staff and patients of general hospitals. A SARS Quarantine Unit, isolation ward, was opened to isolate patients who might have had close contact with SARS patients during a stay in a general hospital or when they returned from home leave. Undoubtedly, both staff and relatives participated in preventing the patients from being infected. No day leave and home leave was reported and the number of hospitalization in general hospital was decreased during the critical period. Three infection control audits were conducted and improvement work was carried out subsequently. Conclusion The practice of grouping within a standard isolation room is recommended to continue in the future. Moreover, intensive infection control training for all staff is of highest importance to safeguard the health of both staff and patient.", "title": "Reflection on SARS precautions in a severe intellectual disabilities hospital in Hong Kong", "pid": "ax7tm4os", "bm25_score": 215.4549102783203}, {"text": "A veterinary team's best work can be undone by a breach in infection control, prevention, and biosecurity (ICPB). Such a breach, in the practice or home-care setting, can lead to medical, social, and financial impacts on patients, clients, and staff, as well as damage the reputation of the hospital. To mitigate these negative outcomes, the AAHA ICPB Guidelines Task Force believes that hospital teams should improve upon their current efforts by limiting pathogen exposure from entering or being transmitted throughout the hospital population and using surveillance methods to detect any new entry of a pathogen into the practice. To support these recommendations, these practice-oriented guidelines include step-by-step instructions to upgrade ICPB efforts in any hospital, including recommendations on the following: establishing an infection control practitioner to coordinate and implement the ICPB program; developing evidence-based standard operating procedures related to tasks performed frequently by the veterinary team (hand hygiene, cleaning and disinfection, phone triage, etc.); assessing the facility's ICPB strengths and areas of improvement; creating a staff education and training plan; cataloging client education material specific for use in the practice; implementing a surveillance program; and maintaining a compliance evaluation program. Practices with few or no ICPB protocols should be encouraged to take small steps. Creating visible evidence that these protocols are consistently implemented within the hospital will invariably strengthen the loyalties of clients to the hospital as well as deepen the pride the staff have in their roles, both of which are the basis of successful veterinary practice.", "title": "2018 AAHA Infection Control, Prevention, and Biosecurity Guidelines.", "pid": "8z3l5k4l", "bm25_score": 215.39178466796875}, {"text": "Staying at home for the prevention of Covid-19 virus is an accepted fact for everyone. Office workers are a group of people, who had to wake up early in the morning and at least had a fixed pattern of sleeping and working. In this situation, complaints about neck, shoulder and lower back tend to increase and this is a good time to learn and do some practical exercise at home. This letter presents some of the home-based exercise notes for prevention of musculoskeletal disorders among office workers, following the guidelines prepared by American College of Sports Medicine.", "title": "Home-based exercise note in Covid-19 quarantine situation for office workers: A commentary.", "pid": "tg02icy0", "bm25_score": 215.38589477539062}, {"text": "Staying at home for the prevention of Covid-19 virus is an accepted fact for everyone. Office workers are a group of people, who had to wake up early in the morning and at least had a fixed pattern of sleeping and working. In this situation, complaints about neck, shoulder and lower back tend to increase and this is a good time to learn and do some practical exercise at home. This letter presents some of the home-based exercise notes for prevention of musculoskeletal disorders among office workers, following the guidelines prepared by American College of Sports Medicine.", "title": "Home-based exercise note in Covid-19 quarantine situation for office workers: A commentary", "pid": "sj4ohk38", "bm25_score": 215.3704071044922}, {"text": "In the new millennium, the centuries-old strategy of quarantine is becoming a powerful component of the public health response to emerging and reemerging infectious diseases. During the 2003 pandemic of severe acute respiratory syndrome, the use of quarantine, border controls, contact tracing, and surveillance proved effective in containing the global threat in just over 3 months. For centuries, these practices have been the cornerstone of organized responses to infectious disease outbreaks. However, the use of quarantine and other measures for controlling epidemic diseases has always been controversial because such strategies raise political, ethical, and socioeconomic issues and require a careful balance between public interest and individual rights. In a globalized world that is becoming ever more vulnerable to communicable diseases, a historical perspective can help clarify the use and implications of a still-valid public health strategy.", "title": "Lessons from the History of Quarantine, from Plague to Influenza A", "pid": "zxe95qy9", "bm25_score": 215.36827087402344}, {"text": "The response to the first health worker case in India and novel strategies adopted in the context of evolving pandemic of COVID-19 is presented here. On the same day of confirmation, institutional COVID cell was established, and contact tracing was started. A total of 184 contacts were identified and quarantined. Hospital services were scaled down, and responsibilities were reassigned. In-house digital platforms were used for daily meetings, contact tracing, line listing, risk stratification, and research. Reverse transcription polymerase chain reaction-based severe acute respiratory syndrome-CoV2 testing facility was established in the institute. All high-risk contacts were given hydroxychloroquine prophylaxis. No secondary cases were found. Hospital preparedness, participatory decision-making through institutional COVID cell, optimal use of in-house digital platforms, and coordination with the state health department and national bodies, including Indian Council of Medical Research, were the supporting factors. Rapidly evolving guidelines, trepidation about the disease, logistic delays, and lack of support systems for people under quarantine were the challenges in the containment exercise.", "title": "Containing the first outbreak of COVID-19 in a healthcare setting in India: The sree chitra experience", "pid": "rkie91hw", "bm25_score": 215.36233520507812}, {"text": "The principles and practices aimed at prevention and control of hospital-acquired infections are directed at various links in the chain of transmission. They include the following: (1) to contain or eliminate the reservoirs of agents and/or to curtail the persistence of agents in a specific setting, (2) to protect the host against disease caused by microorganisms, and (3) to interrupt the transmission of infection. Interventions to modify environmental reservoirs are aimed at interrupting the transmission for these inanimate environmental sources. The barriers, e.g., masks, were used to keep the smells and “contagion” away even before the germ theory of disease was conceived. The appropriate barriers now include gloves, gowns, and eye protection for blood/body fluid–borne infections and high-filtration masks for infections transmitted by droplet nuclei. The most important and effective nosocomial infection control intervention remains the routine washing of hands before, between, and after patient contact in healthcare settings. This chapter focuses on the interruption of transmission of infectious agents in the hospital setting by Standard Precautions recommended for all patients and “isolation” of patients using precautions based on known methods of transmission.", "title": "Current Practices for Infection Prevention in the Hospital Settings", "pid": "mtpbzgr9", "bm25_score": 215.34970092773438}, {"text": "Nursing homes are facing the rapid spread of COVID-19 among residents and staff and are at the centre of the public health emergency due to the COVID-19 pandemic. As policy changes and interventions designed to support nursing homes are put into place, there are barriers to implementing a fundamental, highly effective element of infection control, namely the isolation of suspected or confirmed cases. Many nursing home residents have dementia, associated with impairments in memory, language, insight, and judgment that impact their ability to understand and appreciate the necessity of isolation and to voluntarily comply with isolation procedures. While there is a clear ethical and legal basis for the involuntary confinement of people with dementia, the potential for unintended harm with these interventions is high, and there is little guidance for nursing homes on how to isolate safely, while maintaining the human dignity and personhood of the individual with dementia. In this commentary, we discuss strategies for effective, safe, and compassionate isolation care planning, and present a case vignette of a person with dementia who is placed in quarantine on a dementia unit.", "title": "Achieving Safe, Effective, and Compassionate Quarantine or Isolation of Older Adults With Dementia in Nursing Homes", "pid": "iphuh7wp", "bm25_score": 215.34596252441406}, {"text": "BACKGROUND: Despite available recommendations on infection control for severe acute respiratory syndrome (SARS), information is limited on actual practices in Asian hospitals during the epidemic. We describe practices observed by mobile SARS containment teams (mobile teams) during outbreak investigations. METHODS: We retrospectively summarized infection control practices observed in hospitals visited by mobile teams in the Lao People's Democratic Republic (PDR), Taiwan, and Thailand, during March and April 2003. RESULTS: Mobile teams investigated 22 reports of SARS in 20 hospitals (1, 5, and 14 hospitals in Lao PDR, Taiwan, and Thailand, respectively). Facilities ranged from urban hospitals with negative-pressure isolation rooms and high-efficiency particulate air filtration to rural hospitals with patient rooms open to outside air circulation and intermittent running water. At the time of mobile team visits, 5 (25%) hospitals implemented infection control practices consistent with World Health Organization recommendations on visitor policies, private negative-pressure rooms, and personal protective equipment. CONCLUSIONS: Early in the SARS epidemic, mobile teams found wide variations in infection control practices and resources among Asian hospitals evaluating patients for SARS, indicating the importance of ongoing assessment during SARS preparedness. Mobile teams are one mechanism to assess practices and promote implementation of recommended infection control measures.", "title": "Infection control practices for SARS in Lao People's Democratic Republic, Taiwan, and Thailand: Experience from mobile SARS containment teams, 2003", "pid": "d0ccqrmu", "bm25_score": 215.32337951660156}, {"text": "The response to the first health worker case in India and novel strategies adopted in the context of evolving pandemic of COVID-19 is presented here. On the same day of confirmation, institutional COVID cell was established, and contact tracing was started. A total of 184 contacts were identified and quarantined. Hospital services were scaled down, and responsibilities were reassigned. In-house digital platforms were used for daily meetings, contact tracing, line listing, risk stratification, and research. Reverse transcription polymerase chain reaction-based severe acute respiratory syndrome-CoV2 testing facility was established in the institute. All high-risk contacts were given hydroxychloroquine prophylaxis. No secondary cases were found. Hospital preparedness, participatory decision-making through institutional COVID cell, optimal use of in-house digital platforms, and coordination with the state health department and national bodies, including Indian Council of Medical Research, were the supporting factors. Rapidly evolving guidelines, trepidation about the disease, logistic delays, and lack of support systems for people under quarantine were the challenges in the containment exercise.", "title": "Containing the first outbreak of COVID-19 in a healthcare setting in India: The sree chitra experience.", "pid": "zzzlzo0y", "bm25_score": 215.3121795654297}, {"text": "OBJECTIVE: This paper describes the physical structure and environmental contamination in selected hospital wards in three government hospitals in Bangladesh. METHODS: The qualitative research team conducted 48 hours of observation in six wards from three Bangladeshi tertiary hospitals in 2007. They recorded environmental contamination with body secretions and excretions and medical waste and observed ward occupant handwashing and use of personal protective equipment. They recorded number of persons, number of open doors and windows, and use of fans. They measured the ward area and informally observed waste disposal outside the wards. They conducted nine focus group discussions with doctors, nurses and support staff. RESULTS: A median of 3.7 persons were present per 10 m(2) of floor space in the wards. A median of 4.9 uncovered coughs or sneezes were recorded per 10 m(2) per hour per ward. Floors in the wards were soiled with saliva, spit, mucous, vomitus, feces and blood 125 times in 48 hours. Only two of the 12 patient handwashing stations had running water and none had soap. No disinfection was observed before or after using medical instruments. Used medical supplies were often discarded in open containers under the beds. Handwashing with soap was observed in only 32 of 3,373 handwashing opportunities noted during 48 hours. Mosquitoes and feral cats were commonly observed in the wards. CONCLUSIONS: The physical structure and environment of our study hospitals are conducive to the spread of infection to people in the wards. Low-cost interventions on hand hygiene and cleaning procedures for rooms and medical equipment should be developed and evaluated for their practicality and effectiveness.", "title": "Infrastructure and Contamination of the Physical Environment in Three Bangladeshi Hospitals: Putting Infection Control into Context", "pid": "387htidy", "bm25_score": 215.28103637695312}, {"text": "Quarantine and isolation are public health measures used for centuries to prevent the spread of infectious diseases. Quarantine is separation of persons who have been exposed to an infection but asymptomatic, while isolation is separation of infected patients. Voluntary quarantine is preferred, but if necessary, it can be mandatory. These implementations can lead to restrictions on individual liberties, leading to ethical and legal problems. Isolation and quarantine enforcement are regulated by laws. Those who do not follow the quarantine rules could be punished. Isolation and quarantine practices in our country are described in General Hygiene Law. In this study the importance of quarantine, when and how it is applied, and its ethical and especially legal dimension are discussed.", "title": "Quarantine and its legal dimension", "pid": "ufbmmlmj", "bm25_score": 215.2674102783203}, {"text": "Background: The outbreak of coronavirus disease 2019 (COVID-19) has placed unprecedented challenges on hospital environmental hygiene and medical staff protection. It is crucial to assess hospital environmental hygiene to understand the most important environmental issues for controlling the spread of COVID-19 in hospitals. Objective: To detect the presence of COVID-19 in the samples from the area at risk of contamination in the First Hospital of Jilin University. Methods: Viruses in the air were collected by natural sedimentation and air particle sampler methods. Predetermined environmental surfaces were sampled using swabs at seven o'clock in the morning before disinfection. The real-time reverse-transcription PCR method was used to detect the existence of COVID-19 pathogens. Results: Viruses could be detected on the surfaces of the nurse station in the isolation area with suspected patients and in the air of the isolation ward with an intensive care patient. Conclusion: Comprehensive monitoring of hospital environmental hygiene during pandemic outbreaks is conducive to the refinement of hospital infection control. It is of great significance to ensure the safety of medical treatment and the quality of hospital infection control through the monitoring of environmental hygiene.", "title": "Clinical Data on Hospital Environmental Hygiene Monitoring and Medical Staff Protection during the Coronavirus Disease 2019 Outbreak", "pid": "lad31adx", "bm25_score": 215.23886108398438}, {"text": "One Albuquerque, NM, ED's staff were quarantined after exposure to a suspected severe acute respiratory syndrome (SARS) patient, which underscores the importance of reducing risks of transmission. Reduce the number of contacts by isolating patients immediately. Triage nurses should have quick access to N-95 respirators. Ask security to screen all patients arriving by car before they enter the ED.", "title": "Will your ED have staff quarantined for SARS? Brace yourself for the worst.", "pid": "8z1tko13", "bm25_score": 215.20957946777344}, {"text": "On January 23, 2020, the Chinese government announced the city lockdown of Wuhan. Since then, there have been controversial debates among experts about the efficacy of mass quarantine, the oldest and probably one of the most effective methods for controlling infectious disease outbreaks. The impact of health policymaking section of health system governance becomes visible to all stakeholders and the public in such emergency contexts. The success and failure of such policies should be evaluated in order to find the proper course of action for the local and international communities. In this review, we aim to investigate the efficacy of mass quarantine in China during the coronavirus disease 2019 (COVID-19) pandemic. We found good quality evidence for the effectiveness of mass quarantine during the current stage of COVID-19 pandemic, and these strategies seem to have been highly effective in controlling the spread of the disease.", "title": "Efficacy of Mass Quarantine as Leverage of Health System Governance During COVID-19 Outbreak: A Mini Policy Review.", "pid": "uzqdx3v5", "bm25_score": 215.11192321777344}, {"text": "", "title": "Work Better From Home During the Coronavirus Quarantine", "pid": "jo9fgkwl", "bm25_score": 215.08486938476562}, {"text": "On January 23, 2020, the Chinese government announced the city lockdown of Wuhan. Since then, there have been controversial debates among experts about the efficacy of mass quarantine, the oldest and probably one of the most effective methods for controlling infectious disease outbreaks. The impact of health policymaking section of health system governance becomes visible to all stakeholders and the public in such emergency contexts. The success and failure of such policies should be evaluated in order to find the proper course of action for the local and international communities. In this review, we aim to investigate the efficacy of mass quarantine in China during the coronavirus disease 2019 (COVID-19) pandemic. We found good quality evidence for the effectiveness of mass quarantine during the current stage of COVID-19 pandemic, and these strategies seem to have been highly effective in controlling the spread of the disease.", "title": "Efficacy of Mass Quarantine as Leverage of Health System Governance During COVID-19 Outbreak: A Mini Policy Review", "pid": "a2pqrdln", "bm25_score": 215.074951171875}, {"text": "1. This study has demonstrated that great efforts have been made by the Hospital Authority and the studied hospital cluster to contain and prevent infection, and that high levels of vigilance have been enforced in anticipation of future outbreaks of SARS and other droplet infections. 2. Most health care workers and support workers have good hospital infection control and isolation precaution knowledge levels. 3. Compliance with infection control guidelines is satisfactory and has increased compared with previous studies. 4. Most participants had positive perceptions of the guidelines and found the training programmes useful. 5. This study has identified several structures and infection control practice areas that need strengthening, including improving the clarity of some guidelines and minimising barriers to their implementation.", "title": "An evaluation of SARS and droplet infection control practices in acute and rehabilitation hospitals in Hong Kong.", "pid": "470hwio4", "bm25_score": 215.07241821289062}, {"text": "Knowledge regarding the modes of transmission of pandemic 2009 H1N1 influenza continues to develop, as do recommendations for the prevention of spread within healthcare facilities. The adoption of the most prudent, multifaceted approaches is recommended until there is significant evidence to reduce protective measures. The greatest threat to healthcare personnel and patients appears to be exposure to patients, healthcare personnel, or visitors who have not been recognized as contagious. The processes used within healthcare facilities must hold this concept central to any infection control plan and act in a preventive manner. This article focuses on the development of an algorithm for intensive care unit intake precautions, based on the early identification of potential source patients, as well as appropriate selection and adequate use of personal protective equipment. Visitor management, hand and respiratory hygiene, and cough etiquette have been used as measures to decrease the spread of infection. Vaccination of healthcare personnel, combined with work furlough for ill workers, is also explored. Recommendations include the elimination of potential exposures, engineering and administrative controls, and utilization of personal protective equipment.", "title": "Healthcare personnel and nosocomial transmission of pandemic 2009 influenza.", "pid": "d2axm29e", "bm25_score": 215.0723419189453}, {"text": "The World Health Organization (WHO) has deemed coronavirus disease 2019 (COVID-19) to be a pandemic. The strict prevention and control measures taken by China have proven to be effective, creating a window of opportunity for other countries. The tracking and management of contacts of patients with COVID-19 are important components of prevention and control measures. This article briefly describes the placement of close contacts of patients with COVID-19 under collective quarantine for medical observation in China from the perspective of frontline staff. This article focuses on a community in the Jiading District of Shanghai to provide a reference for placement of close contacts of patients with COVID-19 under collective quarantine for medical observation in other countries and regions.", "title": "Introduction on collective quarantine of close contacts of patients with COVID-19 for medical observation in China: from the perspective of frontline staff", "pid": "oc4puh49", "bm25_score": 215.06700134277344}, {"text": "The World Health Organization announced the coronavirus disease 2019 (COVID-19) outbreak a pandemic on 12 March 2020. Although being in proximity to China, the original epicenter of the COVID-19 outbreak, Taiwan has maintained a low number of COVID-19 cases despite its close social ties and heavy traffic between Taiwan and China. Containment strategies executed by the Taiwanese government have attracted global attention. Similarly, in-hospital settings, high alertness and swift responses to the changing outbreak situation are necessary to ensure hospital staff members' safety so they can continue to save patients' lives. Herein, we present infection control measures that can be adopted in hospital settings that were executed in a Taiwanese hospital to confront the COVID-19 pandemic, including emergency preparedness and responses from the hospital administration, education, surveillance, patient flow arrangement, the partition of hospital zones, and the prevention of a systemic shutdown by using the \"divided cabin, divided flow\" strategy. The measures implemented by a Taiwan hospital during the COVID-19 pandemic may not be universally applicable in every hospital. Nonetheless, the presented infection control methods have been practically executed and can be referenced or modified to fit each hospital's unique condition.", "title": "Infection control measures of a Taiwanese hospital to confront the COVID-19 pandemic", "pid": "z1edhocd", "bm25_score": 215.04519653320312}, {"text": "", "title": "Integrated Hospital Quarantine System against COVID-19", "pid": "pkh8puhp", "bm25_score": 215.04464721679688}, {"text": "BACKGROUND: The severe acute respiratory syndrome (SARS) epidemic and concern about pandemic influenza prompted the Centers for Disease Control and Prevention (CDC) to develop guidelines to prevent the transmission of all respiratory infections in health care settings during first contact with a potentially infected person. The extent to which health care workers and institutions use these CDC recommended practices is uncertain. METHODS: The study examined health care worker adherence to CDC recommended respiratory infection control practices in primary care clinics and emergency departments of 5 medical centers in King County, Washington, using a self-administered questionnaire. All clinical, allied, and administrative health care workers in study settings were invited to participate: 653 (53%) responded, and 630 were included. RESULTS: The survey revealed important shortcomings in overall personal and institutional use of CDC recommended practices, including deficiencies in posted alerts, patient masking and separation, hand hygiene, personal protective equipment, staff training, and written procedures. Use of recommended measures was generally higher among nursing staff than medical practitioners. CONCLUSION: This study found significant gaps in adherence to CDC recommendations for the control of respiratory infections in ambulatory care clinical settings. Practical strategies are needed to identify and reduce barriers to implementation of recommended practices for control of respiratory infections.", "title": "Appraisal of recommended respiratory infection control practices in primary care and emergency department settings", "pid": "v6pqwgsy", "bm25_score": 215.0334930419922}, {"text": "PURPOSE OF REVIEW: Environmental surfaces in healthcare facilities, particularly in a patient room, are a critical pathway for healthcare-associated pathogen transmission. Despite well-established guides and recommendations regarding environmental surface cleaning and disinfection, there are several challenges in resource-limited settings. This viewpoint article will discuss the practice of environmental cleaning in resource-limited settings including challenges and relationship between environment and healthcare-associated infections in this setting and outlines pre-requisites to overcome these challenges. RECENT FINDINGS: Despite several barriers and challenges, environmental cleaning is a crucial component to help reduce transmission of healthcare-associated infections and multi-drug-resistant pathogens as well as emerging infectious disease-associated pathogens in resource-limited settings. However, there is a need to develop a multi-modal strategy together with a mechanism for monitor and feedback to improve the practices of environmental cleaning in resource-limited settings. SUMMARY: Additional researches on the barriers and implementation gaps and the role of collaborative network as well as how to apply technology would provide significant insights on the practices of environmental cleaning in resource-limited settings.", "title": "Environmental Cleaning in Resource-Limited Settings", "pid": "omd5u7eu", "bm25_score": 215.02357482910156}, {"text": "The isolation and treatment of symptomatic individuals, coupled with the quarantining of individuals that have a high risk of having been infected, constitute two commonly used epidemic control measures. Although isolation is probably always a desirable public health measure, quarantine is more controversial. Mass quarantine can inflict significant social, psychological, and economic costs without resulting in the detection of many infected individuals. The authors use probabilistic models to determine the conditions under which quarantine is expected to be useful. Results demonstrate that the number of infections averted (per initially infected individual) through the use of quarantine is expected to be very low provided that isolation is effective, but it increases abruptly and at an accelerating rate as the effectiveness of isolation diminishes. When isolation is ineffective, the use of quarantine will be most beneficial when there is significant asymptomatic transmission and if the asymptomatic period is neither very long nor very short.", "title": "When Is Quarantine a Useful Control Strategy for Emerging Infectious Diseases?", "pid": "e350kj7m", "bm25_score": 215.0093994140625}, {"text": "Abstract Increasing numbers of hospital-acquired infections have generated much attention over the last decade. The public has linked the so-called ‘superbugs’ with their experience of dirty hospitals, but the precise role of cleaning in the control of these organisms in unknown. Hence the importance of a clean environment is likely to remain speculative unless it becomes an evidence-based science. This proposal is a call for bacteriological standards with which to assess clinical surface hygiene in hospitals, based on those used by the food industry. The first standard concerns any finding of a specific ‘indicator’ organism, the presence of which suggests a requirement for increased cleaning. Indicators would include Staphylococcus aureus, including methicillin-resistant S. aureus, Clostridium difficile, vancomycin-resistant enterococci and various Gram-negative bacilli. The second standard concerns a quantitative aerobic colony count of <5cfu/cm2 on frequent hand touch surfaces in hospitals. The principle relates to modern risk management systems such as HACCP, and reflects the fact that pathogens of concern are widespread. Further work is required to evaluate and refine these standards and define the infection risk from the hospital environment.", "title": "How do we assess hospital cleaning? A proposal for microbiological standards for surface hygiene in hospitals", "pid": "o6pjb9a6", "bm25_score": 215.00694274902344}, {"text": "The recent Ebola epidemic has put the words \"isolation and quarantine\" in the spotlight. Isolation and quarantine are tools that are often utilized by public health officials around the United States to address various types of infectious disease, including tuberculosis. While voluntary compliance is preferred, it can be difficult to achieve. In cases where an individual chooses not to voluntarily comply with an isolation or quarantine request, public health officials require assistance from the judiciary and law enforcement to effectuate the order. This article compares 2 recent court cases with different outcomes where public health officials sought assistance from the courts to enforce an isolation or quarantine order.", "title": "Putting the Law Into Practice: A Comparison of Isolation and Quarantine As Tools to Control Tuberculosis and Ebola.", "pid": "ef721182", "bm25_score": 214.9918975830078}, {"text": "The World Health Organization (WHO) has deemed coronavirus disease 2019 (COVID-19) to be a pandemic. The strict prevention and control measures taken by China have proven to be effective, creating a window of opportunity for other countries. The tracking and management of contacts of patients with COVID-19 are important components of prevention and control measures. This article briefly describes the placement of close contacts of patients with COVID-19 under collective quarantine for medical observation in China from the perspective of frontline staff. This article focuses on a community in the Jiading District of Shanghai to provide a reference for placement of close contacts of patients with COVID-19 under collective quarantine for medical observation in other countries and regions.", "title": "Introduction on collective quarantine of close contacts of patients with COVID-19 for medical observation in China: from the perspective of frontline staff.", "pid": "pl2remvk", "bm25_score": 214.970703125}, {"text": "With the coronavirus disease 2019 (COVID-19) pandemic in the United States, a majority of states have instituted \"shelter-in-place\" policies effectively quarantining individuals-including pregnant persons-in their homes. Given the concern for COVID-19 acquisition in health care settings, pregnant persons with high-risk pregnancies-such as persons living with HIV (PLHIV)-are increasingly investigating the option of a home birth. Although we strongly recommend hospital birth for PLHIV, we discuss our experience and recommendations for counseling and preparation of pregnant PLHIV who may be considering home birth or at risk for unintentional home birth due to the pandemic. We also discuss issues associated with implementing a risk mitigation strategy involving high-risk births occurring at home during a pandemic. KEY POINTS: · Coronavirus disease 2019 pandemic has increased interest in home birth.. · Women living with HIV are pursuing home birth.. · Safe planning is paramount for women living with HIV desiring home birth, despite recommending against the practice..", "title": "Home Birth in the Era of COVID-19: Counseling and Preparation for Pregnant Persons Living with HIV.", "pid": "wyuz1az9", "bm25_score": 214.96292114257812}, {"text": "Antimicrobial resistance (AMR) continues to threaten global health. Although global and national AMR action plans are in place, infection prevention and control is primarily discussed in the context of healthcare facilities with home and everyday life settings barely addressed. As seen with the recent global SARS-CoV-2 pandemic, everyday hygiene measures can play an important role in containing the threat from infectious microorganisms. This position paper has been developed following a meeting of global experts in London, 2019. It presents evidence that home and community settings are important for infection transmission and also the acquisition and spread of AMR. It also demonstrates that the targeted hygiene approach offers a framework for maximizing protection against colonization and infections, thereby reducing antibiotic prescribing and minimizing selection pressure for the development of antibiotic resistance. If combined with the provision of clean water and sanitation, targeted hygiene can reduce the circulation of resistant bacteria in homes and communities, regardless of a country's Human Development Index (overall social and economic development). Achieving a reduction of AMR strains in healthcare settings requires a mirrored reduction in the community. The authors call upon national and international policy makers, health agencies and healthcare professionals to further recognize the importance of targeted hygiene in the home and everyday life settings for preventing and controlling infection, in a unified quest to tackle AMR.", "title": "Reducing antibiotic prescribing and addressing the global problem of antibiotic resistance by targeted hygiene in the home and everyday life settings: A Position Paper", "pid": "e0hd3iuu", "bm25_score": 214.95997619628906}, {"text": "", "title": "Implementing Physical Distancing in the Hospital: A Key Strategy to Prevent Nosocomial Transmission of COVID-19.", "pid": "mv4ehst6", "bm25_score": 214.93177795410156}, {"text": "OBJECTIVES An influenza pandemic, as with any disaster involving contagion or contamination, has the potential to influence the number of health care employees who will report for duty. Our project assessed the uptake of proposed interventions to mitigate absenteeism in hospital workers during a pandemic. METHODS Focus groups were followed by an Internet-based survey of a convenience sample frame of 17,000 hospital workers across 5 large urban facilities. Employees were asked to select their top barrier to reporting for duty and to score their willingness to work before and after a series of interventions were offered to mitigate it. RESULTS Overall, 2864 responses were analyzed. Safety concerns were the most frequently cited top barrier to reporting for work, followed by issues of dependent care and transportation. Significant increases in employee willingness to work scores were observed from mitigation strategies that included preferential access to antiviral medication or personal protective equipment for the employee as well as their immediate family. CONCLUSIONS The knowledge base on workforce absenteeism during disasters is growing, although in general this issue is underrepresented in emergency planning efforts. Our data suggest that a mitigation strategy that includes options for preferential access to either antiviral therapy, protective equipment, or both for the employee as well as his or her immediate family will have the greatest impact. These findings likely have import for other disasters involving contamination or contagion, and in critical infrastructure sectors beyond health care.", "title": "Mitigating absenteeism in hospital workers during a pandemic.", "pid": "87987cbk", "bm25_score": 214.92221069335938}, {"text": "The World Health Organization announced the coronavirus disease 2019 (COVID‐19) outbreak a pandemic on 12 March 2020. Although being in proximity to China, the original epicenter of the COVID‐19 outbreak, Taiwan has maintained a low number of COVID‐19 cases despite its close social ties and heavy traffic between Taiwan and China. Containment strategies executed by the Taiwanese government have attracted global attention. Similarly, in‐hospital settings, high alertness and swift responses to the changing outbreak situation are necessary to ensure hospital staff members' safety so they can continue to save patients' lives. Herein, we present infection control measures that can be adopted in hospital settings that were executed in a Taiwanese hospital to confront the COVID‐19 pandemic, including emergency preparedness and responses from the hospital administration, education, surveillance, patient flow arrangement, the partition of hospital zones, and the prevention of a systemic shutdown by using the “divided cabin, divided flow” strategy. The measures implemented by a Taiwan hospital during the COVID‐19 pandemic may not be universally applicable in every hospital. Nonetheless, the presented infection control methods have been practically executed and can be referenced or modified to fit each hospital's unique condition.", "title": "Infection control measures of a Taiwanese hospital to confront the COVID‐19 pandemic", "pid": "x90l7rjs", "bm25_score": 214.9063262939453}, {"text": "Summary Background The management of patients with highly infectious diseases (HIDs) is a challenge for healthcare provision requiring a high level of care without compromising the safety of other patients and healthcare workers. Aim To study the infection control practice in isolation facilities participating in the European Network for Highly Infectious Diseases (EuroNHID) project. Methods A survey was conducted during 2009 of 48 isolation facilities caring for patients with HIDs in 16 European countries. Checklists and standard evaluation forms were used to collect and interpret data on hand hygiene, routine hygiene and disinfection, and waste management. Findings Forty percent of HIDs had no non-hand-operated sinks or alcohol-based antiseptic distributors, while 27% did not have procedures for routine hygiene, final disinfection, or safe discarding of non-disposable objects or equipment. There was considerable variation in the management of waste and in the training of housekeeping personnel. EuroNHID has developed recommendations for hand hygiene, disinfection, routine hygiene, and waste management. Conclusions Most aspects of hand hygiene, routine hygiene and disinfection, and waste management were considered at least partially adequate in the majority of European isolation facilities dedicated for the care of patients with HIDs. But considerable variability was observed, with management of waste and training of housekeeping personnel being generally less satisfactory.", "title": "Infection control practices in facilities for highly infectious diseases across Europe", "pid": "098dcy4z", "bm25_score": 214.88433837890625}, {"text": "Quarantine or physical isolation, used for centuries to contain the spread of infection, isolates those who have (or may have) been infected by a contagious disease to control or limit contamination. The COVID-19, a novel coronavirus first reported in Wuhan, China in late 2019, has rapidly spread across the globe becoming a pandemic. Modern quarantine strategies have been imposed globally in an attempt to curtail the spread of the COVID-19 infection including short- to medium-term lockdowns, voluntary home curfew, restriction on the assembly of groups of people, cancellation of planned social and public events, closure of mass transit systems, and other travel restrictions.", "title": "Life in the pandemic: Social isolation and mental health.", "pid": "fmahx3lx", "bm25_score": 214.87782287597656}, {"text": "The novel coronavirus disease (COVID-19) is a recent pandemic which has spread to over 200 countries of the world since its outbreak. As of 21st April, 2020, more than 2.3 million confirmed cases have been reported. The World Health Organization (WHO) has issued a strategic preparedness response plan for countries at risk. This is based on the knowledge of previous epidemics and experience shared by Chinese health authorities. There is special emphasis on strict 'quarantine and isolation' of suspected/diagnosed cases. Pakistan is a developing country with a weak healthcare system. Pakistan Armed Forces have always provided services to the countrymen during natural and man-made disasters. During this pandemic the largest rehabilitation institute in the country was converted into a 130-bed dedicated isolation and quarantine facility for the COVID-19 patients. We will share our experience of establishing and managing this quarantine and isolation facility and highlight the achievements and out-of-the-box solutions applicable for low resource countries like Pakistan.", "title": "Establishing and managing a quarantine and isolation centre in COVID-19 pandemic", "pid": "rk3d6se9", "bm25_score": 214.85923767089844}, {"text": "With the coronavirus disease 2019 (COVID-19) pandemic in the United States, a majority of states have instituted \"shelter-in-place\" policies effectively quarantining individuals-including pregnant persons-in their homes. Given the concern for COVID-19 acquisition in health care settings, pregnant persons with high-risk pregnancies-such as persons living with HIV (PLHIV)-are increasingly investigating the option of a home birth. Although we strongly recommend hospital birth for PLHIV, we discuss our experience and recommendations for counseling and preparation of pregnant PLHIV who may be considering home birth or at risk for unintentional home birth due to the pandemic. We also discuss issues associated with implementing a risk mitigation strategy involving high-risk births occurring at home during a pandemic. KEY POINTS: · Coronavirus disease 2019 pandemic has increased interest in home birth.. · Women living with HIV are pursuing home birth.. · Safe planning is paramount for women living with HIV desiring home birth, despite recommending against the practice..", "title": "Home Birth in the Era of COVID-19: Counseling and Preparation for Pregnant Persons Living with HIV", "pid": "as5d3hk4", "bm25_score": 214.8575439453125}, {"text": "The Institute of Mental Health in Singapore continues to attempt to prevent the introduction of COVID-19, despite community transmission. Essential services are maintained and quarantine measures are currently unnecessary. To help similar organizations, strategies are listed along three themes: sustaining essential services, preventing infection, and managing human and consumable resources.", "title": "Effective infection prevention and control strategies in a large, accredited, psychiatric facility in Singapore", "pid": "8rs3oep3", "bm25_score": 214.8544158935547}, {"text": "Population adoption of social distancing measures during the COVID-19 pandemic is at times deficient, increasing the risk of SARS-CoV-2 transmission. Healthcare workers and those living in areas of intense transmission may benefit from implementing biosafety measures in their daily lives. A mixed-methods approach, combining components of single negotiation text and the Delphi method, was used to create a COVID-19 biosafety-at-home protocol. A consensus building coordinator liaised with 12 experts to develop the protocol over 11 iterations. Experts had more than 200 years of combined experience in epidemiology, virology, infectious disease prevention, and public health. A flyer, created from the final protocol, was professionally designed and initially distributed via social media and institutional websites/emails in Ecuador beginning on May 2, 2020. Since then, it has been distributed in other countries, reaching ∼7,000 people. Translating research laboratory biosafety measures for the home/street environment might be challenging. The biosafety-at-home flyer addresses this challenge in a user-friendly format.", "title": "Biosafety at Home: How to Translate Biomedical Laboratory Safety Precautions for Everyday Use in the Context of COVID-19.", "pid": "6a9887o8", "bm25_score": 214.8533172607422}, {"text": "Abstract Objectives At the end of 2019, the COVID-19 epidemic broke out in Wuhan, China. On January 20, 2020, Chinese expert group confirmed that the spread of the virus is characterized by human-to-human transmission. Study Design It is difficult for the public to prevent the spread of COVID-19 by only wearing masks, and the most important measureto take is to cut off the route of transmission; otherwise, there is noway to control the disease. Methods The Wuhan Municipal Governmentannounced the control of the migration of the population in Wuhan, and population migration in Hubei Province also continues to be monitored after the confirmation of human-to-human transmission.Unfortunately, some problems remain. Results At the beginning of the epidemic breakout, there were not enough hospital beds for the patients in Wuhan, and a large number of patients were required to self-solate at home. Therefore, home isolation poses significant risks. Conclusions The patient will transmit the virus to other people in the houseif a patient has been confirmed to have the virus and is under home isolation.This can lead to the infection of the patient's entire family.", "title": "Is home isolation appropriate for preventing the spread of COVID-19?", "pid": "dxiyqf9d", "bm25_score": 214.85171508789062}, {"text": "", "title": "Disinfection Policies in Hospitals and the Community", "pid": "utihmwb4", "bm25_score": 214.8487091064453}, {"text": "", "title": "Infection control and prevention in home healthcare: prevention activities are the key to desired patient outcomes.", "pid": "k3vetiqy", "bm25_score": 214.8309326171875}, {"text": "Every recent presidential administration has faced an infectious disease threat, and this trend is certain to continue. The states have primary responsibility for protecting the public's health under their police powers, but modern travel makes diseases almost impossible to contain intrastate. How should the federal government respond in the future? The Ebola scare in the U.S. repeated a typical response--demands for quarantine. In January 2017, the Department of Health and Human Services and the Centers for Disease Control and Prevention issued final regulations on its authority to issue Federal Quarantine Orders. These regulations rely heavily on confining persons who may or may not be ill, raising serious questions about federal commitment to due process protections as well as the scope of statutory authority to impose quarantine. As the Supreme Court has stated in United States v. Salerno, \"liberty is the norm, and detention prior to trial or without trial is the carefully limited exception.\" Unconstrained use of quarantines undermines both the rule of law and public confidence in government decisions in times of crisis. This article analyzes the regulations and argues for a rights-based approach to infectious disease control that also protects public health. By respecting constitutional rights, the federal government can encourage public trust and cooperation and minimize harm, both essential requirements for controlling an epidemic.", "title": "Quarantine and the Federal Role in Epidemics.", "pid": "8tiutamd", "bm25_score": 214.82998657226562}, {"text": "To understand hospital policies and practices as the COVID-19 pandemic accelerated, the Society for Healthcare Epidemiology of America (SHEA) conducted a survey through the SHEA Research Network (SRN). The survey assessed policies and practices around the optimization of personal protection equipment (PPE), testing, healthcare personnel policies, visitors of COVID-19 patients in relation to procedures, and types of patients. Overall, 69 individual healthcare facilities responded in the United States and internationally, for a 73% response rate.", "title": "Policies and practices of SHEA Research Network hospitals during the COVID-19 pandemic", "pid": "f8j89otm", "bm25_score": 214.8290252685547}, {"text": "BACKGROUND: During the Severe Acute Respiratory Syndrome (SARS) outbreak, high compliance in healthcare workers to hand hygiene was primarily driven by fear. However, the post-SARS period confirmed that this practice was not sustainable. At the Singapore General Hospital, a 1,600-bedded acute tertiary care hospital, the hand hygiene program was revised in early 2007 following Singapore's signing of the pledge to the World Health Organization (WHO) \"Clean Care is Safer Care\" program. FINDINGS: A multi-prong approach was used in designing the hand hygiene program. This included system change; training and education; evaluation and feedback; reminders in the workplace; and institutional safety climate. Hand hygiene compliance rate improved from 20% (in January 2007) to 61% (2010). Improvement was also seen annually in the compliance to each of the 5 moments as well as in all staff categories. Healthcare-associated MRSA infections were reduced from 0.6 (2007) to 0.3 (2010) per 1000 patient-days. CONCLUSIONS: Leadership's support of the program evidenced through visible leadership presence, messaging and release of resources is the key factor in helping to make the program a true success. The hospital was recognised as a Global Hand Hygiene Expert Centre in January 2011. The WHO multi-prong interventions work in improving compliance and reducing healthcare associated infections.", "title": "Impact of a hospital-wide hand hygiene promotion strategy on healthcare-associated infections", "pid": "khqvezmu", "bm25_score": 214.82272338867188}, {"text": "PURPOSE OF REVIEW To review recent publications relevant to hospital disinfection (and cleaning) including the reprocessing of medical instruments. RECENT FINDINGS The key question as to whether the use of disinfectants on environmental surfaces rather than cleaning with detergents only reduces nosocomial infection rates still awaits conclusive studies. New disinfectants, mainly peroxygen compounds, show good sporicidal properties and will probably replace more problematical substances such as chlorine-releasing agents. The safe reprocessing of medical devices requires a well-coordinated approach, starting with proper cleaning. New methods and substances show promising activity for preventing the transmission of prions. Different aspects of virus inactivation have been studied, and the transmissibility, e.g. of norovirus, shows the need for sound data on how different disinfectant classes perform. Biofilms or other forms of surface-adherent organisms pose an extraordinary challenge to decontamination. Although resistance to biocides is generally not judged to be as critical as antibiotic resistance, scientific data support the need for proper use, i.e. the avoidance of widespread application, especially in low concentrations and in consumer products. SUMMARY Chemical disinfection of heat-sensitive instruments and targeted disinfection of environmental surfaces are established components of hospital infection control. To avoid danger to staff, patients and the environment, prudent use as well as established safety precautions are required. New technologies and products should be evaluated with sound methods. As emerging resistant pathogens will challenge healthcare facilities in the future even more than at present, there is a need for well-designed studies addressing the role of disinfection in hospital infection control.", "title": "Hospital disinfection: efficacy and safety issues.", "pid": "yjrm88y1", "bm25_score": 214.8203125}, {"text": "", "title": "Implementing Physical Distancing in the Hospital: A Key Strategy to Prevent Nosocomial Transmission of COVID-19", "pid": "ixhm3d20", "bm25_score": 214.7850341796875}, {"text": "Quarantine has been used for centuries in an effort to prevent the introduction, transmission, and spread of communicable diseases. While backed by legal authority, the public and even the health care worker community's understanding of the term is murky at best and scientific evidence to support the use of quarantine is frequently lacking. The multiple interpretations and references to quarantine, the inconsistent application of public health quarantine laws across jurisdictional boundaries, and reports of ineffectiveness are further complicated by associated infringement of civil liberties and human rights abuses. Given the need to balance public safety with human rights, we must be more precise about the meaning of quarantine and consider the efficacy and negative secondary effects resulting from its implementation. This article explains quarantine terminology and then uses a case study from Taiwan during the 2002-2003 severe acute respiratory syndrome (SARS) outbreak to illustrate the key principles associated with quarantine measures taken during the 2014 Ebola outbreak and the potential hazards that can arise from quarantines. Finally, we provide a quarantine and isolation decision tree to assist policy makers and public health officials in applying medically defensible, outcomes-based data and legal authorities to optimize management of emerging infectious diseases.", "title": "Is There a Case for Quarantine? Perspectives from SARS to Ebola.", "pid": "u4uvwpj0", "bm25_score": 214.7684326171875}, {"text": "BACKGROUND: The COVID-19 outbreak has highlighted the role of hospital-acquired infections in spreading epidemics. Adequately cleaning surfaces in patient rooms is an essential part of this fight to reduce the spread. Traditional audits, however, are insufficient. This study assesses surface cleaning practices using UV marker technology and the extent to which this technology can help improve cleaning audits and practices. METHODS: 144 audits (1,235 surfaces) were retrieved. UV marker cleaning audits conducted at a major teaching hospital in 2018 after implementing a new cleaning protocol. In addition, semi-structured interviews were conducted with cleaning staff and supervisors. RESULTS: On average, 63% of surfaces were appropriately cleaned. Toilet handles (80%) and toilet seats underside (83%) scored highest while main room sink fixtures (54%), light switch (55%) and bedrails (56%) scored lowest. Training, staffing and time constraints may play a role in low cleaning rates. DISCUSSION: The high-touch patient surfaces in the bedroom remain neglected and a potential source of infections. UV marker audits provided an objective measure of cleaning practices that managers and staff were unaware of. CONCLUSION: UV markers audits can play a key role in revealing deficiencies in cleaning practices and help in raising awareness of these deficiencies and improving cleaning practices.", "title": "An Evaluation of Cleaning Practices at a Teaching Hospital", "pid": "2g6zeqtd", "bm25_score": 214.7664794921875}, {"text": "This review focuses on best practices and recommendations for hygiene and disinfection to limit exposure and transmission of infection in outpatient glaucoma clinics during the current COVID-19 pandemic.", "title": "Review of Hygiene and Disinfection Recommendations for Outpatient Glaucoma Care: A COVID Era Update", "pid": "welen5fl", "bm25_score": 214.7623291015625}, {"text": "OBJECTIVE. The purpose of this article is to share an experience in the rapid deployment of home workstations that illustrates a creative solution that transcended typical administrative barriers. CONCLUSION. In response to the global coronavirus disease (COVID-19) pandemic, radiology departments need to rapidly deploy home PACS workstations to facilitate physical distancing and to guarantee radiologic expertise despite possible home quarantining or stay home, work safe orders.", "title": "Response to the COVID-19 Pandemic: Practical Guide to Rapidly Deploying Home Workstations to Guarantee Radiology Services During Quarantine, Social Distancing, and Stay Home Orders", "pid": "0vkuxggb", "bm25_score": 214.753662109375}, {"text": "An influenza pandemic can overwhelm the capacities of hospitals, clinics, nursing facilities, and emergency services. The likelihood is that most of the individuals who are stricken will be cared for at home, and there is strong evidence that in-home caregivers bear a disproportionate risk of becoming infected. We reviewed the scientific literature after 2000 to identify steps that in-home caregivers can take to reduce the chances that they and other household members will become infected in the home. Personal hygiene, common masks, and technologies including air filters and UV light each offer incremental benefits, and in combination are expected to reduce a portion of the risk that household members face when caring for a member who has become infected. In pandemics and even seasonal epidemics, seemingly small steps can literally mean the difference between life and death, especially for in-home caregivers.", "title": "A home toolkit for primary prevention of influenza by individuals and families.", "pid": "s4ahnmo8", "bm25_score": 214.75335693359375}, {"text": "Quarantine measure is a commonly used non-pharmaceutical intervention during the outbreak of infectious diseases. A key problem for implementing quarantine measure is to determine the duration of quarantine. In this paper, a policy with optimal quarantine duration is developed. The policy suggests different quarantine durations for every individual with different characteristic. The policy is optimal in the sense that it minimizes the average quarantine duration of uninfected people with the constraint that the probability of symptom presentation for infected people attains the given value closing to 1. The optimal solution for the quarantine duration is obtained and estimated by some statistic methods with application to analyzing COVID-19 data.", "title": "Determination and estimation of optimal quarantine duration for infectious diseases with application to data analysis of COVID-19", "pid": "8crqwe2q", "bm25_score": 214.74339294433594}, {"text": "BACKGROUND: The use of restrictive measures such as quarantine draws into sharp relief the dynamic interplay between the individual rights of the citizen on the one hand and the collective rights of the community on the other. Concerns regarding infectious disease outbreaks (SARS, pandemic influenza) have intensified the need to understand public perceptions of quarantine and other social distancing measures. METHODS: We conducted a telephone survey of the general population in the Greater Toronto Area in Ontario, Canada. Computer-assisted telephone interviewing (CATI) technology was used. A final sample of 500 individuals was achieved through standard random-digit dialing. RESULTS: Our data indicate strong public support for the use of quarantine when required and for serious legal sanctions against those who fail to comply. This support is contingent both on the implementation of legal safeguards to protect against inappropriate use and on the provision of psychosocial supports for those affected. CONCLUSION: To engender strong public support for quarantine and other restrictive measures, government officials and public health policy-makers would do well to implement a comprehensive system of supports and safeguards, to educate and inform frontline public health workers, and to engage the public at large in an open dialogue on the ethical use of restrictive measures during infectious disease outbreaks.", "title": "Public perceptions of quarantine: community-based telephone survey following an infectious disease outbreak", "pid": "lhn34tc4", "bm25_score": 214.7415313720703}, {"text": "The coronavirus disease 2019 (COVID-19) outbreak has been designated a public health emergency of international concern. To prepare for a pandemic, hospitals need a strategy to manage their space, staff, and supplies so that optimum care is provided to patients. In addition, infection prevention measures need to be implemented to reduce in-hospital transmission. In the operating room, these preparations involve multiple stakeholders and can present a significant challenge. Here, we describe the outbreak response measures of the anesthetic department staffing the largest (1,700-bed) academic tertiary level acute care hospital in Singapore (Singapore General Hospital) and a smaller regional hospital (Sengkang General Hospital). These include engineering controls such as identification and preparation of an isolation operating room, administrative measures such as modification of workflow and processes, introduction of personal protective equipment for staff, and formulation of clinical guidelines for anesthetic management. Simulation was valuable in evaluating the feasibility of new operating room set-ups or workflow. We also discuss how the hierarchy of controls can be used as a framework to plan the necessary measures during each phase of a pandemic, and review the evidence for the measures taken. These containment measures are necessary to optimize the quality of care provided to COVID-19 patients and to reduce the risk of viral transmission to other patients or healthcare workers.", "title": "Preparing for a COVID-19 pandemic: a review of operating room outbreak response measures in a large tertiary hospital in Singapore", "pid": "4j3fdjlg", "bm25_score": 214.73049926757812}, {"text": "COVID-19 is a treacherous disease, in which infected patients who appear to fare well can deteriorate rapidly, mostly due to respiratory failure. For general practitioners (and other first-line responders), a clinical evaluation at any given time merely provides a snapshot of the patient's condition. Therefore, frequent monitoring is warranted in at-risk patients. However, there is no one-size-fits-all approach for monitoring, treatment and referral decisions. This is particularly the case in patients with advanced age. In this article, through the use of case examples, we aim to provide guidance when facing difficult management decisions in patients with (suspected) COVID-19.", "title": "[COVID-19: care at home or in hospital? Considerations in primary care].", "pid": "4xny3bn4", "bm25_score": 214.72793579101562}, {"text": "OBJECTIVES: The December 2019 outbreak of coronavirus has once again thrown the vexed issue of quarantine into the spotlight, with many countries asking their citizens to 'self-isolate' if they have potentially come into contact with the infection. However, adhering to quarantine is difficult. Decisions on how to apply quarantine should be based on the best available evidence to increase the likelihood of people adhering to protocols. We conducted a rapid review to identify factors associated with adherence to quarantine during infectious disease outbreaks. STUDY DESIGN: The study design is a rapid evidence review. METHODS: We searched Medline, PsycINFO and Web of Science for published literature on the reasons for and factors associated with adherence to quarantine during an infectious disease outbreak. RESULTS: We found 3163 articles and included 14 in the review. Adherence to quarantine ranged from as little as 0 up to 92.8%. The main factors which influenced or were associated with adherence decisions were the knowledge people had about the disease and quarantine procedure, social norms, perceived benefits of quarantine and perceived risk of the disease, as well as practical issues such as running out of supplies or the financial consequences of being out of work. CONCLUSIONS: People vary in their adherence to quarantine during infectious disease outbreaks. To improve this, public health officials should provide a timely, clear rationale for quarantine and information about protocols; emphasise social norms to encourage this altruistic behaviour; increase the perceived benefit that engaging in quarantine will have on public health; and ensure that sufficient supplies of food, medication and other essentials are provided.", "title": "How to improve adherence with quarantine: rapid review of the evidence", "pid": "kjnnh00e", "bm25_score": 214.72451782226562}, {"text": "Population adoption of social distancing measures during the COVID-19 pandemic is at times deficient, increasing the risk of SARS-CoV-2 transmission. Healthcare workers and those living in areas of intense transmission may benefit from implementing biosafety measures in their daily lives. A mixed-methods approach, combining components of single negotiation text and the Delphi method, was used to create a COVID-19 biosafety-at-home protocol. A consensus building coordinator liaised with 12 experts to develop the protocol over 11 iterations. Experts had more than 200 years of combined experience in epidemiology, virology, infectious disease prevention, and public health. A flyer, created from the final protocol, was professionally designed and initially distributed via social media and institutional websites/emails in Ecuador beginning on May 2, 2020. Since then, it has been distributed in other countries, reaching ∼7,000 people. Translating research laboratory biosafety measures for the home/street environment might be challenging. The biosafety-at-home flyer addresses this challenge in a user-friendly format.", "title": "Biosafety at Home: How to Translate Biomedical Laboratory Safety Precautions for Everyday Use in the Context of COVID-19", "pid": "296k3325", "bm25_score": 214.72390747070312}, {"text": "Cleveland Clinic recognized the importance of mitigating community transmission of COVID-19 by keeping people at home. Patient-care activities quickly pivoted to remote touches, preserving continuity through a variety of digital and telephonic modalities. As the number of confirmed cases grew, standardizing home-based care became critical to managing high-risk patients, moderating the risk of exposure for healthcare workers, and reducing the amount of community spread through appropriate education on home-based care for exposed or infected individuals. This novel, team-based approach to caring for patients with COVID-19 incorporates a self-monitoring app for patient engagement, monitors symptoms for early intervention, and promotes a holistic view of care.", "title": "Home monitoring for COVID-19.", "pid": "mz7nuskv", "bm25_score": 214.7238006591797}, {"text": "December 2019 witnessed the outbreak of COVID-19 in Wuhan, Hubei province of China, which has soon spread nationwide and across national borders, posting a menacing pandemic threat. Children are themselves highly susceptible infectious diseases in normal times not to mention an epidemic period. Coupled with the high incidence of seasonal influenza, it is imperative to strengthen epidemiological screening of children, along with effective isolation, treatment, prevention and control measures. In view of specifics of the hospital, the authors proposed to further improve the medical emergency procedure, strictly enforcing screening and isolation regulations, and standardizing medical procedure. They also proposed scientific layout and use of the infection wards. These measures are designed to control the epidemic and protect the safety of medical staff.", "title": "Discussions on the emergency medical procedure of children's hospitals against COVID-19 epidemic/ 中华医院管理杂志", "pid": "8hg6wi7z", "bm25_score": 214.71548461914062}, {"text": "Preventing transmission of emerging infectious diseases remains a challenge for infection prevention and occupational safety programs. The recent Ebola and measles outbreaks highlight the need for pre-epidemic planning, early identification, and appropriate isolation of infected individuals and health care personnel protection. To optimally allocate limited infection control resources, careful consideration of major modes of transmission, the relative infectiousness of the agent, and severity of the pathogen-specific disease are considered. A framework to strategically approach pathogens proposed for health care settings includes generic principles (1) elimination of potential exposure, (2) implementation of administrative controls, (3) facilitation of engineering and environmental controls, and (4) protection of the health care worker and patient using hand hygiene and personal protective equipment. Additional considerations are pre-epidemic vaccination and incremental costs and benefits of infection prevention interventions. Here, major strategies for preventing health-care-associated transmissions are reviewed, including reducing exposure; vaccination; administrative, engineering, and environmental controls; and personal protective equipment. Examples from recent outbreaks are used to highlight key infection prevention aspects and controversies.", "title": "Using the Pillars of Infection Prevention to Build an Effective Program for Reducing the Transmission of Emerging and Reemerging Infections", "pid": "ou7n57vc", "bm25_score": 214.70367431640625}, {"text": "Abstract Objectives The January 2020 outbreak of coronavirus has once again thrown the vexed issue of quarantine into the spotlight, with many countries asking their citizens to ‘self-isolate’ if they have potentially come into contact with the infection. However, adhering to quarantine is difficult. Decisions on how to apply quarantine should be based on the best available evidence to increase the likelihood of people adhering to protocols. We conducted a rapid review to identify factors associated with adherence to quarantine during infectious disease outbreaks. Study design Rapid evidence review. Methods We searched Medline, PsycINFO and Web of Science for published literature on the reasons for and factors associated with adherence to quarantine during an infectious disease outbreak. Results We found 3163 papers and included 14 in the review. Adherence to quarantine ranged from as little as 0 up to 92.8%. The main factors which influenced or were associated with adherence decisions were the knowledge people had about the disease and quarantine procedure, social norms, perceived benefits of quarantine and perceived risk of the disease, as well as practical issues such as running out of supplies or the financial consequences of being out of work. Conclusions People vary in their adherence to quarantine during infectious disease outbreaks. To improve this, public health officials should provide a timely, clear rationale for quarantine and information about protocols; emphasise social norms to encourage this altruistic behaviour; increase the perceived benefit that engaging in quarantine will have on public health; and ensure that sufficient supplies of food, medication and other essentials are provided.", "title": "How to improve adherence with quarantine: Rapid review of the evidence", "pid": "9hrrkqgi", "bm25_score": 214.70274353027344}, {"text": "Abstract With over 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. The objective of this paper is to critically review the available evidence regarding the lessons learned from the Chinese experience regarding COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hebei and the rest of the country, as well as closure of all schools and non-essential businesses. Other measures included the rapid construction of two new hospitals and the establishment of Fangcang shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin and convalescent plasma infusions. These measures appeared to provide only moderate success. While some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well-controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers and contacts, and early implementation of quarantine measures with an organized, proactive and unified strategy at a national level. Delays result in significantly higher death tolls.", "title": "Management and Treatment of COVID-19: The Chinese Experience", "pid": "gy0kfhy6", "bm25_score": 214.70016479492188}, {"text": "Abstract Hospitals are important sources of pollutants resulted from diagnostic, laboratory and research activities as well as medicine excretion by patients, which include active component of drugs and metabolite, chemicals, residues of pharmaceuticals, radioactive markers, iodinated contrast media, etc. The discharge of hospital wastes and wastewater, especially those without appropriate treatment would expose the public in danger of infection. In particular, under the Coronavirus Disease 2019 (COVID-19) pandemic context in China, it is of great significance to reduce the health risks to the public and environment. In this study, technologies of different types of hospital wastes and wastewater disinfection have been summarized. Liquid chlorine, sodium hypochlorite, chlorine dioxide, ozone, and ultraviolet irradiation disinfection are commonly used for hospital wastewater disinfection. While incineration, chemical disinfection, and physical disinfection are commonly used for hospital wastes disinfection. In addition, considering the characteristics of various hospital wastes, the classification and selection of corresponding disinfection technologies are discussed. On this basis, this study provides scientific suggestions for management, technology selection, and operation of hospital wastes and wastewater disinfection in China, which is of great significance for development of national disinfection strategy for hospital wastes and wastewater during COVID-19 pandemic.", "title": "Disinfection technology of hospital wastes and wastewater: Suggestions for disinfection strategy during coronavirus Disease 2019 (COVID-19) pandemic in China", "pid": "4d6fnjt8", "bm25_score": 214.69802856445312}, {"text": "OBJECTIVE. The purpose of this article is to share an experience in the rapid deployment of home workstations that illustrates a creative solution that transcended typical administrative barriers. CONCLUSION. In response to the global coronavirus disease (COVID-19) pandemic, radiology departments need to rapidly deploy home PACS workstations to facilitate physical distancing and to guarantee radiologic expertise despite possible home quarantining or stay home, work safe orders.", "title": "Response to the COVID-19 Pandemic: Practical Guide to Rapidly Deploying Home Workstations to Guarantee Radiology Services During Quarantine, Social Distancing, and Stay Home Orders.", "pid": "nlfr3lth", "bm25_score": 214.6913299560547}, {"text": "PURPOSE OF REVIEW: Hand hygiene and isolation are basic, but very effective, means of preventing the spread of pathogens in healthcare. Although the principle may be straightforward, this review highlights some of the controversies regarding the implementation and efficacy of these interventions. RECENT FINDINGS: Hand hygiene compliance is an accepted measure of quality and safety in many countries. The evidence for the efficacy of hand hygiene in directly reducing rates of hospital-acquired infections has strengthened in recent years, particularly in terms of reduced rates of staphylococcal sepsis. Defining the key components of effective implementation strategies and the ideal method(s) of assessing hand hygiene compliance are dependent on a range of factors associated with the healthcare system. Although patient isolation continues to be an important strategy, particularly in outbreaks, it also has some limitations and can be associated with negative effects. Recent detailed molecular epidemiology studies of key healthcare-acquired pathogens have questioned the true efficacy of isolation, alone as an effective method for the routine prevention of disease transmission. SUMMARY: Hand hygiene and isolation are key components of basic infection control. Recent insights into the benefits, limitations and even adverse effects of these interventions are important for their optimal implementation.", "title": "Back to basics: hand hygiene and isolation", "pid": "q4nzhbvt", "bm25_score": 214.6868896484375}, {"text": "The novel coronavirus disease (COVID-19) is a recent pandemic which has spread to over 200 countries of the world since its outbreak. As of 21st April, 2020, more than 2.3 million confirmed cases have been reported. The World Health Organization (WHO) has issued a strategic preparedness response plan for countries at risk. This is based on the knowledge of previous epidemics and experience shared by Chinese health authorities. There is special emphasis on strict 'quarantine and isolation' of suspected/diagnosed cases. Pakistan is a developing country with a weak healthcare system. Pakistan Armed Forces have always provided services to the countrymen during natural and man-made disasters. During this pandemic the largest rehabilitation institute in the country was converted into a 130-bed dedicated isolation and quarantine facility for the COVID-19 patients. We will share our experience of establishing and managing this quarantine and isolation facility and highlight the achievements and out-of-the-box solutions applicable for low resource countries like Pakistan.", "title": "Establishing and managing a quarantine and isolation centre in COVID-19 pandemic.", "pid": "ta8sss1s", "bm25_score": 214.6622314453125}, {"text": "This clinical report offers guidance to health care providers and hospitals on options to consider regarding parental presence at the bedside while caring for a child with suspected or proven Ebola virus disease (Ebola) or other highly consequential infection. Options are presented to help meet the needs of the patient and the family while also posing the least risk to providers and health care organizations. The optimal way to minimize risk is to limit contact between the person under investigation or treatment and family members/caregivers whenever possible while working to meet the emotional support needs of both patient and family. At times, caregiver presence may be deemed to be in the best interest of the patient, and in such situations, a strong effort should be made to limit potential risks of exposure to the caregiver, health care providers, and the community. The decision to allow parental/caregiver presence should be made in consultation with a team including an infectious diseases expert and state and/or local public health authorities and should involve consideration of many factors, depending on the stage of investigation and management, including (1) a careful history, physical examination, and investigations to elucidate the likelihood of the diagnosis of Ebola or other highly consequential infection; (2) ability of the facility to offer appropriate isolation for the person under investigation and family members and to manage Ebola; (3) ability to recognize and exclude people at increased risk of worse outcomes (eg, pregnant women); and (4) ability of parent/caregiver to follow instructions, including appropriate donning and doffing of personal protective equipment.", "title": "Parental Presence During Treatment of Ebola or Other Highly Consequential Infection.", "pid": "gdhcpmom", "bm25_score": 214.65939331054688}, {"text": "Summary The recent severe acute respiratory syndrome (SARS) outbreak has almost mandated a re-evaluation of infection control practices in hospitals, clinics, schools and domestic environments, especially for patients with respiratory tract symptoms. Triage, early case detection followed by prompt isolation and quarantine are major preventive measures. Respiratory tract infections are the most common childhood illnesses and paediatric SARS poses special problems in diagnosis because of its non-specific presentation. The main lessons learnt from the outbreak were: (1) despite well established guidelines on infection control precautions, poor understanding of underlying principles and deficiencies in compliance are common among healthcare professionals, especially during emergencies; (2) even a slight lapse can be fatal; and (3) over-protection can be counterproductive. Hence it is important to: (1) be protected to protect others; (2) be vigilant and prepared for emerging infections; (3) be proficient and scrupulous in infection control measures; (4) be apposite and practical on personal protective equipments to ensure sustainability; and (5) be dutiful and prompt in informing of potential threats and work closely with others.", "title": "Post-SARS infection control in the hospital and clinic", "pid": "lu3ngt6r", "bm25_score": 214.656005859375}, {"text": "Infections, troublesome in even optimal health care environments, can be a source of serious and persistent concern for local populations and health care workers during a disaster, and in austere environments such as those found in Iraq and Afghanistan. For these scenarios, it is vital to have standard infection control practices in place and to have them used consistently. Only then will healthcare workers be able to contain the potential spread of disease and improve conditions for those affected.", "title": "Implementing Basic Infection Control Practices in Disaster Situations", "pid": "ys0ndxun", "bm25_score": 214.64979553222656}, {"text": "Cleveland Clinic recognized the importance of mitigating community transmission of COVID-19 by keeping people at home. Patient-care activities quickly pivoted to remote touches, preserving continuity through a variety of digital and telephonic modalities. As the number of confirmed cases grew, standardizing home-based care became critical to managing high-risk patients, moderating the risk of exposure for healthcare workers, and reducing the amount of community spread through appropriate education on home-based care for exposed or infected individuals. This novel, team-based approach to caring for patients with COVID-19 incorporates a self-monitoring app for patient engagement, monitors symptoms for early intervention, and promotes a holistic view of care.", "title": "Home monitoring for COVID-19", "pid": "c3ehp7na", "bm25_score": 214.63992309570312}, {"text": "Hospital-associated infections (HAIs) occur in veterinary hospitals of all types and sizes, and their frequency is likely to increase. Urinary tract infections, pneumonia, bloodstream infections, surgical site infections, and infectious diarrhea are the HAIs most frequently identified in veterinary medicine. A hospital infection control program, consisting of an infectious disease control officer, written protocols, and staff training, is critical to reducing HAIs and promoting patient, staff, and client health. Infection control protocols (plans) should include discussion of hand hygiene and use of personal protective equipment, cleaning and disinfection, patient management, with-in hospital surveillance, and antimicrobial stewardship.", "title": "Hospital-Associated Infections in Small Animal Practice", "pid": "36gyix12", "bm25_score": 214.63983154296875}, {"text": "PURPOSE OF REVIEW The emergence of 2009 pandemic H1N1 influenza A (pH1N1) has provided a unique challenge to influenza control in healthcare settings. We provide an overview of the early lessons from the 2009 pandemic. RECENT FINDINGS The modes of influenza transmission and their contributions to the development of infections remain unclear. Recent studies in the guinea pig model have demonstrated airborne transmission, but data from human studies and outbreaks are inconclusive. Data on physical interventions to prevent transmission support the use of hand hygiene, gowns, gloves, face shields and respiratory protection. The effectiveness of surgical masks compared to N95 respirators has been investigated, and there is evidence from one trial that surgical masks are noninferior to N95 respirators in preventing infection. Experiences with mandatory vaccination suggest that this is a highly successful approach to increase healthcare personnel vaccination rates. Lessons from pH1N1 have multiple implications for future pandemic preparedness planning. SUMMARY Further research is needed on appropriate respiratory protection for influenza. Mandatory vaccination programs should be considered in all healthcare settings. Pandemic preparedness plans should be revised, focusing on flexibility, communication, stockpiling of essential supplies, and staffing support for infection control.", "title": "Control of influenza in healthcare settings: early lessons from the 2009 pandemic.", "pid": "yee0ha2k", "bm25_score": 214.61500549316406}, {"text": "Abstract This paper discusses the application of optimal and sub-optimal controls to a SEQIJR SARS model via the Pontryagin’s Maximum Principle. To this end, two control variables representing the quarantine and isolation strategies are considered in the model. The numerical optimal control laws are implemented in an iterative method, and the sub-optimal solution is computed using a genetic algorithm. The simulation results demonstrate that the maximal applications of quarantining and isolation strategies in the early stage of the epidemic are of very critical impacts in both cases of optimal and sub-optimal control. Otherwise, the control effect will be much worse. This gives a theoretical interpretation to the practical experiences that the early quarantine and isolation strategies are critically important to control the outbreaks of epidemics. Furthermore, our results also show that the proposed sub-optimal control can lead to performances close to the optimal control, but with much simpler strategies for long periods of time in practical use.", "title": "Optimal and sub-optimal quarantine and isolation control in SARS epidemics", "pid": "2xflheth", "bm25_score": 214.6143798828125}, {"text": "The physical design and infrastructure of a hospital or institution is an essential component of its infection control measure. Thus is must be a prerequisite to take these into consideration from the initial conception and planning stages of the building. The balance between designing a hospital to be an open, accessible and public place and the control to reduce the spread of infections diseases is a necessity. At Singapore General Hospital, many lessons were learnt during the SARS outbreak pertaining to this. During and subsequent to the SARS outbreak, many changes evolved in the hospital to enable us to handle and face any emerging infectious situation with calm, confidence and the knowledge that staff and patients will be in good stead. This paper will share some of our experiences as well as challenges", "title": "Hospital design for better infection control", "pid": "untido1h", "bm25_score": 214.61061096191406}, {"text": "OBJECTIVE The purpose of this study was to explore the experience of home quarantine during the severe acute respiratory syndrome (SARS) outbreak in Toronto in 2003. DESIGN Qualitative descriptive design. SAMPLE Stratified random sampling techniques were used to generate a list of potential participants, who varied in terms of gender and closeness of exposure to someone with suspected SARS (contact level). Twenty-one individuals participated in the study. MEASUREMENTS All interviews were audiotaped and followed a semistructured interview guide. Participants were invited to describe their experience of quarantine in detail including their advice for Public Health. RESULTS The experience followed a trajectory of stages beginning before quarantine and ending after quarantine. Despite individual differences, common themes of uncertainty, isolation, and coping intersected the data. CONCLUSIONS Public Health has a dual role of monitoring compliance and providing support to people in quarantine. This study has implications for public health policy and practice in planning for future public health emergencies in terms of the information and the resources required to mount an effective response.", "title": "The experience of quarantine for individuals affected by SARS in Toronto.", "pid": "xdgd11k6", "bm25_score": 214.60711669921875}, {"text": "OBJECTIVE: Measures to decrease hospital length of stay and outpatient visits are crucial during the coronavirus disease 2019 (COVID-19) pandemic. Physician-guided home drain removal presents a potential opportunity for mitigating viral spread and transmission. METHODS: A prospective case series on patients undergoing major head and neck surgery with Jackson-Pratt drain placement was conducted. Patients were shown an infographic detailing drain care and removal at preoperative assessment and prior to discharge. At a 1-week follow-up telemedicine visit, patients were instructed to remove the drain under physician guidance. Patients were assessed 7 days after to determine complication rate and satisfaction. RESULTS: Twenty-five patients were enrolled with 100% patients undergoing successful drain removal at home with caregiver support. There were no complications reported at the 7-day postdrain removal time point, and overall patient satisfaction was high. DISCUSSION: Infographics and telemedicine are 2 synergistic strategies to guide safe and effective home drain removal. IMPLICATIONS FOR PRACTICE: This study demonstrates how telemedicine and an infographic can be effectively used in physician-guided home drain removal. During a time like the COVID-19 pandemic, innovative measures are necessary to curb transmission and infection rates. We propose a unique and replicable yet safe solution to limit unnecessary exposure and encourage other surgical providers to adopt a similar strategy.", "title": "Using Telemedicine and Infographics for Physician-Guided Home Drain Removal", "pid": "fbfiv8p0", "bm25_score": 214.6016845703125}, {"text": "A mandatory 14-day 'centralized medical quarantine' has been instituted in Shanghai, China, to prevent secondary transmission of imported COVID-19. Here we summarize our experiences and describe the work flow and disinfection measures in our quarantine centre.", "title": "Centralized medical quarantine for imported COVID-19 in Shanghai, China.", "pid": "7gmqezm2", "bm25_score": 214.59568786621094}, {"text": "Abstract This article reviews in a historical perspective and by means of documented examples the scientific principles relevant to the concept and effectiveness of quarantine, the logistic, economic, and political barriers to its correct implementation through time, and the health impact of local and large-scale quarantine. Quarantine is overall one of the oldest and most disseminated and, despite its limits, most effective health measures elaborated by mankind. The evidence-based history of medicine and evidence-based modern epidemiology indicate that the implementation of correct quarantine procedures is today still feasible and useful provided that a proactive collaboration is operative among those concerned and that the measures are tailored according to geographical, social, and health conditions.", "title": "Quarantine through History", "pid": "d5p4chhg", "bm25_score": 214.5856170654297}]}
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"ywe89dxd": 0, "ywnmogiy": 0, "yxizepar": 1, "pkkj4udv": 2, "yxmkaqo8": 1, "yyfuu197": 1, "yzloau0d": 0, "z0e97ost": 1, "z0ni2jsr": 0, "z4a8ru9z": 1, "z4lflkmo": 2, "z4vfjlbg": 1, "z5dy8kxf": 0, "031lez19": 0, "z6b91avu": 0, "z6fd4yua": 1, "z6krvfee": 0, "z9cyv0jq": 0, "z9dolxky": 2, "za7qm2on": 0, "zaaj1jw2": 1, "zb3ok9b8": 2, "zb434ve3": 0, "zd4v222b": 1, "zdh8ms1z": 1, "zel9a3u6": 0, "zgr2xkzk": 1, "zhcghyw8": 1, "zi98dq1v": 0, "zifccdqm": 0, "zmaw9lbz": 0, "435tli39": 1, "zoqatt6t": 0, "zp2u7e03": 0, "ft15w83r": 1, "zpek8i5e": 1, "zph4nv75": 0, "zppc6p20": 1, "zriuh5q5": 1, "zrnczve3": 0, "ztl54g6q": 0, "zuedsaqg": 0, "zueghgx5": 1, "b2hirso9": 1, "zxn7psir": 0, "zz4cczuj": 2}, "bm25_results": [{"text": "Since the outbreak of COVID-19 in Wuhan, China, at the end of 2019, it has demonstrated China's ability to identify unknown pathogens. At present, reports showed that the main transmission routes are respiratory droplets and indirect contact, other vertical transmission routes have yet to be confirmed. This review discusses the possible transmission routes of 2019-novel coronavirus (2019-nCoV), based on currently research, the main transmission routes are respiratory droplets and indirect contact, fecal-oral might bepossible, while aerosol, tear (conjunctival) and mother-to-fetus still have yet to be confirmed, providing a reference basis for 2019-nCoV prevention and control and public protection.", "title": "[Transmission routes of 2019-novel coronavirus (2019-nCoV)].", "pid": "85vnyr36", "bm25_score": 217.685791015625}, {"text": "Since the outbreak of COVID-19 in Wuhan, China, at the end of 2019, it has demonstrated China's ability to identify unknown pathogens. At present, reports showed that the main transmission routes are respiratory droplets and indirect contact, other vertical transmission routes have yet to be confirmed. This review discusses the possible transmission routes of 2019-novel coronavirus (2019-nCoV), based on currently research, the main transmission routes are respiratory droplets and indirect contact, fecal-oral might bepossible, while aerosol, tear (conjunctival) and mother-to-fetus still have yet to be confirmed, providing a reference basis for 2019-nCoV prevention and control and public protection.", "title": "[Transmission routes of 2019-novel coronavirus (2019-nCoV)]", "pid": "2yblpbwm", "bm25_score": 217.63470458984375}, {"text": "The advent of novel human coronavirus (SARS-CoV-2) and its potential transmission via fecal-oral and aerosols-borne routes are upcoming challenges to understand the fate of the virus in the environment. In this short communication, we specifically looked at the possibilities of these transmission routes based on the available literature directly related to the SARS-CoV-2 as well as on the closer phylogenetic relatives such as SARS-CoV-1. The available data suggest that, in addition to human-to-human contact, the virus may spread via fecal-oral and aerosols-borne routes. Existing knowledge states that coronaviruses have low stability in the environment due to the natural action of oxidants that disrupt the viral envelope. Previous recommended dosage of chlorination has been found to be not sufficient to inactivate SARS-CoV-2 in places where viral load is high such as hospitals and airports. Although there is no current evidence showing that coronaviruses can be transmitted through contaminated drinking water, there is a growing concern on the impact of the current pandemic wave on underprivileged societies because of their poor wastewater treatment infrastructures, overpopulation, and outbreak management strategies. More research is encouraged to trace the actual fate of SARS-CoV-2 in the environment and to develop/revise the disinfection strategies accordingly.", "title": "Transmission of SARS-CoV-2 via fecal-oral and aerosols-borne routes: Environmental dynamics and implications for wastewater management in underprivileged societies", "pid": "9of9gijc", "bm25_score": 217.2287139892578}, {"text": "Abstract The advent of novel human coronavirus (SARS-CoV-2) and its potential transmission via fecal-oral and aerosols-borne routes are upcoming challenges to understand the fate of the virus in the environment. In this short communication, we specifically looked at the possibilities of these transmission routes based on the available literature directly related to the SARS-CoV-2 as well as on the closer phylogenetic relatives such as SARS-CoV-1. The available data suggest that, in addition to human-to-human contact, the virus may spread via fecal-oral and aerosols-borne routes. Existing knowledge states that coronaviruses have low stability in the environment due to the natural action of oxidants that disrupt the viral envelope. Previous recommended dosage of chlorination has been found to be not sufficient to inactivate SARS-CoV-2 in places where viral load is high such as hospitals and airports. Although there is no current evidence showing that coronaviruses can be transmitted through contaminated drinking water, there is a growing concern on the impact of the current pandemic wave on underprivileged societies because of their poor wastewater treatment infrastructures, overpopulation, and outbreak management strategies. More research is encouraged to trace the actual fate of SARS-CoV-2 in the environment and to develop/revise the disinfection strategies accordingly.", "title": "Transmission of SARS-CoV-2 via fecal-oral and aerosols–borne routes: Environmental dynamics and implications for wastewater management in underprivileged societies", "pid": "ioo17gc3", "bm25_score": 216.9609375}, {"text": "A novel ß-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal-oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.", "title": "Transmission routes of 2019-nCoV and controls in dental practice", "pid": "wywldhr0", "bm25_score": 216.2548828125}, {"text": "Summary Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings.", "title": "Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination", "pid": "pk8u9m7h", "bm25_score": 216.1305694580078}, {"text": "Infections caused by the Middle East respiratory syndrome coronavirus (MERS‐CoV) are a serious health issue due to their prevalence and associated mortality. However, the transmission routes of the virus remain unclear, and thus, the current recommended control strategies are not evidence based. In this study, we investigated the transmission routes of MERS‐CoV during the first nosocomial outbreak in the Republic of Korea in May 2015 using a multi‐agent modeling framework. We identified seven hypothesized transmission modes based on the three main transmission routes (long‐range airborne, close contact, and fomite). The infection risks for each hypothesis were estimated using the multi‐agent modeling framework. Least‐squares fitting was conducted to compare the distribution of the predicted infection risk in the various scenarios with that of the reported attack rates and to identify the hypotheses with the best fit. In the scenarios in which the index patient was a super‐spreader, our model simulations suggested that MERS‐CoV probably spread via the long‐range airborne route. However, it is possible that the index patient shed an average viral load comparable to the loads reported in the literature, and that transmission occurred via a combined long‐range airborne and close contact route.", "title": "A study of the probable transmission routes of MERS‐CoV during the first hospital outbreak in the Republic of Korea", "pid": "4nd5wzrm", "bm25_score": 216.12979125976562}, {"text": "A novel β-coronavirus (2019-nCoV) caused severe and even fetal pneumonia explored in a seafood market of Wuhan city, Hubei province, China, and rapidly spread to other provinces of China and other countries. The 2019-nCoV was different from SARS-CoV, but shared the same host receptor the human angiotensin-converting enzyme 2 (ACE2). The natural host of 2019-nCoV may be the bat Rhinolophus affinis as 2019-nCoV showed 96.2% of whole-genome identity to BatCoV RaTG13. The person-to-person transmission routes of 2019-nCoV included direct transmission, such as cough, sneeze, droplet inhalation transmission, and contact transmission, such as the contact with oral, nasal, and eye mucous membranes. 2019-nCoV can also be transmitted through the saliva, and the fetal–oral routes may also be a potential person-to-person transmission route. The participants in dental practice expose to tremendous risk of 2019-nCoV infection due to the face-to-face communication and the exposure to saliva, blood, and other body fluids, and the handling of sharp instruments. Dental professionals play great roles in preventing the transmission of 2019-nCoV. Here we recommend the infection control measures during dental practice to block the person-to-person transmission routes in dental clinics and hospitals.", "title": "Transmission routes of 2019-nCoV and controls in dental practice", "pid": "lasv4e6a", "bm25_score": 216.05709838867188}, {"text": "", "title": "Transmission routes of SARS-CoV-2", "pid": "up54no93", "bm25_score": 215.98745727539062}, {"text": "SARS-CoV-2, a coronavirus that newly emerged in China in late 2019 1,2 and spread rapidly worldwide, caused the first witnessed pandemic sparked by a coronavirus. As the pandemic progresses, information about the modes of transmission of SARS-CoV-2 among humans is critical to apply appropriate infection control measures and to slow its spread. Here we show that SARS-CoV-2 is transmitted efficiently via direct contact and via the air (via respiratory droplets and/or aerosols) between ferrets. Intranasal inoculation of donor ferrets resulted in a productive upper respiratory tract infection and long-term shedding, up to 11 to 19 days post-inoculation. SARS-CoV-2 transmitted to four out of four direct contact ferrets between 1 and 3 days after exposure and via the air to three out of four independent indirect recipient ferrets between 3 and 7 days after exposure. The pattern of virus shedding in the direct contact and indirect recipient ferrets was similar to that of the inoculated ferrets and infectious virus was isolated from all positive animals, showing that ferrets were productively infected via either route. This study provides experimental evidence of robust transmission of SARS-CoV-2 via the air, supporting the implementation of community-level social distancing measures currently applied in many countries in the world and informing decisions on infection control measures in healthcare settings 3.", "title": "SARS-CoV-2 is transmitted via contact and via the air between ferrets", "pid": "sg1grxlq", "bm25_score": 215.98431396484375}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent for the 2019 coronavirus disease (COVID-19) pandemic, has caused a public health emergency. The need for additional research in viral pathogenesis is essential as the number of cases and deaths rise. Understanding the virus and its ability to cause disease has been the main focus of current literature; however, there is much unknown. Studies have revealed new findings related to the full transmission potential of SARS-CoV-2 and its subsequent ability to cause infection by different means. The virus is hypothesized to be of increased virulence compared with previous coronavirus that caused epidemics, in part due to its overall structural integrity and resilience to inactivation. To date, many studies have discussed that the rationale behind its transmission potential is that viral RNA has unexpectedly been detected in multiple bodily fluids, with some samples having remained positive for extended periods of time. Additionally, the receptor by which the virus gains cellular entry, ACE2, has been found to be expressed in different human body systems, thereby potentiating its infection in those locations. In this evidence-based comprehensive review, we discuss various potential routes of transmission of SARS-CoV-2—respiratory/droplet, indirect, fecal-oral, vertical, sexual, and ocular. Understanding these different routes is important as they pertain to clinical practice, especially in taking preventative measures to mitigate the spread of SARS-CoV-2.", "title": "Transmission of SARS-CoV-2: an update of current literature", "pid": "cfv0ta10", "bm25_score": 215.9191131591797}, {"text": "In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral-fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral-fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.", "title": "Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "pid": "zztydksw", "bm25_score": 215.90069580078125}, {"text": "SARS-CoV-2, a coronavirus that emerged in late 2019, has spread rapidly worldwide, and information about the modes of transmission of SARS-CoV-2 among humans is critical to apply appropriate infection control measures and to slow its spread. Here we show that SARS-CoV-2 is transmitted efficiently via direct contact and via the air (via respiratory droplets and/or aerosols) between ferrets, 1 to 3 days and 3 to 7 days after exposure respectively. The pattern of virus shedding in the direct contact and indirect recipient ferrets is similar to that of the inoculated ferrets and infectious virus is isolated from all positive animals, showing that ferrets are productively infected via either route. This study provides experimental evidence of robust transmission of SARS-CoV-2 via the air, supporting the implementation of community-level social distancing measures currently applied in many countries in the world and informing decisions on infection control measures in healthcare settings.", "title": "SARS-CoV-2 is transmitted via contact and via the air between ferrets", "pid": "umq8rupb", "bm25_score": 215.7541961669922}, {"text": "In December 2019, a novel coronavirus (2019-nCoV) caused an outbreak in Wuhan, China, and soon spread to other parts of the world. It was believed that 2019-nCoV was transmitted through respiratory tract and then induced pneumonia, thus molecular diagnosis based on oral swabs was used for confirmation of this disease. Likewise, patient will be released upon two times of negative detection from oral swabs. However, many coronaviruses can also be transmitted through oral–fecal route by infecting intestines. Whether 2019-nCoV infected patients also carry virus in other organs like intestine need to be tested. We conducted investigation on patients in a local hospital who were infected with this virus. We found the presence of 2019-nCoV in anal swabs and blood as well, and more anal swab positives than oral swab positives in a later stage of infection, suggesting shedding and thereby transmitted through oral–fecal route. We also showed serology test can improve detection positive rate thus should be used in future epidemiology. Our report provides a cautionary warning that 2019-nCoV may be shed through multiple routes.", "title": "Molecular and serological investigation of 2019-nCoV infected patients: implication of multiple shedding routes", "pid": "4aps0kvp", "bm25_score": 215.72862243652344}, {"text": "We explore here how variation in the SARS-CoV-2 virus tropism could influence epidemic spread. We use a compartmental model fit to the existing data. The model indicates that Wuhan quarantine measures were effective but that alternative virus forms (gut tropism) and a second propagation route (through environment) was present. For Singapore and Shenzhen region the secondary route does not seem to be active yet. Adequate prevention measures taking into account both routes should be implemented.", "title": "A new transmission route for the propagation of the SARS-CoV-2 coronavirus", "pid": "4ah705nc", "bm25_score": 215.69505310058594}, {"text": "Since December 2019, a newly identified coronavirus (2019 novel coronavirus, 2019-nCov) is causing outbreak of pneumonia in one of largest cities, Wuhan, in Hubei province of China and has draw significant public health attention. The same as severe acute respiratory syndrome coronavirus (SARS-CoV), 2019-nCov enters into host cells via cell receptor angiotensin converting enzyme II (ACE2). In order to dissect the ACE2-expressing cell composition and proportion and explore a potential route of the 2019-nCov infection in digestive system infection, 4 datasets with single-cell transcriptomes of lung, esophagus, gastric, ileum and colon were analyzed. The data showed that ACE2 was not only highly expressed in the lung AT2 cells, esophagus upper and stratified epithelial cells but also in absorptive enterocytes from ileum and colon. These results indicated along with respiratory systems, digestive system is a potential routes for 2019-nCov infection. In conclusion, this study has provided the bioinformatics evidence of the potential route for infection of 2019-nCov in digestive system along with respiratory tract and may have significant impact for our healthy policy setting regards to prevention of 2019-nCoV infection.", "title": "The digestive system is a potential route of 2019-nCov infection: a bioinformatics analysis based on single-cell transcriptomes", "pid": "vpcx2t3w", "bm25_score": 215.61318969726562}, {"text": "The risk of newly emerging diseases is constantly present in a world where changes occur significantly in climatic, commercial, and ecological conditions, in addition to the development of biomedical investigations in new situations. An epidemic respiratory disease instigated by a new coronavirus was initially identified in and has resulted in the current global dissemination. This viral strain and its related disease has been termed “SARS-CoV-2” and “coronavirus disease 2019” (abbreviated “COVID-19” or “2019-nCoV”), respectively, which is transmitted simply between individuals. The World Health Organization (WHO) announced the COVID-19 outburst as a pandemic on March 11, which necessitates a cooperative endeavour globally for mitigating the spread of COVID-19. The absence of previous, and minimum present-day information, particularly concerning the path of contagion have precluded the control of this disease. The present article, therefore, describes the SARS-CoV-2 paths of contagion such as drinking water, solid waste, sewer water, ambient air, and the rest of emerging likely paths.", "title": "An updated min-review on environmental route of the SARS-CoV-2 transmission", "pid": "e697v9d0", "bm25_score": 215.5963134765625}, {"text": "Abstract Coronavirus disease 2019 (COVID-19) emerged in Hubei Province, China in December 2019 and has since become a global pandemic, with hundreds of thousands of cases and over 165 affected countries. Primary routes of transmission of the causative virus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), are through respiratory droplets and close person-to-person contact. While information about other potential modes of transmission are relatively sparse, evidence supporting the possibility of a fecally-mediated mode of transmission has been accumulating. Here, current knowledge on the potential for fecal transmission is briefly reviewed and the possible implications are discussed from a public health perspective.", "title": "Potential Fecal Transmission of SARS-CoV-2: Current Evidence and Implications for Public Health", "pid": "ruk46455", "bm25_score": 215.564697265625}, {"text": "Coronavirus disease 2019 (COVID-19) emerged in Hubei Province, China in December 2019 and has since become a global pandemic, with hundreds of thousands of cases and over 165 countries affected. Primary routes of transmission of the causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are through respiratory droplets and close person-to-person contact. While information about other potential modes of transmission are relatively sparse, evidence supporting the possibility of a fecally mediated mode of transmission has been accumulating. Here, current knowledge on the potential for fecal transmission is briefly reviewed and the possible implications are discussed from a public health perspective.", "title": "Potential fecal transmission of SARS-CoV-2: Current evidence and implications for public health", "pid": "12sbikmx", "bm25_score": 215.56239318847656}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is rapidly spreading across the world to cause thousands of mortalities each day. Poor responses from the authorities to the spread of infection, lack of effective measures for prevention, unavailability of promising treatment options, and sufficient diagnostic options have created an alarming for the world. The transmission routes from human to human of SARS-CoV-2 can be the direct transmission, droplet inhalation transmission, contact transmission, transmission through saliva, and transmission via fecal–oral routes. Due to the asymptomatic spread of SARS-CoV-2's, developing control and prevention measures is challenging. Implementing proper strategies addressing the infection control and clinical supplies, understanding the mechanism associated with pathogenesis, advancing in preventive measures and effective treatment and diagnostic options are necessary to control the ongoing pandemic. In this article, we briefly discuss the features, entry mechanism, infectiousness, and health consequences related to the COVID-19 outbreak.", "title": "Transmission of SARS-CoV-2, Required Developments in Research and Associated Public Health Concerns", "pid": "2e4gz2bo", "bm25_score": 215.53753662109375}, {"text": "@#SARS-CoV-2 has been spreading rapidly since its outbreak in December 2019.Understanding its epidemiological characteristics, especially cutting off transmission routes, is crucial to controlling the spread of the disease. In the study of transmission pathway, the issue of whether SARS-CoV-2 is transmitted through ocular surface tissue has also aroused concerns, but there are still no clinically confirmed cases and laboratory evidence of its infection through ocular surface tissue. New research suggests that the SARS-CoV-2 belongs to the same genus as SARS coronavirus(SARS-CoV), and that it enters cells in the same way as SARS-CoV. This paper reviews the research on SARS-CoV to investigate the possible mechanism of eye transmission of SARS-CoV-2.", "title": "Investiagation of possible mechanism of eye transmission of SARS-CoV-2 based on SARS-CoV/ 国际眼科杂志(Guoji Yanke Zazhi)", "pid": "4v4ko0o4", "bm25_score": 215.39999389648438}, {"text": "World Health Organization has suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted through person-to-person transmission and contact with contaminated surfaces. However, rapid spread of the coronavirus disease 2019 (COVID-19) suggests other routes such as airborne transmission may be involved. A few research studies have been conducted to evaluate the potential transmission of this virus through air. Although some studies have found no evidence of airborne transmission, other more recent work is proving the presence of SARS-CoV-2 even in public places. Also, the past experiences and knowledge about the mechanisms of similar viruses such as SARS-CoV support this hypothesis. It seems that the best decision at the moment is to follow a conservative approach, and accept the hypothesis that SARS-CoV-2 is able to be transmitted through air. By this, control measures could be employed to prevent further COVID-19 infection.", "title": "A letter about the airborne transmission of sars-cov-2 based on the current evidence", "pid": "a1ha0hx4", "bm25_score": 215.36959838867188}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic, in part due to the highly infectious nature of the disease. Because SARS-CoV-2 is new, much is unknown regarding mechanisms of transmission, and such information is urgently needed. Here, based on previous findings from related human betacoronaviruses, it is suggested that one possible route of transmission may be via infectious sweat. It is suggested that research be conducted in order to determine whether sweat in SARS-CoV-2 infected individuals harbors virus in quantities that can infect others. Findings could be used for formulations of mitigation strategies and empirically based public health messaging.", "title": "Is sweat a possible route of transmission of SARS-CoV-2?", "pid": "5cygqkgk", "bm25_score": 215.3679656982422}, {"text": "The COVID-19 pandemic caused the shutdown of entire nations all over the world. In addition to mobility restrictions of people, the World Health Organization and the Governments have prescribed maintaining an inter-personal distance of 1.5 or 2 m (about 6 feet) from each other in order to minimize the risk of contagion through the droplets that we usually disseminate around us from nose and mouth. However, recently published studies support the hypothesis of virus transmission over a distance of 2 m from an infected person. Researchers have proved the higher aerosol and surface stability of SARS-COV-2 as compared with SARS-COV-1 (with the virus remaining viable and infectious in aerosol for hours) and that airborne transmission of SARS-CoV can occur besides close-distance contacts. Indeed, there is reasonable evidence about the possibility of SARS-COV-2 airborne transmission due to its persistence into aerosol droplets in a viable and infectious form. Based on the available knowledge and epidemiological observations, it is plausible that small particles containing the virus may diffuse in indoor environments covering distances up to 10 m from the emission sources, thus representing a kind of aerosol transmission. On-field studies carried out inside Wuhan Hospitals showed the presence of SARS-COV-2 RNA in air samples collected in the hospitals and also in the surroundings, leading to the conclusion that the airborne route has to be considered an important pathway for viral diffusion. Similar findings are reported in analyses concerning air samples collected at the Nebraska University Hospital. On March 16th, we have released a Position Paper emphasizing the airborne route as a possible additional factor for interpreting the anomalous COVID-19 outbreaks in northern Italy, ranked as one of the most polluted areas in Europe and characterized by high particulate matter (PM) concentrations. The available information on the SARS-COV-2 spreading supports the hypothesis of airborne diffusion of infected droplets from person to person at a distance greater than two meters (6 feet). The inter-personal distance of 2 m can be reasonably considered as an effective protection only if everybody wears face masks in daily life activities.", "title": "Airborne Transmission Route of COVID-19: Why 2 Meters/6 Feet of Inter-Personal Distance Could Not Be Enough", "pid": "nc9fhjga", "bm25_score": 215.34982299804688}, {"text": "The spread of a neurotropic coronavirus, mouse hepatitis virus strain A59, in the mouse central nervous system was studied after intranasal inoculation. Mouse hepatitis virus strain A59 spread during the 3- to 5-day postinoculation period, through the olfactory pathway into the limbic system. Coronavirus particles were detected in the limbic system by electron microscopy. The combination of temporal propagation through an anatomical-physiological central nervous system pathway and anatomical restriction of viral infection suggests that specific interneuronal transport is important in spread of the virus. This experimental system may represent a model for diseases associated with human coronaviruses (common cold viruses) and/or the human limbic system.", "title": "Limbic encephalitis after inhalation of a murine coronavirus.", "pid": "om35s8u9", "bm25_score": 215.3362274169922}, {"text": "Human coronaviruses (HCoVs) are recognized respiratory pathogens for which accumulating evidence indicates that in vulnerable patients the infection can cause more severe pathologies. HCoVs are not always confined to the upper respiratory tract and can invade the central nervous system (CNS) under still unclear circumstances. HCoV-induced neuropathologies in humans are difficult to diagnose early enough to allow therapeutic interventions. Making use of our already described animal model of HCoV neuropathogenesis, we describe the route of neuropropagation from the nasal cavity to the olfactory bulb and piriform cortex and then the brain stem. We identified neuron-to-neuron propagation as one underlying mode of virus spreading in cell culture. Our data demonstrate that both passive diffusion of released viral particles and axonal transport are valid propagation strategies used by the virus. We describe for the first time the presence along axons of viral platforms whose static dynamism is reminiscent of viral assembly sites. We further reveal that HCoV OC43 modes of propagation can be modulated by selected HCoV OC43 proteins and axonal transport. Our work, therefore, identifies processes that may govern the severity and nature of HCoV OC43 neuropathogenesis and will make possible the development of therapeutic strategies to prevent occurrences.IMPORTANCE Coronaviruses may invade the CNS, disseminate, and participate in the induction of neurological diseases. Their neuropathogenicity is being increasingly recognized in humans, and the presence and persistence of human coronaviruses (HCoV) in human brains have been proposed to cause long-term sequelae. Using our mouse model relying on natural susceptibility to HCoV OC43 and neuronal cell cultures, we have defined the most relevant path taken by HCoV OC43 to access and spread to and within the CNS toward the brain stem and spinal cord and studied in cell culture the underlying modes of intercellular propagation to better understand its neuropathogenesis. Our data suggest that axonal transport governs HCoV OC43 egress in the CNS, leading to the exacerbation of neuropathogenesis. Exploiting knowledge on neuroinvasion and dissemination will enhance our ability to control viral infection within the CNS, as it will shed light on underlying mechanisms of neuropathogenesis and uncover potential druggable molecular virus-host interfaces.", "title": "Axonal Transport Enables Neuron-to-Neuron Propagation of Human Coronavirus OC43.", "pid": "xptxoc3t", "bm25_score": 215.3140869140625}, {"text": "Identifying the exact transmission route(s) of infectious diseases in indoor environments is a crucial step in developing effective intervention strategies. In this study, we proposed a comparative analysis approach and built a model to simulate outbreaks of 3 different in‐flight infections in a similar cabin environment, that is, influenza A H1N1, severe acute respiratory syndrome (SARS) coronavirus (CoV), and norovirus. The simulation results seemed to suggest that the close contact route was probably the most significant route (contributes 70%, 95% confidence interval [CI]: 67%‐72%) in the in‐flight transmission of influenza A H1N1 transmission; as a result, passengers within 2 rows of the index case had a significantly higher infection risk than others in the outbreak (relative risk [RR]: 13.4, 95% CI: 1.5‐121.2, P = .019). For SARS CoV, the airborne, close contact, and fomite routes contributed 21% (95% CI: 19%‐23%), 29% (95% CI: 27%‐31%), and 50% (95% CI: 48%‐53%), respectively. For norovirus, the simulation results suggested that the fomite route played the dominant role (contributes 85%, 95% CI: 83%‐87%) in most cases; as a result, passengers in aisle seats had a significantly higher infection risk than others (RR: 9.5, 95% CI: 1.2‐77.4, P = .022). This work highlighted a method for using observed outbreak data to analyze the roles of different infection transmission routes.", "title": "Routes of transmission of influenza A H1N1, SARS CoV, and norovirus in air cabin: Comparative analyses", "pid": "sfa9d1ux", "bm25_score": 215.31011962890625}, {"text": "BACKGROUND: In December 2019, an unbelievable outbreak of pneumonia associated with coronavirus was reported in the city of Wuhan, Hubei Province. This virus was called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although much effort has been spent on clarifying the transmission route of SARS-CoV-2, but, very little evidence is available regarding the relationship between human body fluids and transmission of SARS-CoV-2 virus. Considerable evidence from hospital in Wuhan indicates that strict rules to avoid occupational exposure to patients’ body fluids in healthcare settings, particularly among every medical staff, limited person-to-person transmission of nosocomial infections by direct or indirect contact. CONCLUSION: We tried to provide important information for understanding the possible transmission routes of SARS-CoV-2 via body fluids including bronchoalveolar-lavage, saliva, blood, urine, feces, sputum, tears, and semen in order to control coronavirus disease 2019 (COVID-19) occurrences.", "title": "Body fluids may contribute to human-to-human transmission of severe acute respiratory syndrome coronavirus 2: evidence and practical experience", "pid": "0a5fccio", "bm25_score": 215.29354858398438}, {"text": "In as few as 3 months, coronavirus disease 2019 (COVID-19) has spread and ravaged the world at an unprecedented speed in modern history, rivaling the 1918 flu pandemic. Severe acute respiratory syndrome coronavirus-2, the culprit virus, is highly contagious and stable in the environment and transmits predominantly among humans via the respiratory route. Accumulating evidence suggest that this virus, like many of its related viruses, may also be an enteric virus that can spread via the fecal-oral route. Such a hypothesis would also contribute to the rapidity and proliferation of this pandemic. Here we briefly summarize what is known about this family of viruses and literature basis of the hypothesis that severe acute respiratory syndrome coronavirus-2 is capable of infecting the gastrointestinal tract and shedding in the environment for potential human-to-human transmission.", "title": "Is SARS-CoV-2 Also an Enteric Pathogen With Potential Fecal-Oral Transmission? A COVID-19 Virological and Clinical Review", "pid": "yyfuu197", "bm25_score": 215.28475952148438}, {"text": "The routes of COVID-19 transmission to healthcare personnel from infected patients is the subject of debate, but is critical to the selection of personal protective equipment. The objective of this paper was to explore the contributions of three transmission routes-contact, droplet, and inhalation-to the risk of occupationally acquired COVID-19 infection among healthcare personnel (HCP). The method was quantitative microbial risk assessment, and an exposure model, where possible model parameters were based on data specific to the SARS-CoV-2 virus when available. The key finding was that droplet and inhalation transmission routes predominate over the contact route, contributing 35%, 57%, and 8.2% of the probability of infection, on average, without use of personal protective equipment. On average, 80% of inhalation exposure occurs when HCP are near patients. The relative contribution of droplet and inhalation depends upon the emission of SARS-CoV-2 in respirable particles (<10 µm) through exhaled breath, and inhalation becomes predominant, on average, when emission exceeds five gene copies per min. The predicted concentration of SARS-CoV-2 in the air of the patient room is low (< 1 gene copy per m3 on average), and likely below the limit of quantification for many air sampling methods. The findings demonstrate the value of respiratory protection for HCP, and that field sampling may not be sensitive enough to verify the contribution of SARS-CoV-2 inhalation to the risk of occupationally acquired COVID-19 infection among healthcare personnel. The emission and infectivity of SARS-CoV-2 in respiratory droplets of different sizes is a critical knowledge gap for understanding and controlling COVID-19 transmission.", "title": "Relative contributions of transmission routes for COVID-19 among healthcare personnel providing patient care", "pid": "k4twbzkm", "bm25_score": 215.25274658203125}, {"text": "The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019-nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many initial patients were exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To investigate possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on the 2019-nCoV sequence. Results obtained from our analyses suggest that the 2019-nCoV may appear to be a recombinant virus between the bat coronavirus and an origin-unknown coronavirus. The recombination may occurred within the viral spike glycoprotein, which recognizes a cell surface receptor. Additionally, our findings suggest that 2019-nCoV has most similar genetic information with bat coronovirus and most similar codon usage bias with snake. Taken together, our results suggest that homologous recombination may occur and contribute to the 2019-nCoV cross-species transmission.", "title": "Cross-species transmission of the newly identified coronavirus 2019-nCoV", "pid": "76laky91", "bm25_score": 215.244873046875}, {"text": "BACKGROUND Coronavirus (CoV) is the single stranded sense RNA virus that has been known so far with the largest genomic capacity and plenty of natural hosts. In the past dozens of years, SARS-CoV under the branch of the new evolutionary tree has threatens greatly global public health and the severe acute respiratory syndrome new coronavirus (COVID-19) reported in China could cause fatal pathological lesions. Especially in areas with poor medical care, neglect of indirect transmission can cause more serious consequences. METHODS First of all, with reference to SARS-CoV and other relevant studies, the possibility of virus residues on the surface of multiple media is discussed. Further, it is found that the surface residue of this substance may be an important factor in iatrogenic infection. RESULTS This correspondence could point out the direction to study the pathomechanism of COVID-19 infecting human beings. CONCLUSIONS Mucosa exposure and inappropriate treatment of medical and non-medical articles used by the patients all could increase the risks of COVID-19 transmission.", "title": "COVID‐19 indirect contact transmission through the oral mucosa must not be ignored", "pid": "adsgiizl", "bm25_score": 215.22653198242188}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can transmit through respiratory droplets, aerosols, or contacts. Frequent touching of contaminated surfaces in public areas is therefore a potential route of SARS-CoV-2 transmission. The inanimate surfaces have often been described as a source of nosocomial infections. However, summaries on the transmissibility of coronaviruses from contaminated surfaces to induce the coronavirus disease 2019 are rare at present. This review aims to summarize data on the persistence of different coronaviruses on inanimate surfaces. The literature was systematically searched on Medline without language restrictions. All reports with experimental evidence on the duration persistence of coronaviruses on any type of surface were included. Most viruses from the respiratory tract, such as coronaviruses, influenza, SARS-CoV, or rhinovirus, can persist on surfaces for a few days. Persistence time on inanimate surfaces varied from minutes to up to one month, depending on the environmental conditions. SARS-CoV-2 can be sustained in air in closed unventilated buses for at least 30 min without losing infectivity. The most common coronaviruses may well survive or persist on surfaces for up to one month. Viruses in respiratory or fecal specimens can maintain infectivity for quite a long time at room temperature. Absorbent materials like cotton are safer than unabsorbent materials for protection from virus infection. The risk of transmission via touching contaminated paper is low. Preventive strategies such as washing hands and wearing masks are critical to the control of coronavirus disease 2019.", "title": "Stability and infectivity of coronaviruses in inanimate environments", "pid": "ou7w3zkv", "bm25_score": 215.1872100830078}, {"text": "Coronaviruses (CoVs) are a group of ancient and common viruses, posing a severe threat to the health of humans and other animals. Currently, seven human CoVs (HCoVs) have been identified. They are all animal-derived zoonotic pathogens that jump the species barrier from their natural host animals to humans in a direct or indirect manner and lead to interpersonal transmission. The receptor binding domain (RBD) on the S1 subunit of CoV spike (S) protein is one of the key factors determining the cross-species transmission and the invasion potential. This review summarized and analyzed the transmission modes of seven HCoVs and the available structures of HCoV-RBD that mediated the cross-species transmission in order to better understanding the mechanism of CoV cross-species transmission and providing valuable knowledge in response to the potential cross-species transmission of novel CoVs in the future.", "title": "Progress in cross-species transmission of human coronaviruses (HCoVs)/ 人冠状病毒跨种传播的研究进展", "pid": "4ct9d311", "bm25_score": 215.1746826171875}, {"text": "", "title": "Transmission of coronavirus by nebulizer: a serious, underappreciated risk.", "pid": "bhn8kcwv", "bm25_score": 215.16928100585938}, {"text": "SARS-CoV-2 has been spreading rapidly since its outbreak in December 2019.Understanding its epidemiological characteristics, especially cutting off transmission routes, is crucial to controlling the spread of the disease. In the study of transmission pathway, the issue of whether SARS-CoV-2 is transmitted through ocular surface tissue has also aroused concerns, but there are still no clinically confirmed cases and laboratory evidence of its infection through ocular surface tissue. New research suggests that the SARS-CoV-2 belongs to the same genus as SARS coronavirus (SARS-CoV), and that it enters cells in the same way as SARS-CoV. This paper reviews the research on SARS-CoV to investigate the possible mechanism of eye transmission of SARS-CoV-2.", "title": "Investiagation of possible mechanism of eye transmission of SARS-CoV-2 based on SARS-CoV/ 从SARS冠状病毒探讨新型冠状病毒眼途径传播的可能机制", "pid": "bo75x9f1", "bm25_score": 215.16848754882812}, {"text": "Infection of healthcare workers with the severe acute respiratory syndrome–associated coronavirus (SARS-CoV) is thought to occur primarily by either contact or large respiratory droplet transmission. However, infrequent healthcare worker infections occurred despite the use of contact and droplet precautions, particularly during certain aerosol-generating medical procedures. We investigated a possible cluster of SARS-CoV infections in healthcare workers who used contact and droplet precautions during attempted cardiopulmonary resuscitation of a SARS patient. Unlike previously reported instances of transmission during aerosol-generating procedures, the index case-patient was unresponsive, and the intubation procedure was performed quickly and without difficulty. However, before intubation, the patient was ventilated with a bag-valve-mask that may have contributed to aerosolization of SARS-CoV. On the basis of the results of this investigation and previous reports of SARS transmission during aerosol-generating procedures, a systematic approach to the problem is outlined, including the use of the following: 1) administrative controls, 2) environmental engineering controls, 3) personal protective equipment, and 4) quality control.", "title": "Possible SARS Coronavirus Transmission during Cardiopulmonary Resuscitation", "pid": "zccd1mq5", "bm25_score": 215.1541748046875}, {"text": "Pathogen transmission from a vertebrate animal to a human, also known as zoonotic spillover, represents a global public health burden, which while associated with multiple outbreaks, still remains a poorly understood phenomenon. Coronaviruses, like influenza viruses, circulate in nature in various animal species. Alpha-coronaviruses and beta-coronaviruses can infect mammals and gamma-coronaviruses and delta-coronaviruses tend to infect birds, but some of them can also be transmitted to mammals. Although still preliminary, current data suggest that bats are the most probable initial source of the current 2019 novel CoV (2019nCoV) outbreak, that begun on December 2019 in Wuhan, China, apparently spreading from a \"wet market\" to multiple cities and provinces in China. This epidemic of 2019nCoV, already reaching more than 6,000 cases to-day (end of January 2020) (>90% in China), will not be the last one linked to zoonotic spillover events.", "title": "History is repeating itself, a probable zoonotic spillover as a cause of an epidemic: the case of 2019 novel Coronavirus.", "pid": "q8im1agz", "bm25_score": 215.15240478515625}, {"text": "@#At present, the new coronavirus(COVID-19)epidemic is spreading rapidly in Wuhan city Hubei province of China, and has aroused great attention of the international community. There have been clues that the conjunctiva may be one of the entries for the new coronavirus(SARS-CoV-2). In the absence of clinical evidence on ocular infection with SARS-CoV-2. Therefore, understanding the mechanism and cell receptors of coronavirus transmission through ocular surface and the transmission characteristics of homologous coronavirus can provide some suggestions for appropriately ocular protection and identify COVID-19 coexisting with ocular signs for ophthalmologists during this epidemic disease.", "title": "Caution of coronavirus transmission through ocular surface/ 国际眼科杂志(Guoji Yanke Zazhi)", "pid": "a58lo0oy", "bm25_score": 215.15109252929688}, {"text": "The routes of COVID-19 transmission to healthcare personnel from infected patients is the subject of debate, but is critical to the selection of personal protective equipment. The objective of this paper was to explore the contributions of three transmission routes-contact, droplet, and inhalation-to the risk of occupationally acquired COVID-19 infection among healthcare personnel (HCP). The method was quantitative microbial risk assessment, and an exposure model, where possible model parameters were based on data specific to the SARS-CoV-2 virus when available. The key finding was that droplet and inhalation transmission routes predominate over the contact route, contributing 35%, 57%, and 8.2% of the probability of infection, on average, without use of personal protective equipment. On average, 80% of inhalation exposure occurs when HCP are near patients. The relative contribution of droplet and inhalation depends upon the emission of SARS-CoV-2 in respirable particles (<10 µm) through exhaled breath, and inhalation becomes predominant, on average, when emission exceeds five gene copies per min. The predicted concentration of SARS-CoV-2 in the air of the patient room is low (< 1 gene copy per m3 on average), and likely below the limit of quantification for many air sampling methods. The findings demonstrate the value of respiratory protection for HCP, and that field sampling may not be sensitive enough to verify the contribution of SARS-CoV-2 inhalation to the risk of occupationally acquired COVID-19 infection among healthcare personnel. The emission and infectivity of SARS-CoV-2 in respiratory droplets of different sizes is a critical knowledge gap for understanding and controlling COVID-19 transmission.", "title": "Relative contributions of transmission routes for COVID-19 among healthcare personnel providing patient care.", "pid": "izxqtril", "bm25_score": 215.1285858154297}, {"text": "Coronaviruses are highly transmissible and are pathogenic viruses of the 21(st) century worldwide. In general, these viruses are originated in bats or rodents. At the same time, the transmission of the infection to the human host is caused by domestic animals that represent in the habitat the intermediate host. In this study, we review the currently collected information about coronaviruses and establish a model of differential equations with piecewise constant arguments to discuss the spread of the infection from the natural host to the intermediate, and from them to the human host, while we focus on the potential spillover of bat-borne coronaviruses. The local stability of the positive equilibrium point of the model is considered via the Linearized Stability Theorem. Besides, we discuss global stability by employing an appropriate Lyapunov function. To analyze the outbreak in early detection, we incorporate the Allee effect at time t and obtain stability conditions for the dynamical behavior. Furthermore, it is shown that the model demonstrates the Neimark-Sacker Bifurcation. Finally, we conduct numerical simulations to support the theoretical findings.", "title": "A Mathematical Model of the Evolution and Spread of Pathogenic Coronaviruses from Natural Host to Human Host", "pid": "afx977mr", "bm25_score": 215.1197052001953}, {"text": "", "title": "Transmission of coronavirus by nebulizer: a serious, underappreciated risk", "pid": "yhb6n9ii", "bm25_score": 215.11795043945312}, {"text": "Coronavirus disease 2019 (COVID-19), the respiratory illness caused by the novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has lead to high morbidity and mortality rates worldwide, has been causing major public health concerns since first detected in late 2019. Following identification of novel pathogens, questions in relation to dissemination of the pathogen and transmission routes begin to emerge. This rapidly spreading SARS-CoV-2 virus has been detected in both faecal and wastewater samples across the globe, highlighting the potential for faecal-oral transmission of the virus. As a result, concerns regarding the transmission of the virus in the environment and the risk associated with contracting the virus in recreational waters, particularly where inadequately treated wastewater is discharged, have been emerging in recent weeks. This paper highlights the need for further research to be carried out to investigate the presence, infectivity and viability of this newly identified SARS-CoV-2 virus in wastewater effluent and receiving recreational waters.", "title": "Recreational waters - A potential transmission route for SARS-CoV-2 to humans?", "pid": "nl8z6u5v", "bm25_score": 215.114501953125}, {"text": "Severe acute respiratory syndrome (SARS) is a pandemic that has shocked the world twice over the last two decades caused by a highly transmissible and pathogenic coronavirus (CoV). It causes disease in the lower respiratory tract in humans that was first reported in late 2002 in Guangdong province, China, and later on in December 2019 in Wuhan, China. The two viruses designated as SARS-CoV and SARS-CoV-2, respectively, originated probably from the bat and infected humans via carrier animals. The constant recombination and evolution in the CoV genome may have facilitated their cross-species transmission resulting in recurrent emergence as a pandemic. This chapter intends to accumulate recent findings related to CoV transmission and tentative molecular mechanisms governing the process.", "title": "Transmission Cycle of SARS-CoV and SARS-CoV-2", "pid": "tcrxm7jy", "bm25_score": 215.08644104003906}, {"text": "Influenza is a long-standing public health concern, but its transmission remains poorly understood. To have a better knowledge of influenza transmission, we carried out a detailed modelling investigation in a nosocomial influenza outbreak in Hong Kong. We identified three hypothesised transmission modes between index patient and other inpatients based on the long-range airborne and fomite routes. We considered three kinds of healthcare workers' routine round pathways in 1140 scenarios with various values of important parameters. In each scenario, we used a multi-agent modelling framework to estimate the infection risk for each hypothesis and conducted least-squares fitting to evaluate the hypotheses by comparing the distribution of the infection risk with that of the attack rates. Amongst the hypotheses tested in the 1140 scenarios, the prediction of modes involving the long-range airborne route fit better with the attack rates, and that of the two-route transmission mode had the best fit, with the long-range airborne route contributing about 94% and the fomite route contributing 6% to the infections. Under the assumed conditions, the influenza virus was likely to have spread via a combined long-range airborne and fomite routes, with the former predominant and the latter negligible.", "title": "Probable transmission routes of the influenza virus in a nosocomial outbreak.", "pid": "rpu6aewp", "bm25_score": 215.0768585205078}, {"text": "Healthcare workers are at risk of infection during the severe acute respiratory syndrome coronavirus-2 pandemic. International guidance suggests direct droplet transmission is likely and airborne transmission occurs only with aerosol-generating procedures. Recommendations determining infection control measures to ensure healthcare worker safety follow these presumptions. Three mechanisms have been described for the production of smaller sized respiratory particles ('aerosols') that, if inhaled, can deposit in the distal airways. These include: laryngeal activity such as talking and coughing; high velocity gas flow; and cyclical opening and closure of terminal airways. Sneezing and coughing are effective aerosol generators, but all forms of expiration produce particles across a range of sizes. The 5-µm diameter threshold used to differentiate droplet from airborne is an over-simplification of multiple complex, poorly understood biological and physical variables. The evidence defining aerosol-generating procedures comes largely from low-quality case and cohort studies where the exact mode of transmission is unknown as aerosol production was never quantified. We propose that transmission is associated with time in proximity to severe acute respiratory syndrome coronavirus-1 patients with respiratory symptoms, rather than the procedures per se. There is no proven relation between any aerosol-generating procedure with airborne viral content with the exception of bronchoscopy and suctioning. The mechanism for severe acute respiratory syndrome coronavirus-2 transmission is unknown but the evidence suggestive of airborne spread is growing. We speculate that infected patients who cough, have high work of breathing, increased closing capacity and altered respiratory tract lining fluid will be significant producers of pathogenic aerosols. We suggest several aerosol-generating procedures may in fact result in less pathogen aerosolisation than a dyspnoeic and coughing patient. Healthcare workers should appraise the current evidence regarding transmission and apply this to the local infection prevalence. Measures to mitigate airborne transmission should be employed at times of risk. However, the mechanisms and risk factors for transmission are largely unconfirmed. Whilst awaiting robust evidence, a precautionary approach should be considered to assure healthcare worker safety.", "title": "Airborne transmission of severe acute respiratory syndrome coronavirus-2 to healthcare workers: a narrative review", "pid": "j4abgq88", "bm25_score": 215.06983947753906}, {"text": "World war “C”(1) has set in against an invisible virus. The routes of transmission include *Contact of contaminated objects,*Circulating droplets in the air called aerosols disseminated through *Cough, sneeze, ocular secretions(2) from an infected individual.", "title": "10 “C” in COVID19", "pid": "6pwqa8zk", "bm25_score": 215.0592041015625}, {"text": "Novel coronavirus pneumonia broke out from Wuhan, and spreading to the whole nation and world since Dec, 2019. It is now the critical stage to fight against the virus. Previous epidemiological investigations and animal experiments suggest aerosol could perform as virus transmitter. Based on the clinical observation, the possibility of aerosol transmission of 2019 novel coronavirus has aroused a lot of attention. This study focuses on the feature of aerosol transmission, and the pathogens involved in. We analyzed the possibility of aerosol transmission for the novel coronavirus. Relevant strategies to prevent novel coronavirus pneumonia are established, serving as references to the medical personnel and general public during their work or daily life. ( Chin J Ophthalmol, 2020, 56: ).", "title": "[Consideration and prevention for the aerosol transmission of 2019 novel coronavirus].", "pid": "qz9rzie2", "bm25_score": 215.05650329589844}, {"text": "Coronavirus disease 2019 (COVID-19), the respiratory illness caused by the novel virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has lead to high morbidity and mortality rates worldwide, has been causing major public health concerns since first detected in late 2019. Following identification of novel pathogens, questions in relation to dissemination of the pathogen and transmission routes begin to emerge. This rapidly spreading SARS-CoV-2 virus has been detected in both faecal and wastewater samples across the globe, highlighting the potential for faecal-oral transmission of the virus. As a result, concerns regarding the transmission of the virus in the environment and the risk associated with contracting the virus in recreational waters, particularly where inadequately treated wastewater is discharged, have been emerging in recent weeks. This paper highlights the need for further research to be carried out to investigate the presence, infectivity and viability of this newly identified SARS-CoV-2 virus in wastewater effluent and receiving recreational waters.", "title": "Recreational waters – A potential transmission route for SARS-CoV-2 to humans?", "pid": "rfkcjpl1", "bm25_score": 215.0367889404297}, {"text": "The coronavirus disease 2019 (COVID-19) emerged in Wuhan city, China, in late 2019 and has rapidly spread throughout the world. The major route of transmission of SARS-CoV-2 is in contention, with the airborne route a likely transmission pathway for carrying the virus within indoor environments. Until now, there has been no evidence for detection of airborne severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and this may have implication for the potential spread of the COVID-19. We investigated the air of patient rooms with confirmed COVID-19 in the largest hospital in Iran, on March 17, 2020. To collect the SARS-CoV-2 particles, ten air samples were collected into the sterile standard midget impingers containing 20 mL DMEM with 100 µg/mL streptomycin, 100 U/mL penicillin and 1% antifoam reagent for 1 h. Besides, indoor particle number concentrations, CO2, relative humidity and temperature were recorded throughout the sampling duration. Viral RNA was extracted from samples taken from the impingers and Reverse-Transcription PCR (RT-PCR) was applied to confirm the positivity of collected samples based on the virus genome sequence. Fortunately, in this study all air samples which were collected 2 to 5 m from the patients' beds with confirmed COVID-19 were negative. Despite we indicated that all air samples were negative, however, we suggest further in vivo experiments should be conducted using actual patient cough, sneeze and breath aerosols in order to show the possibility of generation of the airborne size carrier aerosols and the viability fraction of the embedded virus in those carrier aerosols.", "title": "A field indoor air measurement of SARS-CoV-2 in the patient rooms of the largest hospital in Iran", "pid": "e4bt3mgf", "bm25_score": 215.02850341796875}, {"text": "To determine possible modes of virus transmission, we investigated a cluster of coronavirus disease cases associated with a shopping mall in Wenzhou, China. Data indicated that indirect transmission of the causative virus occurred, perhaps resulting from virus contamination of common objects, virus aerosolization in a confined space, or spread from asymptomatic infected persons.", "title": "Indirect Virus Transmission in Cluster of COVID-19 Cases, Wenzhou, China, 2020", "pid": "yp7bniwt", "bm25_score": 215.01629638671875}, {"text": "Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R0 of 2019-nCoV to be around 2.2 (90% high density interval: 1.4-3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.", "title": "Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020", "pid": "px5go7rc", "bm25_score": 215.0105438232422}, {"text": "We propose a simple model for understanding the kinetics of corona virus transmission. Our model assume spreading of corona virus can happen from one to another only, if someone without enough protection comes close contact to a person carrying the corona virus. Therefore this virus spreads on a large scale within a short time through chains of such events. Using our model we provide an estimation of the number of people affected by this virus within reasonable duration of time. We choose values of different parameters of our model by non-linear least square fit of the real time data and we predict fate of this corona virus transmission using our model.", "title": "Understanding the fate of corona virus transmission using a simple model", "pid": "6p592gwa", "bm25_score": 215.00881958007812}, {"text": "Pathogen transmission from a vertebrate animal to a human, also known as zoonotic spillover, represents a global public health burden, which while associated with multiple outbreaks, still remains a poorly understood phenomenon. Coronaviruses, like influenza viruses, circulate in nature in various animal species. Alpha-coronaviruses and beta-coronaviruses can infect mammals and gamma-coronaviruses and delta-coronaviruses tend to infect birds, but some of them can also be transmitted to mammals. Although still preliminary, current data suggest that bats are the most probable initial source of the current 2019 novel CoV (2019nCoV) outbreak, that begun on December 2019 in Wuhan, China, apparently spreading from a \"wet market\" to multiple cities and provinces in China. This epidemic of 2019nCoV, already reaching more than 6,000 cases to-day (end of January 2020) (>90% in China), will not be the last one linked to zoonotic spillover events.", "title": "History is repeating itself: Probable zoonotic spillover as the cause of the 2019 novel Coronavirus Epidemic", "pid": "cjwy2bcx", "bm25_score": 214.9968719482422}, {"text": "The current outbreak of the novel coronavirus disease 2019 (COVID-19) in more than 250 countries has become a serious threat to the health of people around the world. Human-to-human transmission of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs most often when people are in the incubation stage of the disease or are carriers and have no symptoms. Therefore, in this study, was discussed the role of environmental factors and conditions such as temperature, humidity, wind speed as well as food, water and sewage, air, insects, inanimate surfaces, and hands in COVID-19 transmission. The results of studies on the stability of the SARS-CoV-2 on different levels showed that the resistance of this virus on smooth surfaces was higher than others. Temperature increase and sunlight can facilitate the destruction of SARS-COV-2 and the stability of it on surfaces. When the minimum ambient air temperature increases by 1 °C, the cumulative number of cases decreases by 0.86%. According to the latest evidence, the presence of coronavirus in the sewer has been confirmed, but there is no evidence that it is transmitted through sewage or contaminated drinking water. Also, SARS-COV-2 transmission through food, food packages, and food handlers has not been identified as a risk factor for the disease. According to the latest studies, the possibility of transmitting SARS-COV-2 bioaerosol through the air has been reported in the internal environment of ophthalmology. The results additionally show that infectious bio-aerosols can move up to 6 feet. There have been no reports of SARS-COV-2 transmission by blood-feeding arthropods such as mosquitoes.", "title": "The role of environmental factors to transmission of SARS-CoV-2 (COVID-19)", "pid": "t01njoxo", "bm25_score": 214.99603271484375}, {"text": "Over the past 30 years, several cross-species transmission events, as well as changes in virus tropism, have mediated significant animal and human diseases. Most notable is severe acute respiratory syndrome (SARS), a lower respiratory tract disease of humans that was first reported in late 2002 in Guangdong Province, China. The disease, which quickly spread worldwide over a period of 4 months spanning late 2002 and early 2003, infected over 8,000 individuals and killed nearly 800 before it was successfully contained by aggressive public health intervention strategies. A coronavirus (SARS-CoV) was identified as the etiological agent of SARS, and initial assessments determined that the virus crossed to human hosts from zoonotic reservoirs, including bats, Himalayan palm civets (Paguma larvata), and raccoon dogs (Nyctereutes procyonoides), sold in exotic animal markets in Guangdong Province. In this review, we discuss the molecular mechanisms that govern coronavirus cross-species transmission both in vitro and in vivo, using the emergence of SARS-CoV as a model. We pay particular attention to how changes in the Spike attachment protein, both within and outside of the receptor binding domain, mediate the emergence of coronaviruses in new host populations.", "title": "Recombination, reservoirs, and the modular spike: mechanisms of coronavirus cross-species transmission.", "pid": "dfyshke7", "bm25_score": 214.99278259277344}, {"text": "The World Health Organization (WHO) on March 11, 2020, has declared the novel Corona virus (COVID-19) outbreak a global pandemic. It is essential to understand how coronavirus transmits from one person to another and this knowledge will help protect the vulnerable and limit the spread of the Corona virus. The mode of respiratory transmission of Corona virus is not completely understood as of date. Using a computer simulation, this paper analyses the probability of spreading of Corona virus through air among the people who are standing in a queue. The parameters such as the diameter of the virus particle, room temperature, relative humidity, height of the person, distance between the people and the waiting time in the queue are considered in the computer model to determine the distribution of Corona virus and hence identify the risk factor of spreading the Covid-19. This paper describes the possibilities of getting infectious when a Covid-19 infected person present in a queue and the impact on the waiting time and the position in the queue on the transmission of Corona virus.", "title": "A Computer Simulation Study on novel Corona Virus Transmission among the People in a Queue", "pid": "9x4d6skf", "bm25_score": 214.980224609375}, {"text": "The world has now paid a lot of attention to the outbreak of novel coronavirus (COVID-19). This virus mainly transmitted between humans through directly respiratory droplets and close contacts. However, there is currently some evidence where it has been claimed that it may be indirectly transmitted. In this work, we study the mode of transmission of COVID-19 epidemic system based on the susceptible-infected-recovered (SIR) model. We have calculated the basic reproduction number R0 by next-generation matrix method. We observed that if R0<1, then disease-free equilibrium point is locally as well as globally asymptotically stable but when $R0>1, the endemic equilibrium point exists and is globally stable. Finally, some numerical simulation is presented to validate our results.", "title": "Modes of transmission of COVID-19 outbreak- a mathematical study", "pid": "5rwcyg4z", "bm25_score": 214.9693145751953}, {"text": "Oculo-centric factors may provide a key to understanding invasion success by SARS-CoV-2, a highly contagious, potentially lethal, virus with ocular tropism. Respiratory infection transmission via the eye and lacrimal-nasal pathway elucidated during the 1918 influenza pandemic, remains to be explored in this crisis. The eye and its adnexae represent a large surface area directly exposed to airborne viral particles and hand contact. The virus may bind to corneal and conjunctival angiotensin converting enzyme 2 (ACE2) receptors and potentially to the lipophilic periocular skin and superficial tear film with downstream carriage into the nasopharynx and subsequent access to the lungs and gut. Adenoviruses and influenza viruses share this ocular tropism and despite differing ocular and systemic manifestations and disease patterns, common lessons, particularly in management, emerge. Slit lamp usage places ophthalmologists at particular risk of exposure to high viral loads (and poor prognosis) and as for adenoviral epidemics, this may be a setting for disease transmission. Local, rather than systemic treatments blocking virus binding in this pathway (advocated for adenovirus) are worth considering. This pathway is accessible with eye drops or aerosols containing drugs which appear efficacious via systemic administration. A combination such as hydroxychloroquine, azithromycin and zinc, all of which have previously been used topically in the eye and which work at least in part by blocking ACE2 receptors, may offer a safe, cost-effective and resource-sparing intervention.", "title": "The eye as the discrete but defensible portal of coronavirus infection", "pid": "0e8afa5h", "bm25_score": 214.9670867919922}, {"text": "", "title": "Uncertainties about the transmission routes of 2019 novel coronavirus", "pid": "9hq8xdhi", "bm25_score": 214.96066284179688}, {"text": "Since December 2019, China has been experiencing a large outbreak of a novel coronavirus (2019-nCoV) which can cause respiratory disease and severe pneumonia. We estimated the basic reproduction number R(0) of 2019-nCoV to be around 2.2 (90% high density interval: 1.4–3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and pandemic influenza, indicating a risk of global spread.", "title": "Pattern of early human-to-human transmission of Wuhan 2019 novel coronavirus (2019-nCoV), December 2019 to January 2020", "pid": "zz4cczuj", "bm25_score": 214.94110107421875}, {"text": "An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, now known as coronavirus disease 2019 (COVID-19), beginning in December 2019, has attracted an intense amount of attention worldwide. As the natural history and variety of clinical presentations of this disease unfolds, extrapulmonary symptoms of COVID-19 have emerged, especially in the digestive system. While the respiratory mode of transmission is well known and is probably the principal mode of transmission of this disease, a possibility of the fecal-oral route of transmission has also emerged in various case series and clinical scenarios. In this review article, we summarize four different aspects in published studies to date: (a) gastrointestinal manifestations of COVID-19; (b) microbiological and virological investigations; (c) the role of fecal-oral transmission; and (d) prevention and control of SARS-CoV-2 infection in the digestive endoscopy room. A timely understanding of the relationship between the disease and the digestive system and implementing effective preventive measures are of great importance for a favorable outcome of the disease and can help climnicians to mitigate further transmission by taking appropriate measures.", "title": "Digestive system involvement of novel coronavirus infection: Prevention and control infection from a gastroenterology perspective", "pid": "dz8blrzm", "bm25_score": 214.93934631347656}, {"text": "The outbreak of Corona Virus Disease 2019 caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2) is highly transmitted. The potential extra-respiratory transmission routes remain uncertain. Five rhesus macaques were inoculated with 1×106 TCID50 of SARS-CoV-2 via conjunctival (CJ), intratracheal (IT), and intragastric (IG) routes, respectively. Remarkably, the CJ inoculated-macaques developed mild interstitial pneumonia and viral load was detectable in the conjunctival swabs at 1 days post-inoculation (dpi). Only via IT inoculation, viral load was detected in the anal swab at 1-7 dpi and macaque showed weight loss. However, viral load was undetectable after IG inoculation. Comparatively, viral load was higher in the nasolacrimal system but lesions of lung were relatively mild and local via CJ inoculation compared with that via IT inoculation, demonstrating distinct characteristics of virus dispersion. Both the two routes affected the alimentary tract. Therefore the clinicians need to protect eye while working with patients.", "title": "Ocular conjunctival inoculation of SARS-CoV-2 can cause mild COVID-19 in Rhesus macaques", "pid": "ih1py5n9", "bm25_score": 214.9279022216797}, {"text": "We simulated 3 transmission modes, including close-contact, respiratory droplets and aerosol routes, in the laboratory. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can be highly transmitted among naive human angiotensin-converting enzyme 2 (hACE2) mice via close contact because 7 of 13 naive hACE2 mice were SARS-CoV-2 antibody seropositive 14 days after being introduced into the same cage with 3 infected-hACE2 mice. For respiratory droplets, SARS-CoV-2 antibodies from 3 of 10 naive hACE2 mice showed seropositivity 14 days after introduction into the same cage with 3 infected-hACE2 mice, separated by grids. In addition, hACE2 mice cannot be experimentally infected via aerosol inoculation until continued up to 25 minutes with high viral concentrations.", "title": "Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 via Close Contact and Respiratory Droplets Among Human Angiotensin-Converting Enzyme 2 Mice", "pid": "obh0q8gg", "bm25_score": 214.92459106445312}, {"text": "Novel coronavirus pneumonia broke out from Wuhan, and spreading to the whole nation and world since Dec, 2019. It is now the critical stage to fight against the virus. Previous epidemiological investigations and animal experiments suggest aerosol could perform as virus transmitter. Based on the clinical observation, the possibility of aerosol transmission of 2019 novel coronavirus has aroused a lot of attention. This study focuses on the feature of aerosol transmission, and the pathogens involved in. We analyzed the possibility of aerosol transmission for the novel coronavirus. Relevant strategies to prevent novel coronavirus pneumonia are established, serving as references to the medical personnel and general public during their work or daily life. ( Chin J Ophthalmol, 2020, 56: ).", "title": "[Consideration and prevention for the aerosol transmission of 2019 novel coronavirus]", "pid": "cfwtyud2", "bm25_score": 214.92364501953125}, {"text": "BACKGROUND: Coronavirus disease 2019 (COVID-19) was first reported in Wuhan in December 2019 and has rapidly spread across different cities within and outside China. Hong Kong started to prepare for COVID-19 on 31st December 2019 and infection control measures in public hospitals were tightened to limit nosocomial transmission within healthcare facilities. However, the recommendations on the transmission-based precautions required for COVID-19 in hospital settings vary from droplet and contact precautions, to contact and airborne precautions with placement of patients in airborne infection isolation rooms. AIM: To describe an outbreak investigation of a patient with COVID-19 who was nursed in an open cubicle of a general ward before the diagnosis was made. METHOD: Contacts were identified and risk categorized as 'close' or 'casual' for decisions on quarantine and/or medical surveillance. Respiratory specimens were collected from contacts who developed fever, and/or respiratory symptoms during the surveillance period and were tested for SARS-CoV-2. FINDINGS: A total of 71 staff and 49 patients were identified from contact tracing, seven staff and 10 patients fulfilled the criteria of 'close contact'. At the end of 28-day surveillance, 76 tests were performed on 52 contacts and all were negative, including all patient close contacts and six of the seven staff close contacts. The remaining contacts were asymptomatic throughout the surveillance period. CONCLUSION: Our findings suggest that SARS-CoV-2 is not spread by an airborne route, and nosocomial transmissions can be prevented through vigilant basic infection control measures, including wearing of surgical masks, hand and environmental hygiene.", "title": "Risk of nosocomial transmission of coronavirus disease 2019: an experience in a general ward setting in Hong Kong", "pid": "4lz45ywi", "bm25_score": 214.92239379882812}, {"text": "Human coronaviruses (HCoV) have been implicated in neonatal nosocomial respiratory infection. Prior to our study, several cases of neonatal infection were observed in infants born at our hospital. This prospective pilot monocentric pilot study investigates the possibility of maternofetal transmission of HCoV responsible for cases of neonatal infection observed within the first 24 hours of life. MATERIALS AND METHODS: Three samples from mother–child couples, maternal vaginal (VM) and respiratory (RM) samples during labor; newborn gastric sample (GNN), were assessed for viral analysis using real time RT-PCR for the detection of HCoV 229-E and OC43. Clinical follow-up of infants and mothers was up to Day 3 after birth. RESULTS: One hundred (and) fifty-nine mother–child couples were included between July 2003 and August 2005. HCoV 229-E only was detected in 11 samples from 6 mother–child couples. For 2 couples, all 3 samples (VM, RM and GNN) were tested positive (cases 1 and 2). For case 3, both VM and GNN were positive. For 2 couples, only RM was positive (cases 4 and 5). In case 6, only VM was positive. Of the 3 positive GNN, no infant was symptomatic. CONCLUSION: Possible vertical transmission of HCoV was evidenced in this pilot study and requires further investigation on a larger scale. Equally indicated is the inclusion of tests to detect recently identified human coronaviruses HCoV NL63 and HKU1, as well as genomic profile analysis of HCoV 229-E detected in the 3 positive mother-child couples.", "title": "Transmission maternofœtale des coronavirus humains. Étude prospective pilote", "pid": "6pgzlr8k", "bm25_score": 214.91551208496094}, {"text": "A cluster of pneumonia cases linked to a novel coronavirus (2019-nCoV) was reported by China in late December 2019. Reported case incidence has now reached the hundreds, but this is likely an underestimate. As of 24 January 2020, with reports of thirteen exportation events, we estimate the cumulative incidence in China at 5502 cases (95% confidence interval: 3027, 9057). The most plausible number of infections is in the order of thousands, rather than hundreds, and there is a strong indication that untraced exposures other than the one in the epidemiologically linked seafood market in Wuhan have occurred.", "title": "The Extent of Transmission of Novel Coronavirus in Wuhan, China, 2020", "pid": "cg4ess9h", "bm25_score": 214.9143524169922}, {"text": "Abstract The coronavirus disease 2019 (COVID-19) emerged in Wuhan city, China, in late 2019 and has rapidly spread throughout the world. The major route of transmission of SARS-CoV-2 is in contention, with the airborne route a likely transmission pathway for carrying the virus within indoor environments. Until now, there has been no evidence for detection of airborne severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and this may have implication for the potential spread of the COVID-19. We investigated the air of patient rooms with confirmed COVID-19 in the largest hospital in Iran, on March 17, 2020. To collect the SARS-CoV-2 particles, ten air samples were collected into the sterile standard midget impingers containing 20 mL DMEM with 100 μg/mL streptomycin, 100 U/mL penicillin and 1% antifoam reagent for 1 h. Besides, indoor particle number concentrations, CO2, relative humidity and temperature were recorded throughout the sampling duration. Viral RNA was extracted from samples taken from the impingers and Reverse-Transcription PCR (RT-PCR) was applied to confirm the positivity of collected samples based on the virus genome sequence. Fortunately, in this study all air samples which were collected 2 to 5 m from the patients' beds with confirmed COVID-19 were negative. Despite we indicated that all air samples were negative, however, we suggest further in vivo experiments should be conducted using actual patient cough, sneeze and breath aerosols in order to show the possibility of generation of the airborne size carrier aerosols and the viability fraction of the embedded virus in those carrier aerosols.", "title": "A field indoor air measurement of SARS-CoV-2 in the patient rooms of the largest hospital in Iran", "pid": "a2gmy1f0", "bm25_score": 214.90687561035156}, {"text": "The severe respiratory disease COVID-19 was initially reported in Wuhan, China, in December 2019, and spread into many provinces from Wuhan. The corresponding pathogen was soon identified as a novel coronavirus named SARS-CoV-2 (formerly, 2019-nCoV). As of 2 May, 2020, over 3 million COVID-19 cases had been confirmed, and 235,290 deaths had been reported globally, and the numbers are still increasing. It is important to understand the phylogenetic relationship between SARS-CoV-2 and known coronaviruses, and to identify its hosts for preventing the next round of emergency outbreak. In this study, we employ an effective alignment-free approach, the Natural Vector method, to analyze the phylogeny and classify the coronaviruses based on genomic and protein data. Our results show that SARS-CoV-2 is closely related to, but distinct from the SARS-CoV branch. By analyzing the genetic distances from the SARS-CoV-2 strain to the coronaviruses residing in animal hosts, we establish that the most possible transmission path originates from bats to pangolins to humans.", "title": "Analysis of the Hosts and Transmission Paths of SARS-CoV-2 in the COVID-19 Outbreak", "pid": "i14gkdw0", "bm25_score": 214.89637756347656}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is responsible for a pandemic that is causing thousands of deaths worldwide. The virus can be transmitted from person to person, directly or indirectly, via the respiratory, oro‐fecal and probably sexual routes.(1) The eventual vertical transmission route is still poorly explored. However, mother‐to‐child SARS‐CoV‐2 transmission through the placenta probably does not occur, or likely occurs very rarely.(2) All the studies conducted on COVID‐19 pregnant women involved patients undergoing cesarean section, but the indications for such delivery modality were not clearly stated.", "title": "SARS‐CoV‐2 possible contamination of genital area: implications for sexual and vertical transmission routes", "pid": "scptrala", "bm25_score": 214.8937530517578}, {"text": "Abstract The world is faced with a remarkable coronavirus outbreak with epicentre in Wuhan, China. Altogether 40554 cases have been confirmed globally with novel coronavirus (SARS-CoV-2) until February 10, 2020. Rigorous surveillance in other countries is required to prevent further global expansion of the outbreak, but resolving the exact mechanism of the initial transmission events is crucial. Most initial cases had visited Huanan South Seafood Market in Wuhan selling also various exotic live animals. Based on the limited initial human-to-human transmission and timely clustering of cases in Huanan market among elderly men, coupled with knowledge that coronaviruses are derived from animals and relationship of SARS-CoV-2 to bat coronavirus, zoonotic transmission in the first instance is probable. To target the actions, similar epidemiological actions to human cases are needed with animal or food exposures. According to current information, an exceptionally wide contamination of seafood market might explain the initiation of the SARS-CoV-2 outbreak. Seafood tanks, air contamination by live animals or rodents are possibilities, but sold animals normally come from various sources. The mode of transmission may become clearer in future: usually in outbreak investigations, hindsight is easy, but for now information about the initial source of this outbreak is limited.", "title": "First respiratory transmitted food borne outbreak?", "pid": "he853mwa", "bm25_score": 214.88653564453125}, {"text": "The current outbreak of viral pneumonia in the city of Wuhan, China, was caused by a novel coronavirus designated 2019‐nCoV by the World Health Organization, as determined by sequencing the viral RNA genome. Many initial patients were exposed to wildlife animals at the Huanan seafood wholesale market, where poultry, snake, bats, and other farm animals were also sold. To investigate possible virus reservoir, we have carried out comprehensive sequence analysis and comparison in conjunction with relative synonymous codon usage (RSCU) bias among different animal species based on the 2019‐nCoV sequence. Results obtained from our analyses suggest that the 2019‐nCoV may appear to be a recombinant virus between the bat coronavirus and an origin‐unknown coronavirus. The recombination may occurred within the viral spike glycoprotein, which recognizes a cell surface receptor. Additionally, our findings suggest that 2019‐nCoV has most similar genetic information with bat coronovirus and most similar codon usage bias with snake. Taken together, our results suggest that homologous recombination may occur and contribute to the 2019‐nCoV cross‐species transmission.", "title": "Cross‐species transmission of the newly identified coronavirus 2019‐nCoV", "pid": "pwvcwlh8", "bm25_score": 214.87583923339844}, {"text": "The world is faced with a remarkable coronavirus outbreak with epicentre in Wuhan, China. Altogether 40554 cases have been confirmed globally with novel coronavirus (SARS-CoV-2) until February 10, 2020. Rigorous surveillance in other countries is required to prevent further global expansion of the outbreak, but resolving the exact mechanism of the initial transmission events is crucial. Most initial cases had visited Huanan South Seafood Market in Wuhan selling also various exotic live animals. Based on the limited initial human-to-human transmission and timely clustering of cases in Huanan market among elderly men, coupled with knowledge that coronaviruses are derived from animals and relationship of SARS-CoV-2 to bat coronavirus, zoonotic transmission in the first instance is probable. To target the actions, similar epidemiological actions to human cases are needed with animal or food exposures. According to current information, an exceptionally wide contamination of seafood market might explain the initiation of the SARS-CoV-2 outbreak. Seafood tanks, air contamination by live animals or rodents are possibilities, but sold animals normally come from various sources. The mode of transmission may become clearer in future: usually in outbreak investigations, hindsight is easy, but for now information about the initial source of this outbreak is limited.", "title": "First respiratory transmitted food borne outbreak?", "pid": "4bmq3wwg", "bm25_score": 214.8755645751953}, {"text": "We read with interest recent article by Zhang et al 1 on the diagnosis of Coronavirus disease 2019 (COVID-19) by fecal specimen test. Following the recent outbreak of pneumonia with unknown pathogen in Hubei province in China, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolated from human airway epithelial cells and the disease was named COVID-19.2 It is a public health emergency of international concern and rapidly spearing all over the world.3 This article is protected by copyright. All rights reserved.", "title": "Fecal transmission in COVID‐19: A potential shedding route", "pid": "0bz4micv", "bm25_score": 214.87353515625}, {"text": "BACKGROUND: Coronavirus disease 2019 (COVID-19) was first reported in Wuhan in December 2019 and has rapidly spread across different cities within and outside China. Hong Kong started to prepare for COVID-19 on 31(st) December 2019 and infection control measures in public hospitals were tightened to limit nosocomial transmission within healthcare facilities. However, the recommendations on the transmission-based precautions required for COVID-19 in hospital settings vary from droplet and contact precautions, to contact and airborne precautions with placement of patients in airborne infection isolation rooms. AIM: To describe an outbreak investigation of a patient with COVID-19 who was nursed in an open cubicle of a general ward before the diagnosis was made. METHOD: Contacts were identified and risk categorized as ‘close’ or ‘casual’ for decisions on quarantine and/or medical surveillance. Respiratory specimens were collected from contacts who developed fever, and/or respiratory symptoms during the surveillance period and were tested for SARS-CoV-2. FINDINGS: A total of 71 staff and 49 patients were identified from contact tracing, seven staff and 10 patients fulfilled the criteria of ‘close contact’. At the end of 28-day surveillance, 76 tests were performed on 52 contacts and all were negative, including all patient close contacts and six of the seven staff close contacts. The remaining contacts were asymptomatic throughout the surveillance period. CONCLUSION: Our findings suggest that SARS-CoV-2 is not spread by an airborne route, and nosocomial transmissions can be prevented through vigilant basic infection control measures, including wearing of surgical masks, hand and environmental hygiene.", "title": "Risk of nosocomial transmission of coronavirus disease 2019: an experience in a general ward setting in Hong Kong", "pid": "4uslmbmw", "bm25_score": 214.87184143066406}, {"text": "The three known human highly pathogenic coronaviruses are severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus, (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Human highly pathogenic coronaviruses are composed of non-structural proteins, structural proteins and accessory proteins Viral particles recognize host receptors via spike glycoprotein (S protein), enter host cells by membrane fusion, replicate in host cells through large replication-transcription complexes, and promote proliferation by interfering with and suppressing the host's immune response Human highly pathogenic coronaviruses are hosted by humans and vertebrates Viral particles are transmitted through droplets, contact and aerosols or likely through digestive tract, urine, eyes and other routes This review discusses the mechanisms of proliferation and transmission of highly pathogenic human coronaviruses based on the results of existing research, providing basis for future study on interrupting the transmission and pathogenicity of human highly pathogenic coronaviruses", "title": "[Replication and transmission mechanisms of highly pathogenic human coronaviruses]", "pid": "iwy2nn17", "bm25_score": 214.85398864746094}, {"text": "Coughs and sneezes disperse a large number of droplets of varying size into the environment, and they transmit respiratory viral infections by direct or indirect physical contact, by droplets or inhalation of fine particulate droplet nuclei. Larger droplets in the cloud produced by coughing and sneezing settle quickly, and the force with which they are expelled determines how far they are dispersed. The respiratory droplets evaporate to form smaller droplet nuclei that carry infectious agents, remain suspended in air, and susceptible individuals farther away from the source could inhale them. The particle size distribution within the multi-phase cloud produced by coughs/sneezes changes with time and distance from the source depending on several environmental factors. After inhalation, larger respiratory droplets are filtered by the nose or deposit in the oropharynx, whereas smaller droplet nuclei are carried by the airstream into the lungs where their site of deposition depends on their mass, size and shape and is governed by various mechanisms. Airborne particles could also be produced by various aerosol generating procedures, such as suctioning or tracheal intubation, and by aerosol generators, especially jet nebulizers. Prevention of respiratory viral infections depends upon whether they are carried in respiratory droplets or as fine droplet nuclei (airborne or aerosol transmission). The SARS-CoV-2 virus that causes COVID-19 is mainly transmitted by respiratory droplets or by contact. Airborne transmission of this virus has not been established, but is possible under special circumstances. Appropriate protective measures are necessary to prevent transmission of SARS-CoV-2 virus in various settings. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).", "title": "Coughs and Sneezes: Their Role in Transmission of Respiratory Viral Infections, Including SARS-CoV-2", "pid": "p825xabq", "bm25_score": 214.84059143066406}, {"text": "Coughs and sneezes disperse a large number of droplets of varying size into the environment, and they transmit respiratory viral infections by direct or indirect physical contact, by droplets or inhalation of fine particulate droplet nuclei. Larger droplets in the cloud produced by coughing and sneezing settle quickly, and the force with which they are expelled determines how far they are dispersed. The respiratory droplets evaporate to form smaller droplet nuclei that carry infectious agents, remain suspended in air, and susceptible individuals farther away from the source could inhale them. The particle size distribution within the multi-phase cloud produced by coughs/sneezes changes with time and distance from the source depending on several environmental factors. After inhalation, larger respiratory droplets are filtered by the nose or deposit in the oropharynx, whereas smaller droplet nuclei are carried by the airstream into the lungs where their site of deposition depends on their mass, size and shape and is governed by various mechanisms. Airborne particles could also be produced by various aerosol generating procedures, such as suctioning or tracheal intubation, and by aerosol generators, especially jet nebulizers. Prevention of respiratory viral infections depends upon whether they are carried in respiratory droplets or as fine droplet nuclei (airborne or aerosol transmission). The SARS-CoV-2 virus that causes COVID-19 is mainly transmitted by respiratory droplets or by contact. Airborne transmission of this virus has not been established, but is possible under special circumstances. Appropriate protective measures are necessary to prevent transmission of SARS-CoV-2 virus in various settings. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).", "title": "Coughs and Sneezes: Their Role in Transmission of Respiratory Viral Infections, Including SARS-CoV-2.", "pid": "03aarmvd", "bm25_score": 214.8331756591797}, {"text": "Coronaviruses are widespread in the environment, infecting humans, domesticated and wild mammals, and birds. Infections cause a variety of diseases including bronchitis, gastroenteritis, hepatitis, and encephalitis, with symptoms ranging from being nearly undetectable to rapidly fatal. A combination of interacting variables determine the pattern and severity of coronavirus-induced disease, including the infecting virus strain, its transmission strategy, and the age and immune status of the infected host. Coronavirus pathogenesis is best understood by discerning how each of these variables dictates clinical outcomes. This chapter focuses on variabilities amongst the spike (S) proteins of infecting virus strains. Diversity of coronavirus surface proteins likely contributes to epidemic disease, an important and timely topic given the recent emergence of the human SARS coronavirus.", "title": "Diversity of Coronavirus Spikes: Relationship to Pathogen Entry and Dissemination", "pid": "ork8mgkz", "bm25_score": 214.82923889160156}, {"text": "", "title": "Enteric involvement of coronaviruses: is faecal-oral transmission of SARS-CoV-2 possible?", "pid": "4ry75ex9", "bm25_score": 214.82400512695312}, {"text": "The outbreak of the current 2019 novel coronavirus (2019-nCoV, now named SARS-CoV-2) infection has become a worldwide health threat. Currently, more information is needed so as to further understand the transmission and clinical characteristics of 2019-nCoV infection and the infection control procedures required. Recently, the role of the eye in transmitting 2019-nCoV has been intensively discussed. Previous investigations of other highly infectious human CoVs, that is, severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV), may provide useful information. In this review, we describe the genomics and morphology of human CoVs, the epidemiology, systemic and ophthalmic manifestations, and mechanisms of human CoV infection, and recommendations for infection control procedures. The role of the eye in the transmission of 2019-nCoV is discussed in detail. Although the conjunctiva is directly exposed to extraocular pathogens, and the mucosa of the ocular surface and upper respiratory tract are connected by the nasolacrimal duct and share the same entry receptors for some respiratory viruses, the eye is rarely involved in human CoV infection, conjunctivitis is quite rare in patients with 2019-nCoV infection, and the CoV RNA positive rate by RT-PCR test in tears and conjunctival secretions from patients with 2019-nCoV and SARS-CoV infection is also extremely low. This suggests that the eye is neither a preferred organ of human CoV infection nor a preferred gateway of entry for human CoVs for infecting the respiratory tract. However, pathogens that the ocular surface is exposed to might be transported to nasal and nasopharyngeal mucosa by constant tear rinsing through the lacrimal duct system and then cause respiratory tract infection. Considering that close doctor-patient contact is quite common in ophthalmic practice and is apt to transmit human CoVs by droplets and fomites, strict hand hygiene and proper personal protection are highly recommended for health care workers to avoid hospital-related viral transmission during ophthalmic practice.", "title": "Role of the Eye in Transmitting Human Coronavirus: What We Know and What We Do Not Know", "pid": "6rqd3fmj", "bm25_score": 214.8204803466797}, {"text": "Following the outbreak of severe acute respiratory syndrome coronavirus (SARS-CoV-2) in China, airborne water droplets (aerosols) have been identified as the main transmission route, although other transmission routes are likely to exist. We quantify SARS-CoV-2 virus survivability within water and the risk of infection posed by faecal contaminated water within 39 countries. We identify that the virus can remain stable within water for up to 25 days, and country specific relative risk of infection posed by faecal contaminated water is related to the environment. Faecal contaminated rivers, waterways and water systems within countries with high infection rates can provide infectious doses >100 copies within 100 ml of water. The implications for freshwater systems, the coastal marine environment and virus resurgence are discussed.", "title": "Risk of SARS-CoV-2 infection from contaminated water systems", "pid": "ycdok8fc", "bm25_score": 214.81253051757812}, {"text": "The community spread of coronavirus at great Chicago area has severely threatened the residents health, family and normal activities. CDC daily updates on infected cases on County level are not satisfying to address publics concern on virus spread. On March 20th, NBC5 published case information of 435 coronavirus infections. The data is relative comprehensive and of high value for understanding on the virus spread patterns at Chicago. Data engineering, natural language processing and Google map technology are applied to organize the data and retrieve geographic information of the virus. The analysis shows community spread in Chicago areas has a potential proximity relation with public commuter rail. Residents nearby major public commuter rails need limit outdoor activities during the outbreak and even the post-peak time.", "title": "Coronavirus Geographic Dissemination at Chicago and its Potential Proximity to Public Commuter Rail", "pid": "fbrbobaj", "bm25_score": 214.80599975585938}, {"text": "The fourth outbreak of the Coronaviruses, known as the 2019-nCoV, has occurred in Wuhan city of Hubei province in China in December 2019. We propose a time-varying sparse vector autoregressive (VAR) model to retrospectively analyze and visualize the dyamic transmission routes of this outbreak in mainland China over January 31 - February 19, 2020. Our results demonstrate that the influential inter-province routes from Hubei have become unidentifiable since February 4, whereas the self-transmission in each province was accelerating over February 4-15. From February 16, all routes became less detectable, and no influential transmissions could be identified on February 18 and 19. Such evidence supports the effectiveness of government interventions, including the travel restrictions in Hubei. Implications of our results suggest that in addition to the origin of the outbreak, virus preventions are of crucial importance in provinces with the largest migrant workers percentages (e.g., Jiangxi, Henan and Anhui) to controlling the spread of 2019-nCoV.", "title": "How does the outbreak of 2019-nCoV spread in mainland China? A retrospective analysis of the dynamic transmission routes", "pid": "4k1i6y98", "bm25_score": 214.79991149902344}, {"text": "During the 2020 COVID-19 pandemic, an outbreak occurred following attendance of a symptomatic index case at a regular weekly rehearsal on 10 March of the Skagit Valley Chorale (SVC). After that rehearsal, 53 members of the SVC among 61 in attendance were confirmed or strongly suspected to have contracted COVID-19 and two died. Transmission by the airborne route is likely. It is vital to identify features of cases such as this so as to better understand the factors that promote superspreading events. Based on a conditional assumption that transmission during this outbreak was by inhalation of respiratory aerosol, we use the available evidence to infer the emission rate of airborne infectious quanta from the primary source. We also explore how the risk of infection would vary with several influential factors: the rates of removal of respiratory aerosol by ventilation; deposition onto surfaces; and viral decay. The results indicate an emission rate of the order of a thousand quanta per hour (mean [interquartile range] for this event = 970 [680-1190] quanta per hour) and demonstrate that the risk of infection is modulated by ventilation conditions, occupant density, and duration of shared presence with an infectious individual.", "title": "Transmission of SARS-CoV-2 by inhalation of respiratory aerosol in the Skagit Valley Chorale superspreading event", "pid": "mazqe344", "bm25_score": 214.7992401123047}, {"text": "Covid‑19 origin and transmission to humans. Covid‑19 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid‑19 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS‑CoV‑2 transmission. However, the source(s) and transmission routine(s) of SARS‑CoV‑2 remain elusive' (1).", "title": "Possibility of transmission through dogs being a contributing factor to the extreme Covid-19 outbreak in North Italy", "pid": "k9lcpjyo", "bm25_score": 214.79286193847656}, {"text": "An epidemic of an acute respiratory syndrome caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in Wuhan, China, now known as coronavirus disease 2019 (COVID‐19), beginning in December 2019, has attracted an intense amount of attention worldwide. As the natural history and variety of clinical presentations of this disease unfolds, extrapulmonary symptoms of COVID‐19 have emerged, especially in the digestive system. While the respiratory mode of transmission is well known and is probably the principal mode of transmission of this disease, a possibility of the fecal‐oral route of transmission has also emerged in various case series and clinical scenarios. In this review article, we summarize four different aspects in published studies to date: (a) gastrointestinal manifestations of COVID‐19; (b) microbiological and virological investigations; (c) the role of fecal‐oral transmission; and (d) prevention and control of SARS‐CoV‐2 infection in the digestive endoscopy room. A timely understanding of the relationship between the disease and the digestive system and implementing effective preventive measures are of great importance for a favorable outcome of the disease and can help climnicians to mitigate further transmission by taking appropriate measures.", "title": "Digestive system involvement of novel coronavirus infection: Prevention and control infection from a gastroenterology perspective", "pid": "xj9md751", "bm25_score": 214.79122924804688}, {"text": "Outbreaks of emerging coronaviruses in the past two decades and the current pandemic of a novel coronavirus (SARS-CoV-2) that emerged in China highlight the importance of this viral family as a zoonotic public health threat. To gain a better understanding of coronavirus presence and diversity in wildlife at wildlife-human interfaces in three southern provinces in Viet Nam 2013-2014, we used consensus Polymerase Chain Reactions to detect coronavirus sequences. In comparison to previous studies, we observed high proportions of positive samples among field rats (34.0%, 239/702) destined for human consumption and insectivorous bats in guano farms (74.8%, 234/313) adjacent to human dwellings. Most notably among field rats, the odds of coronavirus RNA detection significantly increased along the supply chain from field rats sold by traders (reference group; 20.7% positivity, 39/188) by a factor of 2.2 for field rats sold in large markets (32.0%, 116/363) and 10.0 for field rats sold and served in restaurants (55.6%, 84/151). Coronaviruses were detected in the majority of wildlife farms (60.7%, 17/28) and in the Malayan porcupines (6.0%, 20/331) and bamboo rats (6.3%, 6/96) that are farmed. We identified six known coronaviruses in bats and rodents, clustered in three Coronaviridae genera, including the Alpha-, Beta-, and Gammacoronaviruses. Our analysis also suggested either mixing of animal excreta in the environment or interspecies transmission of coronaviruses, as both bat and avian coronaviruses were detected in rodent feces in the trade. The mixing of multiple coronaviruses, and their apparent amplification along the wildlife supply chain into restaurants, suggests maximal risk for end consumers and likely underpins the mechanisms of zoonotic spillover to people.", "title": "Coronavirus testing indicates transmission risk increases along wildlife supply chains for human consumption in Viet Nam, 2013-2014", "pid": "3awtlpxw", "bm25_score": 214.7865753173828}, {"text": "Covid­19 origin and transmission to humans. Covid­19 infection began in Wuhan (Hubei, China) in December, 2019. Although to date it is considered that Covid­19 originates from bats (96.2% overall genome sequence identity) (1), the type of intermediate animals that caused the transmission to humans remains unknown (2-4). Zhou et al (1) mentioned that 'Direct contact with intermediate host animals or consumption of wild animals was suspected to be the main route of SARS­CoV­2 transmission. However, the source(s) and transmission routine(s) of SARS­CoV­2 remain elusive' (1).", "title": "[Editorial] Possibility of transmission through dogs being a contributing factor to the extreme Covid­19 outbreak in North Italy", "pid": "jwxt4ygt", "bm25_score": 214.77381896972656}, {"text": "Background: The transmission of respiratory viruses such as influenza and corona viruses from one person to another is still not fully understood. Methods: A literature search showed that there is a strong scientific rationale and evidence that viruses are very efficiently spread through aerosols by the patient's breathing only. It is not necessary for the patient to cough or sneeze. Results: The exhaled aerosol particles are generated by normal breathing in the deep lung through reopening of collapsed small airways during inspiration. These mucus/surfactant aerosols (size range between 0.2 and 0.6 μm) can transport viruses out of the lungs of patients and be present in the room air for hours. Conclusion: These aerosol particles are difficult to filter out of the air; because of their physical properties, new strategies must be developed to protect people from these virus aerosols.", "title": "Breathing Is Enough: For the Spread of Influenza Virus and SARS-CoV-2 by Breathing Only.", "pid": "liye4zyf", "bm25_score": 214.75926208496094}, {"text": "COVID-19 is highly contagious pathogenic viral infection initiated from Wuhan seafood wholesale market of China on December 2019 and spread rapidly around the whole world due to onward transmission. This recent outbreak of novel coronavirus (CoV) was believed to be originated from bats and causing respiratory infections such as common cold, dry cough, fever, headache, dyspnea, pneumonia and finally Severe Acute Respiratory Syndrome (SARS) in humans. For this widespread zoonotic virus, human-to-human transmission has resulted in nearly 83 lakh cases in 213 countries and territories with 4,50,686 deaths as on 19th June 2020. This review presents a report on the origin, transmission, symptoms, diagnosis, possible vaccines, animal models and immunotherapy for this novel virus and will provide ample references for the researchers towards the ongoing development of therapeutic agents and vaccines and also preventing the spread of this disease.", "title": "The recent challenges of highly contagious COVID-19; causing respiratory infections: symptoms, diagnosis, transmission, possible vaccines, animal models and immunotherapy", "pid": "jxbk30gh", "bm25_score": 214.7592315673828}, {"text": "BACKGROUND. Transmission heterogeneity was observed during the 2015 Korean outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection. Only 22 of 186 cases transmitted the infection, and 5 super-spreading events caused 150 transmissions. We investigated the risk factors for MERS-CoV transmission. METHODS. Epidemiological reports were used to classify patients as nonspreaders, spreaders, or those associated with a super-spreading event (5 or more transmissions). Logistic regression analyses were used to evaluate the factors for MERS-CoV transmission. RESULTS. Compared to nonspreaders, spreaders exhibited a longer interval from symptom onset to isolation (7 days vs 3 days) and more frequent pre-isolation pneumonia diagnoses (68.2% vs 17.1%). Spreaders also exhibited higher values for pre-isolation contacts (149 vs 17.5), pre-isolation hospitalization (68.2% vs 16.5%), and emergency room (ER) visits (50% vs 7.3%). Spreaders exhibited lower cycle thresholds for the upE and ORF1a genes (22.7 vs 27.2 and 23.7 vs 27.9, respectively). In multivariate analysis, transmission was independently associated with the cycle threshold (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.75–0.96) and pre-isolation hospitalization or ER visits (OR, 6.82; 95% CI, 2.06–22.84). The super-spreading events exhibited higher values for pre-isolation contacts (777 vs 78), pre-isolation ER visits (100% vs 35.3%), and doctor shopping (100% vs 47.1%) compared to non-super-spreading events. CONCLUSIONS. These findings indicate that transmission is determined by host infectivity and the number of contacts, whereas super-spreading events were determined by the number of contacts and hospital visits. These relationships highlight the importance of rapidly enforcing infection control measures to prevent outbreaks.", "title": "Risk Factors for Transmission of Middle East Respiratory Syndrome Coronavirus Infection During the 2015 Outbreak in South Korea", "pid": "f0ny4ur5", "bm25_score": 214.75096130371094}, {"text": "Rhinorrhea, nasal congestion, and sore throat herald the beginning of the cold season for both children and adults. Although the common cold is a self-limited infection, there are no effective treatments presently available and complications, missed time from work and school, and overall discomfort are not insignificant. Understanding how infections are transmitted may lead to interventions to reduce rates of infection. In order to establish a route of transmission, certain conditions must be met. The virus must be produced and shed at the site of infection. The virus must be deposited in the environment and be able to survive there. The virus must then be able to reach the portal of entry. Finally, interruption of the proposed route of transmission must reduce the incidence of infection under natural conditions. Applying this framework, there is clear evidence in both experimental and home settings that colds can be transmitted via self-inoculation. A small amount of evidence is available relating to large and small particle aerosol transmission. Because rhinovirus is responsible for half of all colds, it has been used as the model to understand how virus is transmitted from one person to another in experimental settings. Rhinovirus has been shown to infect via self-inoculation following hand-to-hand contact with contaminated hands or hand-to-surface contact with contaminated objects in the environment. Similarly, there is convincing evidence that the self-inoculation method of cold virus transmission occurs in the home environment, where colds arre most often transmitted. Aerosol transmission has been studied in the experimental setting and may provide another, albeit less common method for transmission of rhinovirus infection. As more is understood about the transmission of cold viruses, effective methods to interrupt transmission may be devised.", "title": "Transmission of colds", "pid": "1rghbp72", "bm25_score": 214.746826171875}, {"text": "We previously identified the major pathological changes in the respiratory and immune systems of patients who died of severe acute respiratory syndrome (SARS) but gained little information on the organ distribution of SARS‐associated coronavirus (SARS‐CoV). In the present study, we used a murine monoclonal antibody specific for SARS‐CoV nucleoprotein, and probes specific for a SARS‐CoV RNA polymerase gene fragment, for immunohistochemistry and in situ hybridization, respectively, to detect SARS‐CoV systematically in tissues from patients who died of SARS. SARS‐CoV was found in lung, trachea/bronchus, stomach, small intestine, distal convoluted renal tubule, sweat gland, parathyroid, pituitary, pancreas, adrenal gland, liver and cerebrum, but was not detected in oesophagus, spleen, lymph node, bone marrow, heart, aorta, cerebellum, thyroid, testis, ovary, uterus or muscle. These results suggest that, in addition to the respiratory system, the gastrointestinal tract and other organs with detectable SARS‐CoV may also be targets of SARS‐CoV infection. The pathological changes in these organs may be caused directly by the cytopathic effect mediated by local replication of the SARS‐CoV; or indirectly as a result of systemic responses to respiratory failure or the harmful immune response induced by viral infection. In addition to viral spread through a respiratory route, SARS‐CoV in the intestinal tract, kidney and sweat glands may be excreted via faeces, urine and sweat, thereby leading to virus transmission. This study provides important information for understanding the pathogenesis of SARS‐CoV infection and sheds light on possible virus transmission pathways. This data will be useful for designing new strategies for prevention and treatment of SARS. Copyright © 2004 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.", "title": "Organ distribution of severe acute respiratory syndrome (SARS) associated coronavirus (SARS‐CoV) in SARS patients: implications for pathogenesis and virus transmission pathways", "pid": "tygyp55h", "bm25_score": 214.7449188232422}, {"text": "The world is facing a pandemic of unseen proportions caused by a corona virus named SARS-CoV-2 with unprecedent worldwide measures being taken to tackle its contagion. Person-to-person transmission is accepted but WHO only considers aerosol transmission when procedures or support treatments that produce aerosol are performed. Transmission mechanisms are not fully understood and there is evidence for an airborne route to be considered, as the virus remains viable in aerosols for at least 3 h and that mask usage was the best intervention to prevent infection. Heating, Ventilation and Air Conditioning Systems (HVAC) are used as a primary infection disease control measure. However, if not correctly used, they may contribute to the transmission/spreading of airborne diseases as proposed in the past for SARS. The authors believe that airborne transmission is possible and that HVAC systems when not adequately used may contribute to the transmission of the virus, as suggested by descriptions from Japan, Germany, and the Diamond Princess Cruise Ship. Previous SARS outbreaks reported at Amoy Gardens, Emergency Rooms and Hotels, also suggested an airborne transmission. Further studies are warranted to confirm our hypotheses but the assumption of such way of transmission would cause a major shift in measures recommended to prevent infection such as the disseminated use of masks and structural changes to hospital and other facilities with HVAC systems.", "title": "Airborne route and bad use of ventilation systems as non-negligible factors in SARS-CoV-2 transmission", "pid": "rqw9jir0", "bm25_score": 214.7433319091797}, {"text": "Backgroung: Coronaviruses (CoV) make up a large family of viruses, known since the mid-1960s, which received this name due to the spikes on its surface, which resemble a crown (from the Latin corona). CoV infections can cause everything from a common cold to severe respiratory syndromes, such as severe acute respiratory syndrome (SARS-CoV) and Middle Eastern respiratory syndrome (MERS-CoV).COVID-19 (SARS-CoV2) is a new variant of the coronavirus, and its isolation occurred in China on January 7th, 2020. COVID-19 has stood out with a high impact on public health due to the high number of cases with infection in a short period of time. However, it is possible to observe that 17% of patients confirmed with COVID-19 have severe infections and about 2.5% of these patients die. Current studies have shown that the number of mild and asymptomatic cases may be even greater. Thus, the challenges for controlling unreported cases of patients with mild symptoms that are spreading the virus and interfering with the magnitude and real data of the cases stand out. The transmission of the coronavirus occurs between humans, and it can occur from person to person through the air, through coughing or sneezing, by touching or shaking hands or by contact with contaminated objects or surfaces, followed by contact with the mouth, nose or eyes. Given the fluctuation in the incidence and the lethality rate, it is essential to stand out the precepts of health promotion in search of reorienting hygiene practices, considering that there is validity in health care models, still with a curative approach and the current situation experienced by the world population requires a preventive stance.(AU)", "title": "The dissemination of COVID-19: an expectant and preventive role in global health", "pid": "9efi8hf9", "bm25_score": 214.74085998535156}, {"text": "BACKGROUND Respiratory viruses spread in humans across wide geographical areas in short periods of time, resulting in high levels of morbidity and mortality. We undertook a systematic review to assess the evidence that air, ground and sea mass transportation systems or hubs are associated with propagating influenza and coronaviruses. METHODS Healthcare databases and sources of grey literature were searched using pre-defined criteria between April and June 2014. Two reviewers screened all identified records against the protocol, undertook risk of bias assessments and extracted data using a piloted form. Results were analysed using a narrative synthesis. RESULTS Forty-one studies met the eligibility criteria. Risk of bias was high in the observational studies, moderate to high in the reviews and moderate to low in the modelling studies. In-flight influenza transmission was identified substantively on five flights with up to four confirmed and six suspected secondary cases per affected flight. Five studies highlighted the role of air travel in accelerating influenza spread to new areas. Influenza outbreaks aboard cruise ships affect 2-7% of passengers. Influenza transmission events have been observed aboard ground transport vehicles. High heterogeneity between studies and the inability to exclude other sources of infection means that the risk of influenza transmission from an index case to other passengers cannot be accurately quantified. A paucity of evidence was identified describing severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus transmission events associated with transportation systems or hubs. CONCLUSION Air transportation appears important in accelerating and amplifying influenza propagation. Transmission occurs aboard aeroplanes, at the destination and possibly at airports. Control measures to prevent influenza transmission on cruise ships are needed to reduce morbidity and mortality. There is no recent evidence of sea transport accelerating influenza or coronavirus spread to new areas. Further investigation is required regarding the roles of ground transportation systems and transport hubs in pandemic situations.", "title": "The roles of transportation and transportation hubs in the propagation of influenza and coronaviruses: a systematic review.", "pid": "4yufh9rz", "bm25_score": 214.73817443847656}, {"text": "COVID-19 is highly contagious pathogenic viral infection initiated from Wuhan seafood wholesale market of China on December 2019 and spread rapidly around the whole world due to onward transmission. This recent outbreak of novel coronavirus (CoV) was believed to be originated from bats and causing respiratory infections such as common cold, dry cough, fever, headache, dyspnea, pneumonia and finally Severe Acute Respiratory Syndrome (SARS) in humans. For this widespread zoonotic virus, human-to-human transmission has resulted in nearly 83 lakh cases in 213 countries and territories with 4,50,686 deaths as on 19th June 2020. This review presents a report on the origin, transmission, symptoms, diagnosis, possible vaccines, animal models and immunotherapy for this novel virus and will provide ample references for the researchers towards the ongoing development of therapeutic agents and vaccines and also preventing the spread of this disease.", "title": "The recent challenges of highly contagious COVID-19; causing respiratory infections: symptoms, diagnosis, transmission, possible vaccines, animal models and immunotherapy.", "pid": "r2ynbnxx", "bm25_score": 214.7354736328125}, {"text": "Middle East respiratory syndrome coronavirus (MERS-CoV) infection causes a spectrum of respiratory illness, from asymptomatic to mild to fatal. MERS-CoV is transmitted sporadically from dromedary camels to humans and occasionally through human-to-human contact. Current epidemiologic evidence supports a major role in transmission for direct contact with live camels or humans with symptomatic MERS, but little evidence suggests the possibility of transmission from camel products or asymptomatic MERS cases. Because a proportion of case-patients do not report direct contact with camels or with persons who have symptomatic MERS, further research is needed to conclusively determine additional mechanisms of transmission, to inform public health practice, and to refine current precautionary recommendations.", "title": "Middle East Respiratory Syndrome Coronavirus Transmission", "pid": "s8fitxwd", "bm25_score": 214.7332763671875}]}
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It is known that all cases do not spread the infection equally; super spreaders play an important role as they contribute disproportionately to a much larger number of cases including in the ongoing COVID-19 pandemic. Super spreaders have been reported for more than a century, but limited information is available in scientific literature. An epidemic containment strategy needs to include early identification of super spreaders to limit an explosive growth. Super spreaders tend to get stigmatized, resulting in late reporting and hiding of cases. It is important for program managers to be sensitive to the manner in which related information is shared with media and general public.", "title": "Significance of super spreader events in COVID-19.", "pid": "na3vrf5q", "bm25_score": 218.169189453125}, {"text": "The number of secondary cases from each primary case determines how fast an epidemic grows. It is known that all cases do not spread the infection equally; super spreaders play an important role as they contribute disproportionately to a much larger number of cases including in the ongoing COVID-19 pandemic. Super spreaders have been reported for more than a century, but limited information is available in scientific literature. An epidemic containment strategy needs to include early identification of super spreaders to limit an explosive growth. Super spreaders tend to get stigmatized, resulting in late reporting and hiding of cases. It is important for program managers to be sensitive to the manner in which related information is shared with media and general public.", "title": "Significance of super spreader events in COVID-19", "pid": "p48bw6s4", "bm25_score": 218.04734802246094}, {"text": "Uncertainty around the role 'super-spreaders' play in the transmission and escalation of infectious disease is compounded by its broad and vague definition. It is a term that has been much used in relation to COVID-19, particularly in social media. On its widest definition, it refers to a propensity to infect a larger than average number of people. Given the biological, behavioural and environmental variables relevant to infectivity, this might be pertinent to almost any infected individual who is not physically isolated from others. Nor is the term confined to individuals with a propensity to spread infectious disease: it can potentially be used to describe events, policies or settings. This article explores the use of the term and considers circumstances in which the wide definition can be problematic. One problem is that it can lead to undeserved apportionment of moral blame to alleged super-spreaders. Another is that it can detract from scientific investigation of the heterogeneity of COVID-19 transmission. The author calls for a clearer epidemiological definition.", "title": "COVID-19 Super-spreaders: Definitional Quandaries and Implications", "pid": "v0vjkwy9", "bm25_score": 217.58055114746094}, {"text": "Uncertainty around the role ‘super-spreaders’ play in the transmission and escalation of infectious disease is compounded by its broad and vague definition. It is a term that has been much used in relation to COVID-19, particularly in social media. On its widest definition, it refers to a propensity to infect a larger than average number of people. Given the biological, behavioural and environmental variables relevant to infectivity, this might be pertinent to almost any infected individual who is not physically isolated from others. Nor is the term confined to individuals with a propensity to spread infectious disease: it can potentially be used to describe events, policies or settings. This article explores the use of the term and considers circumstances in which the wide definition can be problematic. One problem is that it can lead to undeserved apportionment of moral blame to alleged super-spreaders. Another is that it can detract from scientific investigation of the heterogeneity of COVID-19 transmission. The author calls for a clearer epidemiological definition.", "title": "COVID-19 Super-spreaders: Definitional Quandaries and Implications", "pid": "s9dy7iyf", "bm25_score": 217.396240234375}, {"text": "", "title": "Superspreaders and the spread pattern of COVID-19: Response to: \"Do superspreaders generate new superspreaders? A hypothesis to explain the propagation pattern of COVID-19\", International Journal of Infectious Diseases 96 (2020) 461-463", "pid": "koq7upoq", "bm25_score": 217.2327880859375}, {"text": "", "title": "Superspreaders and the spread pattern of COVID-19: Response to: “Do superspreaders generate new superspreaders? A hypothesis to explain the propagation pattern of COVID-19”, International Journal of Infectious Diseases 96 (2020) 461–463", "pid": "g83oxgig", "bm25_score": 217.13414001464844}, {"text": "If the covid-19 virus is transmitted largely by superspreaders, it might not go pandemic, reports Debora MacKenzie", "title": "Is it super-spreading?", "pid": "kb8dz8hd", "bm25_score": 216.91209411621094}, {"text": "An outbreak of Coronavirus Disease 2019 (COVID-19) has spread rapidly. It is imperative to control the epidemic by understanding the epidemiological feature, preventative quarantine, and effective hygiene measures. In the present study, we report a case of super-spreader who transmitted the disease to over twenty-eight persons in Ningbo, Zhejiang. Identifying and isolated super-spreaders, understanding the reasons behind the efficient transmission ability are important for the control and management of the ongoing COVID-19 pandemic.", "title": "A super-spreader of COVID-19 in Ningbo city in China", "pid": "37katpp3", "bm25_score": 216.81561279296875}, {"text": "The current global propagation of COVID-19 is heterogeneous, with slow transmission continuing in many countries and exponential propagation in others, where the time that it took for the explosive spread to begin varied greatly. It is proposed that this could be explained by cascading superspreading events, in which new infections caused by a superspreader are more likely to be highly infectious. The mechanism suggested for this is related to viral loads. Exposure to high viral loads may result in high-intensity infection, which exposes new cases to high viral loads. This notion is supported by experimental veterinary research.", "title": "Do superspreaders generate new superspreaders? A hypothesis to explain the propagation pattern of COVID-19", "pid": "oocco483", "bm25_score": 216.76455688476562}, {"text": "Abstract The current global propagation of COVID-19 is heterogeneous, with slow transmission continuing in many countries, and exponential propagation in others, in which the time that took to begin this explosive spread varies greatly. It is proposed that this could be explained by cascading superspreading events, in which new infections caused by a superspreader are more likely to be highly infectious. The mechanism suggested for this is related to viral loads. Exposure to high viral loads may result in infections of high intensity, which exposes new cases to high viral loads, and so on. This notion is supported by experimental veterinary research.", "title": "Do superspreaders generate new superspreaders? a hypothesis to explain the propagation pattern of COVID-19", "pid": "5906wju4", "bm25_score": 216.75167846679688}, {"text": "Purpose: The United States has the highest number of confirmed COVID-19 cases in the world to date, with over 94,000 COVID-19-related deaths. The true risk of a COVID-19 resurgence as states prepare to reopen businesses is unknown. This paper aims to classify businesses by their risk of transmission and quantify the relationship between the density of super-spreader businesses and COVID-19 cases. Methods: We constructed a COVID-19 Business Transmission Risk Index based upon the frequency and duration of visits and square footage of businesses pre-pandemic in 2019 in 8 states (Massachusetts, Rhode Island, Connecticut, New Hampshire, Vermont, Maine, New York, and California). We used this index to classify businesses as super-spreaders. Then, we analyzed the association between the density of super-spreader businesses in a county and the rate of COVID-19 cases. We performed significance testing using a negative binomial regression. The main outcome of interest is the cumulative number of COVID-19 cases each week. Results: We found a positive association between the density of super-spreader businesses and COVID-19 cases. A 1 percentage point increase in the density of super-spreader businesses is associated with 5% higher COVID-19 cases, all else equal. Conclusion: Higher densities of super-spreader businesses are associated with higher rates of COVID-19 cases. This may have important implications for how states reopen super-spreader businesses.", "title": "Super-Spreader Businesses and Risk of COVID-19 Transmission", "pid": "8ngri1x0", "bm25_score": 216.63006591796875}, {"text": "Background: Super-spreading events were associated with the outbreaks of SARS and MERS, but their association with the outbreak of COVID-19 remains unknown. Here, we report a super-spreading transmission chain of SARS-CoV-2 involving an index patient, seven cancer patients, 40 health care workers and four family members. Methods: We conducted a retrospective study to identify the index patient and the exposed individuals linked to a chain of transmission associated with COVID-19. We collected and analyzed the data on demographic features, exposure history, clinical presentation, laboratory investigation, radiological examination, and disease outcome of these patients. Results: We identified the index patient and another presumptive super-spreader, who initiated and amplified a super-spreading transmission chain associated with COVID-19, respectively. There were 31 female and 21 male patients in this cohort, and the median age was 37 years (range: 22-79 years). Each of them had an exposure history with the index patient or his close contacts. Approximately 87% (45/52) of the patients had fever or other symptoms, 96% (50/52) had abnormal chest CT-scan findings, 86% of the tested patients (39/45) were positive for SARS-CoV-2 in the nasopharyngeal or throat swab specimen, 85% of the tested patients (29/34) were positive for SARS-CoV-2-specific IgM and/or IgG, 15% of the RT-PCR positive patients were tested negative for the specific IgM and/or IgG at the convalescent phase, and 15% of the RT-PCR negative patients were tested positive for the specific IgM and/or IgG. The severe patients experienced a significant decrease in oximetry saturation, lymphocyte, and platelet counts, along with a significant increase in C-reactive protein, D-dimer, and lactate dehydrogenase. All six fatal cases had comorbidities and five of the seven cancer patients (71%) died within 2-20 days of the disease onset. Conclusions: The super-spreading events were associated with the outbreak of COVID-19 in Wuhan and its impact on disease transmission warrants further investigation. Cancer patients appeared highly vulnerable to COVID-19. The finding that a significant portion of SARS-CoV-2 infected patients were tested negative for the serum specific IgM and IgG at the convalescent phase should be addressed by additional studies.", "title": "Identification of a super-spreading chain of transmission associated with COVID-19", "pid": "yp38t4yb", "bm25_score": 216.35984802246094}, {"text": "Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine if an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R(0)) and the dispersion factor (k) from empirical data on clusters of epidemiologically-linked COVID-19 cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.", "title": "Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan and Singapore", "pid": "w4l2vpiy", "bm25_score": 216.33709716796875}, {"text": "Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine if an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R0) and the dispersion factor (k) from empirical data on clusters of epidemiologically-linked COVID-19 cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.", "title": "Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan and Singapore", "pid": "2t4fsfy9", "bm25_score": 216.19961547851562}, {"text": "A newly emerged coronavirus, SARS-CoV-2, caused severe pneumonia outbreaks in China in December 2019 and has since spread to various countries around the world. To trace the evolution route and probe the transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences available in the GISAID platform as of 5 March 2020. Among them, four genetic clusters, defined as super-spreaders (SSs), could be identified and were found to be responsible for the major outbreaks that subsequently occurred in various countries. SS1 was widely disseminated in Asia and the US, and mainly responsible for outbreaks in the states of Washington and California as well as South Korea, whereas SS4 contributed to the pandemic in Europe. Using the signature mutations of each SS as markers, we further analysed 1539 genome sequences reported after 29 February 2020 and found that 90% of these genomes belonged to SSs, with SS4 being the most dominant. The relative degree of contribution of each SS to the pandemic in different continents was also depicted. Identification of these super-spreaders greatly facilitates development of new strategies to control the transmission of SARS-CoV-2.", "title": "Genetic cluster analysis of SARS-CoV-2 and the identification of those responsible for the major outbreaks in various countries", "pid": "3uzsx715", "bm25_score": 216.16497802734375}, {"text": "Super-spreading occurs when a single patient infects a disproportionate number of contacts. The 2015 MERS-CoV, 2003 SARS-CoV, and to a lesser extent 2014–15 Ebola virus outbreaks were driven by super-spreaders. We summarize documented super-spreading in these outbreaks, explore contributing factors, and suggest studies to better understand super-spreading.", "title": "MERS, SARS, and Ebola: The Role of Super-Spreaders in Infectious Disease", "pid": "414grqif", "bm25_score": 216.15525817871094}, {"text": "The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the 21st century. We analyzed >4,700 SARS-CoV-2 genomes and associated meta-data retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and >160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a uniform mutation occurrence along branches that could complicate the design of future vaccines. The root of SARS-CoV-2 genomes locates at the Chinese haplogroup B1, with a TMRCA dating to 12 November 2019 - thus matching epidemiological records. Sub-haplogroup A2a originates in China and represents the major non-Asian outbreak. Multiple founder effect episodes, most likely associated with super-spreader hosts, explain COVID-19 pandemic to a large extent.", "title": "The impact of super-spreaders in COVID-19: mapping genome variation worldwide", "pid": "qw05apnf", "bm25_score": 216.12551879882812}, {"text": "A newly emerged coronavirus, SARS-CoV-2, caused severe pneumonia outbreaks in China in December 2019 and has since spread to various countries around the world. To trace the evolution route and probe the transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences available in the GISAID platform as of 5 March 2020. Among them, four genetic clusters, defined as super-spreaders (SSs), could be identified and were found to be responsible for the major outbreaks that subsequently occurred in various countries. SS1 was widely disseminated in Asia and the US, and mainly responsible for outbreaks in the states of Washington and California as well as South Korea, whereas SS4 contributed to the pandemic in Europe. Using the signature mutations of each SS as markers, we further analysed 1539 genome sequences reported after 29 February 2020 and found that 90% of these genomes belonged to SSs, with SS4 being the most dominant. The relative degree of contribution of each SS to the pandemic in different continents was also depicted. Identification of these super-spreaders greatly facilitates development of new strategies to control the transmission of SARS-CoV-2.", "title": "Genetic cluster analysis of SARS-CoV-2 and the identification of those responsible for the major outbreaks in various countries.", "pid": "4zyfc0y4", "bm25_score": 216.036376953125}, {"text": "", "title": "Super-spreading events and contribution to transmission of MERS, SARS, and SARS-CoV-2 (COVID-19)", "pid": "zpib6e2z", "bm25_score": 215.99679565429688}, {"text": "A simple two-cohort SIR like model can explain the qualitative behaviour of the logarithmic derivative estimations of the covid-19 epidemic evolution as observed in several countries. The model consists of a general population in which the R_0 value is slightly below 1, but in which a super-spreading small subgroup with high R_0, coupled to the general population, is contaminating a significant fraction of the population. The epidemic starts to slow down when herd immunity is reached in this subgroup. The dynamics of this system is quite robust against non-pharmaceutical measures.", "title": "Super spreader cohorts and covid-19", "pid": "123i465d", "bm25_score": 215.90438842773438}, {"text": "We use anonymized and aggregated data from Facebook to show that areas with stronger social ties to two early COVID-19\"hotspots\"(Westchester County, NY, in the U.S. and Lodi province in Italy) generally have more confirmed COVID-19 cases as of March 30, 2020. These relationships hold after controlling for geographic distance to the hotspots as well as for the income and population density of the regions. These results suggest that data from online social networks may prove useful to epidemiologists and others hoping to forecast the spread of communicable diseases such as COVID-19.", "title": "The geographic spread of COVID-19 correlates with structure of social networks as measured by Facebook", "pid": "ij6ciglx", "bm25_score": 215.79507446289062}, {"text": "We use a model of covid-19 spread, an SEIR agent-based model on a graph, which takes into account several important real-life attributes of covid-19: Super-spreaders, realistic epidemiological parameters of the disease, testing and quarantine policies. We provide simulation results and mathematical arguments to argue that certain results of our simulations hold in more general settings. We find that mass-testing is much less effective than testing the symptomatic and contact tracing, and some blend of these with social distancing is required to get suppression. We also find that the fat tail of the degree distribution matters a lot for epidemic growth, and many standard models do not account for this. Additionally, the average reproduction number for individuals is not an upper bound for the effective reproduction number, R. Even with an expectation of less than one new case per person, this model shows that exponential spread is possible. The parameter which closely predicts growth rate is the ratio between 2nd to 1st moments of the degree distribution.", "title": "Modeling COVID-19 on a network: super-spreaders, testing and containment", "pid": "7kovd82v", "bm25_score": 215.78237915039062}, {"text": "", "title": "Super-spreading events and contribution to transmission of MERS, SARS, and COVID-19", "pid": "0h8b051i", "bm25_score": 215.72732543945312}, {"text": "COVID-19 is a new type of coronavirus disease which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It originated in China in the month of December 2019 and quickly started to spread within the country. On 31st December 2019, it was first reported to country office of World Health Organization (WHO) in China. Since then, it has spread to most of the countries around the globe. However, there has been a recent rise in trend in believing that it would go away during summer days, which has not yet been properly investigated. In this paper, relationship of daily number of confirmed cases of COVID-19 with three environmental factors, viz. maximum relative humidity (RH_max), maximum temperature (T_max) and highest wind speed (WS_max), considering the incubation period, have been investigated statistically, for four of the most affected places of China, viz. Beijing, Chongqing, Shanghai, Wuhan and five of the most affected places of Italy, viz. Bergamo, Cremona, Lodi, Milano. It has been found that the relationship with maximum relative humidity and highest wind is mostly negligible, whereas relationship with maximum temperature is ranging between negligible to moderate.", "title": "Statistical investigation of relationship between spread of coronavirus disease (COVID-19) and environmental factors based on study of four mostly affected places of China and five mostly affected places of Italy", "pid": "4ay3hsi7", "bm25_score": 215.6025848388672}, {"text": "Summary Early studies that explored host–pathogen interactions assumed that infected individuals within a population have equal chances of transmitting the infection to others. Subsequently, in what became known as the 20/80 rule, a small percentage of individuals within any population was observed to control most transmission events. This empirical rule was shown to govern inter-individual transmission dynamics for many pathogens in several species, and individuals who infect disproportionately more secondary contacts, as compared to most others, became known as super-spreaders. Studies conducted in the wake of the severe acute respiratory syndrome (SARS) pandemic revealed that, in the absence of super-spreading events, most individuals infect few, if any, secondary contacts. The analysis of SARS transmission, and reports from other outbreaks, unveil a complex scenario in which super-spreading events are shaped by multiple factors, including co-infection with another pathogen, immune suppression, changes in airflow dynamics, delayed hospital admission, misdiagnosis, and inter-hospital transfers. Predicting and identifying super-spreaders open significant medical and public health challenges, and represent important facets of infectious disease management and pandemic preparedness plans.", "title": "Super-spreaders in infectious diseases", "pid": "j74wnaef", "bm25_score": 215.55506896972656}, {"text": "The novel Coronavirus Disease 2019 (COVID-19) has spread quickly across the globe. Here, we evaluated the role of climate (temperature and precipitation), region-specific susceptibility (BCG vaccination, malaria infection, and elderly population) and international traveller population (human mobility) in shaping the geographical patterns of COVID-19 cases across 1,055 countries/regions, and examined the sequential shift of multiple drivers of the accumulated cases from December, 2019 to April 12, 2020. The accumulated numbers of COVID-19 cases (per 1 million population) were well explained by a simple regression model. The explanatory power (R2) of the model increased up to > 70% in April 2020 as the COVID-19 spread progressed. Climate, host mobility, and host susceptibility largely explained the variance of the COVID-19 cases (per 1 million population), and their explanatory power improved as the pandemic progressed; the relative importance of host mobility and host susceptibility have been greater than that of climate. The number of days from outbreak onset showed greater explanatory power in the earlier stages of COVID-19 spread but rapidly lost its influence. Our findings demonstrate that the COVID-19 pandemic is deterministically driven by climate suitability, cross-border human mobility, and region-specific susceptibility. The present distribution of COVID-19 cases has not reached an equilibrium and is changing daily, especially in the Southern Hemisphere. Nevertheless, the present results, based on mapping the spread of COVID-19 and identifying multiple drivers of this outbreak trajectory, may contribute to a better understanding of the COVID-19 disease transmission risk and the measures against long-term epidemic.", "title": "Multiple drivers of the COVID-19 spread: role of climate, international mobility, and region-specific conditions", "pid": "d9zu9an6", "bm25_score": 215.53097534179688}, {"text": "Mechanisms underlying the acute respiratory distress syndrome (ARDS)-like clinical manifestations leading to deaths in patients who develop COVID-19 remain uncharacterized. While multiple factors could influence these clinical outcomes, we explored if differences in transmissibility and pathogenicity of SARS-CoV2 variants could contribute to these terminal clinical consequences of COVID-19. We analyzed 34,412 SARS-CoV2 sequences deposited in the Global Initiative for Sharing All Influenza Data (GISAID) SARS-CoV2 sequence database to determine if regional differences in circulating strain variants correlated with increased mortality in Europe, the United States, and California. We found two subclades descending from the Wuhan HU-1 strain that rapidly became dominant in Western Europe and the United States. These variants contained nonsynonymous nucleotide mutations in the Orf1ab segment encoding RNA-dependent RNA polymerase (C14408T), the spike protein gene (A23403G), and Orf1a (G25563T), which resulted in non-conservative amino acid substitutions P323L, D614G, and Q57H, respectively. In Western Europe, the A23403G-C14408T subclade dominated, while in the US, the A23403G-C14408T-G25563T mutant became the dominant strain in New York and parts of California. The high cumulative frequencies of both subclades showed inconsistent but significant association with high cumulative CFRs in some of the regions. When the frequencies of the subclades were analyzed by their 7-day moving averages across each epidemic, we found co-circulation of both subclades to temporally correlate with peak mortality periods. We postulate that in areas with high numbers of these co-circulating subclades, a person may get serially infected. The second infection may trigger a hyperinflammatory response similar to the antibody-dependent enhancement (ADE) response, which could explain the ARDS-like manifestations observed in people with co-morbidity, who may not mount sufficient levels of neutralizing antibodies against the first infection. Further studies are necessary but the implication of such a mechanism will need to be considered for all current COVID-19 vaccine designs.", "title": "Dissemination and co-circulation of SARS-CoV2 subclades exhibiting enhanced transmission associated with increased mortality in Western Europe and the United States", "pid": "02bwyi1w", "bm25_score": 215.3935089111328}, {"text": "COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics, including heterogeneity and the emergence of super spreading events (SSEs) where certain individuals infect large numbers of secondary cases, is of vital importance for prediction and intervention of future epidemics. Here, we collected information of all infected cases (135 cases) between 21 January and 26 February 2020 from official public sources in Tianjin, a metropolis of China, and grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of four generations. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k (lower value indicating higher heterogeneity) to be 0.67 (95% CI: 0.54-0.84) and 0.25 (95% CI: 0.13-0.88), respectively. A super-spreader causing six infections was identified in Tianjin. In addition, our simulation allowing for heterogeneity showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since 28 January. Our results highlighted more efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors.", "title": "Evaluating Transmission Heterogeneity and Super-Spreading Event of COVID-19 in a Metropolis of China", "pid": "uo7ixk9r", "bm25_score": 215.35122680664062}, {"text": "COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics, including heterogeneity and the emergence of super spreading events (SSEs) where certain individuals infect large numbers of secondary cases, is of vital importance for prediction and intervention of future epidemics. Here, we collected information of all infected cases (135 cases) between 21 January and 26 February 2020 from official public sources in Tianjin, a metropolis of China, and grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of four generations. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k (lower value indicating higher heterogeneity) to be 0.67 (95% CI: 0.54–0.84) and 0.25 (95% CI: 0.13–0.88), respectively. A super-spreader causing six infections was identified in Tianjin. In addition, our simulation allowing for heterogeneity showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since 28 January. Our results highlighted more efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors.", "title": "Evaluating Transmission Heterogeneity and Super-Spreading Event of COVID-19 in a Metropolis of China", "pid": "3v4sedfo", "bm25_score": 215.32815551757812}, {"text": "A newly emerged coronavirus, SARS-CoV-2, caused severe outbreaks of pneumonia in China in December 2019 and has since spread to various countries around the world. To probe the origin and transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences of viruses available in the GISAID platform as of March 05, 2020. A substantial number of earliest sequences reported in Wuhan in December 2019, including those of viruses recovered from the Huanan Seafood Market (HNSM), the site of the initial outbreak, were genetically diverse, suggesting that viruses of multiple sources were involved in the original outbreak. The viruses were subsequently disseminated to different parts of China and other countries, with diverse mutational profiles being recorded in strains recovered subsequently. Interestingly, four genetic clusters defined as Super-transmitters (STs) were found to become dominant and were responsible for the major outbreaks in various countries. Among the four clusters, ST1 is widely disseminated in Asia and the US and mainly responsible for outbreaks in the states of Washington and California in the US as well as those in South Korea at the end of February and early March, whereas ST4 contributed to the pandemic in Europe. Each ST cluster carried a signature mutation profile which allowed us to trace the origin and transmission patterns of specific viruses in different parts of the world. Using the signature mutations as markers of STs, we further analysed 1539 genome sequences reported after February 29, 2020. We found that around 90% of these genomes belonged to STs with ST4 being the dominant one and their contribution to pandemic in different continents were also depicted. The identification of these super-transmitters provides insight into the control of further transmission of SARS-CoV-2.", "title": "Identification of super-transmitters of SARS-CoV-2", "pid": "tnfgbl05", "bm25_score": 215.27609252929688}, {"text": "", "title": "Children are not COVID-19 super spreaders: time to go back to school.", "pid": "m005jyta", "bm25_score": 215.2681121826172}, {"text": "On the base of logic discrete equations system mathematical modeling of COVID-19 epidemic spread was carried out in the world and in the countries with the largest number of infected people such as the USA, Brasil, Russia and India in the first half of 2020. It was shown that for the countries with strong restrictive measures the spread of COVID-19 fit on a single wave with small capacity as for a number of countries with violation of restrictive measures the spread of the epidemic fit on a waves superposition. For countries with large population mixing, the spread of the epidemic today also fits into a single wave, but with a huge capacity value (for Brazil - 80 million people, for India - 40 million people). We estimated that the epidemic spread in the world today fits into 5 waves. The first two waves are caused by the epidemic spread in China (the first - in Wuhan), the third - by the epidemic spread in European countries, the fourth mainly by the epidemic spread in Russia and the USA, the fifth wave is mainly caused by the epidemic spread in Latin America and South Asia. It was the fifth wave that led to the spread of the coronavirus epidemic COVID-19 entering a new phase, with an increase in the number of infected more than 100 thousand inhabitants. For all the studied countries and the world, for each of the superposition waves, the wave capacities and growth indicators were calculated. The local peaks of the waves and their ending times are determined. It was the fifth wave that led to the fact that COVID-19 spread is entering a new phase, with the increase in the number of infected people being more than 100 thousand inhabitants. For all the countries being examined and for the whole world, for each of the superposition waves we calculated the waves capacities and index of infected people growth.", "title": "Superposition of waves for modeling COVID-19 epidemic in the world and in the countries with the maximum number of infected people in the first half of 2020", "pid": "tkfbx9kz", "bm25_score": 215.23501586914062}, {"text": "Background: COVID-19 caused rapid mass infection worldwide. Understanding its transmission characteristics including heterogeneity is of vital importance for prediction and intervention of future epidemics. In addition, transmission heterogeneity usually envokes super spreading events (SSEs) where certain individuals infect large numbers of secondary cases. Till now, studies of transmission heterogeneity of COVID-19 and its underlying reason are far from reaching an agreement. MethodsWe collected information of all infected cases between January 21 and February 26, 2020 from official public sources in Tianjin, a metropolis of China. Utilizing a heterogeneous transmission model based on branching process along with a negative binomial offspring distribution, we estimated the reproductive number R and the dispersion parameter k which characterized the transmission potential and heterogeneity, respectively. Furthermore, we studied the SSE in Tianjin outbreak and evaluated the effect of control measures undertaken by local government based on the heterogeneous model. Results: A total of 135 confirmed cases (including 34 imported cases and 101 local infections) in Tianjin by February 26th 2020 entered the study. We grouped them into 43 transmission chains with the largest chain of 45 cases and the longest chain of 4 generations. The estimated reproduction number R was at 0.67 (95%CI: 0.54[~]0.84), and the dispersion parameter k was at 0.25 (95% CI: 0.13[~]0.88). A super spreader causing six infections in Tianjin, was identified. In addition, our simulation results showed that the outbreak in Tianjin would have caused 165 infections and sustained for 7.56 generations on average if no control measures had been taken by local government since January 28th. Conclusions: Our analysis suggested that the transmission of COVID-19 was subcritical but with significant heterogeneity and may incur SSE. More efforts are needed to verify the transmission heterogeneity of COVID-19 in other populations and its contributing factors, which is important for developing targeted measures to curb the pandemic.", "title": "Evaluating transmission heterogeneity and super-spreading event of COVID-19 in a metropolis of China", "pid": "uicvudil", "bm25_score": 215.2327880859375}, {"text": "The COVID-19 pandemic started in Wuhan, China, and caused the worldwide spread of the RNA virus SARS-CoV-2, the causative agent of COVID-19. Because of its mutational rate, wide geographical distribution, and host response variance this coronavirus is currently evolving into an array of strains with increasing genetic diversity. Most variants apparently have neutral effects for disease spread and symptoms severity. However, in the viral Spike protein, which is responsible for host cell attachment and invasion, an emergent variant, containing the amino acid substitution D to G in position 614 (D614G), was suggested to increase viral infection capability. To test whether this variant has epidemiological impact, the temporal distributions of the SARS-CoV-2 samples bearing D or G at position 614 were compared in the USA, Asia and Europe. The epidemiological curves were compared at early and late epidemic stages. At early stages, where containment measures were still not fully implemented, the viral variants are supposed to be unconstrained and its growth curves might approximate the free viral dynamics. Our analysis shows that the D614G prevalence and the growth rates of COVID-19 epidemic curves are correlated in the USA, Asia and Europe. Our results suggest a selective sweep that can be explained, at least in part, by a propagation advantage of this variant, in other words, that the molecular level effects of D614G have sufficient impact on population transmission dynamics as to be detected by differences in rate coefficients of epidemic growth curves.", "title": "Temporal data series of COVID-19 epidemics in the USA, Asia and Europe suggests a selective sweep of SARS-CoV-2 Spike D614G variant", "pid": "8iyynbup", "bm25_score": 215.22535705566406}, {"text": "BACKGROUD: Effective communication of accurate information through social media constitutes an important component of public health interventions in modern time, when traditional public health approaches such as contact tracing, quarantine and isolation are among the few options for the containing the disease spread in the population. The success of control of COVID-19 outbreak started from Wuhan, the capital city of Hubei Province of China relies heavily on the resilience of residents to follow public health interventions which induce substantial interruption of social-economic activities, and evidence shows that opinion leaders have been playing significant roles in the propagation of epidemic information and public health policy and implementations. METHODS: We design a mathematical model to quantify the roles of information superspreaders in single specific information which outbreaks rapidly and usually has a short duration period, and to examine the information propagation dynamics in the Chinese Sina-microblog. Our opinion-leader susceptible-forwarding-immune (OL-SFI) model is formulated to track the temporal evolution of forwarding quantities generated by opinion leaders and normal users. RESULTS: Data fitting from the real data of COVID-19 obtained from Chinese Sina-microblog can identify the different contact rates and forwarding probabilities (and hence calculate the basic information forwarding reproduction number of superspreaders), and can be used to evaluate the roles of opinion leaders in different stages of the information propagation and the outbreak unfolding. CONCLUSIONS: The parameterized model can be used to nearcast the information propagation trend, and the model-based sensitivity analysis can help to explore important factors for the roles of opinion leaders.", "title": "Quantify the role of superspreaders -opinion leaders- on COVID-19 information propagation in the Chinese Sina-microblog", "pid": "v5js0ssk", "bm25_score": 215.20654296875}, {"text": "The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) reached over two million confirmed cases worldwide, and numbers are still growing at a fast rate. The majority of new infections are now being reported outside of China, where the outbreak officially originated in December 2019 in Wuhan. Despite the wide outbreak of the infection, a remarkable asymmetry is observed in the number of cases and in the distribution of the severity of the COVID-19 symptoms in patients with respect to the countries/regions. In the early stages of a new pathogen outbreak, it is critical to understand the dynamics of the infection transmission, in order to follow contagion over time and project the epidemiological situation in the near future. While it is possible to reason that observed variation in the number and severity of cases stem from the initial number of infected individuals, the difference in the testing policies and social aspects of community transmissions, the factors that could explain high discrepancy in areas with a similar level of healthcare still remain unknown. Here we introduce a binary classifier based on an artificial neural network that can help in explaining those differences and that can be used to support the design of containment policies. We propose that air pollutants, and specifically particulate matter (PM) 2.5 and ozone, are oppositely related with the SARS-CoV-2 infection frequency and could serve as surrogate markers to complement the infection outbreak anticipation.", "title": "Spatial-temporal variations of atmospheric factors contribute to SARS-CoV-2 outbreak", "pid": "4omocd8q", "bm25_score": 215.17774963378906}, {"text": "", "title": "Children are not COVID-19 super spreaders: time to go back to school", "pid": "zy1byu51", "bm25_score": 215.171875}, {"text": "Most models of epidemic spread, including many designed specifically for COVID-19, implicitly assume that social networks are undirected, i.e., that the infection is equally likely to spread in either direction whenever a contact occurs. In particular, this assumption implies that the individuals most likely to spread the disease are also the most likely to receive it from others. Here, we review results from the theory of random directed graphs which show that many important quantities, including the reproductive number and the epidemic size, depend sensitively on the joint distribution of in- and out-degrees (\"risk\"and\"spread\"), including their heterogeneity and the correlation between them. By considering joint distributions of various kinds we elucidate why some types of heterogeneity cause a deviation from the standard Kermack-McKendrick analysis of SIR models, i.e., so called mass-action models where contacts are homogeneous and random, and some do not. We also show that some structured SIR models informed by complex contact patterns among types of individuals (age or activity) are simply mixtures of Poisson processes and tend not to deviate significantly from the simplest mass-action model. Finally, we point out some possible policy implications of this directed structure, both for contact tracing strategy and for interventions designed to prevent superspreading events. In particular, directed networks have a forward and backward version of the classic\"friendship paradox\"-- forward links tend to lead to individuals with high risk, while backward links lead to individuals with high spread -- such that a combination of both forward and backward contact tracing is necessary to find superspreading events and prevent future cascades of infection.", "title": "The role of directionality, heterogeneity and correlations in epidemic risk and spread", "pid": "e450ugcb", "bm25_score": 215.15150451660156}, {"text": "We describe in this paper an analysis of the spatial evolution of coronavirus pandemic around the world by using a particular type of unsupervised neural network, which is called self-organizing maps. Based on the clustering abilities of self-organizing maps we are able to spatially group together countries that are similar according to their coronavirus cases, in this way being able to analyze which countries are behaving similarly and thus can benefit by using similar strategies in dealing with the spread of the virus. Publicly available datasets of coronavirus cases around the globe from the last months have been used in the analysis. Interesting conclusions have been obtained, that could be helpful in deciding the best strategies in dealing with this virus. Most of the previous papers dealing with data of the Coronavirus have viewed the problem on temporal aspect, which is also important, but this is mainly concerned with the forecast of the numeric information. However, we believe that the spatial aspect is also important, so in this view the main contribution of this paper is the use of unsupervised self-organizing maps for grouping together similar countries in their fight against the Coronavirus pandemic, and thus proposing that strategies for similar countries could be established accordingly.", "title": "Analysis of Spatial Spread Relationships of Coronavirus (COVID-19) Pandemic in the World using Self Organizing Maps", "pid": "h90shco6", "bm25_score": 215.0745086669922}, {"text": "Nosocomial transmission is an important characteristic of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection. Risk factors for transmission of MERS-CoV in healthcare settings are not well defined. During the Korean outbreak in 2015, 186 patients had laboratory-confirmed MERS-CoV infection. Those suspected as a source of viral transmission were categorized into the spreader groups (super-spreader [n = 5] and usual-spreader [n = 10]) and compared to the non-spreader group (n = 171). Body temperature of ≥ 38.5°C (adjusted odds ratio [aOR], 5.54; 95% confidence interval [CI], 1.38–22.30; P = 0.016), pulmonary infiltration of ≥ 3 lung zones (aOR, 7.33; 95% CI, 1.93–27.79; P = 0.003), and a more nonisolated in-hospital days (aOR, 1.32 per 1 day; 95% CI, 1.09–1.60; P = 0.004) were significant risk factors in the spreader group. There was no different clinical factor between super-spreaders and usual-spreaders. Nonisolated in-hospital days was the only factor which tended to be higher in super-spreaders than usual-spreaders (Mean, 6.6 vs. 2.9 days; P = 0.061). Early active quarantine might help reducing the size of an outbreak.", "title": "Clinical and Epidemiologic Characteristics of Spreaders of Middle East Respiratory Syndrome Coronavirus during the 2015 Outbreak in Korea", "pid": "v5egtgdo", "bm25_score": 215.05873107910156}, {"text": "The outbreak of corona virus disease 2019 (Covid-19) imposes a major challenge in managing patients undergoing surgical operation. In this study, we analyzed clinical and transmission features of 25 cases of Covid-19 from a single thoracic department, including 13 patients and 12 health care staff. There were 13 males and 12 females. The median age of the patients was 61 (range: 51 to 69) years. The median age of the health care staff was 35 (range: 22 to 51) years. By the end of follow-up date (Mar. 3, 2020), there were 16 non-severe cases (64%) and 9 severe cases (36%), 5 cases were dead (20%). Nineteen (76%) of the infected cases were confirmed by SARS-CoV-2 nucleic acid test, the rest were clinically diagnosed as suspected Covid-19 cases, and 19 (76%) of the infected cases had positive exposure history. We found that COPD was significantly associated with severity and death (P=0.040, and P=0.038, respectively), and chest operation was significantly associated with death for Covid-19 patients (P=0.039). A potential \"super spreader\" may be the source of the transmission before the implementation of quarantine and comprehensive protection. It was concluded that Covid-19 is associated with poor prognosis for patients undergoing thoracic operation, especially for those with COPD. Implementation of comprehensive protective measures is important to control nosocomial infection.", "title": "Clinical and Transmission Characteristics of Covid-19 - A Retrospective Study of 25 Cases from a Single Thoracic Surgery Department", "pid": "xwqxji63", "bm25_score": 215.04725646972656}, {"text": "The novel coronavirus COVID-19 originally identified in December 2019, based on the data issued by March 30, 2020 daily report, the epidemic of SARS-CoV-2 so far has caused 693224 cases and resulted in 33106 deaths in more than 200 countries. Referring to the data reported, World Health Organization declared the outbreak a pandemic. We considered the chain-binomial type of the model which involves short stages of high infectivity and approximately constant incubation periods. This research paper is to study and analyze the COVID-19 Virus spreading statistics on the examples of the cases from the different counties. High correlation coefficients (91.64%) and determinants (83.98%) between the total volumes of virus spread and recovery are considered to be high and indicate the correctness of the Bailey model. Thus, as of March 30, with the results of statistical and mathematical data processing, it is difficult to predict the future spread-reduction variables of the pandemic.", "title": "Research on COVID-19 virus spreading statistics based on the examples of the cases from different counties", "pid": "xepq1v7x", "bm25_score": 215.0463104248047}, {"text": "In December 2019, severe cases of pneumonia of unknown aetiology were reported in Wuhan city, in China. Lately, the pneumonia was related to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), and the diseases was termed coronavirus disease-2019 (COVID-19). At the end of January 2020, the infection spread all over Italy, but with high infection rates and mortality in the northern part, especially in Lombardy, the most industrialized and polluted region of the country. It is noteworthy that a strong association between severe viral respiratory disease and air pollution has been described. Air pollutant could be solid particles, liquid droplets, or gases and can be of natural origin (such as ash from a volcanic eruption) or released from motor vehicle depletes (carbon monoxide gas) or factories (sulfur dioxide). Volcanic eruptions release large amounts of sulphuric acid, hydrogen sulfide, and hydrochloric acid into the atmosphere. Pulmunary diseases spread by means of small droplets in the breath, also called aerosols, and air pollution may facilitate the outside survival of viruses. We suppose that ash and gases emitted from the Mount Etna contributed to air pollution, potentially favouring the major contagion of COVID-19 in the eastern flank of the mountain, as in Catania city. In fact, ash and gases (with regard to radon) are usually particularly intense in winter, with a reduction of emission of specific metals with warmer weather. This is the first paper that elaborates the hypothesis of a potential role of volcanic gases and heavy metals-related air pollution, combined to specific climatic conditions and regional topography, in favouring severe COVID-19 diffusion in Sicily. Clinical and epidemiological studies are needed to support the hypothesis and plan the due prevention and awareness-raising campaigns.", "title": "Can volcanic trace elements facilitate Covid-19 diffusion? A hypothesis stemming from the Mount Etna area, Sicily", "pid": "20u06444", "bm25_score": 215.03651428222656}, {"text": "Abstract We describe a stochastic small-world network model of transmission of the SARS virus. Unlike the standard Susceptible-Infected-Removed models of disease transmission, our model exhibits both geographically localised outbreaks and “super-spreaders”. Moreover, the combination of localised and long range links allows for more accurate modelling of partial isolation and various public health policies. From this model, we derive an expression for the probability of a widespread outbreak and a condition to ensure that the epidemic is controlled. Moreover, multiple simulations are used to make predictions of the likelihood of various eventual scenarios for fixed initial conditions. The main conclusions of this study are: (i) “super-spreaders” may occur even if the infectiousness of all infected individuals is constant; (ii) consistent with previous reports, extended exposure time beyond 3–5 days (i.e. significant nosocomial transmission) was the key factor in the severity of the SARS outbreak in Hong Kong; and, (iii) the spread of SARS can be effectively controlled by either limiting long range links (imposing a partial quarantine) or enforcing rapid hospitalisation and isolation of symptomatic individuals.", "title": "Super-spreaders and the rate of transmission of the SARS virus", "pid": "dqkjofw2", "bm25_score": 215.03012084960938}, {"text": "We present results on the existence of various common patterns in the growth of the total number of patients affected by COVID-19, a disease acquired through infection by a novel coronavirus, in different countries. For this purpose we propose a scaling model that can have general applicability in the understanding of real data of epidemics. This is analogous to the finite-size scaling, a technique used in the literature of phase transition to identify universality classes. In the disease model, the size of a system is proportional to the volume of the population, within a geographical region, that have been infected at the death of the epidemic or are eventually going to be infected when an epidemic ends. Outcome of our study, for COVID-19, via application of this model, suggests that in most of the countries, after the `onset' of spread, the growths are described by rapid exponential function, for significantly long periods. In addition to accurately identifying this superuniversal feature, we point out that the model is helpful in grouping countries into universality classes, based on the late time behavior, characterized by physical distancing practices, in a natural way. This feature of the model can provide direct comparative understanding of the effectiveness of lockdown-like social measures adopted in different places.", "title": "Spread of COVID-19: Investigation of universal features in real data", "pid": "xp8uoj9z", "bm25_score": 215.02102661132812}, {"text": "On February 1, 2020, China announced a novel coronavirus CoVID-19 outbreak to the public. CoVID-19 was classified as an epidemic by the World Health Organization (WHO). Although the disease was discovered and concentrated in Hubei Province, China, it was exported to all of the other Chinese provinces and spread globally. As of this writing, all plans have failed to contain the novel coronavirus disease, and it has continued to spread to the rest of the world. This study aimed to explore and interpret the effect of environmental and metrological variables on the spread of coronavirus disease in 30 provinces in China, as well as to investigate the impact of new China regulations and plans to mitigate further spread of infections. This article forecasts the size of the disease spreading based on time series forecasting. The growing size of CoVID-19 in China for the next 210 days is estimated by predicting the expected confirmed and recovered cases. The results revealed that weather conditions largely influence the spread of coronavirus in most of the Chinese provinces. This study has determined that increasing temperature and short-wave radiation would positively increase the number of confirmed cases, mortality rate, and recovered cases. The findings of this study agree with the results of our previous study.", "title": "The correlation between the spread of COVID-19 infections and weather variables in 30 Chinese provinces and the impact of Chinese government mitigation plans", "pid": "al7gffw2", "bm25_score": 214.97511291503906}, {"text": "As new cases of COVID-19 are being confirmed pressure is mounting to increase understanding of the factors underlying the spread the disease. Using data on local transmissions until the 23rd of March 2020, we develop an ensemble of 200 ecological niche models to project monthly variation in climate suitability for spread of SARS-CoV-2 throughout a typical climatological year. Although cases of COVID-19 are reported all over the world, most outbreaks display a pattern of clustering in relatively cool and dry areas. The predecessor SARS-CoV-1 was linked to similar climate conditions. Should the spread of SARS CoV-2 continue to follow current trends, asynchronous seasonal global outbreaks could be expected. According to the models, temperate warm and cold climates are more favorable to spread of the virus, whereas arid and tropical climates are less favorable. However, model uncertainties are still high across much of sub- Saharan Africa, Latin America and South East Asia. While models of epidemic spread utilize human demography and mobility as predictors, climate can also help constrain the virus. This is because the environment can mediate human-to-human transmission of SARS-CoV-2, and unsuitable climates can cause the virus to destabilize quickly, hence reducing its capacity to become epidemic.", "title": "Spread of SARS-CoV-2 Coronavirus likely to be constrained by climate", "pid": "jjdtuofy", "bm25_score": 214.9586944580078}, {"text": "The new coronavirus known as COVID-19 is rapidly spreading since December 2019. Without any vaccination or medicine, the means of controlling it are limited to quarantine and social distancing. Here we study the spatio-temporal propagation of the COVID-19 virus in China and compare it to other global locations. Our results suggest that the disease propagation is highly related to population migration from Hubei resembling a Lévy flight which is characteristic of human mobility and thus could be controlled by efficient quarantines. Since quarantine is usually applied on a city level, more insight can be obtained in analyzing the epidemic in cities. Our results suggest that the disease spread in a city in China is characterized by two-stages process. At early times, at order of few days, the infection rate in the city is close to constant probably due to the lack of means to detect infected individuals before infection signs are observed and at later times it decays approximately exponentially due to quarantines. These two stages can explain the significant differences between the propagation in China and in other world-wide locations. While most cities in China control the disease which resulted in the decaying stage, in other world-wide countries the situation is still becoming worse probably due to less social interactions control and overloaded health systems which reflects in the death and recovery rates.", "title": "Spatio-temporal propagation of COVID-19 pandemics", "pid": "x2bi3v3u", "bm25_score": 214.9425811767578}, {"text": "To evaluate the effectiveness of the containment on the epidemic spreading of the new Coronavirus disease 2019, we carry on an analysis of the time evolution of the infection in a selected number of different Countries, by considering well-known macroscopic growth laws, the Gompertz law, and the logistic law. We also propose here a generalization of Gompertz law. Our data analysis permits an evaluation of the maximum number of infected individuals. The daily data must be compared with the obtained fits, to verify if the spreading is under control. From our analysis it appears that the spreading reached saturation in China, due to the strong containment policy of the national government. In Singapore a large growth rate, recently observed, suggests the start of a new strong spreading. For South Korea and Italy, instead, the next data on new infections will be crucial to understand if the saturation will be reached for lower or higher numbers of infected individuals.", "title": "Data analysis on Coronavirus spreading by macroscopic growth laws", "pid": "3r4r65h0", "bm25_score": 214.9337158203125}, {"text": "Although the unprecedented efforts the world has been taking to control the spread of the human coronavirus disease (COVID-19) and its causative etiology [Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)], the number of confirmed cases has been increasing drastically. Therefore, there is an urgent need for devising more efficient preventive measures, to limit the spread of the infection until an effective treatment or vaccine is available. The preventive measures depend mainly on the understanding of the transmission routes of this virus, its environmental stability, and its persistence on common touch surfaces. Due to the very limited knowledge about SARS-CoV-2, we can speculate its stability in the light of previous studies conducted on other human and animal coronaviruses. In this review, we present the available data on the stability of coronaviruses (CoVs), including SARS-CoV-2, from previous reports to help understand its environmental survival. According to available data, possible airborne transmission of SARS-CoV-2 has been suggested. SARS-CoV-2 and other human and animal CoVs have remarkably short persistence on copper, latex, and surfaces with low porosity as compared to other surfaces like stainless steel, plastics, glass, and highly porous fabrics. It has also been reported that SARS-CoV-2 is associated with diarrhea and that it is shed in the feces of COVID-19 patients. Some CoVs show persistence in human excrement, sewage, and waters for a few days. These findings suggest a possible risk of fecal-oral, foodborne, and waterborne transmission of SARS-CoV-2 in developing countries that often use sewage-polluted waters in irrigation and have poor water treatment systems. CoVs survive longer in the environment at lower temperatures and lower relative humidity. It has been suggested that large numbers of COVID-19 cases are associated with cold and dry climates in temperate regions of the world and that seasonality of the virus spread is suspected.", "title": "Stability of SARS-CoV-2 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: a review", "pid": "z4vfjlbg", "bm25_score": 214.91697692871094}, {"text": "As lockdowns and stay-at-home orders start to be lifted across the globe, governments are struggling to establish effective and practical guidelines to reopen their economies. In dense urban environments with people returning to work and public transportation resuming full capacity, enforcing strict social distancing measures will be extremely challenging, if not practically impossible. Governments are thus paying close attention to particular locations that may become the next cluster of disease spreading. Indeed, certain places, like some people, can be\"super-spreaders.\"Is a bustling train station in a central business district more or less susceptible and vulnerable as compared to teeming bus interchanges in the suburbs? Here, we propose a quantitative and systematic framework to identify spatial super-spreaders and the novel concept of super-susceptibles, i.e. respectively, places most likely to contribute to disease spread or to people contracting it. Our proposed data-analytic framework is based on the daily-aggregated ridership data of public transport in Singapore. By constructing the directed and weighted human movement networks and integrating human flow intensity with two neighborhood diversity metrics, we are able to pinpoint super-spreader and super-susceptible locations. Our results reveal that most super-spreaders are also super-susceptibles and that counterintuitively, busy peripheral bus interchanges are riskier places than crowded central train stations. Our analysis is based on data from Singapore, but can be readily adapted and extended for any other major urban center. It therefore serves as a useful framework for devising targeted and cost-effective preventive measures for urban planning and epidemiological preparedness.", "title": "Spatial super-spreaders and super-susceptibles in human movement networks", "pid": "cywjp5jh", "bm25_score": 214.9001922607422}, {"text": "On February 1, 2020, China announced a novel coronavirus CoVID-19 outbreak to the public. CoVID-19 was classified as an epidemic by the World Health Organization (WHO). Although the disease was discovered and concentrated in Hubei Province, China, it was exported to all of the other Chinese provinces and spread globally. As of this writing, all plans have failed to contain the novel coronavirus disease, and it has continued to spread to the rest of the world. This study aimed to explore and interpret the effect of environmental and metrological variables on the spread of coronavirus disease in 30 provinces in China, as well as to investigate the impact of new China regulations and plans to mitigate further spread of infections. This article forecasts the size of the disease spreading based on time series forecasting. The growing size of CoVID-19 in China for the next 210 days is estimated by predicting the expected confirmed and recovered cases. The results revealed that weather conditions largely influence the spread of coronavirus in most of the Chinese provinces. This study has determined that increasing temperature and short-wave radiation would positively increase the number of confirmed cases, mortality rate, and recovered cases. The findings of this study agree with the results of our previous study.", "title": "The correlation between the spread of COVID-19 infections and weather variables in 30 Chinese provinces and the impact of Chinese government mitigation plans.", "pid": "6a9to2w9", "bm25_score": 214.89466857910156}, {"text": "To understand the roles of different transport modes in the spread of COVID-19 pandemic across Chinese cities, this paper looks at the factors influencing the number of imported cases from Wuhan and the spread speed and pattern of the pandemic. We find that frequencies of air flights and high-speed train (HST) services out of Wuhan are significantly associated with the number of COVID-19 cases in the destination cities. The presence of an airport or HST station at a city is significantly related to the speed of the pandemic spread, but its link with the total number of confirmed cases is weak. The farther the distance from Wuhan, the lower number of cases in a city and the slower the dissemination of the pandemic. The longitude and latitude coordinates do not have a significant relationship with the number of total cases but can increase the speed of the COVID-19 spread. Specifically, cities in the higher longitudinal region tended to record a COVID-19 case earlier than their counterparties in the west. Cities in the north were more likely to report the first case later than those in the south. The pandemic may emerge in large cities earlier than in small cities as GDP is a factor positively associated with the spread speed.", "title": "Exploring the roles of high-speed train, air and coach services in the spread of COVID-19 in China", "pid": "1sn5tv21", "bm25_score": 214.8648681640625}, {"text": "We explore here how variation in the SARS-CoV-2 virus tropism could influence epidemic spread. We use a compartmental model fit to the existing data. The model indicates that Wuhan quarantine measures were effective but that alternative virus forms (gut tropism) and a second propagation route (through environment) was present. For Singapore and Shenzhen region the secondary route does not seem to be active yet. Adequate prevention measures taking into account both routes should be implemented.", "title": "A new transmission route for the propagation of the SARS-CoV-2 coronavirus", "pid": "4ah705nc", "bm25_score": 214.86233520507812}, {"text": "Background: The emerging SARS-CoV-2 virus has caused a global pandemic characterized by superspreader events. Heterogeneity in transmission risk is a known phenomenon in infectious diseases and was also seen in SARS and MERS outbreaks since 2003. The pandemic has led countries to control the pandemic spread using unprecedented severe mitigation strategies that include quarantine and lock-down. This has has been highly successful in terms of halting the spread, but had enormous socioeconomic cost. We set out to theoretically explore whether a model that includes the phenomenon of superspreaders may guide us towards a cost-effective mitigation strategy. Methods: We developed an agent-based model that includes persons that spread the disease far more readily than other persons. This allow us to investigate effect of containment strategies in both a random SEIR like scenario, and in a transmission model that work with structured society. Our model considered even contact patterns in three settings: home, work and a category of \"other\" settings representing diffuse social contacts. We introduced superspreaders either as a fixed proportion of the population, or as a broad spectrum of infectivity. For each choice, the model was then calibrated to an overall realistic daily growth rate of 23 percentage. As sensitivity analyses we varied the fraction of superspreaders as well the distribution of their infectivity. To compare the simulation findings for each mitigation scenario we considered the maximum daily ICU utility. Results: As expected, without mitigation imposed, the inclusion of superspreaders does not meaningfully change the epidemic trajectory. However when introducing mitigation strategies imposed on each of the three settings, we find that the presence of superspreaders made a substantial difference. The simulations demonstrate that the best strategy is to focus on limiting contacts in the other category. This in particular suggests that limiting diffuse social contacts in settings such as bars, transportation, restaurants, parties, concerts and lecture halls is far more effective than limiting the same amount of contact events in the home and work setting. Conclusions: To appreciate effect of heterogeneity in various social spheres we need to rethink disease transmission models. Doing so, we found that wide distribution of infectivity favours strategies that reduces the max, while leaving the typical behaviour undisturbed. We found that most workplaces may be opened without much influence on the epidemic, while one could snuff out transmission with an effective avoidance of other contacts. Interestingly, including a consideration of superspreaders can help explain the dramatic success of even moderate lock-down strategies as that practiced in Denmark and Sweden. And it points to the need to avoid mass gatherings until either flock immunity has been achieved or an effective vaccine is available.", "title": "Impact of Superspreaders on dissemination and mitigation of COVID-19", "pid": "m5ptobvz", "bm25_score": 214.82623291015625}, {"text": "Abstract As the microblogging services are becoming more prosperous in everyday life for users on Online Social Networks (OSNs), it is more favorable for hot topics and breaking news to gain more attraction very soon than ever before, which are so-called “super-spreading events”. In the information diffusion process of these super-spreading events, messages are passed on from one user to another and numerous individuals are influenced by a relatively small portion of users, a.k.a. super-spreaders. Acquiring an awareness of super-spreading phenomena and an understanding of patterns of wide-ranged information propagations benefits several social media data mining tasks, such as hot topic detection, predictions of information propagation, harmful information monitoring and intervention. Taking into account that super-spreading in both information diffusion and spread of a contagious disease are analogous, in this study, we build a parameterized model, the SAIR model, based on well-known epidemic models to characterize super-spreading phenomenon in tweet information propagation accompanied with super-spreaders. For the purpose of modeling information diffusion, empirical observations on a real-world Weibo dataset are statistically carried out. Both the steady-state analysis on the equilibrium and the validation on real-world Weibo dataset of the proposed model are conducted. The case study that validates the proposed model shows that the SAIR model is much more promising than the conventional SIR model in characterizing a super-spreading event of information propagation. In addition, numerical simulations are carried out and discussed to discover how sensitively the parameters affect the information propagation process.", "title": "Characterizing super-spreading in microblog: An epidemic-based information propagation model", "pid": "av8ww9fd", "bm25_score": 214.8220672607422}, {"text": "Background: COVID-19 rapidly escalated into a pandemic, threatening 213 countries, areas, and territories the world over. We aimed to identify potential province-level socioeconomic determinants of the virus's dissemination, and explain between-province differences in the speed of its spread, based on data from 36 provinces of Northern Italy. Methods: This is an ecological study. We included all confirmed cases of SARS-CoV-2 reported between February 24th and March 30th, 2020. For each province, we calculated the trend of contagion as the relative increase in the number of individuals infected between two time endpoints, assuming an exponential growth. Pearson's test was used to correlate the trend of contagion with a set of healthcare-associated, economic, and demographic parameters by province. The virus's spread was input as a dependent variable in a stepwise OLS regression model to test the association between rate of spread and province-level indicators. Findings: Multivariate analysis showed that the spread of COVID-19 was correlated negatively with aging index (p-value=0.003), and positively with public transportation per capita (p-value=0.012), the % of private long-term care hospital beds and, to a lesser extent (p-value=0.070), the % of private acute care hospital beds (p-value=0.006). Interpretation: Demographic and socioeconomic factors, and healthcare organization variables were found associated with a significant difference in the rate of COVID-19 spread in 36 provinces of Northern Italy. An aging population seemed to naturally contain social contacts. The availability of healthcare resources and their coordination could play an important part in spreading infection.", "title": "Demographic and Socio-Economic Factors, and Healthcare Resource Indicators Associated with the Rapid Spread of COVID-19 in Northern Italy: An Ecological Study", "pid": "vkbnjw14", "bm25_score": 214.81607055664062}, {"text": "This study presents an in-depth investigation on the transmission of the novel coronavirus (COVID-19) from the urban perspective. It focuses on the “aftermath” of the outbreak and the spread of the infection among cities. Especially, this study provides insights of the fundamentals of the factors that may affect the spread of the infection in cities, where the marginal effects of some most influential factors to the virus transmission are estimated. It reveals that the distance to epicenter is a very strong influential factor, and is negatively linked with the spread of COVID-19. In addition, subway, wastewater and residential garbage are positively connected with the virus transmission. Moreover, both urban area and population density are negatively associated with the spread of COVID-19 at the early stage of the epidemic. Furthermore, this study also provides high precision estimation of the number of COVID-19 infection in Wuhan city, which is the epicenter of the outbreak in China. Based on the real-world data of cities outside Wuhan on March 2, 2020, the estimated number is 56,944.866 (mean value), which is very close to the officially reported number. The methodology and main conclusions shown in this paper are of general interest, and they can be applied to other countries to help understand the local transmission of COVID-19 as well.", "title": "Emerging study on the transmission of the Novel Coronavirus (COVID-19) from urban perspective: Evidence from China", "pid": "1nliar3p", "bm25_score": 214.79562377929688}, {"text": "The global spread of the 2019-nCoV is continuing and is fast moving, as indicated by the WHO raising the risk assessment to high. In this article, we provide a preliminary phylodynamic and phylogeographic analysis of this new virus. A Maximum Clade Credibility tree has been built using the 29 available whole genome sequences of 2019-nCoV and two whole genome sequences that are highly similar sequences from Bat SARS-like Coronavirus available in GeneBank. We are able to clarify the mechanism of transmission among the countries which have provided the 2019-nCoV sequence isolates from their patients. The Bayesian phylogeographic reconstruction shows that the 2019-2020 nCoV most probably originated from the Bat SARS-like Coronavirus circulating in the Rhinolophus bat family. In agreement with epidemiological observations, the most likely geographic origin of the new outbreak was the city of Wuhan, China, where 2019-nCoV time of the most recent common ancestor emerged, according to molecular clock analysis, around November 25th, 2019. These results, together with previously recorded epidemics, suggest a recurring pattern of periodical epizootic outbreaks due to Betacoronavirus. Moreover, our study describes the same population genetic dynamic underlying the SARS 2003 epidemic, and suggests the urgent need for the development of effective molecular surveillance strategies of Betacoronavirus among animals and Rhinolophus of the bat family.", "title": "The global spread of 2019-nCoV: a molecular evolutionary analysis", "pid": "hwjr891o", "bm25_score": 214.75808715820312}, {"text": "Background Most of epidemiological models applied for COVID-19 do not consider heterogeneity in infectiousness and impact of superspreaders, despite the broad viral loading distributions amongst COVID-19 positive people (1-1 000 000 per mL). Also, mass group testing is not used regardless to existing shortage of tests. I propose new strategy for early detection of superspreaders with reasonable number of RT-PCR tests, which can dramatically mitigate development COVID-19 pandemic and even turn it endemic. Methods I used stochastic social-epidemiological SEIAR model, where S-suspected, E-exposed, I-infectious, A-admitted (confirmed COVID-19 positive, who are admitted to hospital or completely isolated), R-recovered. The model was applied to real COVID-19 dynamics in London, Moscow and New York City. Findings Viral loading data measured by RT-PCR were fitted by broad log-normal distribution, which governed high importance of superspreaders. The proposed full scale model of a metropolis shows that top 10% spreaders (100+ higher viral loading than median infector) transmit 45% of new cases. Rapid isolation of superspreaders leads to 4-8 fold mitigation of pandemic depending on applied quarantine strength and amount of currently infected people. High viral loading allows efficient group matrix pool testing of population focused on detection of the superspreaders requiring remarkably small amount of tests. Interpretation The model and new testing strategy may prevent thousand or millions COVID-19 deaths requiring just about 5000 daily RT-PCR test for big 12 million city such as Moscow. Though applied to COVID-19 pandemic the results are universal and can be used for other infectious heterogenous epidemics. Funding No funding", "title": "Early detection of superspreaders by mass group pool testing can mitigate COVID-19 pandemic", "pid": "h7vqmlq9", "bm25_score": 214.74118041992188}, {"text": "Background Coronavirus disease 2019 (COVID-19) has been rapidly spreading throughout China and other countries including South Korea. As of March 12, 2020, a total number of 7,869 cases and 66 deaths had been documented in South Korea. Although the first confirmed case in South Korea was identified on January 20, 2020, the number of confirmed cases showed a rapid growth on February 19, 2020 with a total number of 1,261 cases with 12 deaths based on the Korea Centers for Disease Control and Prevention (KCDC). Method Using the data of confirmed cases of COVID-19 in South Korea that are publicly available from the KCDC, this paper aims to create spatial visualizations of COVID-19 transmission between January 20, 2020 and February 19, 2020. Results Using spatial visualization, this paper identified two early transmission clusters in South Korea (Daegu cluster and capital area cluster). Using a degree-weighted centrality measure, this paper proposes potential super-spreaders of the virus in the visualized clusters. Conclusion Compared to various epidemiological measures such as the basic reproduction number, spatial visualizations of the cluster-specific transmission networks and the proposed centrality measure may be more useful to characterize super-spreaders and the spread of the virus especially in the early epidemic phase.", "title": "Spatial Visualization of Cluster-Specific COVID-19 Transmission Network in South Korea During the Early Epidemic Phase", "pid": "901m6zw0", "bm25_score": 214.74085998535156}, {"text": "A key characteristic of the spread of infectious diseases is their ability to use efficient transmission paths within contact graphs. This enables the pathogen to maximise infection rates and spread within a target population. In this work, we devise techniques to localise infections and decrease infection rates based on a principled analysis of disease transmission paths within human-contact networks (proximity graphs). Experimental results of disease spreading shows that that at low visibility rates contact tracing slows disease spreading. However to stop disease spreading, contact tracing requires both significant visibility (at least 60%) into the proximity graph and the ability to place half of the population under isolation. We find that pro-actively isolating super-links -- key proximity encounters -- has significant benefits: targeted isolation of a fourth of the population based on 35% visibility into the proximity graph prevents an epidemic outbreak. It turns out that isolating super-spreaders is more effective than contact tracing and testing but less effective than targeting super-links. We highlight the important role of topology in epidemic outbreaks. We argue that proactive innoculation of a population by disabling super-links and super-spreaders may have an important complimentary role alongside contact tracing and testing as part of a sophisticated public-health response to epidemic outbreaks.", "title": "Unlinking super-linkers: the topology of epidemic response (Covid-19)", "pid": "qla3go2i", "bm25_score": 214.7297821044922}, {"text": "BACKGROUND: There is sufficient epidemiological and biological evidence of increased human susceptibility to viral pathogens such as Middle East respiratory syndrome coronavirus, respiratory syncytial virus, human metapneumovirus and influenza virus, in cold weather. The pattern of outbreak of the coronavirus disease 2019 (COVID-19) in China during the flu season is further proof that meteorological conditions may potentially influence the susceptibility of human populations to coronaviruses, a situation that may become increasingly evident as the current global pandemic of COVID-19 unfolds. MAIN BODY: A very rapid spread and high mortality rates have characterized the COVID-19 pandemic in countries north of the equator where air temperatures have been seasonally low. It is unclear if the currently high rates of COVID-19 infections in countries of the northern hemisphere will wane during the summer months, or if fewer people overall will become infected with COVID-19 in countries south of the equator where warmer weather conditions prevail through most of the year. However, apart from the influence of seasons, evidence based on the structural biology and biochemical properties of many enveloped viruses similar to the novel severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 (aetiology of COVID-19), support the higher likelihood of the latter of the two outcomes. Other factors that may potentially impact the rate of virus spread include the effectiveness of infection control practices, individual and herd immunity, and emergency preparedness levels of countries. CONCLUSION: This report highlights the potential influence of weather conditions, seasons and non-climatological factors on the geographical spread of cases of COVID-19 across the globe.", "title": "A close look at the biology of SARS-CoV-2, and the potential influence of weather conditions and seasons on COVID-19 case spread", "pid": "eiek6olk", "bm25_score": 214.7279052734375}, {"text": "The pandemic state of COVID-19 caused by the SARS CoV-2 put the world in quarantine and is causing an unprecedented economic crisis. However, COVID-19 is spreading in different rates at different countries. Here, we tested the effect of three classes of predictors, i.e., socioeconomic, climatic and transport, on the rate of daily increase of COVID-19. We found that global connections, represented by countries importance in the global air transportation network, is the main explanation for the growth rate of COVID-19 in different countries. Climate, geographic distance and socioeconomics did not affect this big picture analysis. Geographic distance and climate were significant barriers in the past but were surpassed by the human engine that allowed us to colonize almost every corner on Earth. Based on our global analysis, the global network of air transportation could lead to a worst-case scenario of synchronous global pandemic if board control measures in international airports were not taken and are not sustained during this pandemic. Despite all limitations of a global analysis, our results indicate that the current claims that the growth rate of COVID-19 may be lower in tropical countries should be taken very carefully, at risk to disturb well-established and effective policy of social isolation that may help to avoid higher mortality rates due to collapse of national health systems. This is the case of Brazil, a well-connected tropical country that presents the second highest increase rate of COVID-19 and might experience a serious case of human-induced disasters if decision makers take into consideration unsupported claims of the growth rate of COVID-19 might be lower in tropical countries.", "title": "Exponential phase of covid19 expansion is not driven by climate at global scale", "pid": "f0ahn4iu", "bm25_score": 214.72369384765625}, {"text": "BACKGROUND Globally, there have been many cases of COVID-2019 cases among medical staff, however, the main factors associated with the infection are not well understood. AIM To identify the super-factors causing COVID-19 infection in medical staff in China. METHODS A cross-sectional study was conducted between Jan. 1st, and Feb. 30th, 2020, where front line members of medical staff that took part in the care and treatment of patients with COVID-19 were enrolled. Epidemiological and demographic data between infected and uninfected groups were collected and compared. Social network analysis (SNA) was used to establish socio-metric social links between influencing factors. FINDINGS A total of 92 medical staff were enrolled. In all participant groups, the super-factor identified by the network was wearing a medical protective mask or surgical mask correctly (degree = 572; closeness =25; betweenness centrality = 3·23). Touching the cheek, nose, and mouth while working was the super-factor in the infected group. This was the biggest node in the network and had the strongest influence (degree = 370; closeness = 29; betweenness centrality = 0·37). Self-protection score was the super-factor in the uninfected group but was the isolated factor in the infected group (degree = 201; closeness = 28; betweenness centrality = 5·64). For family members, the exposure history to Huanan Seafood Wholesale Market and the contact history to wild animals were two isolated nodes. CONCLUSION High self-protection score was the main factor that prevented medical staff from contracting COVID-19 infection. The main factor that contributed to COVID-19 infections among medical staff was touching the cheek, nose and mouth while working.", "title": "Super-factors associated with transmission of occupational COVID-2019 infection among healthcare staff in Wuhan , China.", "pid": "lmw1l7gz", "bm25_score": 214.72325134277344}, {"text": "Starting from December 2019 the world has faced an unprecedented health crisis caused by the new Coronavirus (COVID-19) due to the SARS-CoV-2 pathogen. Within this topic, the aim of the paper was to quantify the effect of mobility habits in the spread of the Coronavirus in Italy through a multiple linear regression model. Estimation results showed that mobility habits represent one of the variables that explains the number of COVID-19 infections jointly with the number of tests/day and some environmental variables (i.e. PM pollution and temperature). Nevertheless, a proximity variable to the first outbreak was also significant, meaning that the areas close to the outbreak had a higher risk of contagion, especially in the initial stage of infection (time-decay phenomena). Furthermore, the number of daily new cases was related to the trips performed three weeks before. This threshold of 21 days could be considered as a sort of positivity detection time, meaning that the mobility restrictions quarantine commonly set at 14 days, defined only according to incubation-based epidemiological considerations, is underestimated (possible delays between contagion and detection) as a containment policy and may not always contribute to effectively slowing down the spread of virus worldwide. This result is original and, if confirmed in other studies, will lay the groundwork for more effective containment of COVID-19 in countries that are still in the health emergency, as well as for possible future returns of the virus.", "title": "How mobility habits influenced the spread of the COVID-19 pandemic: Results from the Italian case study", "pid": "zxv2pber", "bm25_score": 214.71282958984375}, {"text": "Background: Faced with the global pandemic of COVID-19, declared by World Health Organization (WHO) on March 11th 2020, and the need to better understand the seasonal behavior of the virus, our team conducted this systematic review to describe current knowledge about the emergence and replicability of the virus and its correlation with different weather factors such as temperature and relative humidity. Methods: The review was registered with the PROSPERO database. The electronic databases PubMed, Scopus, Web of Science, Cochrane Library, LILACS, OpenGrey and Google Scholar were examined with the searches restricted to the years 2019 and 2020. Risk of bias assessment was performed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist tool. The GRADE tool was used to assess the quality of the evidence. Results: The initial screening identified 517 articles. After examination of the full texts, seventeen studies met the review's eligibility criteria. Great homogeneity was observed in the findings regarding the effect of temperature and humidity on the seasonal viability and transmissibility of COVID-19. Cold and dry conditions were potentiating factors on the spread of the virus. After quality assessment, four studies had a high risk of bias and thirteen studies were scored as moderate risk of bias. The certainty of evidence was graded as low for both outcomes evaluated. Conclusion: Considering the existing scientific evidence, warm and wet climates seem to reduce the spread of COVID-19. The certainty of the evidence generated was graded as low. However, these variables alone could not explain most of the variability in disease transmission.", "title": "Effects of temperature and humidity on the spread of COVID-19: A systematic review.", "pid": "w5tc6gmu", "bm25_score": 214.711181640625}, {"text": "BACKGROUND Since the outbreak of the novel coronavirus disease 2019 (COVID-19) in December 2019, the coronavirus has spread all over the world at an unprecedented rate. The transmissibility of coronavirus from asymptomatic patients to healthy individuals has received enormous attention. An important study using the COVID-19 data from the city Ningbo, China, was carried out to estimate and compare the transmission rates of the coronavirus by the symptomatic and asymptomatic patients. However, in the original analysis, the usual chi-squared tests were unduly used for some contingency tables with small cell counts including zero, which may violate the assumptions for the chi-squared test. OBJECTIVE We reanalyze the data from the city Ningbo with more appropriate statistical methods to draw more reliable and sound conclusions on the transmission rates of the coronavirus by the symptomatic and asymptomatic patients. METHODS We exclude the cases associated with the super-spreader and adopt more appropriate statistical methods, including the permutation test and Fisher's exact test, to reanalyze the COVID-19 data from the city Ningbo. RESULTS After excluding the cases related to the super-spreader, Fisher's exact test yields p-value=.84, which indicates stronger evidence of no difference in the transmission rates compared with the original analysis. The odds ratio of transmission rates of coronavirus between the symptomatic and asymptomatic patients is 1.2 with a 95% confidence interval [0.5, 2.8]. CONCLUSIONS Through a more in-depth and comprehensive statistical analysis of the Ningbo data, we conclude that there is no difference in the transmission rates of coronavirus between the symptomatic and asymptomatic patients.", "title": "Comparison of transmissibility of coronavirus between symptomatic and asymptomatic patients: Reanalysis of the Ningbo COVID-19 data.", "pid": "1pnc889f", "bm25_score": 214.70938110351562}, {"text": "The most effective way to stem the spread of a pandemic such as coronavirus disease 2019 (COVID-19) is social distancing, but the introduction of such measures is hampered by the fact that a sizeable part of the population fails to see their need. Three studies conducted during the mass spreading of the virus in the United States toward the end of March 2020 show that this results partially from people's misperception of the virus's exponential growth in linear terms and that overcoming this bias increases support for social distancing. Study 1 shows that American participants mistakenly perceive the virus's exponential growth in linear terms (conservatives more so than liberals). Studies 2 and 3 show that instructing people to avoid the exponential growth bias significantly increases perceptions of the virus's growth and thereby increases support for social distancing. Together, these results show the importance of statistical literacy to recruit support for fighting pandemics such as the coronavirus.", "title": "Correcting misperceptions of exponential coronavirus growth increases support for social distancing", "pid": "7t8yzbr7", "bm25_score": 214.6994171142578}, {"text": "The novel coronavirus (2019-nCoV) appeared in Wuhan in late 2019 have infected 34,598 people, and killed 723 among them until 8th February 2020. The new virus has spread to at least 316 cities (until 1st February 2020) in China. We used the traffic flow data from Baidu Map, and number of air passengers who left Wuhan from 1st January to 26th January, to quantify the potential infectious people. We developed multiple linear models with local population and air passengers as predicted variables to explain the variance of confirmed cases in every city across China. We found the contribution of air passengers from Wuhan was decreasing gradually, but the effect of local population was increasing, indicating the trend of local transmission. However, the increase of local transmission is slow during the early stage of novel coronavirus, due to the super strict control measures carried out by government agents and communities.", "title": "Tracking the spread of novel coronavirus (2019-nCoV) based on big data", "pid": "y4we4rrk", "bm25_score": 214.6710968017578}, {"text": "As thousands of new cases of COVID-19 have been confirmed, there is an increasing demand to understand the factors underlying the spread of this disease. Using country-level data, we modeled the early growth in the number of cases for over 480 cities in all Brazilian states. As the main findings, we found that the percentage of people respecting social distancing protocols was the main explanatory factor for the observed growth rate of COVID-19. Those cities that presented the highest spread of the new coronavirus were also those that had lower averages of social distancing. We also underline that total population of cities and connectivity, represented by the city-level importance to the air transportation of people across the country, plays important roles in the dissemination of SARS-CoV-2. Climate and socioeconomic predictors had little contribution to the big-picture scenario. Our results show that different States had high variability in their growth rates, mostly due to quite different public health strategies to retain the outbreak of COVID-19. In spite of all limitations of such a large-scale approach, our results underline that climatic conditions are likely weak limiting factors for the spread of the new coronavirus, and the circulation of people in the city- and country-level are the most responsible factors for the early outbreak of COVID-19 in Brazil. Moreover, we reinforce that social distancing protocols are fundamental to avoid critical scenarios and the collapse of healthcare systems. We also predict that economic-induced decisions for relaxing social distancing might have catastrophic consequences, especially in large cities.", "title": "Social distancing and movement constraint as the most likely factors for COVID-19 outbreak control in Brazil", "pid": "slnyun4l", "bm25_score": 214.6663818359375}, {"text": "The pandemic spread of severe acute respiratory syndrome coronavirus (SARS-CoV-2) that causes COVID-19 calls for global health emergency with wide prevalence across 94 countries, and around 3073 deaths reported in china on 7thMarch 2020 which created red alert zone in the country. It was further noticed other than China, countries like the republic of Korea ranked first with 6767 cases, Italy with 4747 and Iran with 3513 cases. The spread of COVID-19 made a historical transition between December 2019 to March 2020 by extending the paradigm to a newer territory every day with the highest predicted reproductive number &lt;2. Hence, while combating the epidemic spread, there are spectra of strategies that require crucial validation, some of which include drug repurposing, enzyme inhibition, target drug delivery etc. Among these, the category of drugs called enzyme inhibitors has a unique opportunity in the process of new drug discovery as these enzymes possess structural versatility starting from the host viral interface and up to the release of a new virus. Drugs entrapped within liposomes are highly effective against intracellular microorganisms as per published observations. Regulatory authorities like World Health Organization (WHO) and Centre for disease control and prevention (CDC) strongly recommend the need for the PPE’s like N95 respirator to avoid person to person contact. In this context, Electrospun Nanofiber Technology (ENT) offers ultrathin fibres (20-200nm) with close proximity of 99.97% of high efficient air filtration. Fabrication of ultrafine nano mask by utilizing electospun technology will surely benefit millions of people in a time-dependent manner.", "title": "Current strategies and approaches in combating SARS-CoV-2 virus that causes COVID-19", "pid": "vl6b82ia", "bm25_score": 214.6638946533203}, {"text": "The COVID-19 has caused more than three million infections and over two hundred thousand deaths by April 20201. Limiting socioeconomic activities (SA) is among the most adopted governmental mitigating efforts to combat the transmission of the virus, though the degree varies dramatically among different regimes2. This study aims to quantify the contribution from the SA and weather conditions to the transmission of COVID-19 at global scale. Ruling out the unobservable factors including medical facilities and other control policies (MOC) through region-by-time fixed effects3,4, we show that the limiting SA has a leading contribution to lower the reproductive number by 18.3%, while weather conditions, including ultraviolet, relative humidity, and wind explain a smaller amount of variation. Temperature might have a non-monotonic impact on the transmission. We further show that in developed countries5 and China, the SA effect is more pronounced whereas the weather effect is significantly downplayed possibly because people tend to stay indoors most of the time with a controlled climate. We finally estimate the reduced reproductive number and the population spared from infections due to restricting SA at 40,964, 180,336, 174,494, in China, United States, and Europe respectively. From late January to mid-April, all regions, except for China, Australia, and south Korea show a steep upward trend of spared infections due to restricting SA. US and Europe, in particular, show far steeper upward trends of spared infections in the analyzed timeframe, signaling a greater risk of reopening the economy too soon.", "title": "Quantifying socioeconomic activities and weather effects on the global spread of COVID-19 epidemic", "pid": "6cz0opsf", "bm25_score": 214.6595458984375}, {"text": "BACKGROUND: Since the outbreak of the novel coronavirus disease (COVID-19) in December 2019, the coronavirus has spread all over the world at an unprecedented rate. The transmissibility of the coronavirus from asymptomatic patients to healthy individuals has received enormous attention. An important study using COVID-19 data from the city of Ningbo, China, was carried out to estimate and compare the transmission rates of the coronavirus by the symptomatic and asymptomatic patients. However, in the original analysis, the usual chi-square tests were unduly used for some contingency tables with small cell counts including zero, which may violate the assumptions for the chi-square test. OBJECTIVE: We reanalyze the data from the city of Ningbo with more appropriate statistical methods to draw more reliable and sound conclusions on the transmission rates of the coronavirus by the symptomatic and asymptomatic patients. METHODS: We excluded the cases associated with the super-spreader and adopted a more appropriate statistical method, including the permutation test and the Fisher exact test, to reanalyze the COVID-19 data from the city of Ningbo. RESULTS: After excluding the cases related to the super-spreader, the Fisher exact test yields a P value of .84, which indicates stronger evidence of no difference in the transmission rates compared with the original analysis. The odds ratio of the coronavirus transmission rates between the symptomatic and asymptomatic patients is 1.2 with a 95% confidence interval 0.5-2.8. CONCLUSIONS: Through a more in-depth and comprehensive statistical analysis of the Ningbo data, we concluded that there is no difference in the transmission rates of coronavirus between symptomatic and asymptomatic patients.", "title": "Comparison of Transmissibility of Coronavirus Between Symptomatic and Asymptomatic Patients: Reanalysis of the Ningbo COVID-19 Data", "pid": "o3b5zm5l", "bm25_score": 214.6444549560547}, {"text": "From the end of 2019, an unprecedented novel coronavirus, which was named COVID-19 by the World Health Organization (WHO) emerged from Wuhan city, China. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 has continued to rise, with over 4 million confirmed-cases and over 300,000 deaths worldwide until mid-May. This study aims to present the effect of the promulgation of social distancing measures on the spread of COVID-19 in the cases of 10 highly infected countries. The authors focus on the statistics of the COVID-19 confirmed-cases and deaths in 10 highly infected countries, including The U.S., Spain, Italy, The U.K., France, Germany, Russia, Turkey, Iran and China, and the response to the pandemic of these countries in the period from January 11 to May 2, 2020. The relationships between the social distancing measures and the statistics of COVID-19 confirmed-cases and deaths were analyzed in order to elucidate the effectiveness of the social distancing measures on the spread of COVID-19 in 10 highly infected countries. The results showed it took1-4 weeks since the highest level of social distancing measures promulgation until the daily confirmed-cases and deaths showed signs of decreasing. The effectiveness of the social distancing measures on the spread of COVID-19 was different between the 10 focused countries. This variation is due to the difference in the levels of promulgated social distancing measures, as well as the difference in the COVID-19 spread situation at the time of promulgation between the countries.", "title": "Effect of the social distancing measures on the spread of COVID-19 in 10 highly infected countries", "pid": "1r8dhqi5", "bm25_score": 214.63909912109375}, {"text": "COVID-19 pandemic is a major human tragedy. Worldwide, SARS-CoV-2 has already infected over 3 million and has killed about 230,000 people. SARS-CoV-2 originated in China and, within three months, has evolved to an additional 10 subtypes. One particular subtype with a non-silent (Aspartate to Glycine) mutation at 614th position of the Spike protein (D614G) rapidly outcompeted other pre-existing subtypes, including the ancestral. We assessed that D614G mutation generates an additional serine protease (Elastase) cleavage site near the S1-S2 junction of the Spike protein. We also identified that a single nucleotide deletion (delC) at a known variant site (rs35074065) in a cis-eQTL of TMPRSS2, is extremely rare in East Asians but is common in Europeans and North Americans. The delC allele facilitates entry of the 614G subtype into host cells, thus accelerating the spread of 614G subtype in Europe and North America where the delC allele is common. The delC allele at the cis-eQTL locus rs35074065 of TMPRSS2 leads to overexpression of both TMPRSS2 and a nearby gene MX1. The cis-eQTL site, rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2). IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G mutated Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare.", "title": "Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression of TMPRSS2 and MX1 Genes", "pid": "bbhf4qus", "bm25_score": 214.6383056640625}, {"text": "The pandemic outbreak of the novel coronavirus epidemic disease (COVID-19) is spreading like a diffusion-reaction in the world and almost 208 countries and territories are being affected around the globe. It became a sever health and socio-economic problem, while the world has no vaccine to combat this virus. This research aims to analyze the connection between the fast spread of COVID-19 and regional climate parameters over a global scale. In this research, we collected the data of COVID-19 cases from the time of 1st reported case to the 5th June 2020 in different affected countries and regional climatic parameters data from January 2020 to 5th June 2020. It was found that most of the countries located in the relatively lower temperature region show a rapid increase in the COVID-19 cases than the countries locating in the warmer climatic regions despite their better socio-economic conditions. A correlation between metrological parameters and COVID-19 cases was observed. Average daylight hours are correlated to total the COVID-19 cases with a coefficient of determination of 0.42, while average high-temperature shows a correlation of 0.59 and 0.42 with total COVID-19 cases and death cases respectively. The finding of the study will help international health organizations and local administrations to combat and well manage the spread of COVID-19.", "title": "The effects of regional climatic condition on the spread of COVID-19 at global scale", "pid": "iasv2y2d", "bm25_score": 214.63558959960938}, {"text": "The COVID-19 disease, a respiratory disease transmitted by a new betacoronavirus SARS-CoV-2. As for other viral respiratory agents, SARS-CoV-2 spreads by person to person through respiratory droplets and direct contact and potentially by indirect contact through fomites. The goal of the current study is to evaluate whether the increase of temperature can influence the environmental endurance of SARS-CoV-2.We tested SARS-CoV-2 environmental stability in parallel at room temperature (RT, 20-25 Celsius degrees) and at average maximum temperature of June (JT) estimated at 28 Celsius degrees in Italy. The virus inoculated on plastic surface was harvested at predefined time-points and tested to evaluate viral titres on Vero cells by TCID50. Our results confirm that fomite transmission of the emerging SARS-CoV2 is possible, since the virus remains viable on surfaces up to 84 hours at both RT and JT. Moreover, a remarkable difference between the two temperatures exists, suggesting that virus vitality can be influenced by the environmental temperature. Our results support the hypothesis that in the hot season the increase of temperature could influence the environmental endurance of SARS-CoV2 and reduce Covid-19 transmission probability.", "title": "SARS-CoV-2 infection: the environmental endurance of the virus can be influenced by the increase of temperature", "pid": "h81b4imf", "bm25_score": 214.63522338867188}, {"text": "The most effective way to stem the spread of a pandemic such as coronavirus disease 2019 (COVID-19) is social distancing, but the introduction of such measures is hampered by the fact that a sizeable part of the population fails to see their need. Three studies conducted during the mass spreading of the virus in the United States toward the end of March 2020 show that this results partially from people's misperception of the virus's exponential growth in linear terms and that overcoming this bias increases support for social distancing. Study 1 shows that American participants mistakenly perceive the virus's exponential growth in linear terms (conservatives more so than liberals). Studies 2 and 3 show that instructing people to avoid the exponential growth bias significantly increases perceptions of the virus's growth and thereby increases support for social distancing. Together, these results show the importance of statistical literacy to recruit support for fighting pandemics such as the coronavirus.", "title": "Correcting misperceptions of exponential coronavirus growth increases support for social distancing.", "pid": "c84lpxrn", "bm25_score": 214.63124084472656}, {"text": "Abstract From the end of 2019, an unprecedented novel coronavirus, which was named COVID-19 by the World Health Organization (WHO) emerged from Wuhan city, China. Despite rigorous global containment and quarantine efforts, the incidence of COVID-19 has continued to rise, with over 4 million confirmed-cases and over 300,000 deaths worldwide until mid-May. This study aims to present the effect of the promulgation of social distancing measures on the spread of COVID-19 in the cases of 10 highly infected countries. The authors focus on the statistics of the COVID-19 confirmed-cases and deaths in 10 highly infected countries, including The U.S., Spain, Italy, The U.K., France, Germany, Russia, Turkey, Iran and China, and the response to the pandemic of these countries in the period from January 11 to May 2, 2020. The relationships between the social distancing measures and the statistics of COVID-19 confirmed-cases and deaths were analyzed in order to elucidate the effectiveness of the social distancing measures on the spread of COVID-19 in 10 highly infected countries. The results showed it took1–4 weeks since the highest level of social distancing measures promulgation until the daily confirmed-cases and deaths showed signs of decreasing. The effectiveness of the social distancing measures on the spread of COVID-19 was different between the 10 focused countries. This variation is due to the difference in the levels of promulgated social distancing measures, as well as the difference in the COVID-19 spread situation at the time of promulgation between the countries.", "title": "Effect of the social distancing measures on the spread of COVID-19 in 10 highly infected countries", "pid": "mhmno6vb", "bm25_score": 214.6243133544922}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emergent RNA virus that spread around the planet in about 4 months. The consequences of this rapid spread on the virus evolution are under investigation. In this work, we analyzed ca. 9,000 SARS-CoV-2 genomes from Africa, America, Asia, Europe, and Oceania. We show that the virus is a complex of slightly different genetic variants that are unevenly distributed on Earth. Furthermore, we demonstrate that SARS-CoV-2 phylogeny is spatially structured. We hypothesize this could be the result of founder effects occurring as a consequence of, and local evolution occurring after, long-distance dispersal. In light of our results, we discuss how dispersal may constitute an opportunity for the virus to fix otherwise rare, and/or develop new, mutations. Based on previous studies, the possibility that this could significantly affect the virus phenotype is not remote. Relevance A cluster of pneumonia cases of unknown etiology was reported in December 2019 in Wuhan, Hubei province, China. Since then, hundreds of thousands of people have died all around the planet. Quickly after the pandemic onset, metagenomic studies showed the causative agent, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), belonged to the Betacoronavirus genus, responsible for spillover events in 2002 and 2012 (severe acute respiratory syndrome and Middle East respiratory syndrome, respectively). The zoonotic origins of these viruses (possibly bats, camelids, pangolins and/or palm civets) have received much attention. However, other evolutionary aspects, such as spatial variation, have received comparatively little attention. This study shows that SARS-CoV-2 variants, which we call virotypes, are heterogeneously distributed on Earth and demonstrates that the virus phylogeny is geographically structured. We explain how this may be due to founder effects combined with high mutation rates.", "title": "Mega-phylogeny sheds light on SARS-CoV-2 spatial phylogenetic structure", "pid": "3k5lmawz", "bm25_score": 214.6239776611328}, {"text": "Recent analysis of COVID-19 data from China showed that the number of confirmed cases followed a subexponential power-law increase, with a growth exponent of around 2.2. The power-law behavior was attributed to a combination of effective containment and mitigation measures employed as well as behavioral changes by the population. In this work, we report a random walk Monte Carlo simulation study of proximity-based infection spread. Social distancing is incorporated in the simulations through a single parameter, the size of each step in the random walk process. The step size $l$ is taken to be a multiple of $\\langle r \\rangle$, which is the average separation between individuals. Three temporal growth regimes (quadratic, intermediate power-law and exponential) are shown to emerge naturally from our simulations. For $l = \\langle r \\rangle$, we get intermediate power-law growth exponents that are in general agreement with available data from China. On the other hand, we obtain a quadratic growth for smaller step sizes $l \\lesssim \\langle r \\rangle/2 $, while for large $l$ the growth is found to be exponential. Together with available data, these results suggest that the early containment of the disease within China was close to optimal. We further performed a comparative case study of data from three other countries, India, Brazil and South Africa. We show that reasonable agreement with these data can be obtained by incorporating small-world-like connections in our simulations.", "title": "A random walk Monte Carlo simulation study of COVID-19-like infection spread", "pid": "e4bhues9", "bm25_score": 214.61459350585938}, {"text": "Epidemiological forecasts of COVID-19 spread at the country and/or state level have helped shape public health interventions. However, such models leave a scale-gap between the spatial resolution of actionable information (i.e. the county or city level) and that of modeled viral spread. States and nations are not spatially homogeneous and different areas may vary in disease risk and severity. For example, COVID-19 has age-stratified risk. Similarly, ICU units, PPE and other vital equipment are not equally distributed within states. Here, we implement a county-level epidemiological framework to assess and forecast COVID-19 spread through Georgia, where 1,933 people have died from COVID-19 and 44,638 cases have been documented as of May 27, 2020. We find that county-level forecasts trained on heterogeneity due to clustered events can continue to predict epidemic spread over multi-week periods, potentially serving efforts to prepare medical resources, manage supply chains, and develop targeted public health interventions. We find that the premature removal of physical (social) distancing could lead to rapid increases in cases or the emergence of sustained plateaus of elevated fatalities.", "title": "Spread of COVID-19 through Georgia, USA. Near-term projections and impacts of social distancing via a metapopulation model", "pid": "oejemaei", "bm25_score": 214.61305236816406}, {"text": "The current outbreak of the novel coronavirus disease 2019 (COVID-19) in more than 250 countries has become a serious threat to the health of people around the world. Human-to-human transmission of the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurs most often when people are in the incubation stage of the disease or are carriers and have no symptoms. Therefore, in this study, was discussed the role of environmental factors and conditions such as temperature, humidity, wind speed as well as food, water and sewage, air, insects, inanimate surfaces, and hands in COVID-19 transmission. The results of studies on the stability of the SARS-CoV-2 on different levels showed that the resistance of this virus on smooth surfaces was higher than others. Temperature increase and sunlight can facilitate the destruction of SARS-COV-2 and the stability of it on surfaces. When the minimum ambient air temperature increases by 1 °C, the cumulative number of cases decreases by 0.86%. According to the latest evidence, the presence of coronavirus in the sewer has been confirmed, but there is no evidence that it is transmitted through sewage or contaminated drinking water. Also, SARS-COV-2 transmission through food, food packages, and food handlers has not been identified as a risk factor for the disease. According to the latest studies, the possibility of transmitting SARS-COV-2 bioaerosol through the air has been reported in the internal environment of ophthalmology. The results additionally show that infectious bio-aerosols can move up to 6 feet. There have been no reports of SARS-COV-2 transmission by blood-feeding arthropods such as mosquitoes.", "title": "The role of environmental factors to transmission of SARS-CoV-2 (COVID-19)", "pid": "t01njoxo", "bm25_score": 214.6012725830078}, {"text": "Abstract Starting from December 2019 the world has faced an unprecedented health crisis caused by the new Coronavirus (COVID-19) due to the SARS-CoV-2 pathogen. Within this topic, the aim of the paper was to quantify the effect of mobility habits in the spread of the Coronavirus in Italy through a multiple linear regression model. Estimation results showed that mobility habits represent one of the variables that explains the number of COVID-19 infections jointly with the number of tests/day and some environmental variables (i.e. PM pollution and temperature). Nevertheless, a proximity variable to the first outbreak was also significant, meaning that the areas close to the outbreak had a higher risk of contagion, especially in the initial stage of infection (time-decay phenomena). Furthermore, the number of daily new cases was related to the trips performed three weeks before. This threshold of 21 days could be considered as a sort of positivity detection time, meaning that the mobility restrictions quarantine commonly set at 14 days, defined only according to incubation-based epidemiological considerations, is underestimated (possible delays between contagion and detection) as a containment policy and may not always contribute to effectively slowing down the spread of virus worldwide. This result is original and, if confirmed in other studies, will lay the groundwork for more effective containment of COVID-19 in countries that are still in the health emergency, as well as for possible future returns of the virus.", "title": "How mobility habits influenced the spread of the COVID-19 pandemic: Results from the Italian case study", "pid": "f7mbdfr6", "bm25_score": 214.6007843017578}, {"text": "From January 21 through February 23, 2020, public health agencies detected 14 U.S. cases of coronavirus disease 2019 (COVID-19), all related to travel from China (1,2). The first nontravel-related U.S. case was confirmed on February 26 in a California resident who had become ill on February 13 (3). Two days later, on February 28, a second nontravel-related case was confirmed in the state of Washington (4,5). Examination of four lines of evidence provides insight into the timing of introduction and early transmission of SARS-CoV-2, the virus that causes COVID-19, into the United States before the detection of these two cases. First, syndromic surveillance based on emergency department records from counties affected early by the pandemic did not show an increase in visits for COVID-19-like illness before February 28. Second, retrospective SARS-CoV-2 testing of approximately 11,000 respiratory specimens from several U.S. locations beginning January 1 identified no positive results before February 20. Third, analysis of viral RNA sequences from early cases suggested that a single lineage of virus imported directly or indirectly from China began circulating in the United States between January 18 and February 9, followed by several SARS-CoV-2 importations from Europe. Finally, the occurrence of three cases, one in a California resident who died on February 6, a second in another resident of the same county who died February 17, and a third in an unidentified passenger or crew member aboard a Pacific cruise ship that left San Francisco on February 11, confirms cryptic circulation of the virus by early February. These data indicate that sustained, community transmission had begun before detection of the first two nontravel-related U.S. cases, likely resulting from the importation of a single lineage of virus from China in late January or early February, followed by several importations from Europe. The widespread emergence of COVID-19 throughout the United States after February highlights the importance of robust public health systems to respond rapidly to emerging infectious threats.", "title": "Evidence for Limited Early Spread of COVID-19 Within the United States, January-February 2020", "pid": "777z09h2", "bm25_score": 214.598876953125}, {"text": "The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) has reached over five million confirmed cases worldwide, and numbers are still growing at a fast rate. Despite the wide outbreak of the infection, a remarkable asymmetry is observed in the number of cases and in the distribution of the severity of the COVID-19 symptoms in patients with respect to the countries/regions. In the early stages of a new pathogen outbreak, it is critical to understand the dynamics of the infection transmission, in order to follow contagion over time and project the epidemiological situation in the near future. While it is possible to reason that observed variation in the number and severity of cases stems from the initial number of infected individuals, the difference in the testing policies and social aspects of community transmissions, the factors that could explain high discrepancy in areas with a similar level of healthcare still remain unknown. Here, we introduce a binary classifier based on an artificial neural network that can help in explaining those differences and that can be used to support the design of containment policies. We found that SARS-CoV-2 infection frequency positively correlates with particulate air pollutants, and specifically with particulate matter 2.5 (PM2.5), while ozone gas is oppositely related with the number of infected individuals. We propose that atmospheric air pollutants could thus serve as surrogate markers to complement the infection outbreak anticipation.", "title": "Spatial-Temporal Variations in Atmospheric Factors Contribute to SARS-CoV-2 Outbreak.", "pid": "iwj57sfg", "bm25_score": 214.59725952148438}, {"text": "INTRODUCTION: Climate change has been known to influence infectious diseases. The reason for this being the fact; disease agents and their vectors each have particular environments that are optimal for growth, survival, transport, and dissemination. MATERIALS AND METHODS: The WHO's website was accessed to look for the Novel Coronavirus (COVID-19) situation dashboard and comprehensively study and assess the report. An attempt was made to look for countries, areas or territories with maximum and minimum number of cases of lab confirmed COVID cases. Further, we entered the words “Climate“ in google for each of the aforementioned countries and searched for the results. A comparison was established by including countries from both the hemispheres (northern and southern). The preliminary analysis was based on the reports from countries with established testing facilities for Covid-19. RESULTS: The report suggests that countries with higher number of cases are the countries with cold weather. These are also the countries with low humidity which could be favoring the transmission and survival of the SARS-COV-2. CONCLUSIONS: The results though preliminary point to a pattern which favors the hypothesis that the extensive spread of Covid-19 maybe limited by temperature and humidity.", "title": "Does temperature and humidity influence the spread of Covid-19?: A preliminary report", "pid": "ws03xsho", "bm25_score": 214.5955810546875}, {"text": "This study endeavors to explain the relation between air pollution and particulate compounds emissions, wind resources and energy, and the diffusion of COVID-19 infection to provide insights of sustainable policy to prevent future epidemics. The statistical analysis here focuses on case study of Italy, one of the countries to experience a rapid increase in confirmed cases and deaths. Results reveal two main findings: 1) cities in regions with high wind speed and a high wind energy production in MW have a lower number of infected individuals of COVID-19 infection and total deaths; 2) cities located in hinterland zones (mostly those bordering large urban conurbations) with high polluting industrialization, low wind speed and less cleaner production have a greater number of infected individuals and total deaths. Hence, cities with pollution industrialization and low renewable energy have also to consider low wind speed and other climatological factors that can increase stagnation of the air in the atmosphere with potential problems for public health in the presence of viral agents. Results here suggest that current pandemic of Coronavirus disease and future epidemics similar to COVID-19 infection cannot be solved only with research and practice of medicine, immunology and microbiology but also with a proactive strategy directed to interventions for a sustainable development. Overall, then, this study has to conclude that a strategy to prevent future epidemics similar to COVID-19 infection must also be based on sustainability science to support a higher level of renewable energy and cleaner production to reduce polluting industrialization and, as result, the factors determining the spread of coronavirus disease and other infections in society.", "title": "How sustainable environments have reduced the diffusion of coronavirus disease 2019: the interaction between spread of COVID-19 infection, polluting industrialization, wind (renewable) energy", "pid": "1rvlqdsr", "bm25_score": 214.59454345703125}, {"text": "Background The COVID-19 pandemic caused by the SARS-CoV-2 virus started in China in December 2019 and has since spread globally. Information about the spread of the virus in a country can inform the gradual reopening of a country and help to avoid a second wave of infections. Denmark is currently opening up after a lockdown in mid-March. Methods We perform a phylogenetic analysis of 742 publicly available Danish SARS-CoV-2 genome sequences and put them into context using sequences from other countries. Result Our findings are consistent with several introductions of the virus to Denmark from independent sources. We identify several chains of mutations that occurred in Denmark and in at least one case find evidence that the virus spread from Denmark to other countries. A number of the mutations found in Denmark are non-synonymous, and in general there is a considerable variety of strains. The proportions of the most common haplotypes is stable after lockdown. Conclusion Our work shows how genetic data can be used to identify routes of introduction of a virus into a region and provide alternative means for verifying existing assumptions. For example, our analysis supports the hypothesis that the virus was brought to Denmark by skiers returning from Ischgl. On the other hand, we identify transmission chains suggesting that Denmark was part of a network of countries among which the virus was being transmitted; thus challenging the common narrative that Denmark only got infected from abroad. Our analysis does not indicate that the major haplotypes appearing in Denmark have a different degree of virality. Our methods can be applied to other countries, regions or even highly localised outbreaks. When used in real-time, we believe they can serve to identify transmission events and supplement traditional methods such as contact tracing.", "title": "SARS-CoV-2 transmission chains from genetic data: a Danish case study", "pid": "n7t27fdq", "bm25_score": 214.58653259277344}, {"text": "Background: The role of aerosols in the transmission of SARS-CoV-2 remains debated. We analysed an outbreak involving three non-associated families in Restaurant X in Guangzhou, China, and assessed the possibility of aerosol transmission of SARS-CoV-2 and characterize the associated environmental conditions. Methods: We collected epidemiological data, obtained a video record and a patron seating-arrangement from the restaurant, and measured the dispersion of a warm tracer gas as a surrogate for exhaled droplets from the suspected index patient. Computer simulations were performed to simulate the spread of fine exhaled droplets. We compared the in-room location of subsequently infected cases and spread of the simulated virus-laden aerosol tracer. The ventilation rate was measured using the tracer decay method. Results: Three families (A, B, C), 10 members of which were subsequently found to have been infected with SARS-CoV-2 at this time, or previously, ate lunch at Restaurant X on Chinese New Year's Eve (January 24, 2020) at three neighboring tables. Subsequently, three members of family B and two members of family C became infected with SARS-CoV-2, whereas none of the waiters or 68 patrons at the remaining 15 tables became infected. During this occasion, the ventilation rate was 0.75-1.04 L/s per person. No close contact or fomite contact was observed, aside from back-to-back sitting by some patrons. Our results show that the infection distribution is consistent with a spread pattern representative of exhaled virus-laden aerosols. Conclusions: Aerosol transmission of SARS-CoV-2 due to poor ventilation may explain the community spread of COVID-19.", "title": "Evidence for probable aerosol transmission of SARS-CoV-2 in a poorly ventilated restaurant", "pid": "bbghqy1a", "bm25_score": 214.5840606689453}, {"text": "The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.", "title": "Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces()", "pid": "kxyd5uzp", "bm25_score": 214.55780029296875}, {"text": "BACKGROUND: Globally, there have been many cases of COVID-2019 cases among medical staff, however, the main factors associated with the infection are not well understood. AIM: To identify the super-factors causing COVID-19 infection in medical staff in China. METHODS: A cross-sectional study was conducted between Jan. 1st, and Feb. 30th, 2020, where front line members of medical staff that took part in the care and treatment of patients with COVID-19 were enrolled. Epidemiological and demographic data between infected and uninfected groups were collected and compared. Social network analysis (SNA) was used to establish socio-metric social links between influencing factors. FINDINGS: A total of 92 medical staff were enrolled. In all participant groups, the super-factor identified by the network was wearing a medical protective mask or surgical mask correctly (degree = 572; closeness =25; betweenness centrality = 3·23). Touching the cheek, nose, and mouth while working was the super-factor in the infected group. This was the biggest node in the network and had the strongest influence (degree = 370; closeness = 29; betweenness centrality = 0·37). Self-protection score was the super-factor in the uninfected group but was the isolated factor in the infected group (degree = 201; closeness = 28; betweenness centrality = 5·64). For family members, the exposure history to Huanan Seafood Wholesale Market and the contact history to wild animals were two isolated nodes. CONCLUSION: High self-protection score was the main factor that prevented medical staff from contracting COVID-19 infection. The main factor that contributed to COVID-19 infections among medical staff was touching the cheek, nose and mouth while working.", "title": "Super-factors associated with transmission of occupational COVID-2019 infection among healthcare staff in Wuhan , China", "pid": "x67wh2na", "bm25_score": 214.5511474609375}, {"text": "", "title": "Evidence of short-range aerosol transmission of SARS-CoV-2 and call for universal airborne precautions for anesthesiologists during the COVID-19 pandemic", "pid": "fico54bz", "bm25_score": 214.53846740722656}, {"text": "SARS-CoV-2 causing COVID-19 disease has moved rapidly around the globe, infecting millions and killing hundreds of thousands. The basic reproduction number, which has been widely used and misused to characterize the transmissibility of the virus, hides the fact that transmission is stochastic, is dominated by a small number of individuals, and is driven by super-spreading events (SSEs). The distinct transmission features, such as high stochasticity under low prevalence, and the central role played by SSEs on transmission dynamics, should not be overlooked. Many explosive SSEs have occurred in indoor settings stoking the pandemic and shaping its spread, such as long-term care facilities, prisons, meat-packing plants, fish factories, cruise ships, family gatherings, parties and night clubs. These SSEs demonstrate the urgent need to understand routes of transmission, while posing an opportunity that outbreak can be effectively contained with targeted interventions to eliminate SSEs. Here, we describe the potential types of SSEs, how they influence transmission, and give recommendations for control of SARS-CoV-2.", "title": "Stochasticity and heterogeneity in the transmission dynamics of SARS-CoV-2", "pid": "en6fgilb", "bm25_score": 214.5364227294922}, {"text": "We estimate the basic reproduction number R0 and the overdispersion parameter K at two COVID-19 clusters in Indonesia: Jakarta-Depok and Batam. Based on the first 397 confirmed cases in both clusters, we find a high degree of individual-level variation in the transmission. The basic reproduction number R0 is estimated at 6.79 and 2.47, while the overdispersion parameter K of a negative-binomial distribution is estimated at 0.08 and 0.2 for Jakarta-Depok and Batam, respectively. This suggests that superspreading events played a key role in the early stage of the outbreak, i.e., a small number of infected individuals are responsible for large amounts of COVID-19 transmission.", "title": "Superspreading in Early Transmissions of COVID-19 in Indonesia", "pid": "ogrlidrs", "bm25_score": 214.53074645996094}, {"text": "The global outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) has reached over five million confirmed cases worldwide, and numbers are still growing at a fast rate. Despite the wide outbreak of the infection, a remarkable asymmetry is observed in the number of cases and in the distribution of the severity of the COVID-19 symptoms in patients with respect to the countries/regions. In the early stages of a new pathogen outbreak, it is critical to understand the dynamics of the infection transmission, in order to follow contagion over time and project the epidemiological situation in the near future. While it is possible to reason that observed variation in the number and severity of cases stems from the initial number of infected individuals, the difference in the testing policies and social aspects of community transmissions, the factors that could explain high discrepancy in areas with a similar level of healthcare still remain unknown. Here, we introduce a binary classifier based on an artificial neural network that can help in explaining those differences and that can be used to support the design of containment policies. We found that SARS-CoV-2 infection frequency positively correlates with particulate air pollutants, and specifically with particulate matter 2.5 (PM2.5), while ozone gas is oppositely related with the number of infected individuals. We propose that atmospheric air pollutants could thus serve as surrogate markers to complement the infection outbreak anticipation.", "title": "Spatial-Temporal Variations in Atmospheric Factors Contribute to SARS-CoV-2 Outbreak", "pid": "slplx4ok", "bm25_score": 214.52902221679688}, {"text": "Abstract This paper uses the exploratory spatial data analysis and the geodetector method to analyze the spatial and temporal differentiation characteristics and the influencing factors of the COVID-19 (corona virus disease 2019) epidemic spread in mainland China based on the cumulative confirmed cases, average temperature, and socio-economic data. The results show that: (1) the epidemic spread rapidly from January 24 to February 20, 2020, and the distribution of the epidemic areas tended to be stable over time. The epidemic spread rate in Hubei province, in its surrounding, and in some economically developed cities was higher, while that in western part of China and in remote areas of central and eastern China was lower. (2) The global and local spatial correlation characteristics of the epidemic distribution present a positive correlation. Specifically, the global spatial correlation characteristics experienced a change process from agglomeration to decentralization. The local spatial correlation characteristics were mainly composed of the‘high-high’ and ‘low-low’ clustering types, and the situation of the contiguous layout was very significant. (3) The population inflow from Wuhan and the strength of economic connection were the main factors affecting the epidemic spread, together with the population distribution, transport accessibility, average temperature, and medical facilities, which affected the epidemic spread to varying degrees. (4) The detection factors interacted mainly through the mutual enhancement and nonlinear enhancement, and their influence on the epidemic spread rate exceeded that of single factors. Besides, each detection factor has an interval range that is conducive to the epidemic spread.", "title": "Spatial and temporal differentiation of COVID-19 epidemic spread in mainland China and its influencing factors", "pid": "9gvx3swf", "bm25_score": 214.52590942382812}, {"text": "As the current COVID-19 pandemic continues to impact countries around the globe, refining our understanding of its transmission dynamics and the effectiveness of interventions is imperative. In particular, it is essential to obtain a firmer grasp on the effect of social distancing, potential individual-level heterogeneities in transmission such as age-specific infectivity, and impact of super-spreading. To this end, it is important to exploit multiple data streams that are becoming abundantly available during the pandemic. In this paper, we formulate an individual-level spatio-temporal mechanistic framework to statistically integrate case data with geo-location data and aggregate mobility data, enabling a more granular understanding of the transmission dynamics of COVID-19. We analyze reported cases from surveillance data, between March and early May 2020, in five (urban and rural) counties in the State of Georgia USA. We estimate natural history parameters of COVID-19 and infer unobserved quantities including infection times and transmission paths using Bayesian data-augmentation techniques. First, our results show that the overall median reproductive number was 2.88 (with 95% C.I. [1.85, 4.9]) before the state-wide shelter-in-place order issued in early April, and the effective reproductive number was reduced to below 1 about two weeks by the order. Super-spreading appears to be widespread across space and time, and it may have a particularly important role in driving the outbreak in the rural area and increasing importance towards later stages of outbreaks in both urban and rural settings. Overall, about 2% of cases may have directly infected 20% of all infections. We estimate that the infected children and younger adults (<60 years old) may be 2.38 [1.30, 3.51] times more transmissible than infected elderly (>=60), and the former may be the main driver of super-spreading. Through the synthesis of multiple data streams using our transmission modelling framework, our results enforce and improve our understanding of the natural history and transmission dynamics of COVID-19. More importantly, we reveal the roles of age-specific infectivity and characterize systematic variations and associated risk factors of super-spreading. These have important implications for the planning of relaxing social distancing and, more generally, designing optimal control measures.", "title": "Characterizing super-spreading events and age-specific infectivity of COVID-19 transmission in Georgia, USA", "pid": "2jy2hjwy", "bm25_score": 214.5235595703125}, {"text": "Since its emergence and detection in Wuhan, China in late 2019, the novel coronavirus SARS-CoV-2 has spread to nearly every country around the world, resulting in hundreds of thousands of infections to date. The virus was first detected in the Pacific Northwest region of the United States in January, 2020, with subsequent COVID-19 outbreaks detected in all 50 states by early March. To uncover the sources of SARS-CoV-2 introductions and patterns of spread within the U.S., we sequenced nine viral genomes from early reported COVID-19 patients in Connecticut. Our phylogenetic analysis places the majority of these genomes with viruses sequenced from Washington state. By coupling our genomic data with domestic and international travel patterns, we show that early SARS-CoV-2 transmission in Connecticut was likely driven by domestic introductions. Moreover, the risk of domestic importation to Connecticut exceeded that of international importation by mid-March regardless of our estimated impacts of federal travel restrictions. This study provides evidence for widespread, sustained transmission of SARS-CoV-2 within the U.S. and highlights the critical need for local surveillance.", "title": "Coast-to-coast spread of SARS-CoV-2 in the United States revealed by genomic epidemiology", "pid": "8m06zdho", "bm25_score": 214.5150146484375}]}
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"zd4v222b": 0, "zduueski": 0, "zel9a3u6": 0, "tax8ncny": 0, "zfc9w5y6": 0, "zfm6xjkh": 0, "xoyytg5z": 0, "zg17f7bd": 0, "zh4bewsg": 0, "zhdjtv4j": 0, "zi98dq1v": 0, "zim7nond": 0, "zimj5bh1": 0, "zjufx4fo": 0, "zjyzzm6v": 0, "zkdneyx5": 0, "zlah6u5s": 0, "zmaw9lbz": 1, "435tli39": 1, "zogf65f7": 0, "zp2u7e03": 0, "ft15w83r": 0, "zpek8i5e": 1, "zph6r4il": 0, "zpmdrh4q": 0, "zrzlnptt": 0, "v0v0ahjh": 0, "ztzug9j4": 0, "zu2hfx32": 1, "zubu69fo": 0, "zvngy7zz": 2, "zwwq7td4": 0, "zxn7psir": 0}, "bm25_results": [{"text": "How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this? Douglas Fairchild, Two Harbors, Minnesota, US", "title": "Viral survival", "pid": "hgau3922", "bm25_score": 216.5853271484375}, {"text": "How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this?", "title": "Viral survival", "pid": "959w9sln", "bm25_score": 216.11624145507812}, {"text": "Coronavirus, which can cause respiratory syndrome, to date has affected over seventeen thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical compounds including histamine and protease; while late activation provokes the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus may be inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.", "title": "Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy.", "pid": "0lsniwyv", "bm25_score": 215.50064086914062}, {"text": "Coronavirus can cause respiratory syndrome which to date has affected about twelve thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical copounds including histamine and protease; while late activation provoke the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus maybe inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.", "title": "Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy", "pid": "tokrvi8i", "bm25_score": 215.45315551757812}, {"text": "Dental practices now need to be more vigilant than ever and pay extra attention to hygiene in the surgery Hospitals are currently operating an hourly total clean policy and it would be prudent for dental practices to look to operate something similar to reduce the possibility of viral transmission The Government is encouraging people to stay at home and maintain social distancing during the pandemic However, key workers must go to work, use public transport and mix with high risk people People also need to go to supermarkets to get their groceries The surfaces in these public places are likely to be contaminated;these germs can then be brought into homes or dental practices", "title": "How long does Coronavirus survive on different surfaces?", "pid": "7ftq02ev", "bm25_score": 215.0667724609375}, {"text": "Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "title": "Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents", "pid": "ssq0dwmn", "bm25_score": 214.87445068359375}, {"text": "Summary Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "title": "Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents", "pid": "k9xhphpl", "bm25_score": 214.76129150390625}, {"text": "The advent of severe acute respiratory syndrome and its potential environmental transmission indicates the need for more information on the survival of coronavirus in water and wastewater. The survival of representative coronaviruses, feline infectious peritonitis virus, and human coronavirus 229E was determined in filtered and unfiltered tap water (4 and 23°C) and wastewater (23°C). This was compared to poliovirus 1 under the same test conditions. Inactivation of coronaviruses in the test water was highly dependent on temperature, level of organic matter, and presence of antagonistic bacteria. The time required for the virus titer to decrease 99.9% (T(99.9)) shows that in tap water, coronaviruses are inactivated faster in water at 23°C (10 days) than in water at 4°C (>100 days). Coronaviruses die off rapidly in wastewater, with T(99.9) values of between 2 and 4 days. Poliovirus survived longer than coronaviruses in all test waters, except the 4°C tap water.", "title": "Survival of Coronaviruses in Water and Wastewater", "pid": "0y8lfjkx", "bm25_score": 214.6465301513672}, {"text": "Abstract Strains OC43 and 229E of human coronaviruses (HCoV) cause one-third of common colds and hospital-acquired upper respiratory tract HCoV infections have been reported in premature newborns. To evaluate possible sources of infection, virus survival was studied in aqueous suspensions and on absorptive and non-absorptive surfaces representative of a hospital environment. Virus susceptibility to chemical disinfection with standard products was also characterized. Virus survived in saline solution for as long as six days but less in culture medium, with or without added cells. After drying, HCoV-229E infectivity was still detectable after 3h on various surfaces (aluminum, sterile latex surgical gloves, sterile sponges) but HCoV-OC43 survived 1h or less. Of the various chemical disinfectants tested, Proviodine® reduced the virus infectious titre by at least 50%. This study suggests that surfaces and suspensions can be considered as possible sources of contamination that may lead to hospital-acquired infections with HCoV and should be appropriately disinfected.", "title": "Survival of human coronaviruses 229E and OC43 in suspension and after drying onsurfaces: a possible source ofhospital-acquired infections", "pid": "5gayhkxx", "bm25_score": 214.58233642578125}, {"text": "Abstract The emergence of a previously unknown coronavirus infection, Severe Acute Respiratory Syndrome (SARS), demonstrated that fecally contaminated liquid droplets are a potential vehicle for the spread of a respiratory virus to large numbers of people. To assess potential risks from this pathway, there is a need for surrogates for SARS coronavirus to provide representative data on viral survival in contaminated water. This study evaluated survival of two surrogate coronaviruses, transmissible gastroenteritis (TGEV) and mouse hepatitis (MHV). These viruses remained infectious in water and sewage for days to weeks. At 25°C, time required for 99% reduction in reagent-grade water was 22 days for TGEV and 17 days for MHV. In pasteurized settled sewage, times for 99% reduction were 9 days for TGEV and 7 days for MHV. At 4°C, there was <1log10 infectivity decrease for both viruses after four weeks. Coronaviruses can remain infectious for long periods in water and pasteurized settled sewage, suggesting contaminated water is a potential vehicle for human exposure if aerosols are generated.", "title": "Survival of surrogate coronaviruses in water", "pid": "hky6isk2", "bm25_score": 214.51451110839844}, {"text": "OBJECTIVE The causal agent for SARS is considered as a novel coronavirus that has never been described both in human and animals previously. The stability of SARS coronavirus in human specimens and in environments was studied. METHODS Using a SARS coronavirus strain CoV-P9, which was isolated from pharyngeal swab of a probable SARS case in Beijing, its stability in mimic human specimens and in mimic environment including surfaces of commonly used materials or in household conditions, as well as its resistance to temperature and UV irradiation were analyzed. A total of 10(6) TCID50 viruses were placed in each tested condition, and changes of the viral infectivity in samples after treatments were measured by evaluating cytopathic effect (CPE) in cell line Vero-E6 at 48 h after infection. RESULTS The results showed that SARS coronavirus in the testing condition could survive in serum, 1:20 diluted sputum and feces for at least 96 h, whereas it could remain alive in urine for at least 72 h with a low level of infectivity. The survival abilities on the surfaces of eight different materials and in water were quite comparable, revealing reduction of infectivity after 72 to 96 h exposure. Viruses stayed stable at 4 degrees C, at room temperature (20 degrees C) and at 37 degrees C for at least 2 h without remarkable change in the infectious ability in cells, but were converted to be non-infectious after 90-, 60- and 30-min exposure at 56 degrees C, at 67 degrees C and at 75 degrees C, respectively. Irradiation of UV for 60 min on the virus in culture medium resulted in the destruction of viral infectivity at an undetectable level. CONCLUSION The survival ability of SARS coronavirus in human specimens and in environments seems to be relatively strong. Heating and UV irradiation can efficiently eliminate the viral infectivity.", "title": "Stability of SARS coronavirus in human specimens and environment and its sensitivity to heating and UV irradiation.", "pid": "gp3ib74q", "bm25_score": 214.45449829101562}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly contagious virus that can transmit through respiratory droplets, aerosols, or contacts. Frequent touching of contaminated surfaces in public areas is therefore a potential route of SARS-CoV-2 transmission. The inanimate surfaces have often been described as a source of nosocomial infections. However, summaries on the transmissibility of coronaviruses from contaminated surfaces to induce the coronavirus disease 2019 are rare at present. This review aims to summarize data on the persistence of different coronaviruses on inanimate surfaces. The literature was systematically searched on Medline without language restrictions. All reports with experimental evidence on the duration persistence of coronaviruses on any type of surface were included. Most viruses from the respiratory tract, such as coronaviruses, influenza, SARS-CoV, or rhinovirus, can persist on surfaces for a few days. Persistence time on inanimate surfaces varied from minutes to up to one month, depending on the environmental conditions. SARS-CoV-2 can be sustained in air in closed unventilated buses for at least 30 min without losing infectivity. The most common coronaviruses may well survive or persist on surfaces for up to one month. Viruses in respiratory or fecal specimens can maintain infectivity for quite a long time at room temperature. Absorbent materials like cotton are safer than unabsorbent materials for protection from virus infection. The risk of transmission via touching contaminated paper is low. Preventive strategies such as washing hands and wearing masks are critical to the control of coronavirus disease 2019.", "title": "Stability and infectivity of coronaviruses in inanimate environments", "pid": "ou7w3zkv", "bm25_score": 214.42062377929688}, {"text": "Background. The primary modes of transmission of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) appear to be direct mucus membrane contact with infectious droplets and through exposure to formites. Knowledge of the survival characteristics of the virus is essential for formulating appropriate infection-control measures. Methods. Survival of SARS-CoV strain GVU6109 was studied in stool and respiratory specimens. Survival of the virus on different environmental surfaces, including a laboratory request form, an impervious disposable gown, and a cotton nondisposable gown, was investigated. The virucidal effects of sodium hypochlorite, house detergent, and a peroxygen compound (Virkon S; Antec International) on the virus were also studied. Results. SARS-CoV GVU6109 can survive for 4 days in diarrheal stool samples with an alkaline pH, and it can remain infectious in respiratory specimens for >7 days at room temperature. Even at a relatively high concentration (10(4) tissue culture infective doses/mL), the virus could not be recovered after drying of a paper request form, and its infectivity was shown to last longer on the disposable gown than on the cotton gown. All disinfectants tested were shown to be able to reduce the virus load by >3 log within 5 min. Conclusions. Fecal and respiratory samples can remain infectious for a long period of time at room temperature. The risk of infection via contact with droplet-contaminated paper is small. Absorbent material, such as cotton, is preferred to nonabsorptive material for personal protective clothing for routine patient care where risk of large spillage is unlikely. The virus is easily inactivated by commonly used disinfectants.", "title": "Survival of Severe Acute Respiratory Syndrome Coronavirus", "pid": "h9gj814e", "bm25_score": 214.4195556640625}, {"text": "INTRODUCTION SARS-CoV-2 is dispersed from patients by talking, coughing and sneezing. The generated micro-droplets aerosols can travel up to 8 meters, stay suspended for long periods and preserve viral infectivity for a median of 2.7 hours. An unprotected person exposed to this cloud, might inhale a considerable amount of infectious viral doses, which will attach to the ACE 2 receptors on alveoli epithelium, resulting in infection. N95 respirators and surgical masks block 95% and 50-60% respectively of inhalable particles and protect the wearer from infection. Surgical masks and N95 without exhalation valve, protect both the wearer and the environment from carriers and sick people.", "title": "[RISK ASSESSMENT FOR AEROSOL INFECTION BY THE NEW CORONA VIRUS AND PROTECTION BY RESPIRATORS].", "pid": "k47m3e92", "bm25_score": 214.3582763671875}, {"text": "At room temperature, SARS-CoV-2 was stable on environmental surfaces and remained viable up to 7 days on smooth surfaces. This virus could survive for several hours in feces and 3-4 days in urine.", "title": "Stability of SARS-CoV-2 on environmental surfaces and in human excreta", "pid": "ej93duxi", "bm25_score": 214.2882843017578}, {"text": "BACKGROUND To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. RESULTS The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.", "title": "Clinical Analysis of 25 Novel Coronavirus Infections in Children.", "pid": "yydc7ksy", "bm25_score": 214.2789764404297}, {"text": "The WHO has declared COVID-19 illness a global health concern which is caused by 2019-nCoV, causing severe respiratory tract infections in humans. Transmissibility among individual to individual have been reported through droplets and probably also via contaminated surfaces and hands. Human coronaviruses can persist on inanimate surfaces such as plastic, glass, fibers and metals up to nine days. 2019-nCoV remains infectious in air for 3 h and on inanimate surfaces such as cardboard, copper, plastic and steel up to 24, 4, 72 and 48 h respectively. Disinfectant activity of various biocidal agents against coronaviruses like ethanol (62–71%), sodium hypochlorite (0.1%) and hydrogen peroxide (0.5%) can be regarded effective against 2019-nCoV as well. As no vaccine and antiviral therapies have been discovered for 2019-nCoV, prevention of further spread will viable option to control the ongoing and future outbreaks.", "title": "Inanimate surfaces as potential source of 2019-nCoV spread and their disinfection with biocidal agents", "pid": "esvutpel", "bm25_score": 214.27734375}, {"text": "INTRODUCTION: SARS-CoV-2 is dispersed from patients by talking, coughing and sneezing. The generated micro-droplets aerosols can travel up to 8 meters, stay suspended for long periods and preserve viral infectivity for a median of 2.7 hours. An unprotected person exposed to this cloud, might inhale a considerable amount of infectious viral doses, which will attach to the ACE 2 receptors on alveoli epithelium, resulting in infection. N95 respirators and surgical masks block 95% and 50-60% respectively of inhalable particles and protect the wearer from infection. Surgical masks and N95 without exhalation valve, protect both the wearer and the environment from carriers and sick people.", "title": "[risk Assessment for Aerosol Infection by the New Corona Virus and Protection by Respirators]", "pid": "xlsqikjt", "bm25_score": 214.25164794921875}, {"text": "", "title": "Coronavirus will spread as long as natural host is unknown, say scientists.", "pid": "itij3ect", "bm25_score": 214.2427520751953}, {"text": "Abstract In this study, the persistence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) was observed in feces, urine and water. In addition, the inactivation of SARS-CoV in wastewater with sodium hypochlorite and chlorine dioxide was also studied. In vitro experiments demonstrated that the virus could only persist for 2 days in hospital wastewater, domestic sewage and dechlorinated tap water, while 3 days in feces, 14 days in PBS and 17 days in urine at 20°C. However, at 4°C, the SARS-CoV could persist for 14 days in wastewater and at least 17 days in feces or urine. SARS-CoV is more susceptible to disinfectants than Escherichia coli and f2 phage. Free chlorine was found to inactivate SARS-CoV better than chlorine dioxide. Free residue chlorine over 0.5mg/L for chlorine or 2.19mg/L for chlorine dioxide in wastewater ensures complete inactivation of SARS-CoV while it does not inactivate completely E. coli and f2 phage.", "title": "Study on the resistance of severe acute respiratory syndrome-associated coronavirus", "pid": "gwaqh4dd", "bm25_score": 214.16964721679688}, {"text": "A worldwide outbreak of severe acute respiratory syndrome (SARS) had been reported. Over 8439 SARS cases and 812 SARS-related deaths were reported to the World Health Organization from 32 countries around the world up to 5 July 2003. The mechanism of transmission of SARS-CoV has been limited only to close contacts with patients. Attention was focused on possible transmission by the sewage system because laboratory studies showed that patients excreted coronavirus RNA in their stools in Amoy Gardens in Hong Kong. To explore whether the stool of SARS patients or the sewage containing the stool of patients would transmit SARS-CoV or not, we used a style of electropositive filter media particle to concentrate the SARS-CoV from the sewage of two hospitals receiving SARS patients in Beijing, as well as cell culture, semi-nested RT-PCR and sequencing of genes to detect and identify the viruses from sewage. There was no live SARS-CoV detected in the sewage in these assays. The nucleic acid of SARS-CoV was found in the sewage before disinfection from both hospitals by PCR. After disinfection, SARS-CoV RNA could be detected from some samples from the 309th Hospital of the Chinese People's Liberation Army, but not from Xiao Tang Shan Hospital after disinfection. In this study, we found that the virus can survive for 14 days in sewage at 4 degrees C, 2 days at 20 degrees C, and its RNA can be detected for 8 days though the virus had been inactivated. In conclusion, this study demonstrates that the RNA of SARS-CoV could be detected from the concentrates of sewage of both hospitals receiving SARS patients before disinfection and occasionally after disinfection though there was no live SARS-CoV; thus much attention should be paid to the treatment of stools of patients and the sewage of hospitals receiving SARS patients.", "title": "Concentration and detection of SARS coronavirus in sewage from Xiao Tang Shan Hospital and the 309th Hospital of the Chinese People's Liberation Army.", "pid": "ag8pknow", "bm25_score": 214.14427185058594}, {"text": "Objective: To determine the long-term clinical problems in adult survivors of coronavirus (CoV) infection [Coronavirus disease 2019 (COVID-19), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)] after hospitalisation or Intensive Care Unit (ICU) admission. Design: Systematic review and meta-analysis of the literature. Data sources: Ovid MEDLINE, EMBASE, CINAHL Plus and PsycINFO were searched using the strategy: (Coronavirus OR Coronavirus Infections OR COVID OR SARS virus OR Severe acute respiratory syndrome OR MERS OR Middle east respiratory syndrome) AND (Follow-up OR Follow-up studies OR Prevalence). Original studies reporting the clinical outcomes of adult survivors of coronavirus outbreaks two months after discharge or three months after admission were included. The quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 Level of Evidence Tool. Meta-analysis was conducted to derive pooled estimates of prevalence and severity for different outcomes at time points up to 6 months follow-up and beyond 6 months follow-up. Results: The search yielded 1169 studies of which 28 were included in this review. There were 15 Level 1b, 8 Level 2b, 2 Level 3b and 3 Level 4 studies by OCEBM grading. Pooled analysis of studies revealed that complications commonly observed were impaired diffusing capacity for carbon monoxide (DLCO) [prevalence of 27.26%, 95% CI 14.87 to 44.57] and reduced exercise capacity [(6-minute walking distance (6MWD) mean 461m, 95% CI 449.66 to 472.71] at 6 months with limited improvement beyond 6 months. Coronavirus survivors had considerable prevalence of psychological disorders such as post-traumatic stress disorder (PTSD) [38.80%, CI 30.93 to 47.31], depression [33.20%, CI 19.80 to 50.02] and anxiety [30.04%, CI 10.44 to 61.26) beyond 6 months. These complications were accompanied by low Short Form 36 (SF-36) scores at 6 months and beyond indicating reduced quality of life which is present long-term. Conclusions: The long term clinical problems in survivors of CoV infections (SARS and MERS) after hospitalisation or Intensive Care Unit (ICU) admission include respiratory dysfunction, reduced exercise capacity, psychological problems such as PTSD, depression and anxiety, and reduced quality of life. Critical care, rehabilitation and mental health services should anticipate a high prevalence of these problems following COVID-19 and ensure their adequate and timely management with the aim of restoring premorbid quality of life.", "title": "LONG-TERM CLINICAL OUTCOMES IN SURVIVORS OF CORONAVIRUS OUTBREAKS AFTER HOSPITALISATION OR ICU ADMISSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF FOLLOW-UP STUDIES", "pid": "bzc7luwj", "bm25_score": 214.1063232421875}, {"text": "We prospectively assessed 49 coronavirus disease cases in Guangdong, China, to estimate the frequency and duration of detectable severe acute respiratory syndrome coronavirus 2 RNA in human body fluids. The prolonged persistence of virus RNA in various body fluids may guide the clinical diagnosis and prevention of onward virus transmission.", "title": "Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids", "pid": "pubh7ovn", "bm25_score": 214.0930938720703}, {"text": "Objective@#To study the manifestations of digestive system of hospitalized patients with novel coronavirus pneumonia (NCP) in Wuhan, China, and to provide reference for disease control and treatment.@*Methods@#The data of hospitalized patients with NCP in the Sino-French Branch of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology was retrospectively analyzed, which included general information, nucleic acid test, severity degree of disease, incubation period, initial symptoms and manifestations of digestive system. The general information, positive rate of nucleic acid detection, and manifestations of digestive system were compared between critical patients who required non-invasive or invasive assisted ventilation (critical group) and non-critical patients without assisted ventilation (non-critical group). Continuous corrected chi-square test and independent sample median test were performed for statistical analysis.@*Results@#Among the 305 patients there were 146 males (47.9%) and 159 females (52.1%), median age 57 years old. Nucleic acid assay of nasopharynx swab or pharynx swab of 84.1% (228/271) patients were positive. Forty-six patients (15.1%) were in critical group and 259 patients (84.9%) were in non-critical group. The incubation period was one to fifteen days, and the median period was six days. The initial symptoms mainly were fever (81.1%, 163/201), cough (39.3%, 79/201), fatigue (54.7%, 110/201), and loss of appetite (50.2%, 101/201). In one to ten days after the disease onset, 79.1% (159/201) of patients developed gastrointestinal symptoms including nausea (29.4%, 59/201), vomiting (15.9%, 32/201), or abdominal pain (6.0%, 12/201). 49.5% (146/295) of patients had diarrhea, median time was 3.3 days, (3.3±1.6) times per day, and a duration of (4.1±2.5) days. Excluding possible drug-related diarrhea, the incidence of diarrhea still was 22.2%. Only 6.9% (4/58) of patients were found leukocytes or fecal occult blood positive in regular stool test. ALT, AST, or bilirubin increased in 39.1% (119/304) of patients at admission. Patients with ALT or AST ≥ 80 U/L only accounted for 7.9% (24/304) and 6.3% (19/304), respectively. About 2.0% (6/304) of patients also had increased bilirubin level, average level was (37.4 ± 21.1) &#x03BC;mol/L. The median age of critical group was older than that of non-critical group (65.5 years vs. 56 years), at admission the rates of abnormal liver function test abnormal and slightly increased AST (40~80 U/L) of critical group were both higher than those of non-critical group (67.4% (31/46) vs. 34.1% (88/258) and 47.8% (22/46) vs. 21.7% (56/228)), and the differences were statistically significant (x2=5.885, 18.154 and 15.723;all P &lt;0.05). There were no statistically significant differences in the proportion of male (58.7% (27/46) vs. 45.9% (119/259)), the positive rate of nucleic acid detection (94.6% (35/37) vs. 82.5% (193/234)), the percentage of patients with gastrointestinal symptoms (85.0% (17/20) vs. 78.5% (142/181)), the rate of diarrhea (44.7% (17/38)vs. 50.2% (129/257)) and ratio of patients with abnormal bilirubin level (6.5% (3/46) vs. 1.2% (3/258)) (all P&gt;0.05).@*Conclusions@#The manifestation of digestive system of hospitalized NCP patients in Wuhan is significant, the ratio of patients with diarrhea and abnormal aminotransferase level is high. And at admission the rate of patients with abnormal liver function rate of critical group is higher than that of non-critical group, which will provide reference for the prevention and treatment of NCP.", "title": "Manifestations of Digestive system in hospitalized patients with novel coronavirus pneumonia in Wuhan, China: a single-center, descriptive study/ 中华消化杂志", "pid": "oh4um491", "bm25_score": 214.07916259765625}, {"text": "Background. Human coronavirus NL63 (HCoV-NL63) is a recently discovered human coronavirus found to cause respiratory illness in children and adults that is distinct from the severe acute respiratory syndrome (SARS) coronavirus and human coronaviruses 229E (HCoV-229E) and OC43 (HCoV-OC43). Methods. We investigated the role that HCoV-NL63, HCoV-OC43, and HCoV-229E played in children hospitalized with fever and acute respiratory symptoms in Hong Kong during the period from August 2001 through August 2002. Results. Coronavirus infections were detected in 26 (4.4%) of 587 children studied; 15 (2.6%) were positive for HCoV-NL63, 9 (1.5%) were positive for HCoV-OC43, and 2 (0.3%) were positive for HCoV-229E. In addition to causing upper respiratory disease, we found that HCoV-NL63 can present as croup, asthma exacerbation, febrile seizures, and high fever. The mean age (± standard deviation [SD]) of the infected children was 30.7 ± 19.8 months (range, 6–57 months). The mean maximum temperature (±SD) for the 12 children who were febrile was 39.3°C ± 0.9°C, and the mean total duration of fever (±SD) for all children was 2.6 ± 1.2 days (range, 1–5 days). HCoV-NL63 infections were noted in the spring and summer months of 2002, whereas HCoV-OC43 infection mainly occurred in the fall and winter months of 2001. HCoV-NL63 viruses appeared to cluster into 2 evolutionary lineages, and viruses from both lineages cocirculated in the same season. Conclusions. HCoV-NL63 is a significant pathogen that contributes to the hospitalization of children, and it was estimated to have caused 224 hospital admissions per 100,000 population aged ⩽6 years each year in Hong Kong.", "title": "Human Coronavirus NL63 Infection and Other Coronavirus Infections in Children Hospitalized with Acute Respiratory Disease in Hong Kong, China", "pid": "62qe4fb0", "bm25_score": 214.06494140625}, {"text": "Summary The novel human coronavirus SARS-CoV-2 has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described, probably via droplets but possibly also via contaminated hands or surfaces. In a recent review on the persistence of human and veterinary coronaviruses on inanimate surfaces it was shown that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days. Some disinfectant agents effectively reduce coronavirus infectivity within 1 minute such 62%–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite. Other compounds such as 0.05%–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. An effective surface disinfection may help to ensure an early containment and prevention of further viral spread.", "title": "Potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents", "pid": "80dfqjql", "bm25_score": 214.06394958496094}, {"text": "We prospectively assessed 49 coronavirus disease cases in Guangdong, China, to estimate the frequency and duration of detectable severe acute respiratory syndrome coronavirus 2 RNA in human body fluids. The prolonged persistence of virus RNA in various body fluids may guide the clinical diagnosis and prevention of onward virus transmission.", "title": "Prolonged Persistence of SARS-CoV-2 RNA in Body Fluids.", "pid": "4gj9d181", "bm25_score": 214.061279296875}, {"text": "BACKGROUND: To describe the characteristics of clinical manifestations of children with 2019 novel coronavirus (2019-nCoV) infection in Chongqing. METHODS: All 25 children with laboratory-confirmed 2019-nCoV infection by real-time reverse transcription-PCR (RNA-PCR) were admitted from the 4 designated treatment hospitals of 2019-nCoV in Chongqing from January 19 to March 12, 2020. Clinical data and epidemiological history of these patients were retrospectively collected and analyzed. RESULTS: The diagnosis was confirmed through RNA-PCR testing. Among the 25 cases, 14 were males and 11 were females. The median age was 11.0 (6.3-14.5) years (range 0.6-17.0 years). All children were related to a family cluster outbreak, and 7 children (28%) with a travel or residence history in Hubei Province. These patients could be categorized into different clinical types, including 8 (32%) asymptomatic, 4 (16%) very mild cases and 13 (52%) common cases. No severe or critical cases were identified. The most common symptoms were cough (13 cases, 52%) and fever (6 cases, 24%). The duration time of clinical symptoms was 13.0 (8.0-25.0) days. In the 25 cases, on admission, 21 cases (84%) had normal white blood cell counts, while only 2 cases (8%) more than 10 × 10/L and 2 cases (8%) less than 4 × 10/L, respectively; 22 cases(88%) had normal CD4+ T lymphocyte counts, while in the remaining 3 cases(8%) this increased mildly; 23 cases had normal CD8+ T lymphocyte counts, while in the remaining 2 cases (8%) CD8+ T lymphocyte counts were mildly increased as well. All Lymphocyte counts were normal. There were no statistical differences of lab results between the groups of asymptomatic cases, mild cases and common cases. There were only 13 cases with abnormal CT imaging, most of which were located in the subpleural area of the bottom of the lung. All patients were treated with interferon, 6 cases combined with Ribavirin, and 12 cases combined with lopinavir or ritonavir. The days from onset to RNA turning negative was 15.20 ± 6.54 days. There was no significant difference of RNA turning negative between the groups of interferon, interferon plus ribavirin and interferon plus lopinavir or ritonavir treatment. All the cases recovered and were discharged from hospital. CONCLUSIONS: The morbidity of 2019-nCoV infection in children is lower than in adults and the clinical manifestations and inflammatory biomarkers in children are nonspecific and milder than that in adults. RNA-PCR test is still the most reliable diagnostic method, especially for asymptomatic patients.", "title": "Clinical Analysis of 25 Novel Coronavirus Infections in Children", "pid": "ogcfgy8f", "bm25_score": 214.05401611328125}, {"text": "The SARS-coronavirus (SARS-CoV) is a newly emerged, highly pathogenic agent that caused over 8,000 human infections with nearly 800 deaths between November 2002 and September 2003. While direct person-to-person transmission via respiratory droplets accounted for most cases, other modes have not been ruled out. Faecal shedding is common and prolonged and has caused an outbreak in Hong Kong. We studied the stability of SARS-CoV under different conditions, both in suspension and dried on surfaces, in comparison with other human-pathogenic viruses, including human coronavirus HCoV-229E. In suspension, HCoV-229E gradually lost its infectivity completely while SARS-CoV retained its infectivity for up to 9 days; in the dried state, survival times were 24 h versus 6 days. Thermal inactivation at 56°C was highly effective in the absence of protein, reducing the virus titre to below detectability; however, the addition of 20% protein exerted a protective effect resulting in residual infectivity. If protein-containing solutions are to be inactivated, heat treatment at 60°C for at least 30 min must be used. Different fixation procedures, e.g. for the preparation of immunofluorescence slides, as well as chemical means of virus inactivation commonly used in hospital and laboratory settings were generally found to be effective. Our investigations confirm that it is possible to care for SARS patients and to conduct laboratory scientific studies on SARS-CoV safely. Nevertheless, the agent’s tenacity is considerably higher than that of HCoV-229E, and should SARS re-emerge, increased efforts need to be devoted to questions of environmental hygiene.", "title": "Stability and inactivation of SARS coronavirus", "pid": "8s9671zf", "bm25_score": 214.03152465820312}, {"text": "The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health.", "title": "Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials", "pid": "4d4l6mzl", "bm25_score": 214.022216796875}, {"text": "Abstract The pathogenesis of canine coronavirus (CCV) infection in 10-week-old puppies was studied up to 14 days after oronasal inoculation. Mild diarrhoea was seen from three to 11 days after inoculation, approximately coincident with faecal virus shedding. Virus was initially isolated from the tonsils on day 3, and then from both small and large intestinal tissues up to 14 days after inoculation. Virus was also isolated from liver and lung. Histological changes were not seen in any tissues, but CCV antigen was detected, using a peroxidase antiperoxidase staining technique, mainly in epithelium overlying gut-associated lymphoid tissue. Virus neutralising antibody was first detected on day 10. Specific anti-CCV IgM was first detected in plasma three days after inoculation and IgG on days 4 to 7. Small amounts of anti-CCV IgG, IgM and IgA were detected in duodenal secretion, but none in bile.", "title": "Canine coronavirus infection in the dog following oronasal inoculation", "pid": "hby02g4t", "bm25_score": 214.02154541015625}, {"text": "Serologically coronavirus free kittens were placed in 2 catteries with a history of feline infectious peritonitis (FIP), each cattery representing 1 of the 2 different predominant clinical characteristics of FIP--effusive and granulomatous. The kittens were clinically observed for 100 days. A 100% morbidity and a 90% mortality was observed. The first signs were observed after 14 and 27 days respectively. The clinical pattern of the disease was similar in all kittens and showed a pattern of recurrent periods of conjunctivitis, upper respiratory and gastrointestinal signs. Once developed, wasting and signs of CNS disturbances were consistent. The \"effusive strain\" had a 2 weeks earlier onset of signs and death, and a 40% outcome of effusive FIP. Mean survival times during the observation period were 57 +/- 26 and 57 +/- 16 (mean +/- SD in days), respectively. The death rates were similar in both groups. Feline coronavirus (FCoV) antigen was immunohistochemically detected using indirect immunofluorescence and was present in all kittens and in 93% of the 5 investigated organs (lung, liver, spleen, kidney, and mesenteric lymph node).", "title": "Morbidity, mortality and coronavirus antigen in previously coronavirus free kittens placed in two catteries with feline infectious peritonitis.", "pid": "vhdihfxx", "bm25_score": 214.00460815429688}, {"text": "The end of 2019 marked the start of coronavirus disease (COVID-19) pandemic from China, which went on to envelope more than 190 countries and territories across the globe. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from a group of betacoronaviruses, is responsible for COVID-19. The virulent factors include the presence of envelope and spike proteins having receptor bonding domains (RBD). Clinical manifestations can range from mild respiratory infections to fatal outcomes. The viability of virus ranges from 3 to 72 hours. Polymerase chain reaction (PCR) is the diagnostic test of choice in this pandemic situation. Due to the absence of specific antivirals and vaccine, adoption of preventive option can help to combat the specific life-threatening outcomes.", "title": "The Microbiology of Coronaviruses", "pid": "y6o52xjg", "bm25_score": 213.990478515625}, {"text": "Abstract Canine coronavirus (CCV) is a common faecal agent which is difficult to isolate. This study shows CCV to survive well at temperatures below −20°C but not at temperatures above 4°C. The presence of faecal material markedly reduced CCV survival times at temperatures ranging from 20°C to −70°C. Thus, it is suggested that diagnostic faecal material should be diluted 1:10 (w/v) with growth medium and examined at the earliest opportunity.", "title": "Studies on the survival of canine coronavirus under different environmental conditions", "pid": "fpckqvr5", "bm25_score": 213.95211791992188}, {"text": "BACKGROUND: Norovirus (NoV) transmission occurs mainly through food and fomites. Contaminated human fingers can transfer the virus to inanimate objects, which may then spread the virus to susceptible persons. However, no information is available on the survival of NoVs on fomites, which may be of importance in the transmission of NoVs in institutional settings such as hospitals and nursing homes. METHODS: In the absence of any in vitro cultivation system for NoVs, feline calicivirus (FCV) was used as a surrogate. Several fomites such as computer mouse, keyboard keys, telephone wire, telephone receiver, telephone buttons, and brass disks representing faucets and door handle surfaces were artificially contaminated with known amounts of FCV. Samples were taken at regular time intervals, and virus was titrated in feline kidney cells to determine its survival on these surfaces. RESULTS: Survivability of FCV varied with fomite type. The virus survived for up to 3 days on telephone buttons and receivers, for 1 or 2 days on computer mouse, and for 8 to 12 hours on keyboard keys and brass. The time for 90% virus reduction was <4 hours on computer keys, mouse, brass, and telephone wire; 4 to 8 hours on telephone receiver; and 12 to 24 hours on telephone buttons. CONCLUSION: The results of this study confirm that FCV (and perhaps NoV) can survive on fomites such as computers, telephones, and faucets and may be transmitted to humans using these contaminated materials. This may necessitate regular cleaning or disinfection of these items, especially in hospitals and nursing homes and after known outbreaks of NoVs.", "title": "Survival on uncommon fomites of feline calicivirus, a surrogate of noroviruses", "pid": "wiruhhyz", "bm25_score": 213.93502807617188}, {"text": "The Coronaviridae family, an enveloped RNA virus family, and, more particularly, human coronaviruses (HCoV), were historically known to be responsible for a large portion of common colds and other upper respiratory tract infections. HCoV are now known to be involved in more serious respiratory diseases, i.e. bronchitis, bronchiolitis or pneumonia, especially in young children and neonates, elderly people and immunosuppressed patients. They have also been involved in nosocomial viral infections. In 2002–2003, the outbreak of severe acute respiratory syndrome (SARS), due to a newly discovered coronavirus, the SARS-associated coronavirus (SARS-CoV); led to a new awareness of the medical importance of the Coronaviridae family. This pathogen, responsible for an emerging disease in humans, with high risk of fatal outcome; underline the pressing need for new approaches to the management of the infection, and primarily to its prevention. Another interesting feature of coronaviruses is their potential environmental resistance, despite the accepted fragility of enveloped viruses. Indeed, several studies have described the ability of HCoVs (i.e. HCoV 229E, HCoV OC43 (also known as betacoronavirus 1), NL63, HKU1 or SARS-CoV) to survive in different environmental conditions (e.g. temperature and humidity), on different supports found in hospital settings such as aluminum, sterile sponges or latex surgical gloves or in biological fluids. Finally, taking into account the persisting lack of specific antiviral treatments (there is, in fact, no specific treatment available to fight coronaviruses infections), the Coronaviridae specificities (i.e. pathogenicity, potential environmental resistance) make them a challenging model for the development of efficient means of prevention, as an adapted antisepsis-disinfection, to prevent the environmental spread of such infective agents. This review will summarize current knowledge on the capacity of human coronaviruses to survive in the environment and the efficacy of well-known antiseptic-disinfectants against them, with particular focus on the development of new methodologies to evaluate the activity of new antiseptic-disinfectants on viruses.", "title": "Human Coronaviruses: Insights into Environmental Resistance and Its Influence on the Development of New Antiseptic Strategies", "pid": "bp6st31f", "bm25_score": 213.92295837402344}, {"text": "The end of 2019 marked the start of coronavirus disease (COVID-19) pandemic from China, which went on to envelope more than 190 countries and territories across the globe. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from a group of betacoronaviruses, is responsible for COVID-19. The virulent factors include the presence of envelope and spike proteins having receptor bonding domains (RBD). Clinical manifestations can range from mild respiratory infections to fatal outcomes. The viability of virus ranges from 3 to 72 hours. Polymerase chain reaction (PCR) is the diagnostic test of choice in this pandemic situation. Due to the absence of specific antivirals and vaccine, adoption of preventive option can help to combat the specific life-threatening outcomes.", "title": "The Microbiology of Coronaviruses.", "pid": "al71nyf6", "bm25_score": 213.8805694580078}, {"text": "Background: A patient&rsquo;s infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence Methods: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively The reverse transcription polymerase chain reaction (RT-PCR) results for patients&rsquo;oropharyngeal swab, stool, urine, and serum samples were collected and analyzed Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed Results: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study In total, 28 (42 4%) women and 38 men (57 6%) with a median age of 44 0 (34 0&ndash;62 0) years were analyzed After in-hospital treatment, patients&rsquo;inflammatory indicators decreased with improved clinical condition The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9 5 (6 0&ndash;11 0) days By February 10, 2020, 11 convalescent patients (16 7%) still tested positive for viral RNA from stool specimens and the other 55 patients&rsquo;stool specimens were negative for 2019-nCoV following a median duration of 11 0 (9 0&ndash;16 0) days after symptom onset Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2 0 (1 0&ndash;4 0) days Results for only four (6 9%) urine samples were positive for viral nucleic acid out of 58 cases;viral RNA was still present in three patients&rsquo;urine specimens after throat swabs were negative Using a multiple linear regression model ( F =2 669, P =0 044, and adjusted R 2 =0 122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients&rsquo;stools ( t =-2 699, P =0 010) The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs 8 0 days, respectively;t =2 550, P =0 013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs 11 days, respectively;t =4 631, P &lt;0 001) There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results ( P &gt;0 05) Conclusions: In brief, as the clearance of viral RNA in patients&rsquo;stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease The duration of RNA detection may relate to host cell immunity", "title": "Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients", "pid": "bcl5776f", "bm25_score": 213.83326721191406}, {"text": "[Image: see text] A systematic review and meta-analysis was conducted to identify decay rate constants (k) of human coronaviruses and their viral surrogates (i.e., animal coronaviruses and the enveloped bacteriophage Phi6) in water and wastewater and disinfection rates with exposure to free chlorine and germicidal ultraviolet light (UV(254)). Here, 73 k were identified, with only 12 for human coronaviruses, as opposed to animal coronaviruses or Phi6. In the absence of disinfectants, k increased with temperature. Between 22 and 25 °C, mean k for coronaviruses ranged from 0.19 ± 0.06 d(–1) in laboratory buffer (n = 4) to 2.9 ± 0.03 d(–1) in sterilized wastewater (n = 3), which are within the ranges observed for Phi6 and nonenveloped viruses. No free chlorine or UV(254) disinfection studies for coronaviruses were identified that met the systematic review inclusion criteria, although evidence from the literature suggests that coronaviruses would be inactivated if disinfectant doses recommended for nonenveloped viruses were applied. Three disinfection experiments were identified for Phi6. However, given different genome compositions and virion structures between coronaviruses and Phi6, it is not clear whether Phi6 should be used as a surrogate for evaluating free chlorine or UV(254)k. Therefore, there is a critical need for additional studies that specifically evaluate disinfection kinetics of coronaviruses in the aqueous environment.", "title": "Systematic Review and Meta-Analysis of the Persistence and Disinfection of Human Coronaviruses and Their Viral Surrogates in Water and Wastewater", "pid": "5ufgrlnq", "bm25_score": 213.83050537109375}, {"text": "We report an asymptomatic child who was positive for a coronavirus by reverse transcription PCR in a stool specimen 17 days after the last virus exposure. The child was virus positive in stool specimens for at least an additional 9 days. Respiratory tract specimens were negative by reverse transcription PCR.", "title": "Detection of Novel Coronavirus by RT-PCR in Stool Specimen from Asymptomatic Child, China", "pid": "3n6loyxt", "bm25_score": 213.8269805908203}, {"text": "This study investigated the long-term excretion of severe acute respiratory syndrome–associated coronavirus in sputum and stool specimens from 56 infected patients. The median (range) duration of virus excretion in sputa and stools was 21 (14–52) and 27 (16–126) days, respectively. Coexisting illness or conditions were associated with longer viral excretion in stools.", "title": "Long-term SARS Coronavirus Excretion from Patient Cohort, China", "pid": "ur37plis", "bm25_score": 213.8168182373047}, {"text": "The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 °C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "title": "Making waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health", "pid": "vuzf3dnr", "bm25_score": 213.79132080078125}, {"text": "The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 °C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "title": "Making Waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health", "pid": "c17eijdt", "bm25_score": 213.79132080078125}, {"text": "On December 31, 2019, an outbreak of pneumonia of unknown etiology was detected in the city of Wuhan (China). A week later, a new coronavirus was isolated in these patients, initially designated as 2019-nCoV and subsequently SARS-CoV-2. This is a new virus that is much closer genetically to the coronavirus of bats than to human SARS. The new virus infects and replicates in the lung parenchyma pneumocytes and macrophages in which the ACE-2 cell receptor resides. He has now infected many more people than his predecessors (> 85,000). From the clinical point of view, those infected have an average age of 55 years; the main symptoms are fever, dry cough, lymphopenia, dyspnea, and pneumonia in its severe form. The overall lethality rate is 2-3% in China and 0.1% in cases detected outside of this country. The incubation period has been set at about 3 days (0-24 days). There are no specific antivirals or vaccines.", "title": "El SARS-CoV-2, una nueva zoonosis pandémica que amenaza al mundo", "pid": "kp2ewbn1", "bm25_score": 213.7793731689453}, {"text": "Two stray pups (A and B), three and five months old, respectively, both naturally infected with canine coronavirus (CCoV), were studied for 180 days. The virus was detected intermittently in the pups' faeces by PCR for periods of 156 and 146 days, respectively. Sequence analysis of a fragment of the gene encoding the M protein revealed that the viruses detected at the onset of the infection were very similar to typical strains of CCoV, whereas from 42 days after infection in pup A and 40 days after infection in pup B the viruses had nucleotide and amino acid mutations resembling sequences in feline coronavirus.", "title": "M gene evolution of canine coronavirus in naturally infected dogs.", "pid": "a30ybnzf", "bm25_score": 213.77490234375}, {"text": "Epidemically increased evidence reveals that the link between the 2019-nCoV and other similar strain of coronaviruses circulating in bats and specifically the Rhinopodous bat sub-species. These sub-species are ample and widely present in Southern China, Middle East Africa and Europe. Recent studies show that more than 500 CoV have been identified in bats in China. The Center for Diseases Control and Prevention and the World Health Organization maintains a website that is updated frequently with new cases of MERS-CoV infection. As per WHO Situation report 16th, 24,554 number of cases confirmed globally out of which 99.22% cases from china. A new coronavirus (2019-nCoV) is causing respiratory syndrome mostly in Hubei Province, China. Corona Virus spread over 24 countries including Japan, India, Korea, and other countries 2019-CoV infection vary from mild, moderate or severe illness; the later includes severe pneumonia, ARDS, sepsis and septic shock. There are two diagnostic tests for coronavirus infection i.e. molecular test and serology test. In this review article there are the various recent cases of the patients that are suffering from the corona virus, the outcome of these studies is that corona virus infection is an epidemic disease which affects Central Nervous System (CNS).", "title": "Recent apprise on coronavirus and its terrible insinuations", "pid": "uhi0g9fh", "bm25_score": 213.7608642578125}, {"text": "After preliminary trials, the detailed changes in the concentration of specific circulating and local antibodies were followed in 15 volunteers inoculated with coronavirus 229E. Ten of them, who had significantly lower concentrations of pre-existing antibody than the rest, became infected and eight of these developed colds. A limited investigation of circulating lymphocyte populations showed some lymphocytopenia in infected volunteers. In this group, antibody concentrations started to increase 1 week after inoculation and reached a maximum about 1 week later. Thereafter antibody titres slowly declined. Although concentrations were still slightly raised 1 year later, this did not always prevent reinfection when volunteers were then challenged with the homologous virus. However, the period of virus shedding was shorter than before and none developed a cold. All of the uninfected group were infected on re-challenge although they also appeared to show some resistance to disease and in the extent of infection. These results are discussed with reference to natural infections with coronavirus and with other infections, such as rhinovirus infections.", "title": "The time course of the immune response to experimental coronavirus infection of man.", "pid": "dgizpo1z", "bm25_score": 213.75164794921875}, {"text": "BACKGROUND The outbreak of the new coronavirus infection in Wuhan City, Hubei Province in December 2019, poses a huge threat to China and even global public health security. Respiratory droplets and contact transmission are the main routes of transmission of new coronaviruses. Compared with SARS and Ebola viruses, new coronavirus infections are infectious during the incubation period. Traditional SEIR (susceptibility-exposure-infection-Removal) There are some differences in conditions for the prediction of the epidemic trend of new coronavirus infection. The outbreak of the new coronavirus infection coincided with the Spring Festival before and after the Chinese Spring Festival.It is necessary to make appropriate optimization and amendments to the traditional model to meet the actual evolution of the epidemic situation. METHODS The traditional SEIR model assumes that the virus-infected person is not infectious during the incubation period and that the infected person did not take isolation measures during the illness. The transmission of the new coronavirus no longer meets the basic assumptions of the classical kinetic system. Therefore, this article first establishes a modified SEIR model. Predict and analyze the changing trend of the epidemic situation, then estimate the parameters involved in the infection dynamics model, and then use Matlab to simulate the established dynamic equations based on public data and analyze the results. Recommendations for universal prevention and control of infectious diseases. RESULTS The first case of new coronavirus infection was confirmed in Wuhan on December 8, 2019. When Wuhan City took no action, assuming the average daily number of contacts per infected person k = 5, the number of infected persons will reach about 2,384,803 people; If wuhan adopts the measures of sealing the city on January 22, 2020, under the premise of k=2, the number of infected people decreases by 19,773 compared with that on January 23, and there is no significant change in the time when the number of infected people reaches the peak. Under the premise of k = 1, the number of infected persons was reduced by 14,330 compared with the closure on January 23, and the time to reach the peak of the number of infected persons was reduced by 2 days. If Wuhan City is closed for one day, the number of infected persons will increase from 106,145 to 130,626 under the premise of k = 2; the number of infected persons will increase from 74,369 to 92,010 under the premise of k = 1. CONCLUSIONS Comparing the number of confirmed diagnoses actually notified by the department with the number of infected people obtained from the simulation of the model, it can be seen that the city closure measures adopted by the Wuhan Municipal Government on January 23 and the first-level response measures adopted by the country are effective for the epidemic Prevention and control play a vital role. Wearing a mask when going out and avoiding close contact with people can effectively reduce the infection rate.", "title": "Prediction of New Coronavirus Infection Based on a Modified SEIR Model", "pid": "1mu1z4xd", "bm25_score": 213.74142456054688}, {"text": "Objectives@#To analyze the epidemiological and clinical characteristics of children with 2019 novel coronavirus (2019-nCoV) infection in Shenzhen.@*Methods@#The data of 30 children diagnosed with 2019-nCoV infection in the Third People’s Hospital of Shenzhen from 16th January 2020 to 9th February 2020were collected.@*Results@#Among the 30 children, 14 were boys and 16 were girls. There were 10 mild cases, 13 common cases and one severe case, and six cases with asymptomatic infection. The age ranged from 7 months to 18 years old with the median age of 7 years old. Twenty out of 30 cases (66.7%) were school children. The common clinical characteristics were fever (30.0%, 9/30) and cough (23.3%, 7/30). The body temperature waved below 37.5 ℃. Mostly the auscultations of the lungs were no rales and there was no extrapulmonary complication. A total number of one case had wheezes and hypoxia, and one case had diarrhea and vomiting. There was no critical and death case. There were 29 cases with travelling experience in Hubei province within two weeks, and 24 cases (80.0%) had relatives (parents or grandparents) diagnosed with 2019-nCoV infection. Elevated white blood cell counts (﹥12×109/L), C reaction protein level, lactate dehydrogenase level and the low proportion of T help cells occurred in three, five, five and three cases, respectively. Some cases were coinfected with human respiratory syncytial virus, mycoplasma pneumonia, human herpesvirus, influenza B virus and rubella virus. The predominant pattern of computed tomography findings of childhood patients with 2019-nCoV infection presented with patchy film and ground-glass opacities in bilateral or unilateral lung. The median time for nucleic acid to turn negative was eight days among the enrolled cases. All the cases were cured and discharged home, and the days in hospital waved from 5 - 16 days (the median time was 12 days).@*Conclusions@#The majority of the childhood cases are the school-age children with family cluster. Most cases present mild and common symptoms with good prognosis. Some patients may be complicated with multiple infections.", "title": "Epidemiological and clinical characteristics analysis of 30 childhood cases with 2019 novel coronavirus infection in Shenzhen/ 中华传染病杂志", "pid": "dk565p80", "bm25_score": 213.74124145507812}, {"text": "Human coronavirus (HCoV) accounts for 15-30% of common colds, but only one case report has described the effect of a coronavirus infection, that was asymptomatic, on human respiratory epithelium. The authors examined the effects of infection with HCoV on ciliary structure and function in healthy volunteers infected by intranasal inoculation with HCoV 229E. A further four volunteers were sham infected with ultraviolet-inactivated virus. Immediately before inoculation (day 0) and 3 days later (day 3), ciliated epithelium was obtained by brushing the inferior nasal turbinate. Ciliary beat frequency was determined and beat pattern analysed for evidence of dyskinesia (0=normal, 3=severely dyskinetic) using digital high-speed video photography. Ciliary ultrastructure was examined by transmission electron microscopy. Symptom diaries were kept for the duration of the study. All subjects inoculated with HCoV, including the three who did not develop symptoms of an upper respiratory tract infection, had disruption of their respiratory epithelium on day 3. Although there was no difference in the mean ciliary beat frequency between day 0 (11.3 Hz (95% confidence interval (CI): 8.6-14.0) and day 3 (9.4 Hz (95% CI 7.2-11.6)), there was a significant increase (p<0.05) in the ciliary dyskinesia score between day 0 (0.2 (95% CI 0-0.5)) and day 3 (1.1 (95% CI 0.5-1.7). In sham-infected subjects, no differences in epithelial integrity, or ciliary structure and function were found between day 0 and day 3. Inoculation of healthy volunteers with human coronavirus caused disruption of the ciliated epithelium and ciliary dyskinesia. This is likely to impair mucociliary clearance. Damage to the respiratory epithelium, due to human coronavirus infection, may occur without overt clinical symptoms.", "title": "The effects of coronavirus on human nasal ciliated respiratory epithelium.", "pid": "0lrk08vn", "bm25_score": 213.69581604003906}, {"text": "Coronaviruses are zoonotic viruses and six species of Coronaviruses are known to cause human disease such as cause common cold, severe acute respiratory syndrome and the Middle East Respiratory Syndrome. In January 2020, scientists in Wuhan, China isolated a novel coronavirus (SARS-CoV-2), responsible for an outbreak of unknown pneumonia that had not been previously reported among humans. This virus spreads from person to person, through respiratory droplets, close contact, and by touching surfaces or objects contaminated by the virus. The incubation period varies between 2 days and 14 days. Symptoms usually include fever, cough, difficulty in breathing, pneumonia, severe acute respiratory syndrome. Older age and co-morbid conditions increase the fatality. Any person with a history of travel to and from COVID-19 affected countries in the past 14 days or any person who has had close contact with a laboratory confirmed COVID-19 are suspect cases and needs evaluation. Currently no vaccine is available and treatment is mainly supportive. Measures at workplace should include- avoiding non-essential travel, identifying and isolating sick employees at the earliest, hand hygiene, respiratory hygiene, environmental hygiene and social distancing.", "title": "Tackling Corona Virus Disease 2019 (COVID 19) in Workplaces", "pid": "rzr8qjw8", "bm25_score": 213.69223022460938}, {"text": "The recent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, previously known as 2019-nCoV) outbreak has engulfed an unprepared world amidst a festive season. The zoonotic SARS-CoV-2, believed to have originated from infected bats, is the seventh member of enveloped RNA coronavirus. Specifically, the overall genome sequence of the SARS-CoV-2 is 96.2% identical to that of bat coronavirus termed BatCoV RaTG13. Although the current mortality rate of 2% is significantly lower than that of SARS (9.6%) and Middle East respiratory syndrome (MERS) (35%), SARS-CoV-2 is highly contagious and transmissible from human to human with an incubation period of up to 24 days. Some statistical studies have shown that, on average, one infected patient may lead to a subsequent 5.7 confirmed cases. Since the first reported case of coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 on December 1, 2019, in Wuhan, China, there has been a total of 60,412 confirmed cases with 1370 fatalities reported in 25 different countries as of February 13, 2020. The outbreak has led to severe impacts on social health and the economy at various levels. This paper is a review of the significant, continuous global effort that was made to respond to the outbreak in the first 75 days. Although no vaccines have been discovered yet, a series of containment measures have been implemented by various governments, especially in China, in the effort to prevent further outbreak, whilst various medical treatment approaches have been used to successfully treat infected patients. On the basis of current studies, it would appear that the combined antiviral treatment has shown the highest success rate. This review aims to critically summarize the most recent advances in understanding the coronavirus, as well as the strategies in prevention and treatment.", "title": "The First 75 Days of Novel Coronavirus (SARS-CoV-2) Outbreak: Recent Advances, Prevention, and Treatment", "pid": "efk2jj50", "bm25_score": 213.68246459960938}, {"text": "INTRODUCTION: On 11 March 2020, the Director-General of the World Health Organization (WHO) announced COVID-19 (Coronavirus Disease 2019) as a global pandemic Currently, no vaccines are available and there is little evidence of the efficacy of potential therapeutic agents. Furthermore, there is presumably no pre-existing immunity in the population to the new coronavirus, and it is as-sumed that everyone in the population is susceptible. OBJECTIVE: The aim of the procedures described in the article is to minimize the risk of human-to-human transmission of the SARS-CoV-2 (Severe acute respiratory syndrome - coronavirus 2) virus during procedures carried out in endoscopic laboratories. BRIEF DESCRIPTION OF THE STATE OF THE ART: SARS-CoV-2 infection can be asymptomatic, cause severe pneumonia, or lead to death. Symptoms of COVID-19 range from none (asymptomatic) to severe pneumonia and it can be fatal. Case studies to-date indicate that this infection causes a mild illness (i.e. pneumonia or mild pneumonia) in approximately 80% of cases, and most cases recove; 14% have a more severe illness, 6% experience a critical illness. The vast majority of the most serious illnesses and deaths have occurred among the elderly and people with other chronic underlying diseases. Average progression times include: • in mild cases: from the onset of symptoms to recovery in almost 2 weeks; • in severe cases: from the onset of symptoms to recovery in 3-6 weeks, and from symptoms to death in 2-8 weeks. CONCLUSIONS: Special precautions should be taken and procedures followed when performing invasive medical procedures in endoscopic laboratories in patients with specific or clinically probable SARS-CoV-2 infection. This article contains up-to-date information as at 04/04/2020.", "title": "Preliminary information on prevention of infections caused by SARS-COV-2 virus in endoscopic laboratories", "pid": "wpljegrk", "bm25_score": 213.67874145507812}, {"text": "INTRODUCTION On 11 March 2020, the Director-General of the World Health Organization (WHO) announced COVID-19 (Coronavirus Disease 2019) as a global pandemic Currently, no vaccines are available and there is little evidence of the efficacy of potential therapeutic agents. Furthermore, there is presumably no pre-existing immunity in the population to the new coronavirus, and it is as-sumed that everyone in the population is susceptible. OBJECTIVE The aim of the procedures described in the article is to minimize the risk of human-to-human transmission of the SARS-CoV-2 (Severe acute respiratory syndrome - coronavirus 2) virus during procedures carried out in endoscopic laboratories. BRIEF DESCRIPTION OF THE STATE OF THE ART SARS-CoV-2 infection can be asymptomatic, cause severe pneumonia, or lead to death. Symptoms of COVID-19 range from none (asymptomatic) to severe pneumonia and it can be fatal. Case studies to-date indicate that this infection causes a mild illness (i.e. pneumonia or mild pneumonia) in approximately 80% of cases, and most cases recove; 14% have a more severe illness, 6% experience a critical illness. The vast majority of the most serious illnesses and deaths have occurred among the elderly and people with other chronic underlying diseases. Average progression times include: • in mild cases: from the onset of symptoms to recovery in almost 2 weeks; • in severe cases: from the onset of symptoms to recovery in 3-6 weeks, and from symptoms to death in 2-8 weeks. CONCLUSIONS Special precautions should be taken and procedures followed when performing invasive medical procedures in endoscopic laboratories in patients with specific or clinically probable SARS-CoV-2 infection. This article contains up-to-date information as at 04/04/2020.", "title": "Preliminary information on prevention of infections caused by SARS-COV-2 virus in endoscopic laboratories.", "pid": "osifkqxl", "bm25_score": 213.6634521484375}, {"text": "Coronavirus disease 2019 (COVID‐19), caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has spread rapidly around the world. Currently, the identification of this disease is mainly conducted by using nasopharyngeal swabs([1]), but the presence of SARS‐CoV‐2 RNA in feces of COVID‐19 patients indicates the possibility of transmission via fecal‐oral route([2‐4]). This article is protected by copyright. All rights reserved.", "title": "Asymptomatic SARS‐CoV‐2 infected case with viral detection positive in stool but negative in nasopharyngeal samples lasts for 42 days", "pid": "hzmcrenk", "bm25_score": 213.66250610351562}, {"text": "", "title": "Six months of coronavirus: the mysteries scientists are still racing to solve.", "pid": "bh0q78sq", "bm25_score": 213.6484832763672}, {"text": "", "title": "Corrigendum to \"Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents\" [J Hosp Infect 104 (2020) 246-251]", "pid": "4xhc0lgu", "bm25_score": 213.6453857421875}, {"text": "Coronaviruses (CoVs) are a large family of enveloped, positive-strand RNA viruses Four human CoVs (HCoVs), the non-severe acute respiratory syndrome (SARS)-like HCoVs (namely HCoV 229E, NL63, OC43, and HKU1), are globally endemic and account for a substantial fraction of upper respiratory tract infections Non-SARS-like CoV can occasionally produce severe diseases in frail subjects but do not cause any major (fatal) epidemics In contrast, SARS like CoVs (namely SARS-CoV and Middle-East respiratory syndrome coronavirus, MERS-CoV) can cause intense short-lived fatal outbreaks The current epidemic caused by the highly contagious SARS-CoV-2 and its rapid spread globally is of major concern There is scanty knowledge on the actual pandemic potential of this new SARS-like virus It might be speculated that SARS-CoV-2 epidemic is grossly underdiagnosed and that the infection is silently spreading across the globe with two consequences: (i) clusters of severe infections among frail subjects could haphazardly occur linked to unrecognized index cases;(ii) the current epidemic could naturally fall into a low-level endemic phase when a significant number of subjects will have developed immunity Understanding the role of paucisymptomatic subjects and stratifying patients according to the risk of developing severe clinical presentations is pivotal for implementing reasonable measures to contain the infection and to reduce its mortality Whilst the future evolution of this epidemic remains unpredictable, classic public health strategies must follow rational patterns The emergence of yet another global epidemic underscores the permanent challenges that infectious diseases pose and underscores the need for global cooperation and preparedness, even during inter-epidemic periods", "title": "Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses", "pid": "syt4r964", "bm25_score": 213.63970947265625}, {"text": "Although the unprecedented efforts the world has been taking to control the spread of the human coronavirus disease (COVID-19) and its causative etiology [Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)], the number of confirmed cases has been increasing drastically. Therefore, there is an urgent need for devising more efficient preventive measures, to limit the spread of the infection until an effective treatment or vaccine is available. The preventive measures depend mainly on the understanding of the transmission routes of this virus, its environmental stability, and its persistence on common touch surfaces. Due to the very limited knowledge about SARS-CoV-2, we can speculate its stability in the light of previous studies conducted on other human and animal coronaviruses. In this review, we present the available data on the stability of coronaviruses (CoVs), including SARS-CoV-2, from previous reports to help understand its environmental survival. According to available data, possible airborne transmission of SARS-CoV-2 has been suggested. SARS-CoV-2 and other human and animal CoVs have remarkably short persistence on copper, latex, and surfaces with low porosity as compared to other surfaces like stainless steel, plastics, glass, and highly porous fabrics. It has also been reported that SARS-CoV-2 is associated with diarrhea and that it is shed in the feces of COVID-19 patients. Some CoVs show persistence in human excrement, sewage, and waters for a few days. These findings suggest a possible risk of fecal-oral, foodborne, and waterborne transmission of SARS-CoV-2 in developing countries that often use sewage-polluted waters in irrigation and have poor water treatment systems. CoVs survive longer in the environment at lower temperatures and lower relative humidity. It has been suggested that large numbers of COVID-19 cases are associated with cold and dry climates in temperate regions of the world and that seasonality of the virus spread is suspected.", "title": "Stability of SARS-CoV-2 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: a review", "pid": "z4vfjlbg", "bm25_score": 213.63919067382812}, {"text": "", "title": "Offline: A novel solution to live with coronavirus", "pid": "nik35un1", "bm25_score": 213.6370849609375}, {"text": "Coronaviruses are a genetically highly variable family of viruses that infect vertebrates and have succeeded in infecting humans many times by overcoming the species barrier. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in China at the end of 2019, exhibits a high infectivity and pathogenicity compared to other coronaviruses. As the viral coat and other viral components are recognized as being foreign by the immune system, this can lead to initial symptoms, which are induced by the very efficiently working immune defense system via the respiratory epithelium. During severe courses a systemically expressed proinflammatory cytokine storm and subsequent changes in the coagulation and complement systems can occur. Virus-specific antibodies, the long-term expression of which is ensured by the formation of B memory cell clones, generate a specific immune response that is also detectable in blood (seroconversion). Specifically effective cytotoxic CD8+ T­cell populations are also formed, which recognize viral epitopes as pathogen-specific patterns in combination with MHC presentation on the cell surface of virus-infected cells and destroy these cells. At the current point in time it is unclear how regular, robust and durable this immune status is constructed. Experiences with other coronavirus infections (SARS and Middle East respiratory syndrome, MERS) indicate that the immunity could persist for several years. Based on animal experiments, already acquired data on other coronavirus types and plausibility assumptions, it can be assumed that seroconverted patients have an immunity of limited duration and only a very low risk of reinfection. Knowledge of the molecular mechanisms of viral cycles and immunity is an important prerequisite for the development of vaccination strategies and development of effective drugs.", "title": "Grundlagen der Replikation und der Immunologie von SARS-CoV-2./ [Basic principles of replication and immunology of SARS-CoV-2]", "pid": "r6y70to9", "bm25_score": 213.63345336914062}, {"text": "Abstract Human coronaviruses (HCoVs) are important pathogens that cause upper respiratory tract infections and have neuroinvasive abilities; however, little is known about the dynamic infection process of CoVs in vivo, and there are currently no specific antiviral drugs to prevent or treat HCoV infection. Here, we verified the replication ability and pathogenicity of a reporter HCoV-OC43 strain expressing Renilla luciferase (Rluc; rOC43-ns2DelRluc) in mice with different genetic backgrounds (C57BL/6 and BALB/c). Additionally, we monitored the spatial and temporal progression of HCoV-OC43 through the central nervous system (CNS) of live BALB/c mice after intranasal or intracerebral inoculation with rOC43-ns2DelRluc. We found that rOC43-ns2DelRluc was fatal to suckling mice after intranasal inoculation, and that viral titers and Rluc expression were detected in the brains and spinal cords of mice infected with rOC43-ns2DelRluc. Moreover, viral replication was initially observed in the brain by non-invasive bioluminescence imaging before the infection spread to the spinal cord of BALB/c mice, consistent with its tropism in the CNS. Furthermore, the Rluc readout correlated with the HCoV replication ability and protein expression, which allowed quantification of antiviral activity in live mice. Additionally, we validated that chloroquine strongly inhibited rOC43-ns2DelRluc replication in vivo. These results provide new insights into the temporal and spatial dissemination of HCoV-OC43 in the CNS, and our methods provide an extremely sensitive platform for evaluating the efficacy of antiviral therapies to treat neuroinvasive HCoVs in live mice.", "title": "Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice", "pid": "bhu20y2d", "bm25_score": 213.6326904296875}, {"text": "", "title": "Mini organs reveal how the coronavirus ravages the body.", "pid": "o3rxe56a", "bm25_score": 213.63204956054688}, {"text": "A new coronavirus (SARS-CoV-2) emerged in the winter of 2019 in Wuhan, China, and rapidly spread around the world. The extent and efficiency of SARS-CoV-2 pandemic is far greater than previous coronaviruses that emerged in the 21st Century. Here, we modeled stability of SARS-CoV-2 on skin, paper currency, and clothing to determine if these surfaces may factor in the fomite transmission dynamics of SARS-CoV-2. Skin, currency, and clothing samples were exposed to SARS-CoV-2 under laboratory conditions and incubated at three different temperatures (4C, 22C, and 37C). Stability was evaluated at 0 hours (h), 4 h, 8 h, 24 h, 72 h, 96 h, 7 days, and 14 days post-exposure. SARS-CoV-2 was shown to be stable on skin through the duration of the experiment at 4C (14 days). Virus remained stable on skin for at least 96 h at 22C and for at least 8h at 37C. There were minimal differences between the tested currency samples. The virus remained stable on the $1 U.S.A. Bank Note for at least 96 h at 4C while viable virus was not detected on the $20 U.S.A. Bank Note samples beyond 72 h. The virus remained stable on both Bank Notes for at least 8 h at 22C and 4 h at 37C. Clothing samples were similar in stability to the currency with the virus being detected for at least 96 h at 4C and at least 4 h at 22C. No viable virus was detected on clothing samples at 37C after initial exposure. This study confirms the inverse relationship between virus stability and temperature. Furthermore, virus stability on skin demonstrates the need for continued hand hygiene practices to minimize fomite transmission both in the general population as well as workplaces where close contact is common.", "title": "Modeling the Stability of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on Skin, Currency, and Clothing", "pid": "ywusapij", "bm25_score": 213.62298583984375}, {"text": "Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19's first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.", "title": "Coronaviruses and SARS-COV-2", "pid": "lm9urlat", "bm25_score": 213.62139892578125}, {"text": "", "title": "Mini organs reveal how the coronavirus ravages the body", "pid": "a0c83ujk", "bm25_score": 213.6156005859375}, {"text": "Cases of coronavirus disease 2019 (COVID-19) emigrating from Wuhan escalated the risk of spreading the disease in other cities. This report focused on outside-Wuhan patients to assess the transmission and clinical characteristics of this illness. Contact investigation was conducted on each patient who was admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from 22 January to 23 February 2020. Cases were confirmed by the polymerase chain reaction test. Demographic, clinical, and outcomes were collected and analyzed. Of the 104 patients, 48 (46.15%) were cases who immigrated from Wuhan; 93 (89.42%) had a definite contact history with infection. Family clusters were the major body of patients. Transmission along the chain of three \"generations\" was observed. Five asymptomatic infected cases were found and two of them infected their relatives. Mean age was 43 (range, 8-84) years, and 49 (47.12%) were male. The median incubation period was 6 (range, 1-32) days, which of 8 patients ranged from 18 to 32 days, 96 (92.31%) were discharged, and 1 (0.96%) died. The average hospital stay was 10 (range, 8-14) days. Family but not community transmission became the main body of infections in the two centers, suggesting the timely control measures after the Wuhan shutdown worked well. Asymptomatic transmission demonstrated here warned us that it may lead to the widespread of COVID-19. A 14-day quarantine may need to be prolonged.", "title": "Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside-Wuhan patients, China", "pid": "65kw5eof", "bm25_score": 213.6155242919922}, {"text": "Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a public health emergency of international concern. This was first noted in Wuhan, Hubei Province, China, and since then has become widespread globally. We report a 71-year-old woman with documented viral shedding (based on reverse transcription–polymerase chain reaction (RT-PCR) testing) of SARS-CoV-2 for 60 days from the onset of symptoms (55 days from her first positive test and 36 days after complete resolution of symptoms). This is to our knowledge the longest duration of viral shedding reported to date. This case demonstrates that viral shedding after COVID-19 diagnosis can be prolonged.", "title": "Case Report: Viral Shedding for 60 Days in a Woman with COVID-19", "pid": "vvzga2tm", "bm25_score": 213.6121063232422}, {"text": "Although the unprecedented efforts the world has been taking to control the spread of the human coronavirus disease (COVID‐19) and its causative aetiology [severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)], the number of confirmed cases has been increasing drastically. Therefore, there is an urgent need for devising more efficient preventive measures, to limit the spread of the infection until an effective treatment or vaccine is available. The preventive measures depend mainly on the understanding of the transmission routes of this virus, its environmental stability, and its persistence on common touch surfaces. Due to the very limited knowledge about SARS‐CoV‐2, we can speculate its stability in the light of previous studies conducted on other human and animal coronaviruses. In this review, we present the available data on the stability of coronaviruses (CoVs), including SARS‐CoV‐2, from previous reports to help understand its environmental survival. According to available data, possible airborne transmission of SARS‐CoV‐2 has been suggested. SARS‐CoV‐2 and other human and animal CoVs have remarkably short persistence on copper, latex and surfaces with low porosity as compared to other surfaces like stainless steel, plastics, glass and highly porous fabrics. It has also been reported that SARS‐CoV‐2 is associated with diarrhoea and that it is shed in the faeces of COVID‐19 patients. Some CoVs show persistence in human excrement, sewage and waters for a few days. These findings suggest a possible risk of faecal–oral, foodborne and waterborne transmission of SARS‐CoV‐2 in developing countries that often use sewage‐polluted waters in irrigation and have poor water treatment systems. CoVs survive longer in the environment at lower temperatures and lower relative humidity. It has been suggested that large numbers of COVID‐19 cases are associated with cold and dry climates in temperate regions of the world and that seasonality of the virus spread is suspected.", "title": "Stability of SARS‐CoV‐2 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: A review", "pid": "rhfwbyav", "bm25_score": 213.60501098632812}, {"text": "BACKGROUND: Immunocompromised children might be predisposed to serious infections from human coronaviruses (HCoVs), including strains OC43, NL63, HKU1, and 229E; however, the virologic and clinical features of HCoV infection in immunocompromised children have not been compared to those in nonimmunocompromised children. METHODS: We retrospectively analyzed a cohort of children who presented to Seattle Children’s Hospital and in whom HCoV was detected by a multiplex respiratory polymerase chain reaction assay of a nasal sample between October 2012 and March 2016. Lower respiratory tract disease (LRTD) was defined as possible or definite infiltrate seen in chest imaging, need for oxygen, or abnormal lung examination in conjunction with a physician diagnosis of LRTD. We used logistic regression modeling to evaluate risk factors for LRTD and LRTD that necessitated oxygen use (severe LRTD), including an immunocompromised state, in children with HCoV infection. RESULTS: The median ages of 85 immunocompromised and 1152 nonimmunocompromised children with HCoV infection were 6.3 and 1.6 years, respectively. The prevalence of LRTD and of severe LRTD did not differ greatly between the immunocompromised and nonimmunocompromised patients (22% vs 26% [LRTD] and 15% vs 11% [severe LRTD], respectively); however, in a multivariable model, an immunocompromised state was associated with an increased likelihood of severe LRTD (adjusted odds ratio, 2.5 [95% confidence interval, 1.2–4.9]; P = .01). Younger age, having an underlying pulmonary disorder, and the presence of respiratory syncytial virus were also associated with LRTD or severe LRTD in multivariable models. The risks of LRTD or severe LRTD did not differ among the children with different HCoV strains. CONCLUSIONS: The presence of a copathogen and host factors, including an immunocompromised state, were associated with increased risk for severe LRTD. Recognizing risk factors for severe respiratory illness might assist in risk stratification.", "title": "Characteristics and Outcomes of Coronavirus Infection in Children: The Role of Viral Factors and an Immunocompromised State", "pid": "3qn012qs", "bm25_score": 213.60223388671875}, {"text": "Novel coronavirus disease (COVID-19) caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has become a public health emergency of international concern. This was first noted in Wuhan, Hubei Province, China, and since then has become widespread globally. We report a 71-year-old woman with documented viral shedding (based on reverse transcription-polymerase chain reaction (RT-PCR) testing) of SARS-CoV-2 for 60 days from the onset of symptoms (55 days from her first positive test and 36 days after complete resolution of symptoms). This is to our knowledge the longest duration of viral shedding reported to date. This case demonstrates that viral shedding after COVID-19 diagnosis can be prolonged.", "title": "Case Report: Viral Shedding for 60 Days in a Woman with COVID-19", "pid": "1vba9l42", "bm25_score": 213.5963134765625}, {"text": "", "title": "Corrigendum to \"Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents\" [J Hosp Infect 104 (2020) 246-251].", "pid": "p6x5ovv5", "bm25_score": 213.59092712402344}, {"text": "Coronaviruses are a family of RNA viruses that typically cause mild respiratory disease in humans. However, over the past 20 years, three novel/variant coronaviruses have spilled over from animals into humans and have been associated with severe respiratory illness. In late 2002, severe acute respiratory syndrome (SARS) coronavirus (CoV) emerged in China and, over the following year, went on to cause approximately 8,100 cases and 774 deaths. A decade later, a cluster of severe pneumonia cases occurred on the Arabian Peninsula, marking the beginning of the Middle East respiratory syndrome (MERS)-CoV outbreak, which has resulted in nearly 2,500 confirmed cases and 850 deaths. Now in 2020, we are in the midst of a global pandemic caused by SARS-CoV-2, which, at the time of this writing, has claimed the lives of over 83,500 people and has been confirmed in over 1,500,000 cases. These outbreaks highlight the pathogenic potential of CoVs and the importance of infection prevention and diagnostic testing to reduce the spread of infectious diseases representing a global health threat.", "title": "From the Common Cold to a Chaotic Contagion: the Potential for Coronaviruses To Cause Outbreaks of Severe Respiratory Disease Representing a Global Health Threat", "pid": "85gpu8gu", "bm25_score": 213.56787109375}, {"text": "", "title": "How Coronaviruses Cause Infection : from Colds to Deadly Pneumonia", "pid": "j4oebeur", "bm25_score": 213.56658935546875}, {"text": "Abstract On December 31, 2019, an outbreak of pneumonia of unknown etiology was detected in the city of Wuhan (China). A week later, a new coronavirus was isolated in these patients, initially designated as 2019-nCoV and subsequently SARS-CoV-2. This is a new virus that is much closer genetically to the coronavirus of bats than to human SARS. The new virus infects and replicates in the lung parenchyma pneumocytes and macrophages in which the ACE-2 cell receptor resides. He has now infected many more people than his predecessors (>85,000). From the clinical point of view, those infected have an average age of 55 years; the main symptoms are fever, dry cough, lymphopenia, dyspnea, and pneumonia in its severe form. The overall lethality rate is 2-3% in China and 0.1% in cases detected outside of this country. The incubation period has been set at about 3 days (0-24 days). There are no specific antivirals or vaccines.", "title": "The SARS-CoV-2, a new pandemic zoonosis that threatens the world", "pid": "inlv102z", "bm25_score": 213.56121826171875}, {"text": "Coronaviruses of humans were first identified more than 60 years ago from individuals with respiratory infections, mainly mild. Two different viruses, 229E and OC43 were initially recognized. Because of difficulty in isolating them using standard techniques, many of the early studies of their occurrence were seroepidemiologic. They were confirmed to be worldwide in distribution, and, in the North Temperate Zone, mainly occurring in the winter season. With the development of the reverse transcriptase polymerase chain reaction (PCR) technique, two additional distinct viruses have been identified, HKU1 and NL63. The four viruses have now been recognized as important in the etiology of common respiratory infections, second only to the rhinoviruses. In 2002, a previously unrecognized betacoronavirus emerged from a zoonotic reservoir in Southern China and spread during the following year to several major cities of the world. The resulting illness was termed Severe Acute Respiratory Syndrome (SARS) because of its potential lethality. More than 8,000 probable cases were reported during 2003, mainly from Hong Kong and mainland China, producing social and economic disruption in those areas affected. A constant feature of the outbreak was the importance of nosocomial spread. In spite of an estimated basic reproductive number higher than influenza, the outbreak was ended, in large part because of control of in-hospital transmission. In 2012, another betacoronavirus has emerged in the Arabian peninsula which is producing a somewhat similar illness, termed Middle East Respiratory Syndrome (MERS), also marked by extensive nosocomial transmission. The outcome of this emergence is currently unknown.", "title": "Coronaviruses", "pid": "jep80bed", "bm25_score": 213.56024169921875}, {"text": "As the result of prolonged (17 years) observations of patients with acute respiratory infections hospitalized in basic departments of clinics of the Research Institute of Influenza, coronavirus infection was found to be the cause of respiratory diseases, on the average, in 12% of cases (in some years in 6.8% to 28.6% of cases). The analysis of extensive morbidity rates among different age groups of the population showed that children were affected by coronavirus infection 5-7 times more often than adults. Three year cycles of this infection were established. The periods of coronaviruses activation were accompanied by their detection in patient material by electron-microscopy, a sharp increase of immune response of patients as well as in the number of nosocomial infections and the proportion of the monoinfection of the coronavirus nature. Coronaviruses played the leading role among other viruses in the etiology of hospital respiratory infections. Mucosal antibodies to coronaviruses in the secretions of the nasal cavity proved to be more important than serum antibodies not only in protection from infection, but also in the pattern of clinical manifestations of the disease.", "title": "[Seroepidemiological study of coronavirus infection in children and adults in St. Petersburg].", "pid": "9yg2ikfm", "bm25_score": 213.5587158203125}, {"text": "We report a case of asymptomatic COVID-19 infection in a pregnant woman in the third trimester with good maternal and infant outcomes. The patient was admitted to the Second People&apos;s Hospital of Hefei on February 11, 2020, because of a \"positive novel coronavirus nucleic acid test result for one day\" at 38 weeks of gestation. No abnormality was observed during her previous regular prenatal examinations. A throat swab sample was obtained from the patient four days before admission due to the diagnosis of COVID-19 infection in her husband and sister on the 14th and 7th day before her admission, and the new coronavirus nucleic acid test showed positive. The patient reported no discomfort before admission. Chest CT on the 3rd after admission showed a small amount of bilateral pleural effusion. Irregular contractions occurred three days after admission and labor was considered to be imminent. An emergency cesarean section was performed and the patient delivered a live baby girl. No tests were performed on amniotic fluid, cord blood or placenta for new coronavirus nuclei acid. The patient was isolated from the infant without breastfeeding after surgery. All medical staff involved in the cesarean section were isolated after surgery. Neonatal peripheral blood and nasopharyngeal swabs were collected for the new coronavirus nucleic acid tests on the day of birth and one day of age respectively, and nasopharyngeal swabs and anal suabs were taken at nine days after birth. All test results were negative. The patient recovered well after surgery with stable vital signs. Chest CT on the 8th after operation showed a small amount of bilateral pleural effusion, while the new coronavirus nucleic acid test results of the pharyngeal swabs were positive on the 11th and 12th day after operation. The throat swabs of all medical staff involved in the operation were negative 14 days after the operation. The mother and baby were discharged 14 days after the Cesarean section.", "title": "Asymptomatic COVID-19 infection in pregnant woman in the third trimester: a case report/ 中华围产医学杂志", "pid": "c4r277bi", "bm25_score": 213.55728149414062}, {"text": "", "title": "T cells found in coronavirus patients 'bode well' for long-term immunity.", "pid": "dqnhyqn0", "bm25_score": 213.55703735351562}, {"text": "Coronaviruses are a genetically highly variable family of viruses that infect vertebrates and have succeeded in infecting humans many times by overcoming the species barrier. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which initially appeared in China at the end of 2019, exhibits a high infectivity and pathogenicity compared to other coronaviruses. As the viral coat and other viral components are recognized as being foreign by the immune system, this can lead to initial symptoms, which are induced by the very efficiently working immune defense system via the respiratory epithelium. During severe courses a systemically expressed proinflammatory cytokine storm and subsequent changes in the coagulation and complement systems can occur. Virus-specific antibodies, the long-term expression of which is ensured by the formation of B memory cell clones, generate a specific immune response that is also detectable in blood (seroconversion). Specifically effective cytotoxic CD8+ T‑cell populations are also formed, which recognize viral epitopes as pathogen-specific patterns in combination with MHC presentation on the cell surface of virus-infected cells and destroy these cells. At the current point in time it is unclear how regular, robust and durable this immune status is constructed. Experiences with other coronavirus infections (SARS and Middle East respiratory syndrome, MERS) indicate that the immunity could persist for several years. Based on animal experiments, already acquired data on other coronavirus types and plausibility assumptions, it can be assumed that seroconverted patients have an immunity of limited duration and only a very low risk of reinfection. Knowledge of the molecular mechanisms of viral cycles and immunity is an important prerequisite for the development of vaccination strategies and development of effective drugs.", "title": "Grundlagen der Replikation und der Immunologie von SARS-CoV-2", "pid": "neq2vqym", "bm25_score": 213.55519104003906}, {"text": "Since the mid 60's the human coronaviruses (HCoV), represented by HCoV-OC43 and HCoV-229E, were generally considered relatively harmless viruses. This status changed dramatically with the emergence of SARS-CoV in 2002/2003. The SARS-CoV pandemic took 774 lives around the globe and infected more than 8000 people in 29 countries. SARS-CoV is believed to be of zoonotic origin, transmitted from its natural reservoir in bats through several animal species (e.g., civet cats, raccoon dogs sold for human consumption in markets in southern China). The epidemic was halted in 2003 by a highly effective global public health response, and SARS-CoV is currently not circulating in humans. The outbreak of SARS-CoV and the danger of its re-introduction into the human population, as well as the danger of the emergence of other zoonotic coronaviral infections triggered an intense survey for an efficient treatment that resulted in the evaluation of several anticoronaviral compounds. HCoV-NL63 and HCoV-HKU1 were identified shortly after the SARS-CoV outbreak. The 4 human coronaviruses HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 cause mild respiratory illnesses when compared to SARS, but these infections are involved in 10 - 20 % of hospitalizations of young children and immunocompromised adults with respiratory tract illness. Therefore, there is an urgent need for a successful therapy to prevent disease induction or a vaccine to prevent new infections. This review summarizes the current status of anticoronaviral strategies.", "title": "Antiviral strategies against human coronaviruses.", "pid": "c70kb6vb", "bm25_score": 213.5528106689453}, {"text": "Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19’s first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.", "title": "Coronaviruses and SARS-COV-2", "pid": "gjdlp10q", "bm25_score": 213.55226135253906}, {"text": "The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "title": "Coronaviruses widespread on nonliving surfaces: important questions and promising answers.", "pid": "9xv9t5ba", "bm25_score": 213.5441131591797}, {"text": "The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "title": "Coronaviruses widespread on nonliving surfaces: important questions and promising answers", "pid": "fxx5vrg0", "bm25_score": 213.54302978515625}, {"text": "BACKGROUND: A patient's infectivity is determined by the presence of the virus in different body fluids, secretions, and excreta. The persistence and clearance of viral RNA from different specimens of patients with 2019 novel coronavirus disease (COVID-19) remain unclear. This study analyzed the clearance time and factors influencing 2019 novel coronavirus (2019-nCoV) RNA in different samples from patients with COVID-19, providing further evidence to improve the management of patients during convalescence. METHODS: The clinical data and laboratory test results of convalescent patients with COVID-19 who were admitted to from January 20, 2020 to February 10, 2020 were collected retrospectively. The reverse transcription polymerase chain reaction (RT-PCR) results for patients' oropharyngeal swab, stool, urine, and serum samples were collected and analyzed. Convalescent patients refer to recovered non-febrile patients without respiratory symptoms who had two successive (minimum 24 h sampling interval) negative RT-PCR results for viral RNA from oropharyngeal swabs. The effects of cluster of differentiation 4 (CD4)+ T lymphocytes, inflammatory indicators, and glucocorticoid treatment on viral nucleic acid clearance were analyzed. RESULTS: In the 292 confirmed cases, 66 patients recovered after treatment and were included in our study. In total, 28 (42.4%) women and 38 men (57.6%) with a median age of 44.0 (34.0-62.0) years were analyzed. After in-hospital treatment, patients' inflammatory indicators decreased with improved clinical condition. The median time from the onset of symptoms to first negative RT-PCR results for oropharyngeal swabs in convalescent patients was 9.5 (6.0-11.0) days. By February 10, 2020, 11 convalescent patients (16.7%) still tested positive for viral RNA from stool specimens and the other 55 patients' stool specimens were negative for 2019-nCoV following a median duration of 11.0 (9.0-16.0) days after symptom onset. Among these 55 patients, 43 had a longer duration until stool specimens were negative for viral RNA than for throat swabs, with a median delay of 2.0 (1.0-4.0) days. Results for only four (6.9%) urine samples were positive for viral nucleic acid out of 58 cases; viral RNA was still present in three patients' urine specimens after throat swabs were negative. Using a multiple linear regression model (F = 2.669, P = 0.044, and adjusted R = 0.122), the analysis showed that the CD4+ T lymphocyte count may help predict the duration of viral RNA detection in patients' stools (t = -2.699, P = 0.010). The duration of viral RNA detection from oropharyngeal swabs and fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (15 days vs. 8.0 days, respectively; t = 2.550, P = 0.013) and the duration of viral RNA detection in fecal samples in the glucocorticoid treatment group was longer than that in the non-glucocorticoid treatment group (20 days vs. 11 days, respectively; t = 4.631, P < 0.001). There was no statistically significant difference in inflammatory indicators between patients with positive fecal viral RNA test results and those with negative results (P > 0.05). CONCLUSIONS: In brief, as the clearance of viral RNA in patients' stools was delayed compared to that in oropharyngeal swabs, it is important to identify viral RNA in feces during convalescence. Because of the delayed clearance of viral RNA in the glucocorticoid treatment group, glucocorticoids are not recommended in the treatment of COVID-19, especially for mild disease. The duration of RNA detection may relate to host cell immunity.", "title": "Persistence and clearance of viral RNA in 2019 novel coronavirus disease rehabilitation patients", "pid": "dtmux7iq", "bm25_score": 213.53842163085938}, {"text": "Some characteristics of a virus, isolated from the tonsils of 2 pigs with clinical signs of inappetence and vomition and designated VW572 were examined. It induced the formation of syncytia in primary pig kidney cell cultures, caused hemadsorption and hemagglutination using chicken, turkey, rat and mouse erythrocytes. In growth curve experiments, infectious virus was produced intracellularly starting at 6 hours after inoculation and was followed by rapid release of the virus from the infected cells. The virus contains ribonucleic acid, is ether sensitive and has a size between 100 and 220 nm. At 37° C, the infectivity titer decreased about 2 log(10)TCID(50) per 24 hours. The viral population was heterogeneous as indicated by the rate of inactivation by U.V. irradiation and acid pH. Some hemagglutinating activity was left after complete loss of infectivity by ether-, temperature- and U.V. treatment. The VW 572 isolate is antigenically related if not identical to isolates from Canada, U.S.A. and England which were classified as a porcine coronavirus. Oronasal and intracerebral inoculation of the VW572 isolate in colostrum deprived pigs resulted in clinical disease after an incubation period of 6 and 4 days, respectively. Signs were characterized by depression, vomition, loss of appetence with rapid weakness in young pigs and vomition with progressive wasting in older pigs. Virus was isolated from nasal and pharyngeal swabs, nasal mucosa, tonsils, lungs and hind brains but not from rectal swabs or other organs tested. Virus could not be isolated later than 8 days after inoculation. Hemagglutination inhibiting and neutralizing antibodies were detected in sera at 6 days and 9 days after inoculation, respectively.", "title": "Characteristics of a coronavirus causing vomition and wasting in pigs", "pid": "yy8f30c5", "bm25_score": 213.53729248046875}, {"text": "BACKGROUND: Since December 8, 2019, an epidemic of coronavirus disease 2019 (COVID‐19) has spread rapidly, but information about children with COVID‐19 is limited. METHODS: This retrospective and the single‐center study were done at the Public Health Clinic Center of Changsha, Hunan, China. We identified all hospitalized children diagnosed with COVID‐19 between January 8, 2019 and February 19, 2020, in Changsha. Epidemiological and clinical data of these children were collected and analyzed. Outcomes were followed until February 26th, 2020. RESULTS: By February 19, 2020, nine pediatric patients were identified as having 2019‐nCoV infection in Changsha. Six children had a family exposure and could provide the exact dates of close contact with someone who was confirmed to have 2019‐nCoV infection, among whom the median incubation period was 7.5 days. The initial symptoms of the nine children were mild, including fever (3/9), diarrhea (2/9), cough (1/9), and sore throat (1/9), two had no symptoms. Two of the enrolled patients showed small ground‐glass opacity of chest computed tomography scan. As of February 26, six patients had a negative RT‐PCR for 2019‐nCoV and were discharged. The median time from exposure to a negative RT‐PCR was 14 days. CONCLUSIONS: The clinical symptoms of the new coronavirus infection in children were not typical and showed a less aggressive clinical course than teenage and adult patients. Children who have a familial clustering or have a family member with a definite diagnosis should be reported to ensure a timely diagnosis.", "title": "Novel coronavirus infection in children outside of Wuhan, China", "pid": "txssq1p1", "bm25_score": 213.53546142578125}, {"text": "The etiology of acute respiratory tract illnesses is sometimes unclear due to limitations of diagnostic tests or the existence of as-yet-unidentified pathogens. Here we describe the identification and characterization of a not previously recognized coronavirus obtained from an 8-mo-old boy suffering from pneumonia. This coronavirus replicated efficiently in tertiary monkey kidney cells and Vero cells, in contrast to human coronaviruses (HCoV) 229E and OC43. The entire cDNA genome sequence of the previously undescribed coronavirus was determined, revealing that it is most closely related to porcine epidemic diarrhea virus and HCoV 229E. The maximum amino acid sequence identity between ORFs of the newly discovered coronavirus and related group 1 coronaviruses ranged from 43% to 67%. Real-time RT-PCR assays were designed to test for the prevalence of the previously undescribed coronavirus in humans. Using these tests, the virus was detected in four of 139 individuals (3%) who were suffering from respiratory illness with unknown etiology. All four patients suffered from fever, runny nose, and dry cough, and all four had underlying or additional morbidity. Our data will enable the development of diagnostic tests to study the prevalence and clinical impact of this virus in humans in more detail. Moreover, it will be important to discriminate this previously undescribed coronavirus from HCoV 229E and OC43 and the severe acute respiratory syndrome coronavirus.", "title": "A previously undescribed coronavirus associated with respiratory disease in humans.", "pid": "3zg6lnow", "bm25_score": 213.53311157226562}, {"text": "BACKGROUND: Duration of persistence of SARS-CoV-2 in the upper respiratory tract of infected individuals has important clinical and epidemiological implications. AIM: We aimed to establish the duration and risk factors for persistence of SARS-CoV-2 in the upper respiratory tract of asymptomatic infected individuals. METHODS: Data of repeat rRT-PCR test done for SARS-CoV-2 infected individuals at our institute at Jodhpur, India was analysed from 19 March- 21 May 2020. Duration of virus persistence was estimated with parametric regression models based on Weibull, Log-normal, Log-logistic, Gamma and Generalized Gamma distributions. Factors associated with prolonged viral persistence were analysed with the best fitting model. RESULTS: 51 SARS-CoV-2 infected individuals with repeat rRT-PCR test were identified with 44 asymptomatics. The asymptomatic individuals had median virus persistence duration of 8.87 days (95%CI: 7.65 - 10.27) and 95 percentile duration of 20.70 days (95% CI: 16.08 -28.20). The overall median virus persistence including both symptomatic and asymptomatic individuals was found to be 9.18 days (95 CI 8.04 - 10.48). Around one-fourth asymptomatics (10/44) demonstrated SARS-CoV-2 persistence beyond 2 weeks. Age < 60 years and local transmission were found to be significantly associated with longer virus persistence among asymptomatic individuals on univariate regression but not in multivariate analysis. CONCLUSION: Recommended home isolation duration for SARS-CoV-2 infected individuals in India should be extended from 17 days to at least three weeks. Prolonged persistence of SARS-CoV-2 in a proportion of asymptomatic individuals merits attention with regard to ensuring universal infection prevention precautions irrespective of symptomatic status.", "title": "Prolonged persistence of SARS-CoV-2 in the upper respiratory tract of asymptomatic infected individuals", "pid": "7ggihbfh", "bm25_score": 213.5257110595703}, {"text": "Coronavirus disease 2019 (COVID19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV2), it was first identified in 2019 in Wuhan, China and has resulted in the 2019-20 coronavirus pandemic. As of March 1, 2020, 79,968 patients in China and 7169 outside of China had tested positive for COVID19 and a mortality rate of 3.6% has been observed amongst Chinese patients. Its primary mode of transmission is via respiratory droplets from coughs and sneezes. The virus can remain viable for up to three days on plastic and stainless steel or in aerosols for upto 3 hours and is relatively more stable than the known human coronaviruses. It is stable in faeces at room temperature for at least 1-2 days and can be stable in infected patients for up to 4 days. Heat at 56 degree Celsius kills the SARS coronavirus at around 10000 units per 15 minutes. Thus, temperature is an important factor in survival of COVID19 virus and this article focuses on understanding the relationship between temperature and COVID19 transmission from the data available between January-March 2020.", "title": "Effects of temperature on COVID-19 transmission", "pid": "ycrrsr5c", "bm25_score": 213.5205078125}, {"text": "We present a case report of a healthy neonate born by vaginal delivery to a woman who had recovered from COVID-19 after 37 days of discharge The pregnant woman had fever, cough, and chills at 33 +1 gestational weeks and was diagnosed with COVID-19 by coronavirus nucleic acid test one day later She recovered and was discharged after a series of treatment, and the 2019 novel coronavirus nucleic acid test and pulmonary CT were negative at the 2nd and 4th weeks after being discharged The patient was admitted in early labor at 38 +4 gestational weeks and delivered a healthy newborn vaginally at that day Both the mother and the baby were in good condition All the maternal or neonatal specimens taken immediately after birth in the delivery room for 2019 novel coronavirus nucleic acid tests were negative, including the maternal pharynx, rectal and cervical secretions, amniotic fluid, an neonatal pharynx and rectal swabs The qualitative examination of 2019 novel coronavirus antibodies in the maternal venous blood test showed that both IgG and IgM were positive While the same test for neonatal cord blood and femoral vein blood showed negative results No inflammatory reaction was found in the placenta and immunohistochemistry detection of novel coronavirus N protein was negative The mother and newborn were observed postnatally and treated in the same ward, neither of them had fever, cough or fatigue, and were discharged three days after delivery The qualitative examination of 2019 novel coronavirus antibodies (IgM and IgG) in the femoral vein blood of the nenonate 27 days old showed negative results", "title": "Vaginal delivery after 37 days of a convalescent pregnant woman with COVID-19: a case report", "pid": "w6fk9hgr", "bm25_score": 213.51885986328125}, {"text": "Human coronaviruses (HCV) have been associated mainly with infections of the respiratory tract. Accumulating evidence from in vitro and in vivo observations is consistent with the neurotropism of these viruses in humans. To verify the possibility of a persistent infection within the central nervous system (CNS), various human cell lines of neural origin were tested for their ability to maintain chronic infection by both known strains of HCV, OC43 and 229E. Production of infectious progeny virions was monitored by an immunoperoxydase assay on a susceptible cell line and viral RNA was observed after RT-PCR. Astrocytic cell lines U-373 MG and U-87 MG did not sustain a persistent HCV-229E infection, even though they were susceptible to an acute infection by this virus. On the other hand, these two cell lines could maintain a persistent infection by HCV-OC43 for as many as 25 cell passages (about 130 days of culture). Relatively stable titers of infectious viral particles, as well as apparently constant amounts of viral RNA were detected throughout the persistent infection of U-87 MG cells. However, persistent infection of U-373 MG cells was accompanied by the detection of infectious viral particles from passage 0 to passage 13 and then from passage 20 to the end of the experiment. This gap in the production of infectious virions was correlated by a drop in the apparent amount of viral RNA detected at passages 15 and 20. These results confirm the ability of HCV-OC43 to persistently infect cells of an astrocytic lineage and, together with our previous observations of HCV infection of primary cultures of human astrocytes and the detection of HCV RNA in human brains, are consistent with the possibility that this human coronavirus could persist in the human CNS by targeting astrocytes.", "title": "Persistent infection of neural cell lines by human coronaviruses.", "pid": "b9fhuyzb", "bm25_score": 213.51431274414062}, {"text": "AIMS: To determine how long SARS-CoV-2 virus RNA persists in fecal specimens in children with COVID-19. METHODS: Retrospectively, ten children with confirmed COVID-19 in the Jinan Infectious Disease Hospital Affiliated to Shandong University were enrolled between January 23, 2020 to March 9, 2020. Epidemiological, clinical, laboratory, and radiological characteristics of the children were analyzed. RT-PCR assays were performed to detect the SARS-CoV-2 virus RNA in the respiratory tract and fecal specimens in the follow-up after discharge. RESULTS: Among ten patients, five (50%) were asymptomatic and five (50%) showed mild symptoms of respiratory illness. The average age of asymptomatic children was younger than that of symptomatic children (p = 0.03). The decreases in white blood cell (WBC) (p = 0.03) and lymphocyte (p = 0.03) counts were more severe in symptomatic patients than those in asymptomatic patients. During the follow-up examination after discharge, seven out of ten patients contained SARS-CoV-2 virus RNA in their fecal specimens, despite all patients showed negative results in respiratory tract specimens. One out of those seven patients relapsed. The median time from onset to being negative results in respiratory tract and fecal specimens was 9 days and 34.43 days, respectively. CONCLUSIONS: SARS-CoV-2 virus RNA persists much longer in the gastrointestinal (GI) tract than that in respiratory tract.", "title": "Persistence of SARS-CoV-2 virus RNA in feces: A case series of children", "pid": "ifi041d1", "bm25_score": 213.50535583496094}, {"text": "Coronaviruses (CoVs) belong to the family of Coronaviridae, the order Nidovirales, and the genus Coronavirus. They are the largest group of viruses causing respiratory and gastrointestinal infections. Morphologically, CoVs are enveloped viruses containing a non-segmented positive-sense, single-stranded ribonucleic acid (RNA) viruses. CoVs are categorized into four important genera that include Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. A novel member of human CoV that has recently emerged in Wuhan, China, is now formally named as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). This is a unique strain of RNA viruses that have not been previously observed in humans. The virus has wide host adaptability and is capable of causing severe diseases in humans, masked palm civets, mice, dogs, cats, camels, pigs, chickens, and bats. The SARS-CoV-2 typically causes respiratory and gastrointestinal sickness in both humans and animals. It can be transmitted through aerosols and direct/indirect contact, as well as during medical cases and laboratory sample handling. Specific structural proteins, which might be found on the surface of the virus, play an important role in the pathogenesis and development of the complications. The disease is characterized by distinct medical signs and symptoms that include high fever, chills, cough, and shortness of breath or difficulty in breathing. The infected people may also present with other symptoms such as diarrhea, myalgia, fatigue, expectoration, and hemoptysis. It is important from the public health and economic point of view as it affects the growth of the country, which is majorly attributed to the restriction in the movement of the people and the cost associated with the control and prevention of the disease. Since there is no specific therapeutic intervention nor a vaccine available against the virus, supportive management and treatment with non-specific therapeutic agents (repurposed drugs) may provide relief to the patients. Some preventive strategies of the disease include blocking the routes of transmission of the infections, disinfection of instruments used during medical case handling, using personal protective equipment, proper and early diagnosis of the disease, avoiding contact with the sick patients, and quarantine of the infected/exposed people.", "title": "Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update", "pid": "oq16de67", "bm25_score": 213.50234985351562}, {"text": "Now nCOVID-19 has a foothold in many countries, and the threat of a pandemic situation has risen. Recently a novel coronavirus (nCOVID-19) has first emerged in China, causing multiple symptoms in humans and closely related to those caused by SARS (Severe Acute Respiratory Syndrome) and MERS (Middle East Respiratory Syndrome). The nCOVID-19 has reported in Wuhan city of China has recently infected over six million people and at least 0.4 million confirmed deaths all over the world, while 2.8 million people has recovered from this deadly virus. Many instances of this respiratory syndrome coronavirus infection have already reported in more than 216 countries and territories. In contrast, the majority of cases reported in the USA, Brazil, Russia, Spain, UK, Italy, France and many more countries. In today's context, the coronavirus is one of the significant issues faced by the world with plenty of cases. In these circumstances, rapid reviews which recommended by WHO (World Health Organization), and these recommendations are very significant, helpful and cover current data with different preventive measures developed by the Saudi CDC (Saudi Centre for Disease Prevention and Control). This review article describes the possible modes of transmission so that proper preventive actions should be taking. Importantly, this work mentioned the animal reservoir through which may infect humans, and it must be identified to break the transmission chain. In additions, this review paper briefly discussed the spread of the coronavirus in the Arabian Peninsula and what precaution measures are in place by each country to limit the spreading of this virus. Taking into consideration the preventive measures by pharmacists as part of health care professions, however, the number of infected people, especially those with close contact with nCOVID-19 patients, are rise day by day and currently seems unstoppable.", "title": "Coronavirus nCOVID-19: A Pandemic Disease and the Saudi precautions", "pid": "0twnkv93", "bm25_score": 213.4959716796875}, {"text": "OBJECTIVE: Cases with coronavirus disease 2019 (COVID‐19) emigrated from Wuhan escalated the risk of spreading in other cities. This report focused on the outside‐Wuhan patients to assess the transmission and clinical characteristics of this illness. METHODS: Contact investigation was conducted on each patient who admitted to the assigned hospitals in Hunan Province (geographically adjacent to Wuhan) from Jan 22, 2020 to Feb 23, 2020. Patients were confirmed by PCR test. Demographic, clinical and outcomes were collected and analyzed. RESULTS: Of the 104 patients, 48 (46.15%) were imported cases who were immigrated from Wuhan; 93 (89.42%) had a definite contact history with infections. Family clusters were the major body of patients. Transmission along the chain of 3 “generations” was observed. Five asymptomatic infections were found and 2 of them infected their relatives. Mean age was 43 (rang, 8‐84) years and 49 (47.12%) were male. The median incubation period was 6 (rang, 1‐32) days, of 8 patients ranged from 18 to 32 days, 96 (92.31%) discharged and 1 (0.96%) died. Average hospital stay was 10 (rang, 8‐14) days. CONCLUSIONS: Family but not community transmission occupied the main body of infections in the two centers, suggesting the timely control measures after the Wuhan shutdown wok well. Asymptomatic transmission demonstrated here warned us that it may bring more risk to the spread of COVID‐19. A 14‐day quarantine may need to be prolonged. This article is protected by copyright. All rights reserved.", "title": "Transmission and clinical characteristics of coronavirus disease 2019 in 104 outside‐Wuhan patients, China", "pid": "wfnlp15o", "bm25_score": 213.4912872314453}, {"text": "In addition to enteric viruses of fecal origin, emerging zoonotic viruses such as respiratory coronaviruses and influenza viruses may potentially be transmitted via contaminated foods. The goal of this study was to determine the recovery efficiencies and the survival of two respiratory viruses, namely, adenovirus 2 (Ad2) and coronavirus 229E (CoV229E), on fresh produce in comparison to the enteric poliovirus 1 (PV1). Adenovirus was recovered with efficiencies of 56.5, 31.8, and 34.8 % from lettuce, strawberries, and raspberries, respectively. Coronavirus was recovered from lettuce with an efficiency of 19.6 % yet could not be recovered from strawberries. Poliovirus was recovered with efficiencies of 76.7 % from lettuce, but only 0.06 % from strawberries. For comparison purposes, the survival of Ad2, CoV229E, and PV1 was determined for periods up to 10 days on produce. The enteric PV1 survived better than both respiratory viruses on lettuce and strawberries, with only ≤1.03 log(10) reductions after 10 days of storage at 4 °C compared to CoV229E not being recovered after 4 days on lettuce and reductions of 1.97 log(10) and 2.38 log(10) of Ad2 on lettuce and strawberries, respectively, after 10 days. Nevertheless, these respiratory viruses were able to survive for at least several days on produce. There is therefore the potential for transfer to the hands and subsequently to the mucosa via rubbing the eyes or nose. In addition, some respiratory coronaviruses (e.g., severe acute respiratory syndrome coronavirus) and adenoviruses are also capable of replication in the gut and there is thus some potential for acquisition through the consumption of contaminated produce.", "title": "Survival of Respiratory Viruses on Fresh Produce", "pid": "7e8btgoo", "bm25_score": 213.4894256591797}, {"text": "OBJECTIVE: To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: A retrospective analysis was performed for the clinical data of 13 children with SARS-CoV-2 infection who hospitalized in a Changsha hospital. RESULTS: All 13 children had the disease onset due to family aggregation. Of the 13 children, 2 had no symptoms, and the other 11 children had the clinical manifestations of fever, cough, pharyngeal discomfort, abdominal pain, diarrhea, convulsions, or vomiting. As for clinical typing, 7 had mild type, 5 had common type, and 1 had severe type. The median duration of fever was 2 days in 6 children. All 13 children had normal levels of peripheral blood lymphocyte counts, immunoglobulins, CD4, CD8, and interleukin-6. The median time to clearance of SARS-CoV-2 was 13 days in the nasopharyngeal swabs of the 13 children. Three children presented false negatives for RT-PCR of SARS-CoV-2. SARS-CoV-2 RNA remained detectable in stools for 12 days after the nasopharyngeal swab test yielded a negative result. Abnormal CT findings were observed in 6 children. All 13 children were cured and discharged and they were normal at 2 weeks after discharge. CONCLUSIONS: Intra-family contact is the main transmission route of SARS-CoV-2 infection in children, and there is also a possibility of fecal-oral transmission. Mild and common types are the major clinical types in children with SARS-CoV-2 infection, and cytokine storm is not observed. Children with SARS-CoV-2 infection tend to have a good short-term prognosis, and follow-up is needed to observe their long-term prognosis. Multiple nucleic acid tests should be performed for patients with SARS-CoV-2 infection and their close contacts by multiple site sampling.", "title": "[Clinical features of children with SARS-CoV-2 infection: an analysis of 13 cases from Changsha, China]", "pid": "5sianpwf", "bm25_score": 213.48208618164062}, {"text": "Coronaviruses are widespread in nature and can infect several different species, causing mainly respiratory and enteric diseases. The respiratory involvement of human coronaviruses has been clearly established since the 1960s. Three of the six coronaviruses that infect humans have been shown to be neuroinvasive and neurotropic in humans: HCoV-229E, HCoV-OC43, and SARS-CoV. No reports exist on the detection of HCoV-HKU1 in the human central nervous system (CNS). We report a case of a patient, in whose cerebrospinal fluid (CSF) was detected Coronavirus NL63/HKU1. Coronavirus HKU1 was detected in the sputum. With effective antiviral therapy and the use of glucocorticoids, the patient was eventually discharged from the hospital. This study might help understand more about coronavirus and improve the awareness of pathogen detection in patients with coronavirus encephalitis. Keywords: coronavirus HKU1; encephalitis.", "title": "A case of coronavirus HKU1 encephalitis", "pid": "lahk2lz3", "bm25_score": 213.4803466796875}, {"text": "In December 2019, an outbreak of a new coronavirus (SARS-CoV-2) was reported in Hubei province in China. The disease has since spread worldwide and the World Health Organization declared it a pandemic on 11 March 2020. We describe the case of a 65-year-old woman who clinically recovered from COVID-19 but showed persistent infection with SARS-CoV-2 for 51 days. LEARNING POINTS: A case of persistent infection with SARS-CoV-2 is described. Some tests may pick up viral RNA fragments, giving a false positive result. The quarantining of infected patients to limit possible SARS-CoV-2 spread is important.", "title": "Long-term Positivity to SARS-CoV-2: A Clinical Case of COVID-19 with Persistent Evidence of Infection", "pid": "oao2zppd", "bm25_score": 213.47569274902344}]}
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Frequent touching of contaminated surfaces in public areas is therefore a potential route of SARS-CoV-2 transmission. The inanimate surfaces have often been described as a source of nosocomial infections. However, summaries on the transmissibility of coronaviruses from contaminated surfaces to induce the coronavirus disease 2019 are rare at present. This review aims to summarize data on the persistence of different coronaviruses on inanimate surfaces. The literature was systematically searched on Medline without language restrictions. All reports with experimental evidence on the duration persistence of coronaviruses on any type of surface were included. Most viruses from the respiratory tract, such as coronaviruses, influenza, SARS-CoV, or rhinovirus, can persist on surfaces for a few days. Persistence time on inanimate surfaces varied from minutes to up to one month, depending on the environmental conditions. SARS-CoV-2 can be sustained in air in closed unventilated buses for at least 30 min without losing infectivity. The most common coronaviruses may well survive or persist on surfaces for up to one month. Viruses in respiratory or fecal specimens can maintain infectivity for quite a long time at room temperature. Absorbent materials like cotton are safer than unabsorbent materials for protection from virus infection. The risk of transmission via touching contaminated paper is low. Preventive strategies such as washing hands and wearing masks are critical to the control of coronavirus disease 2019.", "title": "Stability and infectivity of coronaviruses in inanimate environments", "pid": "ou7w3zkv", "bm25_score": 218.22512817382812}, {"text": "At room temperature, SARS-CoV-2 was stable on environmental surfaces and remained viable up to 7 days on smooth surfaces. This virus could survive for several hours in feces and 3-4 days in urine.", "title": "Stability of SARS-CoV-2 on environmental surfaces and in human excreta", "pid": "ej93duxi", "bm25_score": 217.99012756347656}, {"text": "", "title": "Corrigendum to \"Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents\" [J Hosp Infect 104 (2020) 246-251].", "pid": "p6x5ovv5", "bm25_score": 217.7611846923828}, {"text": "Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "title": "Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents", "pid": "ssq0dwmn", "bm25_score": 217.69569396972656}, {"text": "Fecal suspensions with an aerosol route of transmission were responsible for a cluster of severe acute respiratory syndrome (SARS) cases in 2003 in Hong Kong. Based on that event, the World Health Organization recommended that research be implemented to define modes of transmission of SARS coronavirus through sewage, feces, food and water. Environmental studies have shown that animal coronaviruses remain infectious in water and sewage for up to a year depending on the temperature and humidity. In this study, we examined coronavirus stability on lettuce surfaces. A cell culture adapted bovine coronavirus, diluted in growth media or in bovine fecal suspensions to simulate fecal contamination was used to spike romaine lettuce. qRT-PCR detected viral RNA copy number ranging from 6.6 × 10(4) to 1.7 × 10(6) throughout the experimental period of 30 days. Whereas infectious viruses were detected for at least 14 days, the amount of infectious virus varied, depending upon the diluent used for spiking the lettuce. UV and confocal microscopic observation indicated attachment of residual labeled virions to the lettuce surface after the elution procedure, suggesting that rates of inactivation or detection of the virus may be underestimated. Thus, it is possible that contaminated vegetables may be potential vehicles for coronavirus zoonotic transmission to humans.", "title": "Stability of bovine coronavirus on lettuce surfaces under household refrigeration conditions", "pid": "zmaw9lbz", "bm25_score": 217.64163208007812}, {"text": "", "title": "Corrigendum to \"Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents\" [J Hosp Infect 104 (2020) 246-251]", "pid": "4xhc0lgu", "bm25_score": 217.6314697265625}, {"text": "Summary Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "title": "Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents", "pid": "k9xhphpl", "bm25_score": 217.61329650878906}, {"text": "Summary The novel human coronavirus SARS-CoV-2 has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described, probably via droplets but possibly also via contaminated hands or surfaces. In a recent review on the persistence of human and veterinary coronaviruses on inanimate surfaces it was shown that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days. Some disinfectant agents effectively reduce coronavirus infectivity within 1 minute such 62%–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite. Other compounds such as 0.05%–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. An effective surface disinfection may help to ensure an early containment and prevention of further viral spread.", "title": "Potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents", "pid": "80dfqjql", "bm25_score": 217.52664184570312}, {"text": "Abstract Strains OC43 and 229E of human coronaviruses (HCoV) cause one-third of common colds and hospital-acquired upper respiratory tract HCoV infections have been reported in premature newborns. To evaluate possible sources of infection, virus survival was studied in aqueous suspensions and on absorptive and non-absorptive surfaces representative of a hospital environment. Virus susceptibility to chemical disinfection with standard products was also characterized. Virus survived in saline solution for as long as six days but less in culture medium, with or without added cells. After drying, HCoV-229E infectivity was still detectable after 3h on various surfaces (aluminum, sterile latex surgical gloves, sterile sponges) but HCoV-OC43 survived 1h or less. Of the various chemical disinfectants tested, Proviodine® reduced the virus infectious titre by at least 50%. This study suggests that surfaces and suspensions can be considered as possible sources of contamination that may lead to hospital-acquired infections with HCoV and should be appropriately disinfected.", "title": "Survival of human coronaviruses 229E and OC43 in suspension and after drying onsurfaces: a possible source ofhospital-acquired infections", "pid": "5gayhkxx", "bm25_score": 217.4586181640625}, {"text": "The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "title": "Coronaviruses widespread on nonliving surfaces: important questions and promising answers", "pid": "fxx5vrg0", "bm25_score": 217.33216857910156}, {"text": "The world is facing, while writing this review, a global pandemic due to one of the types of the coronaviruses (i.e., COVID-19), which is a new virus. Among the most important reasons for the transmission of infection between humans is the presence of this virus active on the surfaces and materials. Here, we addressed important questions such as do coronaviruses remain active on the inanimate surfaces? Do the types of inanimate surfaces affect the activity of coronaviruses? What are the most suitable ingredients that used to inactivate viruses? This review article addressed many of the works that were done in the previous periods on the survival of many viruses from the coronaviruses family on various surfaces such as steel, glass, plastic, Teflon, ceramic tiles, silicon rubber and stainless steel copper alloys, Al surface, sterile sponges, surgical gloves and sterile latex. The impacts of environmental conditions such as temperature and humidity were presented and discussed. The most important active ingredients that can deactivate viruses on the surfaces were reported here. We hope that these active ingredients will have the same effect on COVID-19.", "title": "Coronaviruses widespread on nonliving surfaces: important questions and promising answers.", "pid": "9xv9t5ba", "bm25_score": 217.22320556640625}, {"text": "Dental practices now need to be more vigilant than ever and pay extra attention to hygiene in the surgery Hospitals are currently operating an hourly total clean policy and it would be prudent for dental practices to look to operate something similar to reduce the possibility of viral transmission The Government is encouraging people to stay at home and maintain social distancing during the pandemic However, key workers must go to work, use public transport and mix with high risk people People also need to go to supermarkets to get their groceries The surfaces in these public places are likely to be contaminated;these germs can then be brought into homes or dental practices", "title": "How long does Coronavirus survive on different surfaces?", "pid": "7ftq02ev", "bm25_score": 217.0458221435547}, {"text": "SARS-CoV-2 survives and remains viable on surfaces for several days under different environments as reported in recent studies. However, it is unclear how the viruses survive for such a long time and why their survivability varies across different surfaces. To address these questions, we conduct systematic experiments investigating the evaporation of droplets produced by a nebulizer and human-exhaled gas on surfaces. We found that these droplets do not disappear with evaporation, but instead shrink to a size of a few micrometers (referred to as residues), persist for more than 24 hours, and are highly durable against changes of environmental conditions. The characteristics of these residues change significantly across surface types. Specifically, surfaces with high thermal conductivity like copper do not leave any resolvable residues, while stainless steel, plastic, and glass surfaces form residues from a varying fraction of all deposited droplets at 40% relative humidity. Lowering humidity level suppresses the formation of residues while increasing humidity level enhances it. Our results suggest that these microscale residues can potentially insulate the virus against environmental changes, allowing them to survive inhospitable environments and remain infectious for prolonged durations after deposition. Our findings can also be extended to other viruses transmitted through respiratory droplets (e.g., SARS-CoV, flu viruses, etc.), and can thus lead to practical guidelines for disinfecting surfaces and other prevention measures (e.g., humidity control) for limiting viral transmission.", "title": "Droplet evaporation residue indicating SARS-COV-2 survivability on surfaces", "pid": "pdmfxssd", "bm25_score": 216.96043395996094}, {"text": "A novel human coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, referred to as HCoV-19 here) that emerged in Wuhan, China in late 2019 is now causing a pandemic. Here, we analyze the aerosol and surface stability of HCoV-19 and compare it with SARS-CoV-1, the most closely related human coronavirus.2 We evaluated the stability of HCoV-19 and SARS-CoV-1 in aerosols and on different surfaces and estimated their decay rates using a Bayesian regression model", "title": "Aerosol and surface stability of HCoV-19 (SARS-CoV-2) compared to SARS-CoV-1", "pid": "hiw576og", "bm25_score": 216.87123107910156}, {"text": "Abstract The emergence of a previously unknown coronavirus infection, Severe Acute Respiratory Syndrome (SARS), demonstrated that fecally contaminated liquid droplets are a potential vehicle for the spread of a respiratory virus to large numbers of people. To assess potential risks from this pathway, there is a need for surrogates for SARS coronavirus to provide representative data on viral survival in contaminated water. This study evaluated survival of two surrogate coronaviruses, transmissible gastroenteritis (TGEV) and mouse hepatitis (MHV). These viruses remained infectious in water and sewage for days to weeks. At 25°C, time required for 99% reduction in reagent-grade water was 22 days for TGEV and 17 days for MHV. In pasteurized settled sewage, times for 99% reduction were 9 days for TGEV and 7 days for MHV. At 4°C, there was <1log10 infectivity decrease for both viruses after four weeks. Coronaviruses can remain infectious for long periods in water and pasteurized settled sewage, suggesting contaminated water is a potential vehicle for human exposure if aerosols are generated.", "title": "Survival of surrogate coronaviruses in water", "pid": "hky6isk2", "bm25_score": 216.8542938232422}, {"text": "OBJECTIVE The causal agent for SARS is considered as a novel coronavirus that has never been described both in human and animals previously. The stability of SARS coronavirus in human specimens and in environments was studied. METHODS Using a SARS coronavirus strain CoV-P9, which was isolated from pharyngeal swab of a probable SARS case in Beijing, its stability in mimic human specimens and in mimic environment including surfaces of commonly used materials or in household conditions, as well as its resistance to temperature and UV irradiation were analyzed. A total of 10(6) TCID50 viruses were placed in each tested condition, and changes of the viral infectivity in samples after treatments were measured by evaluating cytopathic effect (CPE) in cell line Vero-E6 at 48 h after infection. RESULTS The results showed that SARS coronavirus in the testing condition could survive in serum, 1:20 diluted sputum and feces for at least 96 h, whereas it could remain alive in urine for at least 72 h with a low level of infectivity. The survival abilities on the surfaces of eight different materials and in water were quite comparable, revealing reduction of infectivity after 72 to 96 h exposure. Viruses stayed stable at 4 degrees C, at room temperature (20 degrees C) and at 37 degrees C for at least 2 h without remarkable change in the infectious ability in cells, but were converted to be non-infectious after 90-, 60- and 30-min exposure at 56 degrees C, at 67 degrees C and at 75 degrees C, respectively. Irradiation of UV for 60 min on the virus in culture medium resulted in the destruction of viral infectivity at an undetectable level. CONCLUSION The survival ability of SARS coronavirus in human specimens and in environments seems to be relatively strong. Heating and UV irradiation can efficiently eliminate the viral infectivity.", "title": "Stability of SARS coronavirus in human specimens and environment and its sensitivity to heating and UV irradiation.", "pid": "gp3ib74q", "bm25_score": 216.81765747070312}, {"text": "The evolution of new and reemerging historic virulent strains of respiratory viruses from animal reservoirs is a significant threat to human health. Inefficient human-to-human transmission of zoonotic strains may initially limit the spread of transmission, but an infection may be contracted by touching contaminated surfaces. Enveloped viruses are often susceptible to environmental stresses, but the human coronaviruses responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) have recently caused increasing concern of contact transmission during outbreaks. We report here that pathogenic human coronavirus 229E remained infectious in a human lung cell culture model following at least 5 days of persistence on a range of common nonbiocidal surface materials, including polytetrafluoroethylene (Teflon; PTFE), polyvinyl chloride (PVC), ceramic tiles, glass, silicone rubber, and stainless steel. We have shown previously that noroviruses are destroyed on copper alloy surfaces. In this new study, human coronavirus 229E was rapidly inactivated on a range of copper alloys (within a few minutes for simulated fingertip contamination) and Cu/Zn brasses were very effective at lower copper concentration. Exposure to copper destroyed the viral genomes and irreversibly affected virus morphology, including disintegration of envelope and dispersal of surface spikes. Cu(I) and Cu(II) moieties were responsible for the inactivation, which was enhanced by reactive oxygen species generation on alloy surfaces, resulting in even faster inactivation than was seen with nonenveloped viruses on copper. Consequently, copper alloy surfaces could be employed in communal areas and at any mass gatherings to help reduce transmission of respiratory viruses from contaminated surfaces and protect the public health.", "title": "Human Coronavirus 229E Remains Infectious on Common Touch Surface Materials", "pid": "4d4l6mzl", "bm25_score": 216.74476623535156}, {"text": "A new coronavirus (SARS-CoV-2) emerged in the winter of 2019 in Wuhan, China, and rapidly spread around the world. The extent and efficiency of SARS-CoV-2 pandemic is far greater than previous coronaviruses that emerged in the 21st Century. Here, we modeled stability of SARS-CoV-2 on skin, paper currency, and clothing to determine if these surfaces may factor in the fomite transmission dynamics of SARS-CoV-2. Skin, currency, and clothing samples were exposed to SARS-CoV-2 under laboratory conditions and incubated at three different temperatures (4C, 22C, and 37C). Stability was evaluated at 0 hours (h), 4 h, 8 h, 24 h, 72 h, 96 h, 7 days, and 14 days post-exposure. SARS-CoV-2 was shown to be stable on skin through the duration of the experiment at 4C (14 days). Virus remained stable on skin for at least 96 h at 22C and for at least 8h at 37C. There were minimal differences between the tested currency samples. The virus remained stable on the $1 U.S.A. Bank Note for at least 96 h at 4C while viable virus was not detected on the $20 U.S.A. Bank Note samples beyond 72 h. The virus remained stable on both Bank Notes for at least 8 h at 22C and 4 h at 37C. Clothing samples were similar in stability to the currency with the virus being detected for at least 96 h at 4C and at least 4 h at 22C. No viable virus was detected on clothing samples at 37C after initial exposure. This study confirms the inverse relationship between virus stability and temperature. Furthermore, virus stability on skin demonstrates the need for continued hand hygiene practices to minimize fomite transmission both in the general population as well as workplaces where close contact is common.", "title": "Modeling the Stability of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on Skin, Currency, and Clothing", "pid": "ywusapij", "bm25_score": 216.68890380859375}, {"text": "The WHO has declared COVID-19 illness a global health concern which is caused by 2019-nCoV, causing severe respiratory tract infections in humans. Transmissibility among individual to individual have been reported through droplets and probably also via contaminated surfaces and hands. Human coronaviruses can persist on inanimate surfaces such as plastic, glass, fibers and metals up to nine days. 2019-nCoV remains infectious in air for 3 h and on inanimate surfaces such as cardboard, copper, plastic and steel up to 24, 4, 72 and 48 h respectively. Disinfectant activity of various biocidal agents against coronaviruses like ethanol (62–71%), sodium hypochlorite (0.1%) and hydrogen peroxide (0.5%) can be regarded effective against 2019-nCoV as well. As no vaccine and antiviral therapies have been discovered for 2019-nCoV, prevention of further spread will viable option to control the ongoing and future outbreaks.", "title": "Inanimate surfaces as potential source of 2019-nCoV spread and their disinfection with biocidal agents", "pid": "esvutpel", "bm25_score": 216.6571044921875}, {"text": "The disinfection of high-contact surfaces is seen as an infection control practice to prevent the spread of pathogens by fomites. Unfortunately, recontamination of these surfaces can occur any time after the use of common disinfectants. We recently reported on a novel continuously active antimicrobial coating which was shown to reduce the spread of healthcare acquired infections in hospitals. We evaluated a modified coating that demonstrated a residual efficacy against viruses. The coated surfaces were found to be effective against human coronavirus (HCoV) 229E, reducing the concentration of these viruses by greater than 90% in 10 minutes and by greater than 99.9% after two hours of contact. The coating formulation when tested in suspension yielded a greater than 99.99% reduction of HCoV 229E within ten minutes of contact. This outcome presents an opportunity for controlling the transmission of COVID-19 from contaminated fomites.", "title": "A Continuously Active Antimicrobial Coating effective against Human Coronavirus 229E", "pid": "itm0bldp", "bm25_score": 216.6314239501953}, {"text": "Frequently touched surfaces of a university classroom that is cleaned daily contained viable human coronavirus 229E (CoV-229E). Tests of a CoV-229E laboratory strain under conditions that simulated the ambient light, temperature, and relative humidity conditions of the classroom revealed that some of the virus remained viable on various surfaces for 7 days, suggesting CoV-229E is relatively stable in the environment. Our findings reinforce the notion that contact transmission may be possible for this virus.", "title": "Isolation and identification of human coronavirus 229E from frequently touched environmental surfaces of a university classroom that is cleaned daily", "pid": "khpc9f98", "bm25_score": 216.59188842773438}, {"text": "Abstract The human coronavirus NL63 was identified in 2004 and subsequent studies showed its worldwide distribution. Infection with this pathogen is associated with upper and lower respiratory tract diseases of mild to moderate severity. Furthermore, HCoV-NL63 is the main cause of croup in children. Within this study an optimal protocol for freeze-drying that allows safe and effective preservation of HCoV-NL63 infectious material was developed. Lyophilized virus preparations can be stored either at ambient temperature or at +4°C. In the latter case samples may be stored for at least two months. Surprisingly, conducted analysis showed that HCoV-NL63 virions are exquisitely stable in liquid media and can be stored also without preservatives at ambient temperature for up to 14 days.", "title": "Stability of infectious human coronavirus NL63", "pid": "qoi00ydx", "bm25_score": 216.52926635742188}, {"text": "Assessment of the risks posed by severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) on surfaces requires data on survival of this virus on environmental surfaces and on how survival is affected by environmental variables, such as air temperature (AT) and relative humidity (RH). The use of surrogate viruses has the potential to overcome the challenges of working with SARS-CoV and to increase the available data on coronavirus survival on surfaces. Two potential surrogates were evaluated in this study; transmissible gastroenteritis virus (TGEV) and mouse hepatitis virus (MHV) were used to determine effects of AT and RH on the survival of coronaviruses on stainless steel. At 4 degrees C, infectious virus persisted for as long as 28 days, and the lowest level of inactivation occurred at 20% RH. Inactivation was more rapid at 20 degrees C than at 4 degrees C at all humidity levels; the viruses persisted for 5 to 28 days, and the slowest inactivation occurred at low RH. Both viruses were inactivated more rapidly at 40 degrees C than at 20 degrees C. The relationship between inactivation and RH was not monotonic, and there was greater survival or a greater protective effect at low RH (20%) and high RH (80%) than at moderate RH (50%). There was also evidence of an interaction between AT and RH. The results show that when high numbers of viruses are deposited, TGEV and MHV may survive for days on surfaces at ATs and RHs typical of indoor environments. TGEV and MHV could serve as conservative surrogates for modeling exposure, the risk of transmission, and control measures for pathogenic enveloped viruses, such as SARS-CoV and influenza virus, on health care surfaces.", "title": "Effects of air temperature and relative humidity on coronavirus survival on surfaces.", "pid": "tjplc5j6", "bm25_score": 216.48802185058594}, {"text": "The SARS-coronavirus (SARS-CoV) is a newly emerged, highly pathogenic agent that caused over 8,000 human infections with nearly 800 deaths between November 2002 and September 2003. While direct person-to-person transmission via respiratory droplets accounted for most cases, other modes have not been ruled out. Faecal shedding is common and prolonged and has caused an outbreak in Hong Kong. We studied the stability of SARS-CoV under different conditions, both in suspension and dried on surfaces, in comparison with other human-pathogenic viruses, including human coronavirus HCoV-229E. In suspension, HCoV-229E gradually lost its infectivity completely while SARS-CoV retained its infectivity for up to 9 days; in the dried state, survival times were 24 h versus 6 days. Thermal inactivation at 56°C was highly effective in the absence of protein, reducing the virus titre to below detectability; however, the addition of 20% protein exerted a protective effect resulting in residual infectivity. If protein-containing solutions are to be inactivated, heat treatment at 60°C for at least 30 min must be used. Different fixation procedures, e.g. for the preparation of immunofluorescence slides, as well as chemical means of virus inactivation commonly used in hospital and laboratory settings were generally found to be effective. Our investigations confirm that it is possible to care for SARS patients and to conduct laboratory scientific studies on SARS-CoV safely. Nevertheless, the agent’s tenacity is considerably higher than that of HCoV-229E, and should SARS re-emerge, increased efforts need to be devoted to questions of environmental hygiene.", "title": "Stability and inactivation of SARS coronavirus", "pid": "8s9671zf", "bm25_score": 216.45449829101562}, {"text": "The spread of COVID-19 in healthcare settings is concerning, with healthcare workers representing a disproportionately high percentage of confirmed cases. Although SARS-CoV-2 virus has been found to persist on surfaces for a number of days, the extent and duration of fomites as a mode of transmission, particularly in healthcare settings, has not been fully characterized. To shed light on this critical matter, the present study provides the first comprehensive assessment of SARS-CoV-2 stability on experimentally contaminated personal protective equipment (PPE) widely used by healthcare workers and the general public. Persistence of viable virus was monitored over 21 days on eight different materials, including nitrile medical examination gloves, reinforced chemical resistant gloves, N-95 and N-100 particulate respirator masks, Tyvek, plastic, cotton, and stainless steel. Unlike previous reports, viable SARS-CoV-2 in the presence of a soil load persisted for up to 21 days on experimentally inoculated PPE, including materials from filtering facepiece respirators (N-95 and N-100 masks) and a plastic visor. Conversely, when applied to 100% cotton fabric, the virus underwent rapid degradation and became undetectable in less than 24 hours. These findings underline the importance of appropriate handling of contaminated PPE during and following use in high-risk settings and provide interesting insight into the potential utility of cotton, including cotton masks, in limiting COVID-19 transmission.", "title": "Stability of SARS-CoV-2 on Critical Personal Protective Equipment", "pid": "qpc4hyvl", "bm25_score": 216.24285888671875}, {"text": "The advent of severe acute respiratory syndrome and its potential environmental transmission indicates the need for more information on the survival of coronavirus in water and wastewater. The survival of representative coronaviruses, feline infectious peritonitis virus, and human coronavirus 229E was determined in filtered and unfiltered tap water (4 and 23°C) and wastewater (23°C). This was compared to poliovirus 1 under the same test conditions. Inactivation of coronaviruses in the test water was highly dependent on temperature, level of organic matter, and presence of antagonistic bacteria. The time required for the virus titer to decrease 99.9% (T(99.9)) shows that in tap water, coronaviruses are inactivated faster in water at 23°C (10 days) than in water at 4°C (>100 days). Coronaviruses die off rapidly in wastewater, with T(99.9) values of between 2 and 4 days. Poliovirus survived longer than coronaviruses in all test waters, except the 4°C tap water.", "title": "Survival of Coronaviruses in Water and Wastewater", "pid": "0y8lfjkx", "bm25_score": 216.23782348632812}, {"text": "BACKGROUND: Inanimate surfaces have often been described as the source for outbreaks of nosocomial infections. The aim of this review is to summarize data on the persistence of different nosocomial pathogens on inanimate surfaces. METHODS: The literature was systematically reviewed in MedLine without language restrictions. In addition, cited articles in a report were assessed and standard textbooks on the topic were reviewed. All reports with experimental evidence on the duration of persistence of a nosocomial pathogen on any type of surface were included. RESULTS: Most gram-positive bacteria, such as Enterococcus spp. (including VRE), Staphylococcus aureus (including MRSA), or Streptococcus pyogenes, survive for months on dry surfaces. Many gram-negative species, such as Acinetobacter spp., Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, Serratia marcescens, or Shigella spp., can also survive for months. A few others, such as Bordetella pertussis, Haemophilus influenzae, Proteus vulgaris, or Vibrio cholerae, however, persist only for days. Mycobacteria, including Mycobacterium tuberculosis, and spore-forming bacteria, including Clostridium difficile, can also survive for months on surfaces. Candida albicans as the most important nosocomial fungal pathogen can survive up to 4 months on surfaces. Persistence of other yeasts, such as Torulopsis glabrata, was described to be similar (5 months) or shorter (Candida parapsilosis, 14 days). Most viruses from the respiratory tract, such as corona, coxsackie, influenza, SARS or rhino virus, can persist on surfaces for a few days. Viruses from the gastrointestinal tract, such as astrovirus, HAV, polio- or rota virus, persist for approximately 2 months. Blood-borne viruses, such as HBV or HIV, can persist for more than one week. Herpes viruses, such as CMV or HSV type 1 and 2, have been shown to persist from only a few hours up to 7 days. CONCLUSION: The most common nosocomial pathogens may well survive or persist on surfaces for months and can thereby be a continuous source of transmission if no regular preventive surface disinfection is performed.", "title": "How long do nosocomial pathogens persist on inanimate surfaces? A systematic review", "pid": "90qq0xsw", "bm25_score": 216.1473846435547}, {"text": "We found that environmental conditions affect the stability of severe acute respiratory syndrome coronavirus 2 in nasal mucus and sputum. The virus is more stable at low-temperature and low-humidity conditions, whereas warmer temperature and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.", "title": "Effect of Environmental Conditions on SARS-CoV-2 Stability in Human Nasal Mucus and Sputum.", "pid": "4819g00y", "bm25_score": 216.13050842285156}, {"text": "The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 °C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "title": "Making waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health", "pid": "vuzf3dnr", "bm25_score": 216.1131134033203}, {"text": "The main route of transmission of the human coronaviruses (HCoVs), and presumably also of the new pandemic SARS-CoV-2, is via droplets and close contacts, however their fecal elimination also suggests the possible spread via water. A scientific literature search was thus carried out to highlight the current state of the art and knowledge gaps regarding coronavirus in water. Since 1978 only 22 studies have met the inclusion criteria, and considered heterogeneous purposes, detection methods and types of water. In vitro experiments have addressed the recovery efficiency of analytical methods, survival in different types of water and the removal efficiency of water treatments. Field studies have monitored coronaviruses in surface waters, sewage, slurry, and biosolids. Overall, at the lab scale, HCoVs or surrogates can survive for several days at 4 °C, however their persistence is lower compared with non-enveloped viruses and is strongly influenced by temperature and organic or microbial pollution. HCoVs have rarely been detected in field investigations, however may be due to the low recovery efficiency of the analytical methods. The scarcity of information on HCoV in the environment suggests that research is needed to understand the fate of these viruses in the water cycle.", "title": "Making Waves: Coronavirus detection, presence and persistence in the water environment: State of the art and knowledge needs for public health", "pid": "c17eijdt", "bm25_score": 216.1131134033203}, {"text": "The main route of transmission of SARS CoV infection is presumed to be respiratory droplets. However the virus is also detectable in other body fluids and excreta. The stability of the virus at different temperatures and relative humidity on smooth surfaces were studied. The dried virus on smooth surfaces retained its viability for over 5 days at temperatures of 22–25°C and relative humidity of 40–50%, that is, typical air-conditioned environments. However, virus viability was rapidly lost (>3 log(10)) at higher temperatures and higher relative humidity (e.g., 38°C, and relative humidity of >95%). The better stability of SARS coronavirus at low temperature and low humidity environment may facilitate its transmission in community in subtropical area (such as Hong Kong) during the spring and in air-conditioned environments. It may also explain why some Asian countries in tropical area (such as Malaysia, Indonesia or Thailand) with high temperature and high relative humidity environment did not have major community outbreaks of SARS.", "title": "The Effects of Temperature and Relative Humidity on the Viability of the SARS Coronavirus", "pid": "x3b6j5d0", "bm25_score": 216.10855102539062}, {"text": "We investigated the ability of Luminore CopperTouch copper and copper-nickel surfaces to inactivate filoviruses and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). For this purpose, we compared viral titers in Vero cells from viral droplets exposed to copper surfaces for 30 min. The copper and copper-nickel surfaces inactivated 99.9% of the viral titer of both Ebola and Marburg viruses. The copper surfaces also inactivated 99% of SARS-CoV-2 titers in 2 hours to close to the limit of detection. These data add Ebolavirus, Marburgvirus, and SARS-CoV-2 (COVID-19) to the list of pathogens that can be inactivated by exposure to copper ions, validating Luminore CopperTouch technology (currently the only Environmental Protection Agency [EPA]-registered cold spray antimicrobial surface technology) as an efficacious, cost-friendly tool to improve infection control in hospitals, long-term care facilities, schools, hotels, buses, trains, airports, and other highly trafficked areas.", "title": "Luminore CopperTouch™ surface coating effectively inactivates SARS-CoV-2, Ebola and Marburg viruses in vitro", "pid": "v8rbfnhz", "bm25_score": 216.10302734375}, {"text": "We found that environmental conditions affect the stability of severe acute respiratory syndrome coronavirus 2 in nasal mucus and sputum. The virus is more stable at low-temperature and low-humidity conditions, whereas warmer temperature and higher humidity shortened half-life. Although infectious virus was undetectable after 48 hours, viral RNA remained detectable for 7 days.", "title": "Effect of Environmental Conditions on SARS-CoV-2 Stability in Human Nasal Mucus and Sputum", "pid": "04awj06g", "bm25_score": 216.0344696044922}, {"text": "Background. The primary modes of transmission of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) appear to be direct mucus membrane contact with infectious droplets and through exposure to formites. Knowledge of the survival characteristics of the virus is essential for formulating appropriate infection-control measures. Methods. Survival of SARS-CoV strain GVU6109 was studied in stool and respiratory specimens. Survival of the virus on different environmental surfaces, including a laboratory request form, an impervious disposable gown, and a cotton nondisposable gown, was investigated. The virucidal effects of sodium hypochlorite, house detergent, and a peroxygen compound (Virkon S; Antec International) on the virus were also studied. Results. SARS-CoV GVU6109 can survive for 4 days in diarrheal stool samples with an alkaline pH, and it can remain infectious in respiratory specimens for >7 days at room temperature. Even at a relatively high concentration (10(4) tissue culture infective doses/mL), the virus could not be recovered after drying of a paper request form, and its infectivity was shown to last longer on the disposable gown than on the cotton gown. All disinfectants tested were shown to be able to reduce the virus load by >3 log within 5 min. Conclusions. Fecal and respiratory samples can remain infectious for a long period of time at room temperature. The risk of infection via contact with droplet-contaminated paper is small. Absorbent material, such as cotton, is preferred to nonabsorptive material for personal protective clothing for routine patient care where risk of large spillage is unlikely. The virus is easily inactivated by commonly used disinfectants.", "title": "Survival of Severe Acute Respiratory Syndrome Coronavirus", "pid": "h9gj814e", "bm25_score": 216.02459716796875}, {"text": "We evaluated the stability of Ebola virus on surfaces and in fluids under simulated environmental conditions for the climate of West Africa and for climate-controlled hospitals. This virus remains viable for a longer duration on surfaces in hospital conditions than in African conditions and in liquid than in dried blood.", "title": "Ebola Virus Stability on Surfaces and in Fluids in Simulated Outbreak Environments.", "pid": "0ywzv96f", "bm25_score": 216.00729370117188}, {"text": "We aerosolized severe acute respiratory syndrome coronavirus 2 and determined that its dynamic aerosol efficiency surpassed those of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome. Although we performed experiment only once across several laboratories, our findings suggest retained infectivity and virion integrity for up to 16 hours in respirable-sized aerosols.", "title": "Persistence of Severe Acute Respiratory Syndrome Coronavirus 2 in Aerosol Suspensions.", "pid": "jincu9xx", "bm25_score": 215.99224853515625}, {"text": "We spotted severe acute respiratory syndrome coronavirus 2 on polystyrene plastic, aluminum, and glass for 96 hours with and without bovine serum albumin (3 g/L). We observed a steady infectivity (<1 log10 drop) on plastic, a 3.5 log10 decrease on glass, and a 6 log10 drop on aluminum. The presence of proteins noticeably prolonged infectivity.", "title": "Prolonged Infectivity of SARS-CoV-2 in Fomites.", "pid": "vwmjf326", "bm25_score": 215.94387817382812}, {"text": "COVID-19 is the name of the disease supposedly manifested in December 2019 from Wuhan, because of virus named as SARS-CoV-2. Now this disease has spread to almost all other parts of the world. COVID-19 pandemic has various reasons for its dramatic worldwide increase. Here, we have studied Coronavirus sustainability on various surfaces. Various disinfectants and their roles are discussed from the available literature. The infection capabilities of SARS-CoV-1 and SARS-CoV-2 for different materials are discussed and finally studies infection decay for SARS-CoV-1 and SARS-CoV-2.", "title": "Sustainability of Coronavirus on different surfaces", "pid": "9fnpfncr", "bm25_score": 215.93820190429688}, {"text": "It is shown that the evaporation rate of a liquid sample containing the culture of coronavirus affects its survival on a substrate. Possible mechanisms of such influence can be due to the appearance of large, about 140 bar, non comprehensive capillary pressures and the associated dynamic forces during the movement of the evaporation front in a sample with the virus. A simulation of isothermal evaporation of a thin liquid sample based on the Stefan problem was performed. The comparison of simulation data and recent experiments on the coronavirus survival on various surfaces showed that the rate of isothermal evaporation of aqueous samples, which is higher for heat-conducting materials, correlates well with the lifetime of the coronavirus on these surfaces.", "title": "Isothermal evaporation rate of deposited liquid aerosols and the SARS-CoV-2 coronavirus survival", "pid": "80ev0j5a", "bm25_score": 215.87567138671875}, {"text": "We aerosolized severe acute respiratory syndrome coronavirus 2 and determined that its dynamic aerosol efficiency surpassed those of severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome. Although we performed experiment only once across several laboratories, our findings suggest retained infectivity and virion integrity for up to 16 hours in respirable-sized aerosols.", "title": "Persistence of Severe Acute Respiratory Syndrome Coronavirus 2 in Aerosol Suspensions", "pid": "34ayx062", "bm25_score": 215.85760498046875}, {"text": "The novel coronavirus respiratory syndrome (COVID-19) has now spread worldwide. The relative contribution of viral transmission via fomites is still unclear. SARS-CoV-2 has been shown to survive on inanimate surfaces for several days, yet the factors that determine its survival on surfaces are not well understood. Here we combine microscopy imaging with virus viability assays to study survival of three bacteriophages suggested as good models for human respiratory pathogens: the enveloped Phi6 (a surrogate for SARS-CoV-2), and the non-enveloped PhiX174 and MS2. We measured virus viability in human saliva microdroplets, SM buffer, and water following deposition on glass surfaces at various relative humidities (RH). Although saliva microdroplets dried out rapidly at all tested RH levels (unlike SM that remained hydrated at RH ≥ 57%), survival of all three viruses in dry saliva microdroplets was significantly higher than in water or SM. Thus, RH and hydration conditions are not sufficient to explain virus survival, indicating that the suspended medium, and association with saliva components in particular, likely affect physicochemical properties that determine virus survival. The observed high virus survival in dry saliva deposited on surfaces, under a wide range of RH levels, can have profound implications for human public health, specifically the COVID-19 pandemic.", "title": "Virus survival in evaporated saliva microdroplets deposited on inanimate surfaces", "pid": "atisrhas", "bm25_score": 215.82374572753906}, {"text": "", "title": "Respiratory mucus and persistence of virus on surfaces", "pid": "erf4fv59", "bm25_score": 215.78395080566406}, {"text": "SARS-CoV-2, the virus that causes the disease COVID-19, remains viable on solids for periods of up to one week, so one potential route for human infection is via exposure to an infectious dose from a solid. We have fabricated and tested a coating that is designed to reduce the longevity of SARS-CoV-2 on solids. The coating consists of cuprous oxide (Cu2O) particles bound with polyurethane. After one hour on coated glass or stainless steel, the viral titer was reduced by about 99.9% on average compared to the uncoated sample. An advantage of a polyurethane-based coating is that polyurethane is already used to coat a large number of everyday objects. Our coating adheres well to glass and stainless steel, as well as everyday items that people may fear to touch during a pandemic, such as a doorknob, a pen, and a credit card keypad button. The coating performs well in the cross-hatch durability test and remains intact and active after 13 days immersed in water, or after exposure to multiple cycles of exposure to virus and disinfection.", "title": "A Surface Coating that Rapidly Inactivates SARS-CoV-2.", "pid": "gxo13x70", "bm25_score": 215.7600860595703}, {"text": "The infection of healthcare workers during the 2013 -2016 Ebola outbreak raised concerns about fomite transmission. In the wake of the Coronavirus Disease 2019 (COVID-19) pandemic, investigations are ongoing to determine the role of fomites in coronavirus transmission as well. The bacteriophage Phi 6 has a phospholipid envelope and is commonly used in environmental studies as a surrogate for human enveloped viruses. The persistence of Phi 6 was evaluated as a surrogate for EBOV and coronaviruses on porous and nonporous hospital surfaces. Phi 6 was suspended in a body fluid simulant and inoculated onto 1 cm2 coupons of steel, plastic, and two fabric curtain types. The coupons were placed at two controlled absolute humidity (AH) levels; a low AH of 3.0 g/m3 and a high AH of 14.4 g/m3 Phi 6 declined at a slower rate on all materials under low AH conditions with a decay rate of 0.06 log10PFU/d to 0.11 log10PFU/d, as compared to the higher AH conditions with a decay rate of 0.65 log10PFU/h to 1.42 log10PFU/d. There was a significant difference in decay rates between porous and non-porous surfaces at both low AH (P < 0.0001) and high AH (P < 0.0001). Under these laboratory-simulated conditions, Phi 6 was found to be a conservative surrogate for EBOV under low AH conditions, in that it persisted longer than Ebola virus in similar AH conditions. Additionally, some coronaviruses persist longer than phi6 under similar conditions, therefore Phi6 may not be a suitable surrogate for coronaviruses.IMPORTANCE Understanding the persistence of enveloped viruses helps inform infection control practices and procedures in healthcare facilities and community settings. These data convey to public health investigators that enveloped viruses can persist and remain infective on surfaces, thus demonstrating a potential risk for transmission. Under these laboratory-simulated western indoor hospital conditions, Phi 6 was used to assess suitability as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses.", "title": "Persistence of Bacteriophage Phi 6 on Porous and Non-Porous Surfaces; Potential for use as Ebola or Coronavirus Surrogate", "pid": "a27luzwj", "bm25_score": 215.7528839111328}, {"text": "Abstract COVID-19 is the name of the disease supposedly manifested in December 2019 from Wuhan, because of virus named as SARS-CoV-2. Now this disease has spread to almost all other parts of the world. COVID-19 pandemic has various reasons for its dramatic worldwide increase. Here, we have studied Coronavirus sustainability on various surfaces. Various disinfectants and their roles are discussed from the available literature. The infection capabilities of SARS-CoV-1 and SARS-CoV-2 for different materials are discussed and finally studies infection decay for SARS-CoV-1 and SARS-CoV-2.", "title": "Sustainability of Coronavirus on different surfaces", "pid": "f7gr98eb", "bm25_score": 215.75201416015625}, {"text": "Abstract In this study, the persistence of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) was observed in feces, urine and water. In addition, the inactivation of SARS-CoV in wastewater with sodium hypochlorite and chlorine dioxide was also studied. In vitro experiments demonstrated that the virus could only persist for 2 days in hospital wastewater, domestic sewage and dechlorinated tap water, while 3 days in feces, 14 days in PBS and 17 days in urine at 20°C. However, at 4°C, the SARS-CoV could persist for 14 days in wastewater and at least 17 days in feces or urine. SARS-CoV is more susceptible to disinfectants than Escherichia coli and f2 phage. Free chlorine was found to inactivate SARS-CoV better than chlorine dioxide. Free residue chlorine over 0.5mg/L for chlorine or 2.19mg/L for chlorine dioxide in wastewater ensures complete inactivation of SARS-CoV while it does not inactivate completely E. coli and f2 phage.", "title": "Study on the resistance of severe acute respiratory syndrome-associated coronavirus", "pid": "gwaqh4dd", "bm25_score": 215.7333221435547}, {"text": "We spotted severe acute respiratory syndrome coronavirus 2 on polystyrene plastic, aluminum, and glass for 96 hours with and without bovine serum albumin (3 g/L). We observed a steady infectivity (<1 log10 drop) on plastic, a 3.5 log10 decrease on glass, and a 6 log10 drop on aluminum. The presence of proteins noticeably prolonged infectivity.", "title": "Prolonged Infectivity of SARS-CoV-2 in Fomites", "pid": "3mcvp0h6", "bm25_score": 215.71556091308594}, {"text": "", "title": "Stability of human metapneumovirus and human coronavirus NL63 on medical instruments and in the patient environment", "pid": "8ydsyuer", "bm25_score": 215.68894958496094}, {"text": "", "title": "Environmental survival and microbicide inactivation of coronaviruses", "pid": "d4thas7e", "bm25_score": 215.62240600585938}, {"text": "Although the unprecedented efforts the world has been taking to control the spread of the human coronavirus disease (COVID‐19) and its causative aetiology [severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)], the number of confirmed cases has been increasing drastically. Therefore, there is an urgent need for devising more efficient preventive measures, to limit the spread of the infection until an effective treatment or vaccine is available. The preventive measures depend mainly on the understanding of the transmission routes of this virus, its environmental stability, and its persistence on common touch surfaces. Due to the very limited knowledge about SARS‐CoV‐2, we can speculate its stability in the light of previous studies conducted on other human and animal coronaviruses. In this review, we present the available data on the stability of coronaviruses (CoVs), including SARS‐CoV‐2, from previous reports to help understand its environmental survival. According to available data, possible airborne transmission of SARS‐CoV‐2 has been suggested. SARS‐CoV‐2 and other human and animal CoVs have remarkably short persistence on copper, latex and surfaces with low porosity as compared to other surfaces like stainless steel, plastics, glass and highly porous fabrics. It has also been reported that SARS‐CoV‐2 is associated with diarrhoea and that it is shed in the faeces of COVID‐19 patients. Some CoVs show persistence in human excrement, sewage and waters for a few days. These findings suggest a possible risk of faecal–oral, foodborne and waterborne transmission of SARS‐CoV‐2 in developing countries that often use sewage‐polluted waters in irrigation and have poor water treatment systems. CoVs survive longer in the environment at lower temperatures and lower relative humidity. It has been suggested that large numbers of COVID‐19 cases are associated with cold and dry climates in temperate regions of the world and that seasonality of the virus spread is suspected.", "title": "Stability of SARS‐CoV‐2 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: A review", "pid": "rhfwbyav", "bm25_score": 215.60421752929688}, {"text": "The infection of healthcare workers during the 2013 -2016 Ebola outbreak raised concerns about fomite transmission. In the wake of the Coronavirus Disease 2019 (COVID-19) pandemic, investigations are ongoing to determine the role of fomites in coronavirus transmission as well. The bacteriophage Phi 6 has a phospholipid envelope and is commonly used in environmental studies as a surrogate for human enveloped viruses. The persistence of Phi 6 was evaluated as a surrogate for EBOV and coronaviruses on porous and nonporous hospital surfaces. Phi 6 was suspended in a body fluid simulant and inoculated onto 1 cm2 coupons of steel, plastic, and two fabric curtain types. The coupons were placed at two controlled absolute humidity (AH) levels; a low AH of 3.0 g/m3 and a high AH of 14.4 g/m3 Phi 6 declined at a slower rate on all materials under low AH conditions with a decay rate of 0.06 log10PFU/d to 0.11 log10PFU/d, as compared to the higher AH conditions with a decay rate of 0.65 log10PFU/h to 1.42 log10PFU/d. There was a significant difference in decay rates between porous and non-porous surfaces at both low AH (P < 0.0001) and high AH (P < 0.0001). Under these laboratory-simulated conditions, Phi 6 was found to be a conservative surrogate for EBOV under low AH conditions, in that it persisted longer than Ebola virus in similar AH conditions. Additionally, some coronaviruses persist longer than phi6 under similar conditions, therefore Phi6 may not be a suitable surrogate for coronaviruses.IMPORTANCE Understanding the persistence of enveloped viruses helps inform infection control practices and procedures in healthcare facilities and community settings. These data convey to public health investigators that enveloped viruses can persist and remain infective on surfaces, thus demonstrating a potential risk for transmission. Under these laboratory-simulated western indoor hospital conditions, Phi 6 was used to assess suitability as a surrogate for environmental persistence research related to enveloped viruses, including EBOV and coronaviruses.", "title": "Persistence of Bacteriophage Phi 6 on Porous and Non-Porous Surfaces; Potential for use as Ebola or Coronavirus Surrogate.", "pid": "bgodmbru", "bm25_score": 215.60121154785156}, {"text": "Although the unprecedented efforts the world has been taking to control the spread of the human coronavirus disease (COVID-19) and its causative etiology [Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2)], the number of confirmed cases has been increasing drastically. Therefore, there is an urgent need for devising more efficient preventive measures, to limit the spread of the infection until an effective treatment or vaccine is available. The preventive measures depend mainly on the understanding of the transmission routes of this virus, its environmental stability, and its persistence on common touch surfaces. Due to the very limited knowledge about SARS-CoV-2, we can speculate its stability in the light of previous studies conducted on other human and animal coronaviruses. In this review, we present the available data on the stability of coronaviruses (CoVs), including SARS-CoV-2, from previous reports to help understand its environmental survival. According to available data, possible airborne transmission of SARS-CoV-2 has been suggested. SARS-CoV-2 and other human and animal CoVs have remarkably short persistence on copper, latex, and surfaces with low porosity as compared to other surfaces like stainless steel, plastics, glass, and highly porous fabrics. It has also been reported that SARS-CoV-2 is associated with diarrhea and that it is shed in the feces of COVID-19 patients. Some CoVs show persistence in human excrement, sewage, and waters for a few days. These findings suggest a possible risk of fecal-oral, foodborne, and waterborne transmission of SARS-CoV-2 in developing countries that often use sewage-polluted waters in irrigation and have poor water treatment systems. CoVs survive longer in the environment at lower temperatures and lower relative humidity. It has been suggested that large numbers of COVID-19 cases are associated with cold and dry climates in temperate regions of the world and that seasonality of the virus spread is suspected.", "title": "Stability of SARS-CoV-2 and other coronaviruses in the environment and on common touch surfaces and the influence of climatic conditions: a review", "pid": "z4vfjlbg", "bm25_score": 215.56553649902344}, {"text": "", "title": "[Study on the stability of SARS coronavirus].", "pid": "y3bj4e4d", "bm25_score": 215.5235595703125}, {"text": "In addition to enteric viruses of fecal origin, emerging zoonotic viruses such as respiratory coronaviruses and influenza viruses may potentially be transmitted via contaminated foods. The goal of this study was to determine the recovery efficiencies and the survival of two respiratory viruses, namely, adenovirus 2 (Ad2) and coronavirus 229E (CoV229E), on fresh produce in comparison to the enteric poliovirus 1 (PV1). Adenovirus was recovered with efficiencies of 56.5, 31.8, and 34.8 % from lettuce, strawberries, and raspberries, respectively. Coronavirus was recovered from lettuce with an efficiency of 19.6 % yet could not be recovered from strawberries. Poliovirus was recovered with efficiencies of 76.7 % from lettuce, but only 0.06 % from strawberries. For comparison purposes, the survival of Ad2, CoV229E, and PV1 was determined for periods up to 10 days on produce. The enteric PV1 survived better than both respiratory viruses on lettuce and strawberries, with only ≤1.03 log(10) reductions after 10 days of storage at 4 °C compared to CoV229E not being recovered after 4 days on lettuce and reductions of 1.97 log(10) and 2.38 log(10) of Ad2 on lettuce and strawberries, respectively, after 10 days. Nevertheless, these respiratory viruses were able to survive for at least several days on produce. There is therefore the potential for transfer to the hands and subsequently to the mucosa via rubbing the eyes or nose. In addition, some respiratory coronaviruses (e.g., severe acute respiratory syndrome coronavirus) and adenoviruses are also capable of replication in the gut and there is thus some potential for acquisition through the consumption of contaminated produce.", "title": "Survival of Respiratory Viruses on Fresh Produce", "pid": "7e8btgoo", "bm25_score": 215.43869018554688}, {"text": "BACKGROUND: Norovirus (NoV) transmission occurs mainly through food and fomites. Contaminated human fingers can transfer the virus to inanimate objects, which may then spread the virus to susceptible persons. However, no information is available on the survival of NoVs on fomites, which may be of importance in the transmission of NoVs in institutional settings such as hospitals and nursing homes. METHODS: In the absence of any in vitro cultivation system for NoVs, feline calicivirus (FCV) was used as a surrogate. Several fomites such as computer mouse, keyboard keys, telephone wire, telephone receiver, telephone buttons, and brass disks representing faucets and door handle surfaces were artificially contaminated with known amounts of FCV. Samples were taken at regular time intervals, and virus was titrated in feline kidney cells to determine its survival on these surfaces. RESULTS: Survivability of FCV varied with fomite type. The virus survived for up to 3 days on telephone buttons and receivers, for 1 or 2 days on computer mouse, and for 8 to 12 hours on keyboard keys and brass. The time for 90% virus reduction was <4 hours on computer keys, mouse, brass, and telephone wire; 4 to 8 hours on telephone receiver; and 12 to 24 hours on telephone buttons. CONCLUSION: The results of this study confirm that FCV (and perhaps NoV) can survive on fomites such as computers, telephones, and faucets and may be transmitted to humans using these contaminated materials. This may necessitate regular cleaning or disinfection of these items, especially in hospitals and nursing homes and after known outbreaks of NoVs.", "title": "Survival on uncommon fomites of feline calicivirus, a surrogate of noroviruses", "pid": "wiruhhyz", "bm25_score": 215.41876220703125}, {"text": "Coronavirus disease 2019 (COVID-19) was first identified in China in late 2019 and is caused by newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous studies had reported the stability of SARS-CoV-2 in cell culture media and deposited onto surfaces under a limited set of environmental conditions. Here, we broadly investigated the effects of relative humidity, temperature, and droplet size on the stability of SARS-CoV-2 in a simulated clinically relevant matrix dried on nonporous surfaces. The results show that SARS-CoV-2 decayed more rapidly when either humidity or temperature was increased but that droplet volume (1 to 50 µl) and surface type (stainless steel, plastic, or nitrile glove) did not significantly impact decay rate. At room temperature (24°C), virus half-life ranged from 6.3 to 18.6 h depending on the relative humidity but was reduced to 1.0 to 8.9 h when the temperature was increased to 35°C. These findings suggest that a potential for fomite transmission may persist for hours to days in indoor environments and have implications for assessment of the risk posed by surface contamination in indoor environments.IMPORTANCE Mitigating the transmission of SARS-CoV-2 in clinical settings and public spaces is critically important to reduce the number of COVID-19 cases while effective vaccines and therapeutics are under development. SARS-CoV-2 transmission is thought to primarily occur through direct person-to-person transfer of infectious respiratory droplets or through aerosol-generating medical procedures. However, contact with contaminated surfaces may also play a significant role. In this context, understanding the factors contributing to SARS-CoV-2 persistence on surfaces will enable a more accurate estimation of the risk of contact transmission and inform mitigation strategies. To this end, we have developed a simple mathematical model that can be used to estimate virus decay on nonporous surfaces under a range of conditions and which may be utilized operationally to identify indoor environments in which the virus is most persistent.", "title": "Increasing Temperature and Relative Humidity Accelerates Inactivation of SARS-CoV-2 on Surfaces", "pid": "e2paoo2m", "bm25_score": 215.3537139892578}, {"text": "Coronavirus disease 2019 (COVID-19) was first identified in China in late 2019 and is caused by newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Previous studies had reported the stability of SARS-CoV-2 in cell culture media and deposited onto surfaces under a limited set of environmental conditions. Here, we broadly investigated the effects of relative humidity, temperature, and droplet size on the stability of SARS-CoV-2 in a simulated clinically relevant matrix dried on nonporous surfaces. The results show that SARS-CoV-2 decayed more rapidly when either humidity or temperature was increased but that droplet volume (1 to 50 μl) and surface type (stainless steel, plastic, or nitrile glove) did not significantly impact decay rate. At room temperature (24°C), virus half-life ranged from 6.3 to 18.6 h depending on the relative humidity but was reduced to 1.0 to 8.9 h when the temperature was increased to 35°C. These findings suggest that a potential for fomite transmission may persist for hours to days in indoor environments and have implications for assessment of the risk posed by surface contamination in indoor environments. IMPORTANCE Mitigating the transmission of SARS-CoV-2 in clinical settings and public spaces is critically important to reduce the number of COVID-19 cases while effective vaccines and therapeutics are under development. SARS-CoV-2 transmission is thought to primarily occur through direct person-to-person transfer of infectious respiratory droplets or through aerosol-generating medical procedures. However, contact with contaminated surfaces may also play a significant role. In this context, understanding the factors contributing to SARS-CoV-2 persistence on surfaces will enable a more accurate estimation of the risk of contact transmission and inform mitigation strategies. To this end, we have developed a simple mathematical model that can be used to estimate virus decay on nonporous surfaces under a range of conditions and which may be utilized operationally to identify indoor environments in which the virus is most persistent.", "title": "Increasing Temperature and Relative Humidity Accelerates Inactivation of SARS-CoV-2 on Surfaces", "pid": "1vhprok9", "bm25_score": 215.3311309814453}, {"text": "Abstract Canine coronavirus (CCV) is a common faecal agent which is difficult to isolate. This study shows CCV to survive well at temperatures below −20°C but not at temperatures above 4°C. The presence of faecal material markedly reduced CCV survival times at temperatures ranging from 20°C to −70°C. Thus, it is suggested that diagnostic faecal material should be diluted 1:10 (w/v) with growth medium and examined at the earliest opportunity.", "title": "Studies on the survival of canine coronavirus under different environmental conditions", "pid": "fpckqvr5", "bm25_score": 215.31639099121094}, {"text": "Summary Viruses with pandemic potential including H1N1, H5N1, and H5N7 influenza viruses, and severe acute respiratory syndrome (SARS)/Middle East respiratory syndrome (MERS) coronaviruses (CoV) have emerged in recent years. SARS-CoV, MERS-CoV, and influenza virus can survive on surfaces for extended periods, sometimes up to months. Factors influencing the survival of these viruses on surfaces include: strain variation, titre, surface type, suspending medium, mode of deposition, temperature and relative humidity, and the method used to determine the viability of the virus. Environmental sampling has identified contamination in field-settings with SARS-CoV and influenza virus, although the frequent use of molecular detection methods may not necessarily represent the presence of viable virus. The importance of indirect contact transmission (involving contamination of inanimate surfaces) is uncertain compared with other transmission routes, principally direct contact transmission (independent of surface contamination), droplet, and airborne routes. However, influenza virus and SARS-CoV may be shed into the environment and be transferred from environmental surfaces to hands of patients and healthcare providers. Emerging data suggest that MERS-CoV also shares these properties. Once contaminated from the environment, hands can then initiate self-inoculation of mucous membranes of the nose, eyes or mouth. Mathematical and animal models, and intervention studies suggest that contact transmission is the most important route in some scenarios. Infection prevention and control implications include the need for hand hygiene and personal protective equipment to minimize self-contamination and to protect against inoculation of mucosal surfaces and the respiratory tract, and enhanced surface cleaning and disinfection in healthcare settings.", "title": "Transmission of SARS and MERS coronaviruses and influenza virus in healthcare settings: the possible role of dry surface contamination", "pid": "pk8u9m7h", "bm25_score": 215.3035430908203}, {"text": "BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20∼25oC). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.", "title": "Factors affecting stability and infectivity of SARS-CoV-2", "pid": "eke4f5fn", "bm25_score": 215.30345153808594}, {"text": "BACKGROUND: In late 2019, a novel human coronavirus, SARS-CoV-2, emerged in Wuhan, China. This virus has caused a global pandemic involving more than 200 countries. SARS-CoV-2 is highly adapted to humans and readily transmits from person-to-person. AIM: The aim of this study was to investigate the infectivity of SARS-CoV-2 under various environmental factors, disinfectants and different pH conditions. The efficacy of a variety of laboratory virus inactivation methods and home disinfectants against SARS-CoV-2 were investigated. METHODS: The residual virus in dried form or in solution was titrated on Vero E6 cell line at day 0, 1, 3, 5, and 7 after incubation at different temperatures. The viability of virus was determined after treatment with different disinfectants and pH solutions at room temperature (20∼25(o)C). FINDINGS: SARS-CoV-2 was able to retain viability for 3-5 days in dried form or 7 days in solution at room temperature. SARS-CoV-2 could be detected under a wide range of pH conditions from pH4 to pH11 for several days and 1 to 2 days in stool at room temperature but lost 5 logs of infectivity. A variety of commonly used disinfectants and laboratory inactivation procedures were found to reduce viral viability effectively. CONCLUSION: This study demonstrates the stability of SARS-CoV-2 on environmental surfaces and raises the possibility of faecal-oral transmission. Commonly used fixatives, nucleic acid extraction methods and heat inactivation were found to significantly reduce viral infectivity that could ensure hospital and laboratory safety during the COVID-19 pandemic.", "title": "Factors affecting stability and infectivity of SARS-CoV-2", "pid": "kngf6qpe", "bm25_score": 215.29437255859375}, {"text": "BACKGROUND: In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. METHODS: The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). RESULTS: After 1-minute contact time, for TGEV, there was a log(10) reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log(10) reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. CONCLUSION: Only ethanol reduced infectivity of the 2 coronaviruses by >3-log(10) after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus.", "title": "Inactivation of surrogate coronaviruses on hard surfaces by health care germicides", "pid": "yr1dq258", "bm25_score": 215.24301147460938}, {"text": "The distribution of human coronavirus strain 229E (HCV 229E) particles on the surface of human diploid (MRCc) cells was examined. Virus particles showed a totally random distribution on fixed cells and on cells to which virus had been adsorbed in the cold. A marked redistribution of virus particles was observed on warming virus-cell preparations to 33 degrees C for 20 min, the peripheral areas of the cell becoming relatively devoid of virus particles while the majority of particles were now located some distance from the edge of the cell. Redistribution did not occur in the presence of metabolic inhibitors.", "title": "The distribution of human coronavirus strain 229E on the surface of human diploid cells.", "pid": "crvehfnr", "bm25_score": 215.241943359375}, {"text": "Abstract An inactivation of airborne pathogenic Middle East Respiratory Syndrome (MERS-CoV) virus was investigated under controlled laboratory conditions. Two sets of climatic conditions were used in the experiments; (1) representing common office environment (25°C and 79% RH) and (2) climatic conditions of the Middle Eastern region where the virus was originated from (38°C and 24% RH). At the lower temperature, the virus demonstrated high robustness and strong capability to survive with about 63.5% of microorganisms remaining infectious 60min after aerosolisation. Fortunately, virus decay was much stronger for hot and dry air scenario with only 4.7% survival over 60min procedure.", "title": "Survival of aerosolized coronavirus in the ambient air", "pid": "3pd1lre7", "bm25_score": 215.22000122070312}, {"text": "Viral shedding lasted 31 and 19 days from symptom onset in two patients with east respiratory syndrome coronavirus (MERS-CoV) pneumonia, respectively. Environmental real-time RT-PCR was weakly positive for bed guardrail and monitors. Even after cleaning the monitors with 70% alcohol-based disinfectant, RT-PCR was still weakly positive, and converted to negative only after wiping with diluted sodium chlorite. Further studies are required to clarify the appropriate methods to clean environments during and after treatment of patients with MERS-CoV infection.", "title": "Viral Shedding and Environmental Cleaning in Middle East Respiratory Syndrome Coronavirus Infection", "pid": "x11dr866", "bm25_score": 215.20138549804688}, {"text": "[Image: see text] A systematic review and meta-analysis was conducted to identify decay rate constants (k) of human coronaviruses and their viral surrogates (i.e., animal coronaviruses and the enveloped bacteriophage Phi6) in water and wastewater and disinfection rates with exposure to free chlorine and germicidal ultraviolet light (UV(254)). Here, 73 k were identified, with only 12 for human coronaviruses, as opposed to animal coronaviruses or Phi6. In the absence of disinfectants, k increased with temperature. Between 22 and 25 °C, mean k for coronaviruses ranged from 0.19 ± 0.06 d(–1) in laboratory buffer (n = 4) to 2.9 ± 0.03 d(–1) in sterilized wastewater (n = 3), which are within the ranges observed for Phi6 and nonenveloped viruses. No free chlorine or UV(254) disinfection studies for coronaviruses were identified that met the systematic review inclusion criteria, although evidence from the literature suggests that coronaviruses would be inactivated if disinfectant doses recommended for nonenveloped viruses were applied. Three disinfection experiments were identified for Phi6. However, given different genome compositions and virion structures between coronaviruses and Phi6, it is not clear whether Phi6 should be used as a surrogate for evaluating free chlorine or UV(254)k. Therefore, there is a critical need for additional studies that specifically evaluate disinfection kinetics of coronaviruses in the aqueous environment.", "title": "Systematic Review and Meta-Analysis of the Persistence and Disinfection of Human Coronaviruses and Their Viral Surrogates in Water and Wastewater", "pid": "5ufgrlnq", "bm25_score": 215.201171875}, {"text": "", "title": "Coronavirus will spread as long as natural host is unknown, say scientists.", "pid": "itij3ect", "bm25_score": 215.04879760742188}, {"text": "Abstract Canine coronavirus (CCoV) is responsible for mild or moderate enteritis in puppies. The virus is highly contagious and avoiding contact with infected dogs and their excretions is the only way to ensure disease prevention. Since no studies have yet focused on the sensitivity of CCoV to chemical biocides the present investigation examined the efficiency of physical and chemical methods of viral inactivation. CCoV infectivity was stable at +56°C for up to 30min, but tended to decrease rapidly at +65°C and +75°C. Germicidal ultra-violet (UV–C) light exposure demonstrated no significant effects on virus inactivation for up to 3 days. CCoV was observed to be more stable at pH 6.0–6.5 while extreme acidic conditions inactivated the virus. Two tested aldehydes inactivated the virus but their action was temperature- and time-dependent. The methods for CCoV inactivation could be applied as animal models to study human coronavirus infection, reducing the risk of accidental exposure of researchers to pathogens during routine laboratory procedures.", "title": "Canine coronavirus inactivation with physical and chemical agents", "pid": "2j37561h", "bm25_score": 215.04774475097656}, {"text": "", "title": "Coronavirus survival on healthcare personal protective equipment.", "pid": "ixwdkqsz", "bm25_score": 215.04702758789062}, {"text": "The stability of Middle East respiratory syndrome coronavirus (MERS-CoV) was determined at 20°C--40% relative humidity (RH); 30°C--30% RH and 30°C--80% RH. MERS-CoV was more stable at low temperature/low humidity conditions and could still be recovered after 48 hours. During aerosolisation of MERS-CoV, no decrease in stability was observed at 20°C--40% RH. These data suggest the potential of MERS-CoV to be transmitted via contact or fomite transmission due to prolonged environmental presence.", "title": "Stability of Middle East respiratory syndrome coronavirus (MERS-CoV) under different environmental conditions.", "pid": "0wlapuuq", "bm25_score": 215.00808715820312}, {"text": "Previous studies have demonstrated that SARS-CoV-2 is stable on surfaces for extended periods under indoor conditions. In the present study, simulated sunlight rapidly inactivated SARS-CoV-2 suspended in either simulated saliva or culture media and dried on stainless steel coupons. Ninety percent of infectious virus was inactivated every 6.8 minutes in simulated saliva and every 14.3 minutes in culture media when exposed to simulated sunlight representative of the summer solstice at 40°N latitude at sea level on a clear day. Significant inactivation also occurred, albeit at a slower rate, under lower simulated sunlight levels. The present study provides the first evidence that sunlight may rapidly inactivate SARS-CoV-2 on surfaces, suggesting that persistence, and subsequently exposure risk, may vary significantly between indoor and outdoor environments. Additionally, these data indicate that natural sunlight may be effective as a disinfectant for contaminated nonporous materials.", "title": "Simulated Sunlight Rapidly Inactivates SARS-CoV-2 on Surfaces", "pid": "mixy6roy", "bm25_score": 214.99134826660156}, {"text": "We predict and analyze the drying time of respiratory droplets from a COVID-19 infected subject, which is a crucial time to infect another subject. Drying of the droplet is predicted by using a diffusion-limited evaporation model for a sessile droplet placed on a partially wetted surface with a pinned contact line. The variation in droplet volume, contact angle, ambient temperature, and humidity are considered. We analyze the chances of the survival of the virus present in the droplet based on the lifetime of the droplets under several conditions and find that the chances of the survival of the virus are strongly affected by each of these parameters. The magnitude of shear stress inside the droplet computed using the model is not large enough to obliterate the virus. We also explore the relationship between the drying time of a droplet and the growth rate of the spread of COVID-19 in five different cities and find that they are weakly correlated.", "title": "Likelihood of survival of coronavirus in a respiratory droplet deposited on a solid surface", "pid": "6vln3erl", "bm25_score": 214.98800659179688}, {"text": "", "title": "Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1", "pid": "mx1kfy4o", "bm25_score": 214.9295654296875}, {"text": "Coronavirus, which can cause respiratory syndrome, to date has affected over seventeen thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical compounds including histamine and protease; while late activation provokes the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus may be inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.", "title": "Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy.", "pid": "0lsniwyv", "bm25_score": 214.87936401367188}, {"text": "The pattern of shedding of feline coronavirus (FCoV) was established in 155 naturally infected pet cats from 29 households over periods of up to five years. Viral RNA was detected in faeces by reverse-transcriptase PCR (RT-PCR), and plasma antiviral antibodies by immunofluorescence. The cats rarely shed FCoV in their saliva. Three patterns of FCoV shedding were observed. Eighteen of the cats shed virus continuously, so were persistent, and possibly lifelong, carriers; none of them developed feline infectious peritonitis. Fifty-six cats ceased shedding virus, although they were susceptible to reinfection, and 44 shed intermittently or were being continuously reinfected. Four of the cats were resistant to infection. Seventy-three per cent of the virus shedding episodes lasted up to three months and 95 per cent up to nine months. There was a correlation between shedding and antibody titre but the cats could remain seropositive for some time after they had ceased shedding virus. One-off testing for FCoV by RT-PCR is inappropriate. Identification of longterm carriers requires that a positive result be obtained by RT-PCR on faecal samples for at least eight consecutive months. A cat should be shown to be negative over five months, or to have become seronegative, to ensure that it has ceased shedding virus.", "title": "Use of a reverse-transcriptase polymerase chain reaction for monitoring the shedding of feline coronavirus by healthy cats.", "pid": "418pxqvn", "bm25_score": 214.8662872314453}, {"text": "", "title": "Stability and Viability of SARS-CoV-2", "pid": "wyh7t6rr", "bm25_score": 214.82363891601562}, {"text": "Abstract Rhinovirus is the main cause of the common cold, which remains the most frequent infection worldwide among humans. Knowledge and understanding of the rhinovirus transmission route is important to reduce morbidity as only preventive measures are effective. In this study, we investigated the potential of rhinovirus to survive on fingers. Rhinovirus-B14 was deposited on fingers for 30, 60, 90 and 120 min. Survival was defined as the ability of the virus to grow after 7 days, confirmed by immunofluorescence. Rhinovirus survival was not dependent on incubation time on fingers. Droplet disruption had no influence on survival. Survival was frequent with high rhinovirus concentrations, but rare with low-concentration droplets, which corresponded to the usual rhinovirus concentrations in mucus observed in children and adults, respectively. Our study confirms that rhinovirus infectiousness is related to the viral concentration in droplets and suggests that children represent the main transmission source, which occurs only rarely via adults. It confirms also that rhinovirus hand-related transmission is possible and supports hand hygiene as a key prevention measure.", "title": "Survival of rhinoviruses on human fingers", "pid": "eby014gm", "bm25_score": 214.79307556152344}, {"text": "Recently, due to the coronavirus pandemic, many guidelines and anti-contagion strategies continue to report unclear information about the persistence of coronavirus disease 2019 (COVID-19) in the environment. This certainly generates insecurity and fear in people, with an important psychological component that is not to be underestimated at this stage of the pandemic. The purpose of this article is to highlight all the sources currently present in the literature concerning the persistence of the different coronaviruses in the environment as well as in medical and dental settings. As this was a current study, there are still not many sources in the literature, and scientific strategies are moving towards therapy and diagnosis, rather than knowing the characteristics of the virus. Such an article could be an aid to summarize virus features and formulate new guidelines and anti-spread strategies.", "title": "COVID-19 Surface Persistence: A Recent Data Summary and Its Importance for Medical and Dental Settings", "pid": "6fmuh2or", "bm25_score": 214.77830505371094}, {"text": "Coronavirus can cause respiratory syndrome which to date has affected about twelve thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical copounds including histamine and protease; while late activation provoke the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus maybe inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.", "title": "Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy", "pid": "tokrvi8i", "bm25_score": 214.7710418701172}, {"text": "", "title": "Persistence of infectious SARS-CoV-2 on inert surfaces and hand-mediated transmission.", "pid": "2vqxgfea", "bm25_score": 214.75506591796875}, {"text": "The stability of human coronavirus 229E infectivity was maximum at pH 6.0 when incubated at either 4 or 33 degrees C. However, the influence of pH was more pronounced at 33 degrees C. Viral infectivity was completely lost after a 14-day incubation period at 22, 33, or 37 degrees C but remained relatively constant at 4 degrees C for the same length of time. Finally, the infectious titer did not show any significant reduction when subjected to 25 cycles of thawing and freezing. These studies will contribute to optimize virus growth and storage conditions, which will facilitate the molecular characterization of this important pathogen.", "title": "Effect of pH and temperature on the infectivity of human coronavirus 229E.", "pid": "jpw8f2op", "bm25_score": 214.74478149414062}, {"text": "A persistent infection by human coronavirus 229E (HCV/229E) was established in a human continuous cell line (L132). Following the initial infection with stock HCV/229E, several cultures were established of which two (HV1 and HV4) have been maintained by continuous passage for two years. These cultures have shed high titres of infectious virus continuously into the supernatant fluid since their initiation. The persistently infected cells were resistant to homologous super-infection but supported polio virus replication to normal titres. Preliminary tests indicated that 50–100 percent of the cells contain virus. Neither interferon nor reverse transcriptase could be detected in these cultures and the presence of defective interfering particles could not be demonstrated. VH1 and VH4 coronaviruses, isolated from these persistently infected cultures (HV) and identified by 229E antiserum neutralization, were more cytocidal than the parent virus as judged by plaque characteristics and CPE however, they were indistinguishable on the basis of density, EM morphology, and genome size. Present evidence indicates that temperature plays an important but as yet undetermined role in the establishment and maintenance of stable 229E persistently infected cell cultures.", "title": "Establishment and maintenance of a persistent infection of L132 cells by human coronavirus strain 229E", "pid": "6id8rb35", "bm25_score": 214.73753356933594}, {"text": "", "title": "Stability and Viability of SARS-CoV-2.", "pid": "qufuh6yq", "bm25_score": 214.7250518798828}, {"text": "In the present study, we evaluated the viability of non-enveloped viruses, minute virus of mice (MVM) and coxsackievirus B4 (CVB4), and enveloped-viruses, influenza A virus (H1N1) and herpes simplex virus type 1 (HSV-1), on surfaces. We also investigated the impact of the initial concentration of proteins and sodium chloride on the persistence of infectious CVB4 on surfaces. Viral suspensions (>10(4.5) TCID(50)) were applied to petri dish lids and dried under the air flow of a biosafety cabinet. The recovered viral preparations were titered on appropriate cell lines. Enveloped viruses persisted for less than 5 days while CVB4 and MVM persisted for weeks. However, repetitive cycles of drying and resuspension had a stronger virucidal effect on CVB4 than on H1N1 and HSV-1. These repetitive cycles had no effect on the infectious titer of MVM. When exposed to drying, the initial concentrations of bovine serum albumin (from 0 to 90 mg mL(−1)), fetal calf serum (from 0 to 100%), and sodium chloride (from 0 to 300 mg mL(−1)) affected the viability of CVB4. CVB4 was more likely to be inactivated by drying in a protein-rich medium, whereas the impact of drying was reduced in the presence of sodium chloride. The results of the present study demonstrated that the resistance of viruses to drying, as suggested by iterative drying, was not due to the heterogeneity of viral subpopulations, but was influenced by media compositions and component concentrations, as illustrated in the model of CVB4.", "title": "Survival of Enveloped and Non-Enveloped Viruses on Inanimate Surfaces", "pid": "hrcffnpt", "bm25_score": 214.72264099121094}, {"text": "The Middle East Respiratory syndrome coronavirus (MERS-CoV) has been responsible for multiple health care–associated outbreaks. We investigated whether high-touch surfaces in 3 rooms of laboratory-confirmed MERS-CoV patients were contaminated with MERS-CoV RNA. We found 2 out of 51 surfaces were contaminated with MERS-CoV viral genetic material. Hence, environmental contamination may be a potential source of health care transmission and outbreaks. Meticulous environmental cleaning may be important in preventing transmission within the health care setting.", "title": "Middle East respiratory syndrome coronavirus on inanimate surfaces: A risk for health care transmission", "pid": "peqkcix2", "bm25_score": 214.71722412109375}, {"text": "Coronaviruses (CoV) are a large family of viruses causing a spectrum of disease ranging from the common cold to more severe diseases as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). The recent outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency worldwide. SARS-CoV-2, the virus responsible for COVID-19, is spread by human-to-human transmission via droplets or direct contact. However, since SARS-CoV-2 (as well as other coronaviruses) has been found in the fecal samples and anal swabs of some patients, the possibility of fecal-oral (including waterborne) transmission need to be investigated and clarified. This scoping review was conducted to summarize research data on CoV in water environments. A literature survey was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded more than 3000 records, but only 12 met the criteria and were included and discussed in this review. In detail, the review captured relevant studies investigating three main areas: 1) CoV persistence/survival in waters; 2) CoV occurrence in water environments; 3) methods for recovery of CoV from waters. The data available suggest that: i) CoV seems to have a low stability in the environment and is very sensitive to oxidants, like chlorine; ii) CoV appears to be inactivated significantly faster in water than non-enveloped human enteric viruses with known waterborne transmission; iii) temperature is an important factor influencing viral survival (the titer of infectious virus declines more rapidly at 23°C-25 °C than at 4 °C); iv) there is no current evidence that human coronaviruses are present in surface or ground waters or are transmitted through contaminated drinking-water; v) further research is needed to adapt to enveloped viruses the methods commonly used for sampling and concentration of enteric, non enveloped viruses from water environments. The evidence-based knowledge reported in this paper is useful to support risk analysis processes within the drinking and wastewater chain (i.e., water and sanitation safety planning) to protect human health from exposure to coronavirus through water.", "title": "Coronavirus in water environments: Occurrence, persistence and concentration methods - A scoping review", "pid": "hn9fj8h8", "bm25_score": 214.70413208007812}, {"text": "Human coronaviruses (CoVs) are increasingly recognized as important respiratory pathogens associated with a broad range of clinical diseases. We sought to increase the insight into clinically relevant CoV infections by monitoring antigen concentrations in six confirmed CoV-positive patients using a newly developed assay for rapid detection of CoV OC43 infections. Antigen positivity lasted 3 to 6 days in secondary infections and 13 days in primary infection. CoV infections are clinically diverse, are common, and cannot be diagnosed from clinical symptoms alone.", "title": "Rapid detection and monitoring of human coronavirus infections", "pid": "rl66trp0", "bm25_score": 214.66456604003906}, {"text": "Indirect transmission of porcine epidemic diarrhea virus (PEDV) ensues when susceptible animals contact PEDV-contaminated fomite materials. Although the survival of PEDV under various pHs and temperatures has been studied, virus stability on different fomite surfaces under varying temperature conditions has not been explored. Hence, we evaluated the survival of PEDV on inanimate objects routinely used on swine farms such as styrofoam, rubber, plastic, coveralls, and other equipment. The titer of infectious PEDV at 4 °C decreased by only 1 to 2 log during the first 5 days, and the virus was recoverable for up to 15 days on Styrofoam, aluminum, Tyvek(®) coverall, cloth, and plastic. However, viral titers decreased precipitously when stored at room temperature; no virus was detectable after one day on all materials tested. A more sensitive immunoplaque assay was able to detect virus from Styrofoam, metal, and plastic at 20 days post application, representing a 3-log loss of input virus on fomite materials. Recovery of infectious PEDV from Tyvek(®) coverall and rubber was above detection limit at 20 days. Our findings indicate that the type of fomite material and temperatures impact PEDV stability, which is important in understanding the nuances of indirect transmission and epidemiology of PEDV.", "title": "Stability of Porcine Epidemic Diarrhea Virus on Fomite Materials at Different Temperatures", "pid": "u2a26brw", "bm25_score": 214.66188049316406}, {"text": "OBJECTIVE To evaluate the effect of a disinfectant onto viruses in suspension on the one hand and applied onto a surface on the other. METHODS A system combining flocked swabs to recover viruses dried onto stainless steel carriers and gel filtration to eliminate cytotoxic products has been developed to study the virucidal effect of a quaternary ammonium-based disinfectant towards herpes simplex virus type 1 (HSV-1), coxsackievirus B4 (CVB4) and feline calicivirus F9 (FCV). The recovery of FCV has been estimated by RT real-time PCR. RESULTS HSV-1, CVB4 and FCV had a titer over 10(4) TCID50 · ml(-1) after 2 h drying and were recovered from the carriers using flocked swabs. HSV-1 was inactivated in suspension and on stainless steel carriers by the disinfectant (a reduction factor of 4 and 2.83 log, respectively) whereas CVB4 was resistant. The reduction of infectious titer was moderate, 1.5 log in 30 min, when FCV was in suspension, whereas it was up to 4 log in 10 min when the virus was dried on a carrier. Dried FCV was efficiently recovered from carriers as demonstrated by RT real-time PCR. CONCLUSION A non-enveloped virus, FCV, applied on a surface, but not in suspension, was inactivated by a quaternary ammonium-based disinfectant. The resistance of viruses applied onto a surface to the effect of disinfectants should be investigated further.", "title": "Inactivation of coxsackievirus B4, feline calicivirus and herpes simplex virus type 1: unexpected virucidal effect of a disinfectant on a non-enveloped virus applied onto a surface.", "pid": "4kf47ors", "bm25_score": 214.65884399414062}, {"text": "How long do viruses like cold, flu and coronavirus survive outside the body? What factors affect this? Douglas Fairchild, Two Harbors, Minnesota, US", "title": "Viral survival", "pid": "hgau3922", "bm25_score": 214.63941955566406}, {"text": "", "title": "Temperature-dependent surface stability of SARS-CoV-2.", "pid": "8pv1g1m0", "bm25_score": 214.63121032714844}, {"text": "Abstract Coronaviruses (CoV) are a large family of viruses causing a spectrum of disease ranging from the common cold to more severe diseases as Middle East Respiratory Syndrome (MERS-CoV) and Severe Acute Respiratory Syndrome (SARS-CoV). The recent outbreak of coronavirus disease 2019 (COVID-19) has become a public health emergency worldwide. SARS-CoV-2, the virus responsible for COVID-19, is spread by human-to-human transmission via droplets or direct contact. However, since SARS-CoV-2 (as well as other coronaviruses) has been found in the fecal samples and anal swabs of some patients, the possibility of fecal-oral (including waterborne) transmission need to be investigated and clarified. This scoping review was conducted to summarize research data on CoV in water environments. A literature survey was conducted using the electronic databases PubMed, EMBASE, and Web Science Core Collection. This comprehensive research yielded more than 3000 records, but only 12 met the criteria and were included and discussed in this review. In detail, the review captured relevant studies investigating three main areas: 1) CoV persistence/survival in waters; 2) CoV occurrence in water environments; 3) methods for recovery of CoV from waters. The data available suggest that: i) CoV seems to have a low stability in the environment and is very sensitive to oxidants, like chlorine; ii) CoV appears to be inactivated significantly faster in water than non-enveloped human enteric viruses with known waterborne transmission; iii) temperature is an important factor influencing viral survival (the titer of infectious virus declines more rapidly at 23°C–25 °C than at 4 °C); iv) there is no current evidence that human coronaviruses are present in surface or ground waters or are transmitted through contaminated drinking-water; v) further research is needed to adapt to enveloped viruses the methods commonly used for sampling and concentration of enteric, non enveloped viruses from water environments. The evidence-based knowledge reported in this paper is useful to support risk analysis processes within the drinking and wastewater chain (i.e., water and sanitation safety planning) to protect human health from exposure to coronavirus through water.", "title": "Coronavirus in water environments: Occurrence, persistence and concentration methods - A scoping review", "pid": "eyf2dogw", "bm25_score": 214.62771606445312}, {"text": "Low and high passaged cell culture strains of TGE coronavirus were examined for stability in gastric and small intestine juices collected in 3-6 month-old pigs killed at different times after last feeding. Results revealed high fragility of the TGE virus in these digestive liquids. Differences in stability were observed between strains of TGE virus. But no correlation could be made between the level of stability and cell passage status of the virus strain. We conclude that the stability of TGE coronavirus in gastric and small intestine juices could not be considered as a genetic marker of virulence. In future, it will be necessary to take into account these data concerning fragility of TGE coronavirus for improvement of oral vaccination methods in pregnant sows using a live virus vaccine.", "title": "[Transmissible gastroenteritis of swine: stability of coronavirus in gastric and intestinal contents].", "pid": "9agr10pz", "bm25_score": 214.61412048339844}, {"text": "COVID-19 has become a pandemic and is spreading fast worldwide. The COVID-19 virus is transmitted mainly through respiratory droplets and close contact. However, the fecal-oral transmission of the virus has not been ruled out and it is important to ascertain how acidic condition in the stomach affects the infectivity of the virus. Besides, it is unclear how stable the COVID-19 virus is under dry and wet conditions. In the present study, we have shown that the COVID-19 virus is extremely infectious as manifested by the infection of Vero-E6 cells by one PFU (Plaque Forming Unit) of the virus. We then investigated the stability of the COVID-19 virus in wet, dry and acidic (pH2.2) environments at room temperature. Results showed that the COVID-19 virus could survive for three days in wet and dry environments, but the dry condition is less favorable for the survival of the virus. Our study also demonstrated that the COVID-19 virus at a relative high titer (1.2 x 103 PFU) exhibits a certain degree of tolerance to acidic environment at least for 60 minutes. When the virus titer was ≤1.0 x 103 PFU, acid treatment (pH2.2) for 30 or 60 minute resulted in virus inactivation. It suggests that the virus at a high concentration may survive in the acidic environment of the stomach. The finding of the present study will contribute to the control of the spread of the COVID-19 virus.", "title": "Stability of the COVID-19 virus under wet, dry and acidic conditions", "pid": "3cm44rbz", "bm25_score": 214.57923889160156}, {"text": "SARS-CoV-2, the causative agent of the COVID-19 pandemic, may be transmitted via airborne droplets or contact with surfaces onto which droplets have deposited. In this study, the ability of SARS-CoV-2 to survive in the dark, at two different relative humidity values and within artificial saliva, a clinically relevant matrix, was investigated. SARS-CoV-2 was found to be stable, in the dark, in a dynamic small particle aerosol under the four experimental conditions we tested and viable virus could still be detected after 90 minutes. The decay rate and half-life was determined and decay rates ranged from 0.4 to 2.27 % per minute and the half lives ranged from 30 to 177 minutes for the different conditions. This information can be used for advice and modelling and potential mitigation strategies.", "title": "Experimental aerosol survival of SARS-CoV-2 in artificial saliva and tissue culture media at medium and high humidity", "pid": "txc0k2vb", "bm25_score": 214.55592346191406}, {"text": "The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.", "title": "Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces()", "pid": "kxyd5uzp", "bm25_score": 214.5510711669922}, {"text": "In order to answer the question whether coronaviruses (CoVs) can be transmitted via foods, this review made a comparison between CoVs with the most recognized foodborne virus, human noroviruses (NoVs). As a result, although CoVs indeed have shown the possibilities to remain infectious on foods and/or food packaging materials long enough (from several days to several weeks) to potentially cause transmission, they seem to be less persistent than NoVs towards common disinfection practices with alcohols, chlorine and ultraviolet (UV). More importantly, the chance of foodborne transmission of CoVs is considered low as CoVs mainly spread through the respiratory tract and there is no clear evidence showing CoVs can follow fecal-oral routes like human NoVs and other foodborne viruses.", "title": "What makes a foodborne virus: comparison between coronaviruses with human noroviruses", "pid": "zybdv7ic", "bm25_score": 214.53573608398438}, {"text": "The Coronavirus disease 2019 (COVID-19) is spreading around the world, representing a global pandemic, counting, as of June 5th, 2020, over 6,600,000 confirmed cases and more than 390,000 deaths, with exponentially increasing numbers. In the first half of 2020, because of the widespread of the COVID-19, researches were focused on the monitoring of SARS-CoV-2 in water, wastewater, sludge, air, and on surfaces, in order to assess the risk of contracting the viral infection from contaminated environments. So far, the survival of the novel Coronavirus out of the human body has been reported for short time periods (from hours to few days, in optimized in vitro conditions), mainly because of the need of an host organism which could consent the viral attack, and due to the weak external membrane of the virus. SARS-CoV-2 viral shedding strategies in the environment, either through animate and unanimate matrices, or exploiting the organic matter in water, wastewater, and waste in general, have been discussed in the present article. We concluded that, besides the high infectuousness of the novel Coronavirus, the transmission of the pathogen may be efficiently contained applying the adequate preventive measures (e.g., personal protection equipments, and disinfecting agents), indicated by national and international health authories.", "title": "Persistence of SARS-CoV-2 in the environment and COVID-19 transmission risk from environmental matrices and surfaces", "pid": "b5lcv77o", "bm25_score": 214.5176544189453}, {"text": "Temperature and relative humidity are major factors determining virus inactivation in the environment. This article reviews inactivation data of coronaviruses on surfaces and in liquids from published studies and develops secondary models to predict coronaviruses inactivation as a function of temperature and relative humidity. A total of 102 D-values (time to obtain a log10 reduction of virus infectivity), including values for SARS-CoV-2, were collected from 26 published studies. The values obtained from the different coronaviruses and studies were found to be generally consistent. Five different models were fitted to the global dataset of D-values. The most appropriate model considered temperature and relative humidity. A spreadsheet predicting the inactivation of coronaviruses and the associated uncertainty is presented and can be used to predict virus inactivation for untested temperatures, time points or new coronavirus strains.", "title": "Modelling the thermal inactivation of viruses from the Coronaviridae family in suspensions or on surfaces with various relative humidities.", "pid": "4hbwg18z", "bm25_score": 214.48854064941406}, {"text": "The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 or 2019-nCoV) has quickly turned into a global pandemic. Infectious viruses had been isolated from oro- or naso-pharyngeal swabs, sputum and possibly stool samples of infected individuals. Handling these clinical specimens therefore poses a biosafety risk to both healthcare professionals and laboratory workers. In this study, we aimed to evaluate the stability of SARS-CoV-2 under different heat conditions and report that the virus is stable at 37 C for at least 24 hours. Heating at 56 C for 30 minutes, however, effectively inactivated the virus while preserved the stability of viral RNA in both human sera and sputum samples. These findings provide critical information regarding the biology of the virus as well as a practical way to inactivate infectious virus that is potentially found in clinical specimens.", "title": "Effective Heat Inactivation of SARS-CoV-2", "pid": "og69izi3", "bm25_score": 214.47987365722656}]}
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With more and more patients diagnosed, China has carried out more than 100 clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine, and other Western drugs, while Chinese medicine research accounted for half of the studies. Most of the trials were initiated by investigators and the study period would last for 1 to 11 months. The primary endpoints included symptom improvement and virus nucleic acid turning negative, but the optimal endpoint has not been determined. Although the final results of studies will take a long time to complete, the interim research data may provide some help for the current urgent demand for drug treatment. Compared with that of during SARS period in 2003, China has the stronger capability to carry out clinical trials of new drugs in emergency period.", "title": "Clinical trial analysis of 2019-nCoV therapy registered in China", "pid": "g7rjtlht", "bm25_score": 218.75048828125}, {"text": "Since the report of the first case of coronavirus disease 2019 (COVID-19) in China in late December 2019, there have been 204 610 cases worldwide as of 18 March, 2020. As part of the response to this outbreak, there has been an impressive amount of research undertaken to better characterize the disease and to evaluate therapeutic options. By March 12, 2020, there are more than 382 studies registered in the clinical trials databases addressing COVID-19 including more than 80 randomized controlled trials.", "title": "Clinical trials for coronavirus disease 2019: What is being evaluated and what is not", "pid": "jwrheaph", "bm25_score": 218.55667114257812}, {"text": "So far, there is a lack of effective drugs for the new coronavirus pneumonia. With more and more patients diagnosed, China has carried out more than 100 clinical studies of new coronavirus infection, including antiviral drugs, antimalarial drugs, glucocorticoids, plasma therapy, virus vaccine, and other Western drugs, while Chinese medicine research accounted for half of the studies. Most of the trials were initiated by investigators and the study period would last for 1 to 11 months. The primary endpoints included symptom improvement and virus nucleic acid turning negative, but the optimal endpoint has not been determined. Although the final results of studies will take a long time to complete, the interim research data may provide some help for the current urgent demand for drug treatment. Compared with that of during SARS period in 2003, China has the stronger capability to carry out clinical trials of new drugs in emergency period.", "title": "Clinical trial analysis of 2019‐nCoV therapy registered in China", "pid": "o8j17zzs", "bm25_score": 218.50831604003906}, {"text": "", "title": "More than 80 clinical trials launch to test coronavirus treatments.", "pid": "h10o18ss", "bm25_score": 218.21971130371094}, {"text": "", "title": "Coronavirus vaccine trials have delivered their first results - but their promise is still unclear", "pid": "np7for7b", "bm25_score": 218.19740295410156}, {"text": "", "title": "Coronavirus vaccine trials have delivered their first results - but their promise is still unclear.", "pid": "eanrbr0a", "bm25_score": 218.14764404296875}, {"text": "The World Health Organization (WHO) was informed on December 2019 about a coronavirus pneumonia outbreak in Wuhan, Hubei province (China). Subsequently, on March 12, 2020, 125,048 cases and 4,614 deaths were reported. Coronavirus is an enveloped RNA virus, from the genus Betacoronavirus, that is distributed in birds, humans, and other mammals. WHO has named the novel coronavirus disease as COVID-19. More than 80 clinical trials have been launched to test coronavirus treatment, including some drug repurposing or repositioning for COVID-19. Hence, we performed a search in March 2020 of the clinicaltrials.gov database. The eligibility criteria for the retrieved studies were: contain a clinicaltrials.gov base identifier number; describe the number of participants and the period for the study; describe the participants’ clinical conditions; and utilize interventions with medicines already studied or approved for any other disease in patients infected with the novel coronavirus SARS-CoV-2 (2019-nCoV). It is essential to emphasize that this article only captured trials listed in the clinicaltrials.gov database. We identified 24 clinical trials, involving more than 20 medicines, such as human immunoglobulin, interferons, chloroquine, hydroxychloroquine, arbidol, remdesivir, favipiravir, lopinavir, ritonavir, oseltamivir, methylprednisolone, bevacizumab, and traditional Chinese medicines (TCM). Although drug repurposing has some limitations, repositioning clinical trials may represent an attractive strategy because they facilitate the discovery of new classes of medicines; they have lower costs and take less time to reach the market; and there are existing pharmaceutical supply chains for formulation and distribution.", "title": "Clinical trials on drug repositioning for COVID-19 treatment", "pid": "vxqdfiel", "bm25_score": 218.1261444091797}, {"text": "Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.", "title": "Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "pid": "m95bmi9t", "bm25_score": 218.12315368652344}, {"text": "Since coronavirus disease 2019 (COVID-19) emerged in Wuhan, China in December 2019 and spread around the world, over 1100 clinical studies have been registered globally on clinical trials registries, including over 500 randomised controlled trials. Such rapid development and launch of clinical trials is impressive but presents challenges, including the potential for duplication and competition. There is currently no known effective treatment for COVID-19. In order to focus on those studies most likely to influence clinical practice, we summarise the 31 currently registered randomised trials with a target sample size of at least 1000 participants. We have grouped these trials into four categories: prophylaxis; treatment of outpatients with mild COVID-19; treatment of hospitalised patients with moderate COVID-19; and treatment of hospitalised patients with moderate or severe disease. The most common therapeutic agent being trialled currently is hydroxychloroquine (24 trials with potential sample size of over 25 000 participants), followed by lopinavir-ritonavir (seven trials) and remdesevir (five trials) There are many candidate drugs in pre-clinical and early phase development, and these form a pipeline for future large clinical trials if current candidate therapies prove ineffective or unsafe.", "title": "Clinical trials for the prevention and treatment of COVID-19: current state of play", "pid": "pftu5qea", "bm25_score": 217.976806640625}, {"text": "Here, we present an overview of the clinical trials that are currently being conducted or have concluded to date on COVID-19 globally. A comprehensive search was conducted to present 16 trial registries from around the world. Collectively, there are 1,528 trials reported for COVID-19 to date. Out of them, 50 studies included paediatric age group from day 0 to less than or equal to 18 years of age. A few 18 studies involve only females and 20 only males. There are 2 trials currently underway in Bangladesh, 4 in Pakistan and 13 in India. Overall, 940 trials are related to medicines and/or interventions. They include standard of care for any viral illness, antivirals, anti-inflammatory and immune altering medications. Two out of 10 vaccine trials are novel vaccines. It is knowledgeable and resourceful to reach out to the concerned sponsor if a physician thinks his patient can benefit from the trials in the region.", "title": "Comprehensive overview of COVID-19 clinical trials.", "pid": "fti60hts", "bm25_score": 217.92742919921875}, {"text": "The first rumblings about a new coronavirus spreading in China were heard in January 2020. By the end of that month, the World Health Organization, recognizing the severity of the disease and the potential for global spread, had declared a public health emergency. By February 2020, cases had been identified in multiple countries, clinical trials of treatments with some biological plausibility had begun in China, and the initial steps of vaccine development were underway. In mid-March, by which time countries around the world were experiencing rapidly increasing numbers of cases and deaths, the World Health Organization categorized the outbreak as a pandemic. This new coronavirus was designated SARS-COV-2 in recognition of its similarity to the coronavirus responsible for the severe acute respiratory syndrome outbreak in 2002-2003. The race is on to develop treatments that can mitigate the severe consequences of infection and vaccines that can prevent infection and/or diminish the severity of disease in those who do get infected. Many challenges face these development efforts. Some are similar to those faced in the past; others are new. The urgency of finding ways to treat, and ultimately prevent, the consequences of this new and potentially deadly infection has led to unprecedented focus on clinical trials.", "title": "Clinical trials in the time of a pandemic.", "pid": "mux7vu6z", "bm25_score": 217.92709350585938}, {"text": "The first rumblings about a new coronavirus spreading in China were heard in January 2020. By the end of that month, the World Health Organization, recognizing the severity of the disease and the potential for global spread, had declared a public health emergency. By February 2020, cases had been identified in multiple countries, clinical trials of treatments with some biological plausibility had begun in China, and the initial steps of vaccine development were underway. In mid-March, by which time countries around the world were experiencing rapidly increasing numbers of cases and deaths, the World Health Organization categorized the outbreak as a pandemic. This new coronavirus was designated SARS-COV-2 in recognition of its similarity to the coronavirus responsible for the severe acute respiratory syndrome outbreak in 2002-2003. The race is on to develop treatments that can mitigate the severe consequences of infection and vaccines that can prevent infection and/or diminish the severity of disease in those who do get infected. Many challenges face these development efforts. Some are similar to those faced in the past; others are new. The urgency of finding ways to treat, and ultimately prevent, the consequences of this new and potentially deadly infection has led to unprecedented focus on clinical trials.", "title": "Clinical trials in the time of a pandemic", "pid": "mr8s7ocn", "bm25_score": 217.8863525390625}, {"text": "During the recent global outbreak of severe acute respiratory syndrome (SARS), thousands of patients received treatments of uncertain efficacy and known toxicity such as ribavirin and corticosteroids. Despite this, no controlled clinical trials assessing the efficacy of these agents were conducted. If a second global SARS outbreak occurred, clinicians would not have controlled data on which to base therapeutic decisions. We discuss the unique methodologic and logistical challenges faced by researchers who attempt to conduct controlled trials of therapeutic agents during an outbreak of a novel or unknown infectious pathogen. We draw upon our own experience in attempting to conduct a randomized controlled trial (trial) of ribavirin therapy for SARS and discuss the lessons learned. Strategies to facilitate future clinical trials during outbreaks of unknown or novel pathogens are also presented.", "title": "Clinical Trials and Novel Pathogens: Lessons Learned from SARS", "pid": "g0iwfpkg", "bm25_score": 217.88038635253906}, {"text": "Background and objective: Despite medical advances, we are facing the unprecedented disaster of the coronavirus disease 2019 (COVID-19) pandemic without available treatments and effective vaccines. As the COVID-19 pandemic has approached its culmination, desperate efforts have been made to seek proper treatments and response strategies, and the number of clinical trials has been rapidly increasing. In this time of the pandemic, it is believed that learning lessons from it would be meaningful in preparing for future pandemics. Thus, this study aims at providing a comprehensive landscape of COVID-19 related clinical trials based on the ClinicalTrials.gov database. Materials and methods: Up to 30 March 2020, we identified a total of 147 eligible clinical trials and reviewed the overview of the studies. Results: Until then, the most clinical trials were set up in China. Treatment approaches are the most frequent purpose of the registered studies. Chloroquine, interferon, and antiviral agents such as remdesivir, lopinavir, and ritonavir are agents under investigation in these trials. Conclusions: In this study, we introduced the promising therapeutic options that many researchers and clinicians are interested in, and to address the hidden issues behind clinical trials in this COVID-19 pandemic.", "title": "A Comprehensive Analysis of Clinical Trials in the COVID-19 Pandemic Era.", "pid": "bl4d808v", "bm25_score": 217.8625030517578}, {"text": "", "title": "More than 80 clinical trials launch to test coronavirus treatments", "pid": "dzvfaa8z", "bm25_score": 217.78549194335938}, {"text": "Here, we present an overview of the clinical trials that are currently being conducted or have concluded to date on COVID-19 globally. A comprehensive search was conducted to present 16 trial registries from around the world. Collectively, there are 1,528 trials reported for COVID-19 to date. Out of them, 50 studies included paediatric age group from day 0 to less than or equal to 18 years of age. A few 18 studies involve only females and 20 only males. There are 2 trials currently underway in Bangladesh, 4 in Pakistan and 13 in India. Overall, 940 trials are related to medicines and/or interventions. They include standard of care for any viral illness, antivirals, anti-inflammatory and immune altering medications. Two out of 10 vaccine trials are novel vaccines. It is knowledgeable and resourceful to reach out to the concerned sponsor if a physician thinks his patient can benefit from the trials in the region.", "title": "Comprehensive overview of COVID-19 clinical trials", "pid": "7nm7s0l5", "bm25_score": 217.73548889160156}, {"text": "Since coronavirus disease 2019 (COVID‐19) emerged in Wuhan, China in December 2019 and spread around the world, over 1100 clinical studies have been registered globally on clinical trials registries, including over 500 randomised controlled trials. Such rapid development and launch of clinical trials is impressive but presents challenges, including the potential for duplication and competition. There is currently no known effective treatment for COVID‐19. In order to focus on those studies most likely to influence clinical practice, we summarise the 31 currently registered randomised trials with a target sample size of at least 1000 participants. We have grouped these trials into four categories: prophylaxis; treatment of outpatients with mild COVID‐19; treatment of hospitalised patients with moderate COVID‐19; and treatment of hospitalised patients with moderate or severe disease. The most common therapeutic agent being trialled currently is hydroxychloroquine (24 trials with potential sample size of over 25 000 participants), followed by lopinavir–ritonavir (seven trials) and remdesevir (five trials). There are many candidate drugs in pre‐clinical and early phase development, and these form a pipeline for future large clinical trials if current candidate therapies prove ineffective or unsafe.", "title": "Clinical trials for the prevention and treatment of COVID‐19: current state of play", "pid": "6wszpqvx", "bm25_score": 217.71810913085938}, {"text": "There are few published data on the protection of masks or respirators against coronavirus infections. This is an important research question to inform the response to the COVID-19 epidemic. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact and sometimes airborne routes. There are several randomised clinical trials of masks and respirators, but most used clinical endpoints or tested only for influenza. In four trials which we conducted, we tested for human coronaviruses, but only composite viral endpoints were reported in the trials. We reviewed and analysed the coronavirus data from four of our trials. Laboratory-confirmed coronavirus infections were identified in our community household trial (1 case), health worker trials (8 cases) and trial of mask use by sick patients (19 cases). No coronavirus infections were transmitted in households to parents who wore P2 or surgical masks, but one child with coronavirus infection transmitted infection to a parent in the control arm. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections.", "title": "HUMAN CORONAVIRUS DATA FROM FOUR CLINICAL TRIALS OF MASKS AND RESPIRATORS", "pid": "vjg2auh7", "bm25_score": 217.70318603515625}, {"text": "There are few published data on the protection of masks or respirators against coronavirus infections. This is an important research question to inform the response to the COVID-19 epidemic. The transmission modes of human coronaviruses are similar, thought to be by droplet, contact and sometimes airborne routes. There are several randomised clinical trials of masks and respirators, but most used clinical endpoints or tested only for influenza. In four trials which we conducted, we tested for human coronaviruses, but only composite viral endpoints were reported in the trials. We reviewed and analysed the coronavirus data from four of our trials. Laboratory-confirmed coronavirus infections were identified in our community household trial (1 case), health worker trials (8 cases) and trial of mask use by sick patients (19 cases). No coronavirus infections were transmitted in households to parents who wore P2 or surgical masks, but one child with coronavirus infection transmitted infection to a parent in the control arm. No transmissions to close contacts occurred when worn by sick patients with coronavirus infections. There was a higher risk of coronavirus infection in HCWs who wore a mask compared to a respirator, but the difference was not statistically significant. These are the only available data on coronavirus infections associated with mask or respirator use. More clinical trials are needed to assess the efficacy of respiratory protection against coronavirus infections.", "title": "Human Coronavirus Data from Four Clinical Trials of Masks and Respirators", "pid": "gey0nidn", "bm25_score": 217.70318603515625}, {"text": "Background and objective: Despite medical advances, we are facing the unprecedented disaster of the coronavirus disease 2019 (COVID-19) pandemic without available treatments and effective vaccines. As the COVID-19 pandemic has approached its culmination, desperate efforts have been made to seek proper treatments and response strategies, and the number of clinical trials has been rapidly increasing. In this time of the pandemic, it is believed that learning lessons from it would be meaningful in preparing for future pandemics. Thus, this study aims at providing a comprehensive landscape of COVID-19 related clinical trials based on the ClinicalTrials.gov database. Materials and methods: Up to 30 March 2020, we identified a total of 147 eligible clinical trials and reviewed the overview of the studies. Results: Until then, the most clinical trials were set up in China. Treatment approaches are the most frequent purpose of the registered studies. Chloroquine, interferon, and antiviral agents such as remdesivir, lopinavir, and ritonavir are agents under investigation in these trials. Conclusions: In this study, we introduced the promising therapeutic options that many researchers and clinicians are interested in, and to address the hidden issues behind clinical trials in this COVID-19 pandemic.", "title": "A Comprehensive Analysis of Clinical Trials in the COVID-19 Pandemic Era", "pid": "ykfm38tg", "bm25_score": 217.6143035888672}, {"text": "The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a serious threat to global public health and economies Currently, hundreds of clinical trials on a wide variety of treatments against COVID-19 are being conducted around the world Here, we conducted a search for ongoing clinical trials for the treatment of COVID-19 at the clinicaltrials gov database on April 2, 2020 In total, 48 clinical trials were identified, and of these, 41 trials adopted drug intervention and the other 7 trials utilized biological intervention The number of trials stratified by a chief country conducting the investigation were 18 in China, 5 in the United States, 4 in Canada, 3 in Italy, 2 in France and Brazil, and 4 trials are being performed multinationally The drugs utilized in more than one trials were remdesivir (6 trials), lopinavir/ritonavir (6 trials), hydroxychloroquine (6 trials), interferon (5 trials), methylprednisolone (3 trials), nitric oxide gas (3 trials), oseltamivir (2 trials), arbidol (2 trials), and vitamin C (2 trials) We also described the Japanese trials which are now being conducted or scheduled, utilizing lopinavir/ritonavir, remdesivir, favipiravir, ciclesonide and nafamostat", "title": "Major ongoing clinical trials for COVID-19 treatment and studies currently being conducted or scheduled in Japan", "pid": "i4fz2c49", "bm25_score": 217.60459899902344}, {"text": "Objective: To summarize the main characteristics of clinical studies regarding coronavirus disease 2019 (COVID-19) registered on the Chinese and US NIH Official Clinical Trial Registration Websites. Methods: To search all the clinical studies about COVID-19 which were registered on the Chinese and U.S. NIH official clinical trial registration websites until March 9, 2020. The search terms were \"new coronavirus pneumonia (COVID-19), 2019-nCoV, novel coronavirus pneumonia\". Results: Overall, 360 studies with a total sample size of 268, 773 participants are registered on Chinese clinical trial registration website, and 74 studies with a total sample size of 73, 723 participants in the U.S. NIH clinical trial registration website. According to the information provided by the Chinese Clinical Trial Registration Website, there are 237 interventional studies, 108 observational studies, and 15 diagnostic test studies; and the most commonly studied interventions were Traditional Chinese Medicine in 80 studies, antiviral therapy in 58 studies, stem cells in 19 studies, plasma of recovered patients in 13 studies, glucocorticoid in 7 studies, molecular targeted therapy in 4 studies, and vaccine in 2 studies. According to the information provided by the U.S. NIH Clinical Trial Registration Website, there were 54 interventional studies, 17 observational studies, and 3 diagnostic test studies; and the most commonly studied interventions were antiviral therapy in 16 studies, stem cells in 7 studies, Traditional Chinese Medicine in 6 studies, molecular targeted therapy in 3 studies, and vaccine in 3 studies. Conclusions Numerous clinical studies related to COVID-19 have been registered during a very short period. Among them, Traditional Chinese Medicine is the most commonly studied intervention, which suggests the Chinese characteristics in medical care. However, considering such a large sample size needed for these clinical studies, it is very important to ensure the enrollment of participants effectively and orderly in future.", "title": "Current status of clinical trial registration regarding coronavirus disease 2019", "pid": "tjsa86l7", "bm25_score": 217.57568359375}, {"text": "The novel coronavirus strain, severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19 emerged in Wuhan, China, in December 2019 and is skyrocketing throughout the globe and become a global public health emergency. Despite promising preventive measures being taken, there is no vaccine or drug therapy officially approved to prevent or treat the infection. Everybody is waiting the findings of ongoing clinical trials in various chemical and biological products. This review is specifically aimed to summarize the available evidence and ongoing clinical trials of remdesivir as a potential therapeutic option for COVID-19. Remdesivir is an investigational drug having broad spectrum antiviral activity with its target RNA dependent RNA polymerase. It has not yet been officially approved for Ebola and Coronaviruses. Several studies showed that remdesivir had promising in vitro and in vivo antiviral activities against SARS-CoV-1 and MERS-CoV strains. On the top of this, it exhibited a promising in vitro activity against SARS-CoV-2 strains though there are no published studies that substantiate its activity in vivo until the time of this review. There are few phase 3 randomized double-blind placebo controlled trials on the way to investigate the safety and efficacy of remdesivir. Of which, one completed double blind, placebo controlled trial showed that remdesivir showed faster time to clinical improvement in severe COVID-19 patients compared to placebo though not found statistically significant. In addition, two phase 3 randomized open label clinical trials coordinated by Gilead Sciences are being conducted. In addition, WHO Solidarity trial and INSERM DisCoVeRy trials (randomized open labels) were launched recently.", "title": "Available Evidence and Ongoing Clinical Trials of Remdesivir: Could It Be a Promising Therapeutic Option for COVID-19?", "pid": "tasbdhs1", "bm25_score": 217.48240661621094}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached global epidemic status claiming more than 319K lives and affecting more than 4 81M people and counting worldwide Considering the severity of the situation and low recovery rate many research institutions and pharmaceutical industries are rushing to learn more about this new virus and the morbid physiology of this disease with effective diagnostic methods, therapeutic agents and vaccines Various approaches are highlighted for comparing the possible treatment methods available for COVID-19 some of which are BCG vaccination on COVID-19 and Non-pharmaceutical interventions, drug based clinical trials of Hydroxychloroquine-Azithromycin, chloroquine, lopinavir/ritonavir, ChAdOx1 nCoV-19, Remdesivir, Stem Cell therapy and mesenchymal stromal cell therapy, etc", "title": "Current Clinical Trials and Vaccine Development Strategies for Corona Virus Disease (COVID-19)", "pid": "ev8n2n52", "bm25_score": 217.39248657226562}, {"text": "INTRODUCTION: While the global COVID-19 pandemic has challenged the entire humanity and health systems, it also triggered researchers to urgently perform clinical trials to assess the safety and efficacy of many agents and modalities to combat COVID-19. As of April 22, over 650 clinical studies have been registered both in USA and internationally. Results from these studies are also coming at a brisk pace in this unprecedented emergency. AREAS COVERED: We searched the NCI website and Medline and summarize various national and international clinical trials and summarize few of the pivotal ones in this paper, including those specific to oncology population. Two hundred and eighty four studies are actively recruiting adults and children with confirmed COVID-19, including 25 are early-phase I/phase I, 72 phase II, 58 phase III, 12 phase IV, and 31 other trials. They can be categorized into four groups: drugs that combat SARS-CoV-2, immunomodulatory agents to counteract cytokine storm, convalescence plasma therapies and vaccines trials. EXPERT OPINION: It is hoped that these efforts will results in a successful treatment to COVID-19, especially in a timely fashion before the second pandemic expected in fall. It is essential to acknowledge the devotion and hard work of the clinical research team and clinical research volunteers.", "title": "COVID-19 Clinical Research", "pid": "lldfoptb", "bm25_score": 217.31680297851562}, {"text": "As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coronavirus, so that identifying the drug treatment options as soon as possible is critical for the response to the 2019-nCoV outbreak. Three general methods, which include existing broad-spectrum antiviral drugs using standard assays, screening of a chemical library containing many existing compounds or databases, and the redevelopment of new specific drugs based on the genome and biophysical understanding of individual coronaviruses, are used to discover the potential antiviral treatment of human pathogen coronavirus. Lopinavir /Ritonavir, Nucleoside analogues, Neuraminidase inhibitors, Remdesivir, peptide (EK1), abidol, RNA synthesis inhibitors (such as TDF, 3TC), anti-inflammatory drugs (such as hormones and other molecules), Chinese traditional medicine, such ShuFengJieDu Capsules and Lianhuaqingwen Capsule, could be the drug treatment options for 2019-nCoV. However, the efficacy and safety of these drugs for 2019- nCoV still need to be further confirmed by clinical experiments.", "title": "Drug treatment options for the 2019-new coronavirus (2019-nCoV).", "pid": "804r5xzd", "bm25_score": 217.30331420898438}, {"text": "INTRODUCTION Since December 2019, there has been an outbreak of a novel beta-coronavirus (SARS-CoV-2) in Wuhan, China. On March the 11th the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review is to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION After a priori protocol registration with PROSPERO (181483), a systematic research of the published literature was conducted on 24 April 2020 using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database for identifying relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS Our search identified 1359 published papers, 478 pre-print articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.", "title": "The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans.", "pid": "1yrcbm7e", "bm25_score": 217.23651123046875}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir/ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized controlled trials are showing the poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.", "title": "Clinical trials of repurposed antivirals for SARS-CoV-2", "pid": "yvlcorrg", "bm25_score": 217.23561096191406}, {"text": "INTRODUCTION: Since December 2019, there has been an outbreak of a novel beta-coronavirus (SARS-CoV-2) in Wuhan, China. On March the 11th the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review is to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION: After a priori protocol registration with PROSPERO (181483), a systematic research of the published literature was conducted on 24 April 2020 using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database for identifying relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS: Our search identified 1359 published papers, 478 pre-print articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS: This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.", "title": "The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans", "pid": "xt8tld2i", "bm25_score": 217.2344207763672}, {"text": "TYPE: Abstract Publication TOPIC: Respiratory Care PURPOSE: 2019 novel coronavirus (2019-nCoV) is attributed for outbreak with first human infection detected in December 2019 in Wuhan, China, which has caused clusters of severe respiratory illness like severe acute respiratory syndrome coronavirus. The latest mortality was 2.07%. Currently, the standard care is supportive care, and no treatment is proven to be effective METHODS: We systematically analysed the contemporary protocols of the seven ongoing trials through the Chinese Clinical Trial Registry (4 trials) and the trials registry (3 trials) database. The latest evaluation was on January 29, 2020 with key word ‘2019-nCoV’, for the trials evaluating the diagnostic and the therapeutic interventions to manage the respiratory infection caused by 2019-nCoV RESULTS: Therapeutic interventions include, lopinavir-ritonavir with aerosolized interferon-alpha compared with the adjunctive IV methylprednisolone, umifenovir (broad-spectrum antiviral), SARI-nCoV trial for role of glucocorticoid, three comparative antiviral therapies utilising ribavirin, interferon alpha-1b, lopinavir -ritonavir, Xue-Bi-Jing injection (only Chinese medicine injection approved for sepsis) and novel isothermal nucleic acid amplification technique is under trial for simple, fast and portable diagnosis. The mean number of patients being enrolled is 193 (SD ± 183, maximum 500, minimum 40, range 460, 95% CI 24 to 362). Cumulatively, 1350 patients are targeted across 7 trials. CONCLUSIONS: Varied novel approaches based on the current scientific understanding of the disease are being evaluated for quick and effective management CLINICAL IMPLICATIONS: As the 2019-nCoV becomes a global threat, the rapidity of the Chinese trials for an evidence-based approach are in direction to provide rational, efficacious and potential solutions to effectively manage the disease DISCLOSURE: No significant relationships. KEYWORDS: Ongoing Trials, Systematic Review, 2019-nCoV", "title": "SYSTEMATIC REVIEW OF THE ONGOING CLINICAL TRIALS EVALUATING THE DIAGNOSTIC AND THERAPEUTIC INTERVENTIONS TO MANAGE THE RESPIRATORY INFECTION CAUSED BY 2019 NOVEL CORONAVIRUS (2019-NCOV)", "pid": "7r01gnot", "bm25_score": 217.2135009765625}, {"text": "As of January 22, 2020, a total of 571 cases of the 2019-new coronavirus (2019-nCoV) have been reported in 25 provinces (districts and cities) in China. At present, there is no vaccine or antiviral treatment for human and animal coronavirus, so that identifying the drug treatment options as soon as possible is critical for the response to the 2019-nCoV outbreak. Three general methods, which include existing broad-spectrum antiviral drugs using standard assays, screening of a chemical library containing many existing compounds or databases, and the redevelopment of new specific drugs based on the genome and biophysical understanding of individual coronaviruses, are used to discover the potential antiviral treatment of human pathogen coronavirus. Lopinavir /Ritonavir, Nucleoside analogues, Neuraminidase inhibitors, Remdesivir, peptide (EK1), abidol, RNA synthesis inhibitors (such as TDF, 3TC), anti-inflammatory drugs (such as hormones and other molecules), Chinese traditional medicine, such ShuFengJieDu Capsules and Lianhuaqingwen Capsule, could be the drug treatment options for 2019-nCoV. However, the efficacy and safety of these drugs for 2019- nCoV still need to be further confirmed by clinical experiments.", "title": "Drug treatment options for the 2019-new coronavirus (2019-nCoV)", "pid": "e5zjrhoq", "bm25_score": 217.18072509765625}, {"text": "The recent, fatal outbreak of the novel coronavirus strain in the Middle East highlights the real threat posed by this unique virus family. Neither pharmaceutical cures nor preventive vaccines are clinically available to fight against coronavirus associated syndromes, not to mention a lack of symptom soothing drugs. Development of treatment options is complicated by the unpredictable, recurring instances of cross-species viral transmission. The vastly distributing virus reservoir and the rapid rate of host-species exchange of coronavirus demands wide spectrum potency in an ideal therapeutic. Through summarizing the available information and progress in coronavirus research, this review provides a systematic assessment of the potential wide-spectrum features on the most popular drug targets including viral proteases, spike protein, RNA polymerases and editing enzymes as well as host-virus interaction pathways associated with coronaviruses.", "title": "Drug Targets for Rational Design against Emerging Coronaviruses.", "pid": "atxk09kq", "bm25_score": 217.15220642089844}, {"text": "The recent, fatal outbreak of the novel coronavirus strain in the Middle East highlights the real threat posed by this unique virus family. Neither pharmaceutical cures nor preventive vaccines are clinically available to fight against coronavirus associated syndromes, not to mention a lack of symptom soothing drugs. Development of treatment options is complicated by the unpredictable, recurring instances of cross-species viral transmission. The vastly distributing virus reservoir and the rapid rate of host-species exchange of coronavirus demands wide spectrum potency in an ideal therapeutic. Through summarizing the available information and progress in coronavirus research, this review provides a systematic assessment of the potential wide-spectrum features on the most popular drug targets including viral proteases, spike protein, RNA polymerases and editing enzymes as well as host-virus interaction pathways associated with coronaviruses.", "title": "Drug targets for rational design against emerging coronaviruses.", "pid": "731smixj", "bm25_score": 217.15220642089844}, {"text": "", "title": "Coronavirus drugs trials must get bigger and more collaborative.", "pid": "z7issy1i", "bm25_score": 217.0838165283203}, {"text": "In late December 2019, a group of patients was observed with pneumonia-like symptoms that were linked with a wet market in Wuhan, China. The patients were found to have a novel coronavirus genetically related to a bat coronavirus that was termed SARS-CoV-2. The virus gradually spread worldwide and was declared a pandemic by WHO. Scientists have started trials on potential preventive and treatment options. Currently, there is no specific approved treatment for SARS-CoV-2, and various clinical trials are underway to explore better treatments. Some previously approved antiviral and other drugs have shown some in vitro activity. Here we summarize the fight against this novel coronavirus with particular focus on the different treatment options and clinical trials exploring treatment as well as work done toward development of vaccines.", "title": "Emergence of novel coronavirus and progress toward treatment and vaccine", "pid": "uw7qhwne", "bm25_score": 217.0797119140625}, {"text": "The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health crisis since its initial reports in China. Since no effective vaccine or drug has been developed to treat and combat the COVID-19, the current approaches for clinical management focus on supportive care. There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the COVID-19 pandemic. The Chinese scientists supported by private and government resources have adopted extensive efforts to identify effective drugs against the virus. To date, a large number of clinical trials addressing various aspects of COVID-19 have been registered in the Chinese Clinical Trial Registry (ChiCTR), including more than 200 interventional studies. Under such an urgent circumstance, the scope and quality of these clinical studies vary significantly. Hence, this review aims to make a comprehensive analysis on the profiles of COVID-19 clinical trials registered in the ChiCTR, including a wide range of characteristics. Our findings will provide a useful summary on these clinical studies, since most of these studies will encounter major challenges from the design to completion. It will be a long road for the outcomes of these studies to be published and international collaboration will help the ultimate goals of developing new vaccines and antiviral drugs. Trial registration: ClinicalTrials.gov identifier: NCT04252664.. Trial registration: ClinicalTrials.gov identifier: NCT04257656..", "title": "Profiles of COVID-19 clinical trials in the Chinese Clinical Trial Registry.", "pid": "hfo5221v", "bm25_score": 217.06781005859375}, {"text": "We have read the article by Zhang et al. published in the recent issue of the Journal of Medical Virology1 . Zhang and his colleagues have made a cross-sectional survey of currently registered clinical trials concerning 2019-nCoV, including the published literature. As such, they have given a preliminary assessment on the prospects of therapy for 2019-nCoV. This article is protected by copyright. All rights reserved.", "title": "Comments on Zhang et al: Clinical trial analysis of 2019‐nCoV therapy registered in China", "pid": "rmpzsse9", "bm25_score": 217.04188537597656}, {"text": "We thank Dr. Yang and colleagues for their attention to our article1,2 . And we appreciate their meaningful suggestions, which we highly agree with. With the purpose of letting the public know the overall situation of the clinical trials of new coronary pneumonia in China as soon as possible, we completed the data collection and brief analysis in a very short time. This article is protected by copyright. All rights reserved.", "title": "Response to \"Comments on 'Zhang et al.: Clinical trial analysis of 2019-nCoV therapy registered in China '\".", "pid": "tg0z75k7", "bm25_score": 217.00634765625}, {"text": "As of March 10, 2020, more than 100,000 novel coronavirus pneumonia cases have been confirmed globally. With the continuous spread of the new coronavirus pneumonia epidemic in even the world, prevention and treatment of the disease have become urgent tasks. The drugs currently being developed are not adequate to deal with this critical situation. In addition to being controlled through effective isolation, we need a rapid response from the healthcare and biotechnology industries to accelerate drug treatment research. By reviewing the currently available literature published at home and abroad, we summarize the current research progress of drug treatment during the epidemic period. At present, the drugs that can be used for treatment mainly include antiviral drugs, antimalarials, glucocorticoids, plasma therapy, biological agents, and traditional Chinese medicine. The effectiveness and safety of drug therapy need to be confirmed by more clinical studies.", "title": "Research Progress of Drug Treatment in Novel Coronavirus Pneumonia", "pid": "zncfnipp", "bm25_score": 217.00619506835938}, {"text": "Coronaviruses are positive stranded RNA viruses that cause respiratory, enteric and central nervous system diseases in many species, including humans. Until recently, the relatively low burden of disease in humans caused by few of these viruses impeded the development of coronavirus specific therapeutics. However, the emergence of severe acute respiratory syndrome coronavirus (SARS-CoV), and more recently, Middle East respiratory syndrome coronavirus (MERS-CoV), has impelled the development of such drugs. This review focuses on some newly identified SARS-CoV inhibitors, with known mechanisms of action and their potential to inhibit the novel MERS-CoV. The clinical development of optimized versions of such compounds could be beneficial for the treatment and control of SARS-CoV, the current MERS-CoV and other future SARS-like epidemics.", "title": "Antiviral Drugs Specific for Coronaviruses in Preclinical Development", "pid": "0j8rvapz", "bm25_score": 216.97935485839844}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has prompted the repurposing of drugs on the basis of promising in vitro and therapeutic results with other human coronavirus diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). These repurposed drugs have mainly included remdesivir, favipiravir, lopinavir/ritonavir, ribavirin, interferons, and hydroxychloroquine. Unfortunately, the first open-label, randomized controlled trials are showing the poor efficacy of these repurposed drugs. These results highlight the necessity of identifying and characterizing specific and potent SARS-CoV-2 antivirals.", "title": "Clinical trials of repurposed antivirals for SARS-CoV-2.", "pid": "5q5mele8", "bm25_score": 216.94577026367188}, {"text": "Finding efficacious and safe treatments for COVID-19 emerges as a crucial need in order to control the spread of the pandemic. Whereas plasma therapy attracts much interest, the European project Discovery focuses on the potentialities of small molecules like remdesivir, the combination of lopinavir/ritonavir, hydroxychloroquine, and chloroquine. Results recently published on the clinical evaluation of those drugs are compiled in this brief report, although complete data are still impatiently awaited.", "title": "COVID-19: An Update about the Discovery Clinical Trial", "pid": "sqrbj5r4", "bm25_score": 216.90072631835938}, {"text": "The COVID-19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global public health crisis since its initial reports in China. Since no effective vaccine or drug has been developed to treat and combat the COVID-19, the current approaches for clinical management focus on supportive care. There is a pressing need for evidence-based interventions to address the devastating clinical and public health effects of the COVID-19 pandemic. The Chinese scientists supported by private and government resources have adopted extensive efforts to identify effective drugs against the virus. To date, a large number of clinical trials addressing various aspects of COVID-19 have been registered in the Chinese Clinical Trial Registry (ChiCTR), including more than 200 interventional studies. Under such an urgent circumstance, the scope and quality of these clinical studies vary significantly. Hence, this review aims to make a comprehensive analysis on the profiles of COVID-19 clinical trials registered in the ChiCTR, including a wide range of characteristics. Our findings will provide a useful summary on these clinical studies, since most of these studies will encounter major challenges from the design to completion. It will be a long road for the outcomes of these studies to be published and international collaboration will help the ultimate goals of developing new vaccines and antiviral drugs. Trial registration: ClinicalTrials.gov identifier: NCT04252664.. Trial registration: ClinicalTrials.gov identifier: NCT04257656..", "title": "Profiles of COVID-19 clinical trials in the Chinese Clinical Trial Registry", "pid": "pxzbkde0", "bm25_score": 216.8921661376953}, {"text": "BACKGROUND: The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19. In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19. METHOD: An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020. Two independent researchers performed the screening, and finally the related studies were included. RESULTS: Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found. The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits. Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19. In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV. CONCLUSION: The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO). In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics.", "title": "Antiviral therapy in management of COVID-19: a systematic review on current evidence", "pid": "jlqee1b8", "bm25_score": 216.8385772705078}, {"text": "The COVID-19 pandemic has resulted in a proliferation of clinical trials that are designed to slow the spread of SARS-CoV-2, the virus that causes COVID-19. The overwhelming majority of cardiovascular and cancer patients are at increased risk for SARS-CoV-2 infection; accordingly, the cardiovascular and cardio-oncology communities are playing a major role in caring for COVID-19 patients. Many of the therapeutic agents that are being used to treat patients with COVID-19 are repurposed treatments for influenza, drugs that were not effective in Ebola patients, or treatments for malaria that were developed decades ago, and are unlikely to be familiar to the cardiovascular and cardio-oncology communities. Here we have provided a foundation for cardiovascular and cardio-oncology physicians who are on the frontline providing care to COVID-19 patients, so that they can better understand the emerging cardiovascular epidemiology of COVID-19, as well as the biological rationale for the clinical trials that are ongoing for the treatment of COVID-19 patients.", "title": "COVID-19 Clinical Trials: A Primer for the Cardiovascular and Cardio-Oncology Communities", "pid": "y6vhe5bo", "bm25_score": 216.8170166015625}, {"text": "Controlled human challenge trials of SARS-CoV-2 vaccine candidates could accelerate the testing and potential rollout of efficacious vaccines. By replacing conventional phase 3 testing of vaccine candidates, such trials may subtract many months from the licensure process, making efficacious vaccines available more quickly. Obviously, challenging volunteers with this live virus risks inducing severe disease and possibly even death. However, we argue that such studies, by accelerating vaccine evaluation, could reduce the global burden of coronavirus-related mortality and morbidity. Volunteers in such studies could autonomously authorize the risks to themselves, and their net risk could be acceptable if participants comprise healthy young adults, who are at relatively low risk of serious disease following natural infection, if they have a high baseline risk of natural infection, and if during the trial they receive frequent monitoring and, following any infection, the best available care.", "title": "Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure", "pid": "vqxrjtgb", "bm25_score": 216.81146240234375}, {"text": "", "title": "Coronavirus drugs trials must get bigger and more collaborative", "pid": "pwd6a1vr", "bm25_score": 216.79888916015625}, {"text": "Since a novel coronavirus pneumonia outbreak in late December 2019, coronavirus disease -19 (COVID-19) epidemic has gradually spread worldwide, becoming a major public health event. No specific antivirals are currently available for COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The treatments for COVID-19 are mainly based on the experiences of similar virus such SARS-CoV, MERS-CoV, HIV and influenza viruses. Scientists have taken great efforts to investigate the effective methods for the treatment of COVID-19. Up to now, there are over 1000 clinical studies for COVID-19 all over the world. In this article, we reviewed the current options for COVID-19 therapy including small molecules such as Remdesivir, Favipiravir, Lopinavir/Ritonavir etc, peptide inhibitors of ACE2, Traditional Chinese Medicines and Biologics such as SARS-CoV-2-specific neutralizing antibodies, mesenchymal stem cells and vaccines etc. Meanwhile, we systematically reviewed their clinical safety, clinical applications and progress of antiviral researches. The therapeutic effect of these antiviral drugs is summarized and compared, hoping to provide some ideas for clinical options of COVID-19 treatment and also provide experiences for the life-threatening virus diseases in the future.", "title": "An overview of the safety, clinical application and antiviral research of the COVID-19 therapeutics", "pid": "hsbjbwpa", "bm25_score": 216.79794311523438}, {"text": "Background: As novel coronavirus disease (COVID-19) cases continue to steeply rise globally within an unprecedented short period of time, solid evidence from large randomised controlled trials is still lacking. Currently, numerous trials testing potential treatment and preventative options are undertaken globally. Objectives: We summarised all currently registered clinical trials examining treatment and prevention options for COVID-19 pneumonia. Additionally, we evaluated the quality of the retrieved interventional studies. Data sources: The ClinicalTrials.gov, the Chinese Clinical Trial Registry and the European Union Clinical Trials Register were systematically searched. Study eligibility criteria: Registered clinical trials examining treatment and/or prevention options for COVID-19 were included. No language, country or study design restrictions were applied. Withdrawn, cancelled studies and trials not reporting therapeutic or preventative strategies for COVID-19 were excluded. Participants and interventions: No restrictions in terms of participants' age and medical background or type of intervention were enforced. Methods: The registries were searched using the term \"coronavirus\" or \"COVID-19\" from their inception until 26th March 2020. Additional manual search of the registries was also performed. Eligible studies were summarised and tabulated. Interventional trials were methodologically analysed, excluding expanded access studies and trials testing Traditional Chinese Medicine. Results: In total, 309 trials evaluating therapeutic management options, 23 studies assessing preventive strategies and 3 studies examining both were retrieved. Interventional treatment studies were mostly randomised (n=150, 76%) and open-label (n=73, 37%) with a median number of planned inclusions of 90 (IQR 40-200). Major categories of interventions that are currently being investigated are discussed. Conclusion: Numerous clinical trials have been registered since the onset of the COVID-19 pandemic. Summarised data on these trials will assist physicians and researchers to promote patient care and guide future research efforts for COVID-19 pandemic containment. However, up to the end of March, 2020, significant information concerning reported trials was lacking.", "title": "Review and methodological analysis of trials currently testing treatment and prevention options for the novel coronavirus disease (COVID-19) globally.", "pid": "di23na30", "bm25_score": 216.77951049804688}, {"text": "Abstract Coronaviruses may cause respiratory, enteric and central nervous system diseases in many species, including humans. Until recently, the relatively low burden of disease in humans caused by few of these viruses hampered development of coronavirus specific therapeutics. However, the emergence of severe acute respiratory syndrome coronavirus (SARS-CoV) has prompted the discovery of such drugs. Subsequent studies in animal models demonstrated the efficacy of SARS-CoV specific monoclonal antibodies, pegylated-interferon-α and siRNAs against SARS-CoV. Furthermore, several antivirals shown to be effective against other viruses were tested in vitro. Because of availability and shown efficacy, the use of interferons may be considered should SARS-CoV or a related coronavirus (re)-emerge. The more recent design of wide-spectrum inhibitors targeting the coronavirus main proteases may lead to the discovery of new antivirals against multiple coronavirus induced diseases.", "title": "Coronaviruses and their therapy", "pid": "j0496jb7", "bm25_score": 216.77877807617188}, {"text": "Abstract The COVID-19 pandemic has resulted in a proliferation of clinical trials that are designed to slow the spread of SARS-CoV-2, the virus that causes COVID-19. The overwhelming majority of cardiovascular and cancer patients are at increased risk for SARS-CoV-2 infection; accordingly, the cardiovascular and cardio-oncology communities are playing a major role in caring for COVID-19 patients. Many of the therapeutic agents that are being used to treat patients with COVID-19 are repurposed treatments for influenza, drugs that were not effective in Ebola patients, or treatments for malaria that were developed decades ago, and are unlikely to be familiar to the cardiovascular and cardio-oncology communities. Here we have provided a foundation for cardiovascular and cardio-oncology physicians who are on the frontline providing care to COVID-19 patients, so that they can better understand the emerging cardiovascular epidemiology of COVID-19, as well as the biological rationale for the clinical trials that are ongoing for the treatment of COVID-19 patients.", "title": "COVID-19 Clinical Trials: A Primer for the Cardiovascular and Cardio-Oncology Communities", "pid": "y74jbnb2", "bm25_score": 216.77439880371094}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), initially termed 2019-new CoV (2019-nCoV), is a novel coronavirus responsible for the severe respiratory illness currently ongoing worldwide from the beginning of December 2019. This beta gene virus, very close to bat coronaviruses (bat-CoV-RaTG13) and bat-SL-CoVZC45, causes a severe disease, similar to those caused by Middle East respiratory syndrome (MERS)-CoV and SARS-CoV viruses, featured by low to moderate mortality rate. Unfortunately, the antiviral drugs commonly used in clinical practice to treat viral infections, are not applicable to SARS-Cov-2 and no vaccine is available. Thus, it is extremely necessary to identify new drugs suitable for the treatment of the 2019-nCoV outbreak. Different preclinical studies conducted on other coronaviruses suggested that promising clinical outcomes for 2019-nCoV should be obtained by using alpha-interferon, chloroquine phosphate, arabinol, remdesivir, lopinavir/ritonavir, and anti-inflammatory drugs. Moreover, clinical trials with these suitable drugs should be performed on patients affected by SARS-Cov-2 to prove their efficacy and safety. Finally, a very promising therapeutic drug, tocilizumab, is discussed; it is currently used to treat patients presenting COVID-19 pneumonia. Herein, we recapitulate these experimental studies to highlight the use of antiviral drugs for the treatment of SARS-Cov-2 disease.", "title": "Potential Antiviral Drugs for SARS-Cov-2 Treatment: Preclinical Findings and Ongoing Clinical Research.", "pid": "lav2iavi", "bm25_score": 216.7723388671875}, {"text": "Abstract The novel coronavirus disease (COVID-19) is spreading rapidly, a pandemic that has already affected millions of people across the world Currently there are no vaccines or drugs approved for COVID-19 Initial data which are coming from large clinical trials using Hydroxychloroquine, Lopinavir/Ritonavir, Remdesevir, and Favipiravir are not satisfactory against COVID-19 till now and we are in the midst of a worldwide public health threat In this context human convalescent plasma is considered as an option for treatment of COVID-19 disease Convalescent plasma therapy is a classic adaptive immunotherapy which involves the administration of antibodies against COVID-19 to a COVID-19 patient for the purpose of treating the viral disease Over the last two decades, convalescent plasma therapy was used for the treatment of 2003 SARS-CoV-1 epidemic, 2009-2010 H1N1 influenza virus pandemic, the 2012 Middle East Respiratory Syndrome (MERS)-CoV epidemic and 2014-2016 Ebola epidemic", "title": "Randomization amid a pandemic - a critical appraisal regarding convalescent plasma therapy clinical trials for COVID-19 patients", "pid": "eqo1lrjv", "bm25_score": 216.76217651367188}, {"text": "In humans, infections with the human coronavirus (HCoV) strains HCoV-229E, HCoV-OC43, HCoV-NL63 and HCoV-HKU1 usually result in mild, self-limiting upper respiratory tract infections, such as the common cold. By contrast, the CoVs responsible for severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), which were discovered in Hong Kong, China, in 2003, and in Saudi Arabia in 2012, respectively, have received global attention over the past 12 years owing to their ability to cause community and health-care-associated outbreaks of severe infections in human populations. These two viruses pose major challenges to clinical management because there are no specific antiviral drugs available. In this Review, we summarize the epidemiology, virology, clinical features and current treatment strategies of SARS and MERS, and discuss the discovery and development of new virus-based and host-based therapeutic options for CoV infections. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrd.2015.37) contains supplementary material, which is available to authorized users.", "title": "Coronaviruses — drug discovery and therapeutic options", "pid": "4j8b8z4t", "bm25_score": 216.7341766357422}, {"text": "The COVID-19 pandemic represents the greatest global public health crisis since the pandemic influenza outbreak of 1918. We are facing a new virus, so several antiviral agents previously used to treat other coronavirus infections such as SARS and MERS are being considered as the first potential candidates to treat COVID-19. Thus, several agents have been used by the beginning of the current outbreak in China first and all over the word successively, as reported in several different guidelines and therapeutic recommendations. At the same time, a great number of clinical trials have been launched to investigate the potential efficacy therapies for COVID-19 highlighting the urgent need to get as quickly as possible high-quality evidence. Through PubMed, we explored the relevant articles published on treatment of COVID-19 and on trials ongoing up to April 15, 2020.", "title": "Update on treatment of COVID-19: ongoing studies between promising and disappointing results.", "pid": "nmntjk0i", "bm25_score": 216.73098754882812}, {"text": "COVID-19 has rapidly developed into a worldwide pandemic with a significant health and economic burden. There are currently no approved treatments or preventative therapeutic strategies. Hundreds of clinical studies have been registered with the intention of discovering effective treatments. Here, we review currently registered interventional clinical trials for the treatment and prevention of COVID-19 to provide an overall summary and insight into the global response.", "title": "Ongoing Clinical Trials for the Management of the COVID-19 Pandemic", "pid": "ibuqz948", "bm25_score": 216.72821044921875}, {"text": "Background The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19. In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19. Method An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020. Two independent researchers performed the screening, and finally the related studies were included. Results Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found. The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits. Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19. In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV. Conclusion The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO). In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics.", "title": "Antiviral therapy in management of COVID-19: a systematic review on current evidence.", "pid": "bfchqn2g", "bm25_score": 216.72401428222656}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2), initially termed 2019-new CoV (2019-nCoV), is a novel coronavirus responsible for the severe respiratory illness currently ongoing worldwide from the beginning of December 2019. This beta gene virus, very close to bat coronaviruses (bat-CoV-RaTG13) and bat-SL-CoVZC45, causes a severe disease, similar to those caused by Middle East respiratory syndrome (MERS)-CoV and SARS-CoV viruses, featured by low to moderate mortality rate. Unfortunately, the antiviral drugs commonly used in clinical practice to treat viral infections, are not applicable to SARS-Cov-2 and no vaccine is available. Thus, it is extremely necessary to identify new drugs suitable for the treatment of the 2019-nCoV outbreak. Different preclinical studies conducted on other coronaviruses suggested that promising clinical outcomes for 2019-nCoV should be obtained by using alpha-interferon, chloroquine phosphate, arabinol, remdesivir, lopinavir/ritonavir, and anti-inflammatory drugs. Moreover, clinical trials with these suitable drugs should be performed on patients affected by SARS-Cov-2 to prove their efficacy and safety. Finally, a very promising therapeutic drug, tocilizumab, is discussed; it is currently used to treat patients presenting COVID-19 pneumonia. Herein, we recapitulate these experimental studies to highlight the use of antiviral drugs for the treatment of SARS-Cov-2 disease.", "title": "Potential Antiviral Drugs for SARS-Cov-2 Treatment: Preclinical Findings and Ongoing Clinical Research", "pid": "7wbpj88g", "bm25_score": 216.71031188964844}, {"text": "INTRODUCTION: In December 2019, an outbreak of pneumonia caused by a novel coronavirus occurred in Wuhan, the capital of Central China's Hubei Province and has been declared a public health emergency of international concern by the World Health Organization since January 2020. MATERIAL AND METHODS: A comprehensive search using the PubMed database was carried out to summarize the latest published information about the epidemiology, definition, pathogenesis, clinical characteristics, treatment options, prognosis and prevention of coronavirus disease 2019. DISCUSSION: This new strain of coronavirus, named severe acute respiratory syndrome coronavirus 2, enters human cells that express angiotensin-converting enzyme II receptors, which exist in the respiratory, gastrointestinal and genitourinary tracts and heart, causing coronavirus disease. Transmission occurs essentially through the respiratory tract and the main symptoms are fever, cough and dyspnea. Diagnosis is based on epidemiological, clinical and imaging features and confirmed by nucleic acid testing. CONCLUSION: Despite intensive research, the exact origin of the virus and pathophysiology of coronavirus disease is not yet completely known, and clinically approved vaccines and drugs that target severe acute respiratory syndrome coronavirus 2 are lacking.", "title": "Coronavirus Disease 2019: Clinical Review", "pid": "6p71pt8i", "bm25_score": 216.7069091796875}, {"text": "SARS-CoV-2/novel coronavirus (2019-nCoV) is a new strain that has recently been confirmed in Wuhan City, Hubei Province of China, and spreads to more than 165 countries of the world including India. The virus infection leads to 245,922 confirmed cases and 10,048 deaths worldwide as of March 20, 2020. Coronaviruses (CoVs) are lethal zoonotic viruses, highly pathogenic in nature, and responsible for diseases ranging from common cold to severe illness such as Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS) in humans for the past 15 years. Considering the severity of the current and previous outbreaks, no approved antiviral agent or effective vaccines are present for the prevention and treatment of infection during the epidemics. Although, various molecules have been shown to be effective against coronaviruses both in vitro and in vivo, but the antiviral activities of these molecules are not well established in humans. Therefore, this chapter is planned to provide information about available treatment and preventive measures for the coronavirus infections during outbreaks. This chapter also discusses the possible role of supportive therapy, repurposing drugs, and complementary and alternative medicines for the management of coronaviruses including COVID-19.", "title": "Therapeutic Development and Drugs for the Treatment of COVID-19", "pid": "9q7zbmwp", "bm25_score": 216.69798278808594}, {"text": "The severe acute respiratory syndrome virus (SARS-CoV-2), a novel coronavirus first discovered in Wuhan, China in December 2019 causes the Coronavirus Disease 19 (COVID-19), which presents with a wide range of clinical symptoms from mild or moderate to severe and critical illnesses With the continuing transmission of the virus worldwide and the rapidly evolving situation globally, the World Health Organization (WHO) declared the COVID-19 outbreak a pandemic in March Currently, there is no proven specific treatment for this potentially deadly disease beyond supportive care However, a massive effort has been put globally into the investigation of medications and other interventional measures to fight COVID-19 Convalescent plasma therapy from recovered patients has recently drawn considerable interest Several alternative medical treatments, although evidence of their efficacy still lacking, have also gained popularity, especially in countries with such traditions such as India and China Rapid repurposing of drugs for COVID-19 has revealed a few promising candidate antiviral agents, but further research, especially high quality randomized controlled trials, will be needed to prove their efficacy and safety in the clinical use to treat COVID-19 Vaccine development has been the imperative task in the battle against SARS-CoV-2 While clinical trials have been launched for several candidate vaccines, research on COVID-19 vaccines is still at an early stage So far, optimized supportive care remains the best practice against COVID-19", "title": "Current Status of Treatment Options, Clinical Trials, and Vaccine Development for SARS-CoV-2 Infection", "pid": "0j5bg59c", "bm25_score": 216.69439697265625}, {"text": "As this ever-evolving pandemic lays itself, more of its impact is being understood. Until recently, most guidelines were reported to aid in managing and treating suspected or confirmed cases. Research institutions around the world are responding with a sense of confusion. Some are continuing routinely, especially those who are overseeing clinical trials that could offer life-saving therapies, particularly against the novel coronavirus. Since research must continue even in the face of a shutdown, we aim to collate the currently available recommendations from various organizations and provide guidance to head and neck researchers across the world during these trying times.", "title": "Clinical trials during COVID-19", "pid": "2a7t447d", "bm25_score": 216.671142578125}, {"text": "As this ever‐evolving pandemic lays itself, more of its impact is being understood. Until recently, most guidelines were reported to aid in managing and treating suspected or confirmed cases. Research institutions around the world are responding with a sense of confusion. Some are continuing routinely, especially those who are overseeing clinical trials that could offer life‐saving therapies, particularly against the novel coronavirus. Since research must continue even in the face of a shutdown, we aim to collate the currently available recommendations from various organizations and provide guidance to head and neck researchers across the world during these trying times.", "title": "Clinical trials during COVID‐19", "pid": "nesvd10a", "bm25_score": 216.65989685058594}, {"text": "The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has been responsible for millions of infections and hundreds of thousands of deaths. To date, there is no approved targeted treatment, and many investigational therapeutic agents and vaccine candidates are being considered for the treatment of COVID-19. To extract and summarize information on potential vaccines and therapeutic agents against COVID-19 at different stages of clinical trials from January to March 2020, we reviewed major clinical trial databases such as ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP), and other primary registries between January and March 15, 2020. Interventional studies at different phases under the COVID-19 pipeline were included. A total of 249 clinical trials were identified between January to March 15, 2020. After filtering observational studies (194 studies), a total of 56 interventional trials were considered. The majority of clinical trials have been conducted on chloroquine (n=10) and traditional Chinese medications (TCMs; n=10), followed by antivirals (n=8), anti-inflammatory/immunosuppressants (n=9), cellular therapies (n=4), combinations of different antivirals therapies (n=3), antibacterial (n=1), and other therapies (n=5). Five vaccines are under phase I, and there are a couple of phase III trials on the Bacillus Calmette-Guérin (BCG) vaccine under investigation among healthcare workers. Many novel compounds and vaccines against COVID-19 are currently under investigation. Some candidates have been tested for other viral infections and are listed for clinical trials against the COVID-19 pipeline. Currently, there are no effective specific antivirals or drug combinations available for the treatment of COVID-19.", "title": "Vaccines and Drug Therapeutics to Lock Down Novel Coronavirus Disease 2019 (COVID-19): A Systematic Review of Clinical Trials", "pid": "p36zubnf", "bm25_score": 216.64512634277344}, {"text": "The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including favipiravir, a broad-spectrum antiviral drug that interferes with the viral replication, and hydroxychloroquine, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis.", "title": "A Review of SARS-CoV-2 and the Ongoing Clinical Trials", "pid": "yzr7ifbj", "bm25_score": 216.64047241210938}, {"text": "Abstract With the recent emergence of Middle East Respiratory Syndrome coronavirus in humans and the outbreak of devastating porcine epidemic diarrhea coronavirus in swine, therapeutic intervention is urgently needed. However, anti-coronavirus drugs currently are not available. In an effort to assist rapid development of anti-coronavirus drugs, here we screened the NIH Clinical Collection in cell culture using a luciferase reporter-expressing recombinant murine coronavirus. Of the 727 compounds screened, 84 were found to have a significant anti-coronavirus effect. Further experiments revealed that 51 compounds blocked virus entry while 19 others inhibited viral replication. Additional validation studies with the top 3 inhibitors (hexachlorophene, nitazoxanide and homoharringtonine) demonstrated robust anti-coronavirus activities (a reduction of 6 to 8log10 in virus titer) with an IC50 ranging from 11nM to 1.2μM. Furthermore, homoharringtonine and hexachlorophene exhibited broad antiviral activity against diverse species of human and animal coronaviruses. Since the NIH Clinical Collection consists of compounds that have already been through clinical trials, these small molecule inhibitors have a great potential for rapid development as anti-coronavirus drugs.", "title": "A screen of the NIH Clinical Collection small molecule library identifies potential anti-coronavirus drugs", "pid": "79v0hdi9", "bm25_score": 216.63648986816406}, {"text": "Abstract Background The Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was first described in 2012 and attracted a great international attention due to multiple healthcare associated outbreaks. The disease carries a high case fatality rate of 34.5%, and there is no internationally or nationally recommended therapy. Method We searched MEDLINE, Science Direct, Embase and Scopus databases for relevant papers published till March 2019 describing in vitro, in vivo or human therapy of MERS. Results Initial search identified 62 articles: 52 articles were from Medline, 6 from Embase, and 4 from Science Direct. Based on the inclusions and exclusions criteria, 30 articles were included in the final review and comprised: 22 in vitro studies, 8 studies utilizing animal models, 13 studies in humans, and one study included both in vitro and animal model. There are a few promising therapeutic agents on the horizon. The combination of lopinavir/ritonavir and interferon-beta- 1b showed excellent results in common marmosets and currently is in a randomized control trial. Ribavirin and interferon were the most widely used combination and experience comes from a number of observational studies. Although, the data are heterogenous, this combination might be of potential benefit and deserve further investigation. There were no randomized clinical trials to recommend specific therapy for the treatment of MERS-CoV infection. Only one such study is planned for randomization and is pending completion. The study is based on a combination of lopinavir/ritonavir and interferon-beta- 1b. A fully human polyclonal IgG antibody (SAB-301) was safe and well tolerated in healthy individuals and this agent may deserve further testing for efficacy. Conclusion Despite multiple studies in humans there is no consensus on the optimal therapy for MERS-CoV. Randomized clinical trials are needed and potential therapies should be evaluated only in such clinical trials. In order to further enhance the therapeutic aroma for MERS-CoV infection, repurposing old drugs against MERS-CoV is an interesting strategy and deserves further consideration and use in clinical settings.", "title": "A Systematic Review of therapeutic agents for the treatment of the Middle East Respiratory Syndrome Coronavirus (MERS-CoV)", "pid": "wicc796j", "bm25_score": 216.62417602539062}, {"text": "PURPOSE OF REVIEW Severe acute respiratory syndrome is a new, sometimes lethal disease of humans that is caused by a novel coronavirus. To date there have been over 750 related deaths and there is clearly an urgent need to develop specific antiviral drugs to combat this disease. In this review, the authors shall focus on the molecular biology of the coronavirus and suggest how this information can be used to identify possible targets for antiviral drugs. RECENT FINDINGS Within a remarkably short period of time, the severe acute respiratory syndrome coronavirus has been isolated, its genome has been sequenced and the structure of at least one key viral enzyme has been deduced. In addition, bioinformatic analysis has predicted a number of enzymatic activities associated with proteins of the viral replicase-transcriptase complex. In some cases, these functions have been confirmed by biochemical analysis. Thus, there has been significant progress in the rational approach to anti-severe acute respiratory syndrome coronavirus drug design. This approach, combined with the random screening of licensed compounds or existing compound libraries, should result in the identification of novel lead compounds and the expeditious development of antiviral drugs. SUMMARY Although the initial severe acute respiratory syndrome epidemic has been controlled by conventional measures, the animal reservoir for the coronavirus progenitor has not been identified. It is therefore likely that the virus will be reintroduced into the human population in the future. When this happens, the most economical and effective way to contain the virus will be the therapeutic use of antiviral drugs.", "title": "Potential for antiviral treatment of severe acute respiratory syndrome.", "pid": "fcg8bgga", "bm25_score": 216.60276794433594}, {"text": "", "title": "A survey of 434 clinical trials about coronavirus disease 2019 in China", "pid": "68xv786q", "bm25_score": 216.59637451171875}, {"text": "In late December 2019, a group of patients was observed with pneumonia‐like symptoms that were linked with a wet market in Wuhan, China. The patients were found to have a novel coronavirus genetically related to a bat coronavirus that was termed SARS‐CoV‐2. The virus gradually spread worldwide and was declared a pandemic by WHO. Scientists have started trials on potential preventive and treatment options. Currently, there is no specific approved treatment for SARS‐CoV‐2, and various clinical trials are underway to explore better treatments. Some previously approved antiviral and other drugs have shown some in vitro activity. Here we summarize the fight against this novel coronavirus with particular focus on the different treatment options and clinical trials exploring treatment as well as work done toward development of vaccines.", "title": "Emergence of novel coronavirus and progress toward treatment and vaccine", "pid": "3mpymd8a", "bm25_score": 216.59274291992188}, {"text": "INTRODUCTION The Coronavirus disease-19 (COVID-19) caused by the novel beta coronavirus named Severe Acute Respiratory Syndromecoronavirus-2 (SARS-CoV-2) started in late December 2019 in Wuhan, China. Within a short span, COVID-19 was declared a global public health emergency affecting 214 countries with 5,939,234 confirmed cases and 3,67,255 deaths as of 30 May, 2020. With limited knowledge about SARS-CoV-2, no approved treatment or vaccine is available till date. AREAS COVERED We performed a review of literature on PubMed on the SARS-CoV-2 virus and COVID-19 illness including trials of preventive and therapeutic measures. This review presents the basic biology of coronaviruses, epidemiology of COVID-19, clinical presentations, investigational therapies and vaccines, infection prevention and control measures and the lessons from the present pandemic. EXPERT OPINION The scale of the outbreak has brought the governments, healthcare professionals and scientists around the world under tremendous pressure to devise control strategies and develop novel prevention measures. While availability of vaccine for COVID-19 may take time, the disease may be contained through hand hygiene, physical distancing, travel restriction and aggressive steps such as 'lockdown'. Clinical trials at different phases are ongoing across different countries to expedite development of effective drugs and vaccine to overcome the pandemic.", "title": "Covid-19: A Comprehensive Review of a Formidable Foe and the Road Ahead.", "pid": "lj2iu7z0", "bm25_score": 216.59243774414062}, {"text": "BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30(th) January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (≥ 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6(th) February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.", "title": "Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial", "pid": "mur7txck", "bm25_score": 216.5468292236328}, {"text": "INTRODUCTION: The Coronavirus disease-19 (COVID-19) caused by the novel beta coronavirus named Severe Acute Respiratory Syndromecoronavirus-2 (SARS-CoV-2) started in late December 2019 in Wuhan, China. Within a short span, COVID-19 was declared a global public health emergency affecting 214 countries with 5,939,234 confirmed cases and 3,67,255 deaths as of 30 May, 2020. With limited knowledge about SARS-CoV-2, no approved treatment or vaccine is available till date. AREAS COVERED: We performed a review of literature on PubMed on the SARS-CoV-2 virus and COVID-19 illness including trials of preventive and therapeutic measures. This review presents the basic biology of coronaviruses, epidemiology of COVID-19, clinical presentations, investigational therapies and vaccines, infection prevention and control measures and the lessons from the present pandemic. EXPERT OPINION: The scale of the outbreak has brought the governments, healthcare professionals and scientists around the world under tremendous pressure to devise control strategies and develop novel prevention measures. While availability of vaccine for COVID-19 may take time, the disease may be contained through hand hygiene, physical distancing, travel restriction and aggressive steps such as 'lockdown'. Clinical trials at different phases are ongoing across different countries to expedite development of effective drugs and vaccine to overcome the pandemic.", "title": "Covid-19: A Comprehensive Review of a Formidable Foe and the Road Ahead", "pid": "w3avnbpu", "bm25_score": 216.54417419433594}, {"text": "BACKGROUND: On 31 December, 2019, the World Health Organization China Country Office was informed of cases of pneumonia of unknown aetiology. Since then, there have been over 75 000 cases globally of the 2019 novel coronavirus (COVID-19), 2000 deaths, and over 14 000 cases recovered. Outbreaks of novel agents represent opportunities for clinical research to inform real-time public health action. In 2018, we conducted a systematic review to identify priority research questions for Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-related coronavirus (MERS-CoV). Here, we review information available on COVID-19 and provide an evidenced-based framework for priority clinical research in the current outbreak. METHODS: Three bibliographic databases were searched to identify clinical studies published on SARS-CoV and MERS-CoV in the outbreak setting. Studies were grouped thematically according to clinical research questions addressed. In February 2020, available information on COVID19 was reviewed and compared to the results of the SARS-CoV and MERS-CoV systematic review. RESULTS: From the research objectives for SARS-CoV and MERS-CoV, ten themes in the literature were identified: Clinical characterisation, prognosis, diagnosis, clinical management, viral pathogenesis, epidemiological characterisation, infection prevention and control/transmission, susceptibility, psychosocial, and aetiology. For COVID19, some information on clinical presentation, diagnostic testing, and aetiology is available but many clinical research gaps have yet to be filled. CONCLUSIONS: Based on a systematic review of other severe coronaviruses, we summarise the state of clinical research for COVID-19, highlight the research gaps, and provide recommendations for the implementation of standardised protocols. Data based on internationally standardised protocols will inform clinical practice real-time.", "title": "An evidence-based framework for priority clinical research questions for COVID-19", "pid": "i6pv90s9", "bm25_score": 216.54312133789062}, {"text": "Background: On 31 December, 2019, the World Health Organization China Country Office was informed of cases of pneumonia of unknown aetiology. Since then, there have been over 75 000 cases globally of the 2019 novel coronavirus (COVID-19), 2000 deaths, and over 14 000 cases recovered. Outbreaks of novel agents represent opportunities for clinical research to inform real-time public health action. In 2018, we conducted a systematic review to identify priority research questions for Severe Acute Respiratory Syndrome-related coronavirus (SARS-CoV) and Middle East Respiratory Syndrome-related coronavirus (MERS-CoV). Here, we review information available on COVID-19 and provide an evidenced-based framework for priority clinical research in the current outbreak. Methods: Three bibliographic databases were searched to identify clinical studies published on SARS-CoV and MERS-CoV in the outbreak setting. Studies were grouped thematically according to clinical research questions addressed. In February 2020, available information on COVID19 was reviewed and compared to the results of the SARS-CoV and MERS-CoV systematic review. Results: From the research objectives for SARS-CoV and MERS-CoV, ten themes in the literature were identified: Clinical characterisation, prognosis, diagnosis, clinical management, viral pathogenesis, epidemiological characterisation, infection prevention and control/transmission, susceptibility, psychosocial, and aetiology. For COVID19, some information on clinical presentation, diagnostic testing, and aetiology is available but many clinical research gaps have yet to be filled. Conclusions: Based on a systematic review of other severe coronaviruses, we summarise the state of clinical research for COVID-19, highlight the research gaps, and provide recommendations for the implementation of standardised protocols. Data based on internationally standardised protocols will inform clinical practice real-time.", "title": "An evidence-based framework for priority clinical research questions for COVID-19", "pid": "1pgdofj6", "bm25_score": 216.54312133789062}, {"text": "OBJECTIVE: The primary purpose of the study was to investigate and to summarize the registered trials that listed COVID-19 as the primary condition. METHODS: We performed a search on ClinicalTrials.gov using the independent search terms COVID-19, SARS, and SARS-CoV-2 and then downloaded the data file on March 23, 2020. All trials were downloaded to a csv file and searched for appropriateness. RESULTS: Of 124 registered trials, 56 (45.2%) were listed as recruiting. The majority (85 [68.5%]) were classified as interventional, 37 (29.8%) as observational, and one (0.8%) each as either expanded access: individual patients|treatment investigational new drug/protocol or expanded access: intermediate-size population|treatment investigational new drug/protocol. There were 67 (54.0%) trials that listed drug as the type of study. Immunologic and antiviral trials were the most common, representing approximately 30% and 21%, respectively. When immunologic and antiviral drugs were used alone or in combination, they represented 41.9% and 34.4%, respectively. Antimalarial agents are represented in 7.5% of trials. Approximately 14% of trials involved traditional Chinese medicine. The study agents used solely or in combination represented approximately 80% of therapeutic approaches to COVID-19. CONCLUSIONS: There was a large and quick response on ClinicalTrials.gov to the COVID-19 outbreak. Many of the registered trials are currently recruiting new patients, whereas some will begin in the near future. Specific potential experimental therapies, including dosing and monitoring, might be found by reviewing content. Within ClinicalTrials.gov, patients, family members, health care professionals, and researchers can search and find ongoing and future trials for COVID-19.", "title": "Cardiovascular disease due to novel coronavirus and the search for investigational therapies", "pid": "y6mpjjr2", "bm25_score": 216.53955078125}, {"text": "INTRODUCTION In December 2019, an outbreak of pneumonia caused by a novel coronavirus occurred in Wuhan, the capital of Central China's Hubei Province and has been declared a public health emergency of international concern by the World Health Organization since January 2020. MATERIAL AND METHODS A comprehensive search using the PubMed database was carried out to summarize the latest published information about the epidemiology, definition, pathogenesis, clinical characteristics, treatment options, prognosis and prevention of coronavirus disease 2019. DISCUSSION This new strain of coronavirus, named severe acute respiratory syndrome coronavirus 2, enters human cells that express angiotensin-converting enzyme II receptors, which exist in the respiratory, gastrointestinal and genitourinary tracts and heart, causing coronavirus disease. Transmission occurs essentially through the respiratory tract and the main symptoms are fever, cough and dyspnea. Diagnosis is based on epidemiological, clinical and imaging features and confirmed by nucleic acid testing. CONCLUSION Despite intensive research, the exact origin of the virus and pathophysiology of coronavirus disease is not yet completely known, and clinically approved vaccines and drugs that target severe acute respiratory syndrome coronavirus 2 are lacking.", "title": "Coronavirus Disease 2019: Clinical Review.", "pid": "11ku3zho", "bm25_score": 216.53121948242188}, {"text": "The scientific community has risen to the coronavirus disease 2019 (COVID-19) challenge, coming up with an impressive list of candidate drugs and vaccines targeting an array of pharmacological and immunological mechanisms. Yet, generating clinical evidence of efficacy and safety of these candidate treatments may be frustrated by the absence of comprehensive trial coordination mechanisms. Many small stand-alone trials and observational studies of single-agent interventions are currently running or in planning; many of these will likely not deliver robust results that could support regulatory and patient-level treatment decisions. In this paper, we discuss actions that all stakeholders in the clinical trial ecosystem need to take to ensure that the window of opportunity during this pandemic will not shut, both for patients in need of treatment and for researchers to conduct decision-relevant clinical trials.", "title": "Clinical Trials for COVID-19: Can we Better Use the Short Window of Opportunity?", "pid": "fz6eumik", "bm25_score": 216.52688598632812}, {"text": "Despite the ferment aroused in the scientific community by the COVID-19 outbreak and the over 11,000 papers listed in PubMed, published evidence on safe and effective drugs has not progressed yet at the same speed of the pandemic. However, clinical research is rapidly progressing, as shown by the hundreds of registered clinical trials on candidate drugs for COVID-19. Unfortunately, information on protocols of individual studies differs from registry to registry. Furthermore, study designs, criteria for stratification of patients and choice of outcomes are quite heterogeneous. All this makes data sharing and secondary analysis difficult. At last, small single centre studies and the use of drugs on a compassionate basis should be replaced by highly powered, multi-centre, multi-arm clinical trials, in order to provide the required evidence of safety and efficacy of novel or repurposed candidate drugs. Hopefully, the efforts of clinical researchers in the fight against the SARS Cov-2 will result into the identification of effective treatments. To make this possible, clinical research should be oriented by guidelines for more harmonized high-quality studies and by a united commitment of the scientific community to share personal knowledge and data. Allergists and clinical immunologists should have a leading role in this unprecedent challenge.", "title": "COVID-19 Clinical trials: Quality matters more than quantity", "pid": "f590pp4j", "bm25_score": 216.52439880371094}, {"text": "PURPOSE: The primary purpose of the current study was to investigate and summarize the registered trials that listed COVID-19 as the primary condition. METHODS: We performed a search on ClinicalTrials.gov using the independent search terms COVID-19, SARS, and SARS COV2, and then downloaded the data file on March 23, 2020. All trials were downloaded to a csv file and searched for appropriateness. RESULTS: Fifty-six of 124 (45.2%) registered trials were listed as recruiting. The majority (85, 68.5%) classified their study as interventional, 37 (29.8%) classified as observational and one (0.8%) each classified their study as either expanded access:individual patients | treatment IND/Protocol or expanded access:intermediate-size population | treatment IND/Protocol. There were 67 (54.0%) of the trials that listed drug as the type of study. Immunological and antiviral trials were the greatest, representing approximately 30% and 21%, respectively. When immunological and antiviral drugs were used alone or in combination, they represented 41.9% and 34.4%, respectively. Anti-malarial agents are represented in 7.5% of trials. Approximately 14% of trials involved Traditional Chinese Medicine. The aforementioned study agents used solely or in combination represented approximately 80% of therapeutic approaches to COVID19. CONCLUSION: There was a large and quick response on ClinicalTrials.gov to the COVID-19 outbreak. Many of the registered trials are currently recruiting new patients, while some will begin in the near future. Specific potential experimental therapies, including dosing and monitoring, might be found by reviewing content. Within clinicaltrials.gov, patients, family members, health care professionals and researchers can search and find ongoing and future trials for COVID-19.", "title": "Cardiovascular Disease Novel Coronavirus and the Search for Investigational Therapies", "pid": "4nci3fsi", "bm25_score": 216.5199432373047}, {"text": "", "title": "Statins in coronavirus outbreak: It's time for experimental and clinical studies", "pid": "crcmrfif", "bm25_score": 216.51109313964844}, {"text": "SARS-CoV-2 continues to spread rapidly outside of mainland China. As of April 6, there are over 300,000 cases and 10,000 deaths in the US. Effective therapies for the novel Coronavirus are urgently needed and over 200 clinical trials are now underway across the globe. Recognizing the need for robust randomized control trials, the World Health Organization (WHO) recently organized a multinational randomized trial-the SOLIDARITY trial-to study the effect of drugs that have been identified as promising based on in-vitro data and the early clinical experience with COVID-19: Remdesivir, lopinavir and ritonavir; lopinavir and ritonavir + interferon; and chloroquine or hydroxychloroquine.", "title": "Off‐Label Therapies for COVID‐19—Are We All In This Together?", "pid": "f5tpz8ze", "bm25_score": 216.50267028808594}, {"text": "The current coronavirus (SARS-COV-2) pandemic and phenomenal spread to every nook and cranny of the world has raised major apprehensions about the modern public health care system. So far as a result of this epidemic, 4,434,653 confirmed cases and 302,169 deaths are reported. The growing infection rate and death toll demand the use of all possible approaches to design novel drugs and vaccines to curb this disease. In this study, we combined drugs repurposing and virtual drug screening strategies to target 3CLpro, which has an essential role in viral maturation and replication. A total of 31 FDA approved anti-HIV drugs, and Traditional Chinese medicines (TCM) database were screened to find potential inhibitors. As a result, Saquinavir, and five drugs (TCM5280805, TCM5280445, TCM5280343, TCM5280863, and TCM5458190) from the TCM database were found as promising hits. Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. Thus, we suggest that these compounds should be tested experimentally against the SARS-COV-2 as Saquinavir has been reported to inhibit HIV protease experimentally. Considering the intensity of coronavirus dissemination, the present research is in line with the idea of discovering the latest inhibitors against the coronavirus essential pathways to accelerate the drug development cycle.Communicated by Ramaswamy H. Sarma.", "title": "Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro)", "pid": "qp54spam", "bm25_score": 216.50201416015625}, {"text": "The current coronavirus (SARS-COV-2) pandemic and phenomenal spread to every nook and cranny of the world has raised major apprehensions about the modern public health care system. So far as a result of this epidemic, 4,434,653 confirmed cases and 302,169 deaths are reported. The growing infection rate and death toll demand the use of all possible approaches to design novel drugs and vaccines to curb this disease. In this study, we combined drugs repurposing and virtual drug screening strategies to target 3CLpro, which has an essential role in viral maturation and replication. A total of 31 FDA approved anti-HIV drugs, and Traditional Chinese medicines (TCM) database were screened to find potential inhibitors. As a result, Saquinavir, and five drugs (TCM5280805, TCM5280445, TCM5280343, TCM5280863, and TCM5458190) from the TCM database were found as promising hits. Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. Thus, we suggest that these compounds should be tested experimentally against the SARS-COV-2 as Saquinavir has been reported to inhibit HIV protease experimentally. Considering the intensity of coronavirus dissemination, the present research is in line with the idea of discovering the latest inhibitors against the coronavirus essential pathways to accelerate the drug development cycle. Communicated by Ramaswamy H. Sarma.", "title": "Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro)", "pid": "pwi48i20", "bm25_score": 216.50201416015625}, {"text": "", "title": "The coronavirus outbreak could make it quicker and easier to trial drugs.", "pid": "bjsmv3y1", "bm25_score": 216.49295043945312}, {"text": "BACKGROUND: The Middle East Respiratory Syndrome coronavirus (MERS-CoV) is an emerging respiratory pathogen with a high mortality rate and no specific treatments available to date. The purpose of this study was to determine the feasibility of conducting a randomized controlled trial (RCT) of convalescent plasma therapy for MERS-CoV-infected patients by using MERS-CoV-specific convalescent plasma obtained from previously recovered patients. METHODS: A survey was adapted from validated questionnaire originally aimed to measure network capacities and capabilities within the International Severe Acute Respiratory and emerging Infection Consortium (ISARIC). The questionnaire was modified for this study to include 26 items that were divided into three main domains of interest: (1) the ability to care for critically ill MERS-CoV patients; (2) laboratory capacity to diagnose MERS-CoV and blood bank ability to prepare convalescent plasma; and (3), research capacity to conduct randomized controlled trials. The questionnaire was emailed to physicians. RESULTS: Of 582 physicians who were invited to the survey, 327 responded (56.2 %). The professional focus of the majority of respondents was critical care (106/249 (43 %)), pediatrics (59/249, (24 %)) or internal medicine (52/249 (21 %)) but none was blood banking. Nearly all respondents (251/263 (95 %)) reported to have access to ICU facilities within their institutions. Most respondents (219/270 (81 %)) reported that intensivists were the most physician group responsible for treatment decisions about critically ill SARI patients. While 125/165 respondents (76 %) reported that they conduct research in ICUs, and 80/161 (49.7 %) had been involved in the conduct of RCTs, including using a placebo comparison (60/161 (37 %)), only 49/226 (21 %) of respondents regularly participated in research networks. CONCLUSIONS: Our survey indicated that in the Kingdom of Saudi Arabia (KSA), ICUs are the most likely clinical locations for conducting a clinical trial of convalescent plasma therapy for MERS-CoV, and that most ICUs have experience with such research designs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12871-016-0198-x) contains supplementary material, which is available to authorized users.", "title": "Feasibility of a randomized controlled trial to assess treatment of Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection in Saudi Arabia: a survey of physicians", "pid": "7hjsux4m", "bm25_score": 216.48683166503906}, {"text": "OBJECTIVES: The emergence of SARS-CoV-2 has presented clinicians with a difficult therapeutic dilemma. With supportive care as the current mainstay of treatment, the fatality rate of COVID-19 is 6.9%. There are currently several trials assessing the efficacy of different antivirals as treatment. Of these, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have garnered the most attention. METHODS: In this study, the literature currently available on CQ and HCQ as treatment of COVID-19 was surveyed using EMBASE, PubMed, Cochrane Library, MedRxiv, and one clinical trial registry. Upon gathering published and preprint trials, risk of bias was assessed using Cochrane Risk of Bias Tool 2.0. RESULTS: There are currently seven completed clinical trials and 29 registered clinical trials focusing on HCQ or CQ as a therapeutic avenue for COVID-19. Of these, five of seven trials have shown favorable outcomes for patients using CQ or HCQ and two of seven have shown no change compared to control. However, all seven trials carried varying degrees of bias and poor study design. CONCLUSION: There are currently not enough data available to support the routine use of HCQ and CQ as therapies for COVID-19. Pending further results from more extensive studies with more stringent study parameters, clinicians should defer from routine use of HCQ and CQ. There are several clinical trials currently under way with results expected soon.", "title": "A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID-19", "pid": "bfui91w7", "bm25_score": 216.48568725585938}, {"text": "Considering the massive amount of clinical trial registers aimed to find effective drugs for the prevention and treatment of COVID-19, it is challenging to have a comprehensive view of which drugs are being studied more extensively and when is expected that we will have consistent results regarding their effectiveness. This systematic review included all clinical trials on pharmacological therapy related to COVID-19 and SARS-CoV-2 registered at the International Clinical Trials Registry Platform (WHO-ICTRP) up to April 22, 2020. Clinical trials characteristics (country, design, sample size, main outcomes, expected completion data, type of participants, length of the interventions, main outcomes). How many trials and he accumulated sample size by drug or combination of drugs, and by month in 2020 was depicted. We identified 412 clinical trials registers addressing the effect of pharmacological treatments on COVID-19, predominantly from Asia and Europe (42.2% and 31.1% of clinical trials registers, respectively). The most main outcomes studied were clinical recovery (54.4% of the clinical trials registers, respiratory recovery (28.2%) mortality (27.4%), viral load/negativity (20.4%). During 2020, a huge amount of clinical trials are expected to be completed: 41 trials (60,366 participants) using hydroxychloroquine, 20 trials (1,588 participants) using plasma, 18 trials (6,830 participants) using chloroquine, 12 trials (9,938 participants using lopinavir/ritonavir, 11 trials (1,250 participants) using favipiravir, 10 trials ( 2,175 participants) using tocilizumab and 6 trials (13,540 participants) using Remdesivir. The distribution of the number of registered clinical trials among the different therapeutic options leads to an excess of sample size for some and a lack for others. Our data allow us to conclude that by the end of June we will have results of almost 20 trials involving 40000 patients for hydroxychloroquine and 5 trials with 4500 patients for remdesivir; however, low statistical power is expected from the 9 clinical trials testing the efficacy of favipiravir or the 5 testing tocilizumab, since they will recruit less than 1000 patients each one.", "title": "The race to find a SARS-CoV-2 drug can only be won by a few chosen drugs: a systematic review of registers of clinical trials of drugs aimed at preventing or treating COVID-19", "pid": "fsvacjgk", "bm25_score": 216.4805450439453}, {"text": "SARS-coronavirus-2 (SARS-CoV-2), the etiologic agent of the new lung disease COVID-19 is closely related to SARS-CoV, and together with MERS-CoV are three new human coronaviruses that emerged in the last 20 years. The COVID-19 outbreak is a rapidly evolving situation with higher transmissibility and infectivity compared with SARS and MERS. Clinical presentations range from asymptomatic or mild symptoms to severe illness. The prevalent cause of mortality is pneumonia that progresses to ARDS. The ongoing pandemic has already resulted in more than 135,000 deaths and an unprecedented burden on national health systems worldwide. Pending the availability of a vaccine, there is a critical need to identify effective treatments and a number of clinical trials have been implemented worldwide. Trials are based on repurposed drugs that are already approved for other infections, have acceptable safety profiles or have performed well in animal studies against the other two deadly coronaviruses. Supportive care remains the mainstay of therapy at present, as it is still unclear how well these data can be extrapolated to SARS-CoV-2. Most of those emerging re-introduced drugs are administered to patients in the context of clinical trials. In this review, we summarize the strategies currently employed in the treatment of COVID-19.", "title": "[Comment] Treatment strategies to fight the new coronavirus SARS-CoV-2: A challenge for a Rubik's Cube solver", "pid": "g8bu2ene", "bm25_score": 216.474365234375}, {"text": "Background: The purpose of the current systematic review is to evaluate the efficacy of antiviral therapies in treatment of COVID-19 In addition, clinical trials on the efficacy of antiviral therapies in the management of Severe Acute Respiratory Syndrome coronavirus (SARS-Cov) or Middle East Respiratory Syndrome coronavirus (MERS-CoV) have also been reviewed, in order to identify potential treatment options for COVID-19 Method: An extensive search was performed in Medline, Embase, Scopus, Web of Science and CENTRAL databases until the end of March 15, 2020 Two independent researchers performed the screening, and finally the related studies were included Results: Only one clinical trial on the efficacy of antiviral therapy in management of COVID-19 was found The results depicted that adding Lopinavir-Ritonavir to the standard treatment regimen of patients with severe COVID-19 has no benefits Moreover, 21 case-series and case-report studies reported the prescription of antiviral agents in COVID-19, none of which can be used to determine the efficacy of antiviral therapies in confronting COVID-19 In addition, no clinical trials were found to be performed on the efficacy of antiviral agents in the management of SARS-CoV and MERS-CoV Conclusion: The current evidence impede researchers from proposing an appropriate antiviral therapy against COVID-19, making the current situation a serious concern for international organizations such as World Health Organization (WHO) In the time of the current pandemic and future epidemics, organizations such as WHO should pursue more proactive actions and plan well-designed clinical trials so that their results can be used in managing future epidemics", "title": "Antiviral therapy in management of COVID-19: a systematic review on current evidence", "pid": "be3udel6", "bm25_score": 216.47027587890625}, {"text": "No specific antivirals are currently available for two emerging infectious diseases, Middle East respiratory syndrome (MERS) and severe acute respiratory syndrome (SARS). A literature search covering pathogenesis, clinical features and therapeutics, clinically developed drugs for repurposing and novel drug targets was performed. This review presents current knowledge on the epidemiology, pathogenesis and clinical features of the SARS and MERS coronaviruses. The rationale for and outcomes with treatments used for SARS and MERS is discussed. The main focus of the review is on drug development and the potential that drugs approved for other indications provide for repurposing. The drugs we discuss belong to a wide range of different drug classes, such as cancer therapeutics, antipsychotics, and antimalarials. In addition to their activity against MERS and SARS coronaviruses, many of these approved drugs have broad-spectrum potential and have already been in clinical use for treating other viral infections. A wealth of knowledge is available for these drugs. However, the information in this review is not meant to guide clinical decisions, and any therapeutic described here should only be used in context of a clinical trial. Potential targets for novel antivirals and antibodies are discussed as well as lessons learned from treatment development for other RNA viruses. The article concludes with a discussion of the gaps in our knowledge and areas for future research on emerging coronaviruses.", "title": "Middle East Respiratory Syndrome and Severe Acute Respiratory Syndrome: Current Therapeutic Options and Potential Targets for Novel Therapies", "pid": "hyihoelf", "bm25_score": 216.47018432617188}, {"text": "INTRODUCTION: The Coronavirus disease-19 (COVID-19) caused by the novel beta coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) started in late December 2019 in Wuhan, China. Within a short span, COVID-19 was declared a global public health emergency affecting 214 countries with 5,939,234 confirmed cases and 3,67,255 deaths as of 30 May 2020. With limited knowledge about SARS-CoV-2, no approved treatment or vaccine is available till date. AREAS COVERED: We performed a review of literature on PubMed on the SARS-CoV-2 virus and COVID-19 illness including trials of preventive and therapeutic measures. This review presents the basic biology of coronaviruses, epidemiology of COVID-19, clinical presentations, investigational therapies and vaccines, infection prevention and control measures and the lessons from the present pandemic. EXPERT OPINION: The scale of the outbreak has brought the governments, health-care professionals, and scientists around the world under tremendous pressure to devise control strategies and develop novel prevention measures. While availability of vaccine for COVID-19 may take time, the disease may be contained through hand hygiene, physical distancing, travel restriction, and aggressive steps such as 'lockdown.' Clinical trials at different phases are ongoing across different countries to expedite the development of effective drugs and vaccine to overcome the pandemic.", "title": "Covid-19: a comprehensive review of a formidable foe and the road ahead", "pid": "1x0tvnho", "bm25_score": 216.4658660888672}, {"text": "BACKGROUND Severe acute respiratory syndrome (SARS) coronavirus emerged from an animal reservoir in 2002 and has the potential to reemerge, as shown by the occurrence of non-laboratory-associated new cases in the winter of 2003. In the absence of a vaccine, broad spectrum anticoronaviral medications are needed. OBJECTIVE Anticoronavirals targeting viral entry were reviewed in part I. Here we review anticoronaviral therapies directed against the intracellular life cycle, with an emphasis on allowed patents and pending patents. METHOD The published literature, in particular, patent publications is searched for relevant documents. The information is organized and critiqued. RESULTS/CONCLUSION Many promising anticoronaviral strategies are identified. Monoclonal antibodies, protease inhibitors, interferon-based drugs and nucleic-acid based antivirals are most advanced, each having its own advantages and disadvantages. A multi-pronged approach, keeping all venues open, is advocated.", "title": "Therapies for coronaviruses. Part 2: Inhibitors of intracellular life cycle.", "pid": "w98ak1s1", "bm25_score": 216.465087890625}, {"text": "BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by a novel corinavirus (later named SARS-CoV-2 virus), was fistly reported in Wuhan, Hubei Province, China towards the end of 2019. Large-scale spread within China and internationally led the World Health Organization to declare a Public Health Emergency of International Concern on 30th January 2020. The clinical manifestations of COVID-19 virus infection include asymptomatic infection, mild upper respiratory symptoms, severe viral pneumonia with respiratory failure, and even death. There are no antivirals of proven clinical efficacy in coronavirus infections. Remdesivir (GS-5734), a nucleoside analogue, has inhibitory effects on animal and human highly pathogenic coronaviruses, including MERS-CoV and SARS-CoV, in in vitro and in vivo experiments. It is also inhibitory against the COVID-19 virus in vitro. The aim of this study is to assess the efficacy and safety of remdesivir in adult patients with severe COVID-19. METHODS: The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. This is a phase 3, randomized, double-blind, placebo-controlled, multicentre trial. Adults (&#8805; 18 years) with laboratory-confirmed COVID-19 virus infection, severe pneumonia signs or symptoms, and radiologically confirmed severe pneumonia are randomly assigned in a 2:1 ratio to intravenously administered remdesivir or placebo for 10 days. The primary endpoint is time to clinical improvement (censored at day 28), defined as the time (in days) from randomization of study treatment (remdesivir or placebo) until a decline of two categories on a six-category ordinal scale of clinical status (1 = discharged; 6 = death) or live discharge from hospital. One interim analysis for efficacy and futility will be conducted once half of the total number of events required has been observed. DISCUSSION: This is the first randomized, placebo-controlled trial in COVID-19. Enrolment began in sites in Wuhan, Hubei Province, China on 6th February 2020. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04257656. Registered on 6 February 2020.", "title": "Evaluation of the efficacy and safety of intravenous remdesivir in adult patients with severe COVID-19: study protocol for a phase 3 randomized, double-blind, placebo-controlled, multicentre trial", "pid": "lhzcm4bt", "bm25_score": 216.46249389648438}, {"text": "Importance The pandemic of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents an unprecedented challenge to identify effective drugs for prevention and treatment. Given the rapid pace of scientific discovery and clinical data generated by the large number of people rapidly infected by SARS-CoV-2, clinicians need accurate evidence regarding effective medical treatments for this infection. Observations No proven effective therapies for this virus currently exist. The rapidly expanding knowledge regarding SARS-CoV-2 virology provides a significant number of potential drug targets. The most promising therapy is remdesivir. Remdesivir has potent in vitro activity against SARS-CoV-2, but it is not US Food and Drug Administration approved and currently is being tested in ongoing randomized trials. Oseltamivir has not been shown to have efficacy, and corticosteroids are currently not recommended. Current clinical evidence does not support stopping angiotensin-converting enzyme inhibitors or angiotensin receptor blockers in patients with COVID-19. Conclusions and Relevance The COVID-19 pandemic represents the greatest global public health crisis of this generation and, potentially, since the pandemic influenza outbreak of 1918. The speed and volume of clinical trials launched to investigate potential therapies for COVID-19 highlight both the need and capability to produce high-quality evidence even in the middle of a pandemic. No therapies have been shown effective to date.", "title": "Pharmacologic Treatments for Coronavirus Disease 2019 (COVID-19): A Review.", "pid": "8cvjsisw", "bm25_score": 216.45248413085938}, {"text": "At the end of the year 2019, the novel coronavirus (2019-nCoV) was spreading in Wuhan, China, and the outbreak process has a high speed. It was recognized as a pandemic by the World Health Organization (WHO) on 11 March 2020. Coronaviruses are enveloped and single-stranded RNA that have several families including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The pathogenesis mechanism and disease outcomes of SARS and MERS are now clear to some extent, but little information is available for 2019-nCoV. This newly identified corona virus infection represents flu-like symptoms, but usually the first symptoms are fever and dry cough. There has been no specific treatment against 2019-nCoV up to now, and physicians only apply supportive therapy. In the present article, we made an attempt to review the behavior of the virus around the world, epidemiology, a pathway for influx into the host cells, clinical presentation, as well as the treatments currently in use and future approaches; nitazoxanide may be our dream drug. We hope that this review has a positive impact on public knowledge for helping to deal with the 2019-nCoV and move one step forward toward its treatment in the near future.", "title": "Mysterious Virus: A Review on Behavior and Treatment Approaches of the Novel Coronavirus, 2019-nCoV", "pid": "8fxf715e", "bm25_score": 216.44338989257812}, {"text": "SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this, outbreak specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS- CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. UISS is then potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2.", "title": "In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform", "pid": "71n1tgrw", "bm25_score": 216.44168090820312}, {"text": "Background: Although a number of antiviral agents have been evaluated for coronaviruses there are no approved drugs available. To provide an overview of the landscape of therapeutic research for COVID-19, we conducted a review of registered clinical trials. Methods: A review of currently registered clinical trials was performed on registries, including the Chinese (chictr.org.cn) and US (clinicaltrials.gov) databases to identify relevant studies up to March, 7th 2020. The search was conducted using the search terms “2019-nCoV”, “COVID-19”, “SARS-CoV-2”, “Hcov-19”, “new coronavirus”, “novel coronavirus”. We included interventional clinical trials focusing on patients with COVID-19 and assessing antiviral drugs or agents. Findings: Out of the 353 studies identified, 115 clinical trials were selected for data extraction. Phase IV trials were the most commonly reported study type (n=27, 23%). However, 62 trials (54%) did not describe the phase of the study. Eighty percent (n=92) of the trials were randomized with parallel assignment and the median number of planned inclusions was 63 (IQR, 36-120). Open-label studies were the most frequent (46%) followed by double-blind (13%) and single blind studies (10%). The most frequently assessed therapies were: stem cells therapy (n=23 trials), lopinavir/ritonavir (n=15), chloroquine (n=11), umifenovir (n=9), hydroxychloroquine (n=7), plasma treatment (n=7), favipiravir (n=7), methylprednisolone (n=5), and remdesivir (n=5). Remdesivir was tested in 5 trials with a median of 400 (IQR, 394-453) planned inclusions per trial, while stem cells therapy was tested in 23 trials, but had a median of 40 (IQR, 23-60) planned inclusions per trial. Lopinavir/ritonavir was associated with the highest total number of planned inclusions (2606) followed by remdesivir (2155). Only 52% of the clinical trials reported the treatment dose (n=60) and only 34% (n=39) the duration. The primary outcome was clinical in 76 studies (66%), virological in 27 (23%); radiological in 9 (8%) or immunological in three studies (3%). Interpretation: Numerous clinical trials have been registered since the beginning of the COVID-19 outbreak, however, a number of information regarding drugs or trial design were lacking. Funding: None", "title": "A brief review of antiviral drugs evaluated in registered clinical trials for COVID-19", "pid": "t1wpujpm", "bm25_score": 216.43516540527344}, {"text": "Here, we explore the dynamics of the response of the scientific community to several epidemics, including Coronavirus 2019 (COVID-19), as assessed by the numbers of clinical trials, publications, and level of research funding over time. All six prior epidemics studied [bird flu, severe acute respiratory syndrome (SARS), swine flu, Middle East Respiratory Syndrome (MERS), Ebola, and Zika] were characterized by an initial spike of research response that flattened shortly thereafter. Unfortunately, no antiviral medications have been discovered to date as treatments for any of these diseases. By contrast, the HIV/AIDS pandemic has garnered consistent research investment since it began and resulted in drugs being developed within 7 years of its start date, with many more to follow. We argue that, to develop effective treatments for COVID-19 and be prepared for future epidemics, long-term, consistent investment in antiviral research is needed.", "title": "Learning from history: do not flatten the curve of antiviral research!", "pid": "gxtvlji7", "bm25_score": 216.41705322265625}, {"text": "Abstract At the end of the year 2019, the novel coronavirus (2019-nCoV) was spreading in Wuhan, China, and the outbreak process has a high speed. It was recognized as a pandemic by the World Health Organization (WHO) on 11 March 2020. Coronaviruses are enveloped and single-stranded RNA that have several families including Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS). The pathogenesis mechanism and disease outcomes of SARS and MERS are now clear to some extent, but little information is available for 2019-nCoV. This newly identified corona virus infection represents flu-like symptoms, but usually the first symptoms are fever and dry cough. There has been no specific treatment against 2019-nCoV up to now, and physicians only apply supportive therapy. In the present article, we made an attempt to review the behavior of the virus around the world, epidemiology, a pathway for influx into the host cells, clinical presentation, as well as the treatments currently in use and future approaches; nitazoxanide may be our dream drug. We hope that this review has a positive impact on public knowledge for helping to deal with the 2019-nCoV and move one step forward toward its treatment in the near future.", "title": "Mysterious Virus: A Review on Behavior and Treatment Approaches of the Novel Coronavirus, 2019-nCoV", "pid": "o1mrpgvj", "bm25_score": 216.41671752929688}]}
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"z86g8dzs": 2, "zbmncsw2": 2, "7kidc16v": 0, "zfea3qg7": 1, "vgqvgz21": 2, "vvoljc59": 0, "09e5n5zd": 0, "ljzuuij0": 2, "zpqrm0a3": 1, "zrobzakn": 1, "zsxkynim": 0, "zu2hfx32": 1, "zv4jnvy1": 2, "zv7k3k08": 1, "zw46clpt": 2, "zwyueevh": 2, "zx860p73": 2, "i1dbkmfu": 2, "bdfli7l0": 0, "zzumi9h5": 1}, "bm25_results": [{"text": "COVID-19 pandemic is now a global threat on human health reaching up to 2 million infected people all around the World. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipments and especially masks were among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty; is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission.", "title": "Medical mask or N95 respirator: When and how to use?", "pid": "6wxjm7m0", "bm25_score": 217.72421264648438}, {"text": "COVID-19 pandemic is now a global threat to human health reaching up to 2 million infected people all around the world. Since its first recognition in Wuhan, many topics were discussed intensively about COVID-19, both in the public and scientific community. Personal protective equipment, especially masks, has been among the hottest topics during this pandemic. Regardless of which mask is used, performing hand hygiene frequently with an alcohol-based hand rub or with soap and water if hands are dirty is the most effective preventive measure for COVID-19. The type of mask used when caring for COVID-19 patients will vary according to the setting, type of personnel/person, and activity. Although the main transmission route for COVID-19 is droplets, during aerosol generating procedures airborne transmission may occur. Keeping the distancing and medical masks and eye protection during close contact efficiently protects against respiratory diseases transmitted via droplets. Airborne precautions include goggles and respiratory protection with the use of an N95 or an equivalent mask respirator to prevent airborne transmission.", "title": "Medical mask or N95 respirator: When and how to use?", "pid": "r1oqwdkz", "bm25_score": 217.68618774414062}, {"text": "The coronavirus disease 2019 (COVID-19) [2019-nCoV; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] was first detected in Wuhan, China at the end of 2019. In current status, spread of CO-VID-19 in person-to-person could be caused mainly by respiratory droplets, which leads to the spread of the influenza virus in both community and clinicians. Thus, in order to reduce the risk of that, the urgent management strategies against COVID-19 are to block transmission, isolation, protection, and using drug or vaccine updated on an ongoing basis. unfortunately, no drugs or vaccines still has yet been allowed to treat patients with COVID-19, so the rapid detection of effective intercessions against COVID-19 is seemed a major challenge on the all world. Herein, this article attempts summarizing to introduce the characterization of COVID-19, the influence of droplets travel in person-to-person transmission and the effect of wearing masks in the infection prevention of influenza virus, as well as understanding its advantage and role in the coronavirus infection prevention.", "title": "Coronavirus infection prevention by wearing masks", "pid": "q0ey3wib", "bm25_score": 217.559814453125}, {"text": "Controversy exists around the appropriate types of masks and the situations in which they should be used in community and health care settings for the prevention of SARS-CoV-2 infection. In this article, the American College of Physicians (ACP) provides recommendations based on the best available evidence through 14 April 2020 on the effectiveness of N95 respirators, surgical masks, and cloth masks in reducing transmission of infection. The ACP plans periodic updates of these recommendations on the basis of ongoing surveillance of the literature for 1 year from the initial search date.", "title": "Use of N95, Surgical, and Cloth Masks to Prevent COVID-19 in Health Care and Community Settings: Living Practice Points From the American College of Physicians (Version 1)", "pid": "f4sd7vbi", "bm25_score": 217.3763427734375}, {"text": "BACKGROUND: Respiratory protective devices are critical in protecting against infection in healthcare workers at high risk of novel 2019 coronavirus disease (COVID-19); however, recommendations are conflicting and epidemiological data on their relative effectiveness against COVID-19 are limited. PURPOSE: To compare medical masks to N95 respirators in preventing laboratory-confirmed viral infection and respiratory illness including coronavirus specifically in healthcare workers. DATA SOURCES: MEDLINE, Embase, and CENTRAL from January 1, 2014, to March 9, 2020. Update of published search conducted from January 1, 1990, to December 9, 2014. STUDY SELECTION: Randomized controlled trials (RCTs) comparing the protective effect of medical masks to N95 respirators in healthcare workers. DATA EXTRACTION: Reviewer pair independently screened, extracted data, and assessed risk of bias and the certainty of the evidence. DATA SYNTHESIS: Four RCTs were meta-analyzed adjusting for clustering. Compared with N95 respirators; the use of medical masks did not increase laboratory-confirmed viral (including coronaviruses) respiratory infection (OR 1.06; 95% CI 0.90-1.25; I2 = 0%; low certainty in the evidence) or clinical respiratory illness (OR 1.49; 95% CI: 0.98-2.28; I2 = 78%; very low certainty in the evidence). Only one trial evaluated coronaviruses separately and found no difference between the two groups (P = .49). LIMITATIONS: Indirectness and imprecision of available evidence. CONCLUSIONS: Low certainty evidence suggests that medical masks and N95 respirators offer similar protection against viral respiratory infection including coronavirus in healthcare workers during non-aerosol-generating care. Preservation of N95 respirators for high-risk, aerosol-generating procedures in this pandemic should be considered when in short supply.", "title": "Medical masks vs N95 respirators for preventing COVID-19 in healthcare workers: A systematic review and meta-analysis of randomized trials", "pid": "8khrecrf", "bm25_score": 217.29591369628906}, {"text": "Cloth masks have been used in healthcare and community settings to protect the wearer from respiratory infections. The use of cloth masks during the coronavirus disease (COVID-19) pandemic is under debate. The filtration effectiveness of cloth masks is generally lower than that of medical masks and respirators; however, cloth masks may provide some protection if well designed and used correctly. Multilayer cloth masks, designed to fit around the face and made of water-resistant fabric with a high number of threads and finer weave, may provide reasonable protection. Until a cloth mask design is proven to be equally effective as a medical or N95 mask, wearing cloth masks should not be mandated for healthcare workers. In community settings, however, cloth masks may be used to prevent community spread of infections by sick or asymptomatically infected persons, and the public should be educated about their correct use.", "title": "Effectiveness of Cloth Masks for Protection Against Severe Acute Respiratory Syndrome Coronavirus 2", "pid": "tcijnphu", "bm25_score": 217.26068115234375}, {"text": "Cloth masks have been used in healthcare and community settings to protect the wearer from respiratory infections. The use of cloth masks during the coronavirus disease (COVID-19) pandemic is under debate. The filtration effectiveness of cloth masks is generally lower than that of medical masks and respirators; however, cloth masks may provide some protection if well designed and used correctly. Multilayer cloth masks, designed to fit around the face and made of water-resistant fabric with a high number of threads and finer weave, may provide reasonable protection. Until a cloth mask design is proven to be equally effective as a medical or N95 mask, wearing cloth masks should not be mandated for healthcare workers. In community settings, however, cloth masks may be used to prevent community spread of infections by sick or asymptomatically infected persons, and the public should be educated about their correct use.", "title": "Effectiveness of Cloth Masks for Protection Against Severe Acute Respiratory Syndrome Coronavirus 2.", "pid": "xtraspw2", "bm25_score": 217.1837615966797}, {"text": "The Coronavirus Disease 2019 (COVID-19) has swept the whole world with high mortality. Since droplet transmission is the main route of transmission, wearing a mask serves as a crucial preventive measure. However, the virus has spread quite quickly, causing severe mask shortage. Finding alternative materials for homemade masks while ensuring the significant performance indicators will help alleviate the shortage of masks. Referring to the national standard for the \"Surgical Mask\" of China, 17 materials to be selected for homemade masks were tested in four key indicators: pressure difference, particle filtration efficiency, bacterial filtration efficiency and resistance to surface wetting. Eleven single-layer materials met the standard of pressure difference ([≤]49 Pa), of which 3 met the standard of resistance to surface wetting ([≥]3), 1 met the standard of particle filtration efficiency ([≥]30%), but none met the standard of bacterial filtration efficiency ([≥]95%). Based on the testing results of single-layer materials, fifteen combinations of paired materials were tested. The results showed that three double-layer materials including double-layer medical non-woven fabric, medical non-woven fabric plus non-woven shopping bag, and medical non-woven fabric plus granular tea towel could meet all the standards of pressure difference, particle filtration efficiency, and resistance to surface wetting, and were close to the standard of the bacterial filtration efficiency. In conclusion, if resources are severely lacking and medical masks cannot be obtained, homemade masks using available materials, based on the results of this study, can minimize the chance of infection to the maximum extent.", "title": "Selection of homemade mask materials for preventing transmission of COVID-19: a laboratory study", "pid": "o5esfwf4", "bm25_score": 217.07444763183594}, {"text": "Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. It has taken a toll of lots of lives since its outbreak. Infection prevention at present is an appropriate control measure in addition to other measure like hand hygiene and personal protective equipment (PPE). In our country with a large population, supplying PPE to all the health care workers of all hospitals definitely is an economic burden. Hence we have come up with an economic and simple solution for face mask.", "title": "Simple Economical Solution for Personal Protection Equipment (Face Mask/Shield) for Health Care Staff During COVID 19", "pid": "1jpf9kc4", "bm25_score": 217.0725860595703}, {"text": "BACKGROUND: Respiratory protective devices are critical in protecting against infection in healthcare workers at high risk of novel 2019 coronavirus disease (COVID‐19); however, recommendations are conflicting and epidemiological data on their relative effectiveness against COVID‐19 are limited. PURPOSE: To compare medical masks to N95 respirators in preventing laboratory‐confirmed viral infection and respiratory illness including coronavirus specifically in healthcare workers. DATA SOURCES: MEDLINE, Embase, and CENTRAL from January 1, 2014, to March 9, 2020. Update of published search conducted from January 1, 1990, to December 9, 2014. STUDY SELECTION: Randomized controlled trials (RCTs) comparing the protective effect of medical masks to N95 respirators in healthcare workers. DATA EXTRACTION: Reviewer pair independently screened, extracted data, and assessed risk of bias and the certainty of the evidence. DATA SYNTHESIS: Four RCTs were meta‐analyzed adjusting for clustering. Compared with N95 respirators; the use of medical masks did not increase laboratory‐confirmed viral (including coronaviruses) respiratory infection (OR 1.06; 95% CI 0.90‐1.25; I (2) = 0%; low certainty in the evidence) or clinical respiratory illness (OR 1.49; 95% CI: 0.98‐2.28; I (2) = 78%; very low certainty in the evidence). Only one trial evaluated coronaviruses separately and found no difference between the two groups (P = .49). LIMITATIONS: Indirectness and imprecision of available evidence. CONCLUSIONS: Low certainty evidence suggests that medical masks and N95 respirators offer similar protection against viral respiratory infection including coronavirus in healthcare workers during non–aerosol‐generating care. Preservation of N95 respirators for high‐risk, aerosol‐generating procedures in this pandemic should be considered when in short supply.", "title": "Medical masks vs N95 respirators for preventing COVID‐19 in healthcare workers: A systematic review and meta‐analysis of randomized trials", "pid": "1aqf98e0", "bm25_score": 217.03973388671875}, {"text": "Background: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. Results: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials, case-control studies and retrospective studies. Conclusions: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "title": "Efficacy of face mask in preventing respiratory virus transmission: a systematic review and meta-analysis", "pid": "ropgq7tr", "bm25_score": 216.9746856689453}, {"text": "Coronavirus disease 2019 is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. It has taken a toll of lots of lives since its outbreak. Infection prevention at present is an appropriate control measure in addition to other measure like hand hygiene and personal protective equipment (PPE). In our country with a large population, supplying PPE to all the health care workers of all hospitals definitely is an economic burden. Hence we have come up with an economic and simple solution for face mask. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12070-020-01863-4) contains supplementary material, which is available to authorized users.", "title": "Simple Economical Solution for Personal Protection Equipment (Face Mask/Shield) for Health Care Staff During COVID 19", "pid": "05vx82oo", "bm25_score": 216.94564819335938}, {"text": "BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24–0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11–0.37) and 47% (OR = 0.53, 95% CI = 0.36–0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "title": "Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis", "pid": "x9sfgtim", "bm25_score": 216.908203125}, {"text": "BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "title": "Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis", "pid": "b4znk2wr", "bm25_score": 216.8671875}, {"text": "Protecting Health Care Workers (HCWs) during routine care of suspected or confirmed COVID-19 patients is of paramount importance to halt the SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) pandemic. The WHO, ECDC and CDC have issued conflicting guidelines on the use of respiratory filters (N95) by HCWs. We searched PubMed, Embase and The Cochrane Library from the inception to March 21, 2020 to identify randomized controlled trials (RCTs) comparing N95 respirators versus surgical masks for prevention of COVID-19 or any other respiratory infection among HCWs. The grading of recommendations, assessment, development, and evaluation (GRADE) was used to evaluate the quality of evidence. Four RCTs involving 8736 HCWs were included. We did not find any trial specifically on prevention of COVID-19. However, wearing N95 respirators can prevent 73 more (95% CI 46–91) clinical respiratory infections per 1000 HCWs compared to surgical masks (2 RCTs; 2594 patients; low quality of evidence). A protective effect of N95 respirators in laboratory-confirmed bacterial colonization (RR = 0.41; 95%CI 0.28–0.61) was also found. A trend in favour of N95 respirators was observed in preventing laboratory-confirmed respiratory viral infections, laboratory-confirmed respiratory infection, and influenza like illness. We found no direct high quality evidence on whether N95 respirators are better than surgical masks for HCWs protection from SARS-CoV-2. However, low quality evidence suggests that N95 respirators protect HCWs from clinical respiratory infections. This finding should be contemplated to decide the best strategy to support the resilience of healthcare systems facing the potentially catastrophic SARS-CoV-2 pandemic.", "title": "The need of health policy perspective to protect Healthcare Workers during COVID-19 pandemic. A GRADE rapid review on the N95 respirators effectiveness", "pid": "no8bgglk", "bm25_score": 216.71119689941406}, {"text": "The scarcity of facemasks, particularly N95 respirators, combined with the lack of solid data to address the suitability of each mask type for adequate health care worker (HCW) protection have caused turmoil among HCWs. Current recommendations suggest mask usage solely during HCW contact with Covid-19 patients, namely plain medical mask for low-risk contacts and N95 for aerosol generating procedures. The distinction regarding the escalation of mask complexity depending on contact type is nevertheless based on plausible theoretical assumptions rather than hard evidence of a clear benefit. Conversely, we suggest that at least a plain mask should be used during all HCWs' contacts in healthcare facilities which constitute a highly probable but often overlooked means of SARS-CoV-2 transmission among HCWs.", "title": "Providing evidence on the ongoing health care workers' mask debate", "pid": "zx860p73", "bm25_score": 216.70582580566406}, {"text": "Protecting Health Care Workers (HCWs) during routine care of suspected or confirmed COVID-19 patients is of paramount importance to halt the SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) pandemic. The WHO, ECDC and CDC have issued conflicting guidelines on the use of respiratory filters (N95) by HCWs. We searched PubMed, Embase and The Cochrane Library from the inception to March 21, 2020 to identify randomized controlled trials (RCTs) comparing N95 respirators versus surgical masks for prevention of COVID-19 or any other respiratory infection among HCWs. The grading of recommendations, assessment, development, and evaluation (GRADE) was used to evaluate the quality of evidence. Four RCTs involving 8736 HCWs were included. We did not find any trial specifically on prevention of COVID-19. However, wearing N95 respirators can prevent 73 more (95% CI 46-91) clinical respiratory infections per 1000 HCWs compared to surgical masks (2 RCTs; 2594 patients; low quality of evidence). A protective effect of N95 respirators in laboratory-confirmed bacterial colonization (RR = 0.41; 95%CI 0.28-0.61) was also found. A trend in favour of N95 respirators was observed in preventing laboratory-confirmed respiratory viral infections, laboratory-confirmed respiratory infection, and influenza like illness. We found no direct high quality evidence on whether N95 respirators are better than surgical masks for HCWs protection from SARS-CoV-2. However, low quality evidence suggests that N95 respirators protect HCWs from clinical respiratory infections. This finding should be contemplated to decide the best strategy to support the resilience of healthcare systems facing the potentially catastrophic SARS-CoV-2 pandemic.", "title": "The need of health policy perspective to protect Healthcare Workers during COVID-19 pandemic. A GRADE rapid review on the N95 respirators effectiveness", "pid": "334hmwmj", "bm25_score": 216.68997192382812}, {"text": "The COVID-19 (Coronavirus disease 2019) spreads primarily through droplets of saliva or discharge from the nose. COVID-19 is predominantly considered as an unavoidable pandemic, and scientists are very curious about how to provide the best protection to the public before a vaccine can be made available. There is an urge to manufacture a greater number of masks to prevent any aerosol with microbes. Hence, we aim to develop an efficient viral inactivation system by exploiting active compounds from naturally occurring medicinal plants and infusing them into nanofiber-based respiratory masks. Our strategy is to develop fibrous filtration with three-layered masks using the compounds from medicinal plants for viral deactivation. These masks will be beneficial not just to healthcare workers but common citizens as well. In the absence of vaccination, productive masks can be worn to prevent transmission of airborne pathogenic aerosols and control diseases.", "title": "COVID-19: emerging protective measures", "pid": "qi8x5yaq", "bm25_score": 216.68296813964844}, {"text": "The COVID-19 (Coronavirus disease 2019) spreads primarily through droplets of saliva or discharge from the nose. COVID-19 is predominantly considered as an unavoidable pandemic, and scientists are very curious about how to provide the best protection to the public before a vaccine can be made available. There is an urge to manufacture a greater number of masks to prevent any aerosol with microbes. Hence, we aim to develop an efficient viral inactivation system by exploiting active compounds from naturally occurring medicinal plants and infusing them into nanofiber-based respiratory masks. Our strategy is to develop fibrous filtration with three-layered masks using the compounds from medicinal plants for viral deactivation. These masks will be beneficial not just to healthcare workers but common citizens as well. In the absence of vaccination, productive masks can be worn to prevent transmission of airborne pathogenic aerosols and control diseases.", "title": "COVID-19: emerging protective measures.", "pid": "tfrawa9z", "bm25_score": 216.66555786132812}, {"text": "", "title": "Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach", "pid": "84asc8do", "bm25_score": 216.65640258789062}, {"text": "", "title": "Cloth masks versus medical masks for COVID-19 protection.", "pid": "rnle3aji", "bm25_score": 216.65347290039062}, {"text": "The use of face masks in public settings has been widely recommended by public health officials during the current COVID-19 pandemic. The masks help mitigate the risk of cross-infection via respiratory droplets; however, there are no specific guidelines on mask materials and designs that are most effective in minimizing droplet dispersal. While there have been prior studies on the performance of medical-grade masks, there are insufficient data on cloth-based coverings, which are being used by a vast majority of the general public. We use qualitative visualizations of emulated coughs and sneezes to examine how material- and design-choices impact the extent to which droplet-laden respiratory jets are blocked. Loosely folded face masks and bandana-style coverings provide minimal stopping-capability for the smallest aerosolized respiratory droplets. Well-fitted homemade masks with multiple layers of quilting fabric, and off-the-shelf cone style masks, proved to be the most effective in reducing droplet dispersal. These masks were able to curtail the speed and range of the respiratory jets significantly, albeit with some leakage through the mask material and from small gaps along the edges. Importantly, uncovered emulated coughs were able to travel notably farther than the currently recommended 6-ft distancing guideline. We outline the procedure for setting up simple visualization experiments using easily available materials, which may help healthcare professionals, medical researchers, and manufacturers in assessing the effectiveness of face masks and other personal protective equipment qualitatively.", "title": "Visualizing the effectiveness of face masks in obstructing respiratory jets", "pid": "ohkki0ke", "bm25_score": 216.6475830078125}, {"text": "'The Mask' has become a byword and a precious possession universally. Except for its use by the medical fraternity, answers to the common questions-whether it provides enough protection, which type is optimal for the general public and who really needs to don it, remain poorly understood. For a frontline healthcare worker, wearing mask is a necessity as an important person protection equipment, it is perhaps the most-powerful psychological symbol for the general public. Surprisingly, it even undermines all other recommended practices of infection control and breaking the transmission chain of Covid-19, like hand washing, personal hygiene and social distancing. 'The mask' has evolved with time and yet there is a need to further improve the design for safety, tolerability and comfort. In this review we present the journey of face mask, originating from the first masks aimed at stopping the bad smell to its industrial use to its all-important place in the medical field. Various types of face masks, their filtration efficiency, reusability and current recommendations for their use are presented.", "title": "The Face Mask How a Real Protection becomes a Psychological Symbol during Covid-19?", "pid": "uq6kj3qi", "bm25_score": 216.63401794433594}, {"text": "Background Protecting Health Care Workers (HCWs) during routine care of suspected or confirmed COVID-19 patients is of paramount importance to halt the SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) pandemic. The WHO, ECDC and CDC have issued conflicting guidelines on the use of respiratory filters (N95) by HCWs. Methods We searched PubMed, Embase and The Cochrane Library from the inception to March 21, 2020 to identify randomized controlled trials (RCTs) comparing N95 respirators versus surgical masks for prevention of COVID-19 or any other respiratory infection among HCWs. The grading of recommendations, assessment, development, and evaluation (GRADE) was used to evaluate the quality of evidence. Findings Four RCTs involving 8736 HCWs were included. We did not find any trial specifically on prevention of COVID-19. However, wearing N95 respirators can prevent 73 more (95% CI 46-91) clinical respiratory infections per 1000 HCWs compared to surgical masks (2 RCTs; 2594 patients; low quality of evidence). A protective effect of N95 respirators in laboratory-confirmed bacterial colonization (RR= 0.41; 95%CI 0.28-0.61) was also found. A trend in favour of N95 respirators was observed in preventing laboratory-confirmed respiratory viral infections, laboratory-confirmed respiratory infection, and influenza like illness. Interpretation We found no direct high quality evidence on whether N95 respirators are better than surgical masks for HCWs protection from SARS-CoV-2. However, low quality evidence suggests that N95 respirators protect HCWs from clinical respiratory infections. This finding should be contemplated to decide the best strategy to support the resilience of healthcare systems facing the potentially catastrophic SARS-CoV-2 pandemic.", "title": "The need of health policy perspective to protect Healthcare Workers during COVID-19 pandemic. A GRADE rapid review on the N95 respirators effectiveness.", "pid": "1q8tqeg7", "bm25_score": 216.62435913085938}, {"text": "The outbreak of Novel Coronavirus is causing an intensely feared globally. World Health Organization has even declared that it is a global health emergency. The simplest method to limit the spread of this new virus and for people to protect themselves as well as the others is to wear a mask in crowded places. The sudden increase demand on face mask has caused manufacturers the inability to not provide enough products in a short time and the situation properly will stay the same for a period of time. In this article, we aim to give an idea on how to save the number of face masks used but still provides the same protective values using a Cardiopulmonary resuscitation (CPR) mask and a common surgical facemask.", "title": "A Reusable Mask for Coronavirus Disease 2019 (COVID-19)", "pid": "jtyg7ym9", "bm25_score": 216.5846405029297}, {"text": "'The Mask' has become a byword and a precious possession universally. Except for its use by the medical fraternity, answers to the common questions-whether it provides enough protection, which type is optimal for the general public and who really needs to don it, remain poorly understood. For a frontline healthcare worker, wearing mask is a necessity as an important person protection equipment, it is perhaps the most-powerful psychological symbol for the general public. Surprisingly, it even undermines all other recommended practices of infection control and breaking the transmission chain of Covid-19, like hand washing, personal hygiene and social distancing. 'The mask' has evolved with time and yet there is a need to further improve the design for safety, tolerability and comfort. In this review we present the journey of face mask, originating from the first masks aimed at stopping the bad smell to its industrial use to its all-important place in the medical field. Various types of face masks, their filtration efficiency, reusability and current recommendations for their use are presented.", "title": "The face mask: How a real protection becomes a psychological symbol during Covid-19?", "pid": "svtux4dk", "bm25_score": 216.56137084960938}, {"text": "In the context of Coronavirus Disease (2019) (COVID-19) cases globally, there is a lack of consensus across cultures on whether wearing face masks is an effective physical intervention against disease transmission. This study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context. To achieve this goal, government should establish a risk adjusted strategy of mask use to scientifically publicize the use of masks, guarantee sufficient supply of masks, and cooperate for reducing health resources inequities.", "title": "Mask use during COVID-19: A risk adjusted strategy", "pid": "6tod4abn", "bm25_score": 216.55638122558594}, {"text": "The scarcity of facemasks, particularly N95 respirators, combined with the lack of solid data to address the suitability of each mask type for adequate health care worker (HCW) protection have caused turmoil among HCWs. Current recommendations suggest mask usage solely during HCW contact with Covid-19 patients, namely plain medical mask for low-risk contacts and N95 for aerosol generating procedures. The distinction regarding the escalation of mask complexity depending on contact type is nevertheless based on plausible theoretical assumptions rather than hard evidence of a clear benefit. Conversely, we suggest that at least a plain mask should be used during all HCWs’ contacts in healthcare facilities which constitute a highly probable but often overlooked means of SARS-CoV-2 transmission among HCWs.", "title": "Providing evidence on the ongoing health care workers’ mask debate", "pid": "arkf79tn", "bm25_score": 216.5499267578125}, {"text": "The emergence of coronavirus disease 19 pandemic and novel research on the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised controversies over the use of face masks to prevent community transmission. Specific regulations need to be fulfilled to use a face mask as part of the personal protective equipment and high quality of evidence supporting its use to prevent respiratory viral infections, including SARS-CoV-2, is lacking. However, its widespread use is becoming a standard practice in some countries and discrepancies between health authorities on their policy have led to controversy. The aim of this review is to provide an outlook on recent research in this matter and areas of opportunity.", "title": "UNIVERSAL MASKING DURING COVID-19 PANDEMIC - CURRENT EVIDENCE AND CONTROVERSIES.", "pid": "cvulb9t6", "bm25_score": 216.53895568847656}, {"text": "OBJECTIVE: To determine if a repurposed silicone-based dressing used underneath a N95 mask is a safe and beneficial option for facial skin injury prevention without compromising the mask's seal. METHODS: Since February 21, 2020, staff in high risk areas such as the ED and ICU of King Hamad University Hospital have worn N95 masks when doing aerosol-generating procedures to protect against the novel coronavirus 2019. At that time, without education enablers or resources that could be directly translated into practice, the hospital's Pressure Injury Prevention Committee explored and created a stepwise process to protect the skin under these masks. This procedure was developed over time and tested to make sure that it did not interfere with the effectiveness of the N95 mask seal. RESULTS: Skin protection was achieved by repurposing a readily available silicone border dressing cut into strips. This was tested on 10 volunteer staff members of various skin types and both sexes who became part of this evidence generation project. Oxygen saturation values taken before and after the 4-hour wear test confirmed that well-fitted facial protection did not compromise the mask seal, but rather improved it. An added advantage was increased comfort with less friction as self-reported by the staff. An educational enabler to prevent MDRPI from N95 mask wear was an important additional resource for the staff. CONCLUSIONS: This creative and novel stepwise process of developing a safe skin protection method by which staff could apply a repurposed silicone border dressing beneath an N95 mask was largely effective and aided by the creation of the enabler.", "title": "Preventing Facial Pressure Injury for Health Care Providers Adhering to COVID-19 Personal Protective Equipment Requirements", "pid": "dozkil5p", "bm25_score": 216.5377197265625}, {"text": "OBJECTIVE: To determine if a repurposed silicone-based dressing used underneath a N95 mask is a safe and beneficial option for facial skin injury prevention without compromising the mask’s seal. METHODS: Since February 21, 2020, staff in high risk areas such as the ED and ICU of King Hamad University Hospital have worn N95 masks when doing aerosol-generating procedures to protect against the novel coronavirus 2019. At that time, without education enablers or resources that could be directly translated into practice, the hospital’s Pressure Injury Prevention Committee explored and created a stepwise process to protect the skin under these masks. This procedure was developed over time and tested to make sure that it did not interfere with the effectiveness of the N95 mask seal. RESULTS: Skin protection was achieved by repurposing a readily available silicone border dressing cut into strips. This was tested on 10 volunteer staff members of various skin types and both sexes who became part of this evidence generation project. Oxygen saturation values taken before and after the 4-hour wear test confirmed that well-fitted facial protection did not compromise the mask seal, but rather improved it. An added advantage was increased comfort with less friction as self-reported by the staff. An educational enabler to prevent MDRPI from N95 mask wear was an important additional resource for the staff. CONCLUSIONS: This creative and novel stepwise process of developing a safe skin protection method by which staff could apply a repurposed silicone border dressing beneath an N95 mask was largely effective and aided by the creation of the enabler.", "title": "Preventing Facial Pressure Injury for Health Care Providers Adhering to COVID-19 Personal Protective Equipment Requirements", "pid": "l68ewxar", "bm25_score": 216.53530883789062}, {"text": "OBJECTIVE The successful management of an influenza pandemic will be reliant on the expertise of healthcare workers at high risk for occupationally acquired influenza. Recommended infection control measures for healthcare workers include surgical masks to protect against droplet-spread respiratory transmissible infections and N95 masks to protect against aerosol-spread infections. A literature review was undertaken for evidence of superior protective value of N95 masks or surgical masks for healthcare workers against influenza and extraneous factors influencing conferred protection. METHODS Four scientific search engines using 12 search sequences identified 21 mask studies in healthcare settings for the prevention of transmission of respiratory syncytial virus, Bordetella pertussis, and severe acute respiratory syndrome. Each was critically assessed in accordance with Australian National Health Medical Research Council guidelines. An additional 25 laboratory-based publications were also reviewed. RESULTS All studies reviewed used medium or lower level evidence study design. In the majority of studies, important confounders included the unrecognized impact of concurrent bundling of other infection control measures, mask compliance, contamination from improper doffing of masks, and ocular inoculation. Only three studies directly compared the protective value of surgical masks with N95 masks. The majority of laboratory studies identified both mask types as having a range of filtration efficiency, yet N95 masks afford superior protection against particles of a similar size to influenza. CONCLUSIONS World Health Organization guidelines recommend surgical masks for all patient care with the exception of N95 masks for aerosol generating procedures. Because of the paucity of high-quality studies in the healthcare setting, the advocacy of mask types is not entirely evidence-based. Evidence from laboratory studies of potential airborne spread of influenza from shedding patients indicate that guidelines related to the current 1-meter respiratory zone may need to be extended to a larger respiratory zone and include protection from ocular inoculation.", "title": "Protecting healthcare workers from pandemic influenza: N95 or surgical masks?", "pid": "rxk1x3mi", "bm25_score": 216.53404235839844}, {"text": "Ma's research shows N95 masks, medical masks, even homemade masks could block at least 90% of the virus in aerosols(1). This study puts the debate on whether the public wear masks back on the table. Recently Science interviewed Dr. Gao, director‐general of Chinese Center for Disease Control and Prevention (CDC). This article is protected by copyright. All rights reserved.", "title": "Mask is the possible key for self‐isolation in COVID‐19 pandemic", "pid": "p5hljkkm", "bm25_score": 216.5328826904297}, {"text": "The present COVID-19 pandemic, caused by the airborne SARS-CoV-2 virus, has highlighted the vital importance of appropriate personal protective equipment for all exposed health care workers The single most important part of this armor is the N-95 mask With the awareness that the virus is spread by both droplets and through the aerosolized route, the N-95 provides protection that a surgical mask cannot match This timely review looks at the special advantages that an N-95 offers over a surgical mask with specific reference to the COVID-19 epidemic It also emphasizes the crucial importance of ensuring quality masks with a proper fit Finally, with acute scarcities of N-95 masks being reported from hospitals globally, it reviews recent literature which attempts to prolong the life of these masks with extended use, reuse and decontamination of used masks", "title": "The N-95 mask: invaluable ally in the battle against the COVID-19 pandemic", "pid": "i1w2snyy", "bm25_score": 216.51004028320312}, {"text": "BACKGROUND: Recommendations on masks for preventing coronavirus disease 2019 (COVID-19) vary. PURPOSE: To examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks. DATA SOURCES: Multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server (2003 through 14 April 2020; surveillance through 2 June 2020), and reference lists. STUDY SELECTION: Randomized trials of masks and risk for respiratory virus infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and observational studies of mask use and coronavirus infection risk were included. New evidence will be incorporated by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; a second reviewer provided verification. DATA SYNTHESIS: 39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies. In high- or moderate-risk health care settings, observational studies found that risk for infection with SARS-CoV-1 and Middle East respiratory syndrome coronavirus probably decreased with mask use versus nonuse and possibly decreased with N95 versus surgical mask use. Randomized trials in community settings found possibly no difference between N95 versus surgical masks and probably no difference between surgical versus no mask in risk for influenza or influenza-like illness, but compliance was low. In health care settings, N95 and surgical masks were probably associated with similar risks for influenza-like illness and laboratory-confirmed viral infection; clinical respiratory illness had inconsistency. Bothersome symptoms were common. LIMITATIONS: There were few SARS-CoV-2 studies, observational studies have methodological limitations, and the review was done by using streamlined methods. CONCLUSION: Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.", "title": "Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings: A Living Rapid Review", "pid": "kshjqsdj", "bm25_score": 216.48974609375}, {"text": "BACKGROUND: Recommendations on masks for preventing coronavirus disease 2019 (COVID-19) vary. PURPOSE: To examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks. DATA SOURCES: Multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server (2003 through 14 April 2020; surveillance through 2 June 2020), and reference lists. STUDY SELECTION: Randomized trials of masks and risk for respiratory virus infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and observational studies of mask use and coronavirus infection risk were included. New evidence will be incorporated by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; a second reviewer provided verification. DATA SYNTHESIS: 39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies. In high- or moderate-risk health care settings, observational studies found that risk for infection with SARS-CoV-1 and Middle East respiratory syndrome coronavirus probably decreased with mask use versus nonuse and possibly decreased with N95 versus surgical mask use. Randomized trials in community settings found possibly no difference between N95 versus surgical masks and probably no difference between surgical versus no mask in risk for influenza or influenza-like illness, but compliance was low. In health care settings, N95 and surgical masks were probably associated with similar risks for influenza-like illness and laboratory-confirmed viral infection; clinical respiratory illness had inconsistency. Bothersome symptoms were common. LIMITATIONS: There were few SARS-CoV-2 studies, observational studies have methodological limitations, and the review was done by using streamlined methods. CONCLUSION: Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. Update Alerts: The authors have specified in the Methods section the interval and stop date for updates to this Living Review. As Annals receives updates, they will appear in the Comments section of the article on Annals.org. Reader inquiries about updates that are not available at approximately the specified intervals should be submitted as Comments to the article.", "title": "Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings: A Living Rapid Review", "pid": "j0lpy07l", "bm25_score": 216.48974609375}, {"text": "", "title": "Are face masks useful for limiting the spread of COVID-19?", "pid": "a6gaoeie", "bm25_score": 216.48204040527344}, {"text": "Cloth masks are a simple, economic and sustainable alternative to surgical mask as a means of source control of SARS-CoV-2 for general community.", "title": "Universal use of face masks for success against COVID-19: evidence and implications for prevention policies", "pid": "z86g8dzs", "bm25_score": 216.45474243164062}, {"text": "The use of face masks for the general public has been suggested in literature as a means to decrease virus transmission during the global COVID-19 pandemic. However, literature findings indicate that most mask designs do not provide reliable protection. This paper investigates the hypothesis that the impaired protection is mainly due to imperfect fitting of the masks, so that airflow, which contains virus-transporting droplets, can leak through gaps into or out of the mask. The fluid dynamics of face masks are investigated via analytical and numerical computations. The results demonstrate that the flow can be satisfactorily predicted by simplified analytical 1D-flow models, by efficient 2D-flow simulations and by 3D-flow simulations. The present results show that already gap heights larger than 0.1mm can result in the mask not fulfilling FFP2 or FFP3 standards, and for gap heights of ca. 1mm most of the airflow and droplets may pass through the gap. The implications of these findings are discussed and improvements to existing mask designs are suggested.", "title": "Analytical and numerical investigation of the airflow in face masks used for protection against COVID-19 virus -- implications for mask design and usage", "pid": "hiierdmt", "bm25_score": 216.4534912109375}, {"text": "In the context of Coronavirus Disease (2019) (COVID-19) cases globally, there is a lack of consensus across cultures on whether wearing face masks is an effective physical intervention against disease transmission. This study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context. To achieve this goal, government should establish a risk adjusted strategy of mask use to scientifically publicize the use of masks, guarantee sufficient supply of masks, and cooperate for reducing health resources inequities.", "title": "Mask use during COVID-19: A risk adjusted strategy()", "pid": "iaiosjlu", "bm25_score": 216.44143676757812}, {"text": "", "title": "Cloth masks versus medical masks for COVID-19 protection", "pid": "1j3ou5yv", "bm25_score": 216.43849182128906}, {"text": "The emergence of coronavirus disease 19 pandemic and novel research on the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised controversies over the use of face masks to prevent community transmission. Specific regulations need to be fulfilled to use a face mask as part of the personal protective equipment and high quality of evidence supporting its use to prevent respiratory viral infections, including SARS-CoV-2, is lacking. However, its widespread use is becoming a standard practice in some countries and discrepancies between health authorities on their policy have led to controversy. The aim of this review is to provide an outlook on recent research in this matter and areas of opportunity.", "title": "Universal Masking during Covid-19 Pandemic - Current Evidence and Controversies", "pid": "fdkqs3rg", "bm25_score": 216.4254608154297}, {"text": "Abstract The outbreak of Novel Coronavirus is causing an intensely feared globally. World Health Organization has even declared that it is a global health emergency. The simplest method to limit the spread of this new virus and for people to protect themselves as well as the others is to wear a mask in crowded places. The sudden increase demand on face mask has caused manufacturers the inability to not provide enough products in a short time and the situation properly will stay the same for a period of time. In this article, we aim to give an idea on how to save the number of face masks used but still provides the same protective values using a Cardiopulmonary resuscitation (CPR) mask and a common surgical facemask.", "title": "A Reusable Mask for Coronavirus Disease 2019 (COVID-19)", "pid": "rasjpg8v", "bm25_score": 216.42330932617188}, {"text": "Doctors need to wear complete protective equipment when large numbers of patients flood into the emergency room. Taiwan has so far managed to prevent a large scale community outbreak, city forces wearing face masks on public transportation, and keep social distancing to stem the virus from spreading. The protective device may be contaminated and must be replaced. In the situation of limited resources, how to take care of the physiological needs of the doctor without increasing the chance of contamination during replacement is a consideration. By reducing the chance of contamination during removal and storage, the previous designs were analyzed and improved. We proposed three improved designs to reduce the contact. Design-A features a mask with a water channel that allows the user to remain hydrated without removing the cover. Design-B has a folding pattern that hides the outer surface. Design-C combines the mask with the brim of a cap which form an extended air-intake area. Through understanding the problem, related product began distribute on the market, Design-D extend the mask usages period with less contact.", "title": "Face mask designs following novel Coronavirus", "pid": "ydrdvdif", "bm25_score": 216.376708984375}, {"text": "", "title": "Do facemasks protect against COVID-19?", "pid": "4w60qyfi", "bm25_score": 216.36953735351562}, {"text": "ABSTRACT Background The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally. Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public. Methods A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms. Results A total of 19 randomised controlled trials were included in this study – 8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be more effective than hand hygiene alone, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently. Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts. Conclusion The study suggests that community mask use by well people could be beneficial, particularly for COVID-19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift. This may prevent health worker infections and deaths from COVID-19, as aerosolisation in the hospital setting has been documented.", "title": "A RAPID SYSTEMATIC REVIEW OF THE EFFICACY OF FACE MASKS AND RESPIRATORS AGAINST CORONAVIRUSES AND OTHER RESPIRATORY TRANSMISSIBLE VIRUSES FOR THE COMMUNITY, HEALTHCARE WORKERS AND SICK PATIENTS", "pid": "h7ftu3ax", "bm25_score": 216.36532592773438}, {"text": "The use of medical masks and respirators as personal protective equipment is pivotal to reducing the level of biological hazard to which healthcare workers are exposed during the outbreak of highly diffusible pathogens, such as the recent novel coronavirus SARS-CoV-2. Unfortunately, during this pandemic, supplies are rapidly running out worldwide, with potential consequences for the rate of occupational infections. Also, knowledge about specific characteristics of respirators is of utmost importance to select the proper type according to the clinical setting. A wide variety of literature is available on the topic, but mostly based on Influenza viruses infection models. Clinical evidence on the use of respirators is poor and interest in the topic has not been constant over time. A better understanding of SARS-CoV-2 transmission is needed, together with high-quality clinical data on the use of respirators or alternative devices. Moreover, healthcare workers, regardless of their level of experience, should receive specific training. This review aims to summarize the available evidence on the use of medical masks and respirators in the context of viral infections, especially the current coronavirus disease 2019 (COVID-19).", "title": "Medical masks and Respirators for the Protection of Healthcare Workers from SARS-CoV-2 and other viruses", "pid": "uuau3n7s", "bm25_score": 216.36146545410156}, {"text": "BACKGROUND: The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally. Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public. METHODS: A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms. RESULTS: A total of 19 randomised controlled trials were included in this study - 8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be effective with and without hand hygiene, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently. Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts. CONCLUSION: The study suggests that community mask use by well people could be beneficial, particularly for COVID-19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift. This may prevent health worker infections and deaths from COVID-19, as aerosolisation in the hospital setting has been documented.", "title": "A rapid systematic review of the efficacy of face masks and respirators against coronaviruses and other respiratory transmissible viruses for the community, healthcare workers and sick patients", "pid": "in16u4pm", "bm25_score": 216.3514404296875}, {"text": "Abstract The use of medical masks and respirators as personal protective equipment is pivotal to reducing the level of biological hazard to which healthcare workers are exposed during the outbreak of highly diffusible pathogens, such as the recent novel coronavirus SARS-CoV-2. Unfortunately, during this pandemic, supplies are rapidly running out worldwide, with potential consequences for the rate of occupational infections. Also, knowledge about specific characteristics of respirators is of utmost importance to select the proper type according to the clinical setting. A wide variety of literature is available on the topic, but mostly based on Influenza viruses infection models. Clinical evidence on the use of respirators is poor and interest in the topic has not been constant over time. A better understanding of SARS-CoV-2 transmission is needed, together with high-quality clinical data on the use of respirators or alternative devices. Moreover, healthcare workers, regardless of their level of experience, should receive specific training. This review aims to summarize the available evidence on the use of medical masks and respirators in the context of viral infections, especially the current coronavirus disease 2019 (COVID-19).", "title": "Medical masks and Respirators for the Protection of Healthcare Workers from SARS-CoV-2 and other viruses", "pid": "86rb6hov", "bm25_score": 216.34754943847656}, {"text": "", "title": "Mask is the possible key for self-isolation in COVID-19 pandemic", "pid": "sdl5a5bm", "bm25_score": 216.34385681152344}, {"text": "Many governments have instructed the population to wear simple mouth-and-nose covers or surgical face masks to protect themselves from droplet infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in public. However, the basic protection mechanisms and benefits of these masks remain controversial. Therefore, the aim of this work is to show from a fluid physics point of view under which circumstances these masks can protect against droplet infection. First of all, we show that the masks protect people in the surrounding area quite well, since the flow resistance of the face masks effectively prevents the spread of exhaled air, e.g. when breathing, speaking, singing, coughing and sneezing. Secondly, we provide visual evidence that typical household materials used by the population to make masks do not provide highly efficient protection against respirable particles and droplets with a diameter of 0.3–2 μm as they pass through the materials largely unfiltered. According to our tests, only vacuum cleaner bags with fine dust filters show a comparable or even better filtering effect than commercial particle filtering FFP2/N95/KN95 half masks. Thirdly, we show that even simple mouth-and-nose covers made of good filter material cannot reliably protect against droplet infection in contaminated ambient air, since most of the air flows through gaps at the edge of the masks. Only a close-fitting, particle-filtering respirator without an outlet valve offers good self-protection and protection against droplet infection. Nevertheless, wearing simple homemade or surgical face masks in public is highly recommended if no particle filtrating respiratory mask is available. Firstly, because they protect against habitual contact of the face with the hands and thus serve as self-protection against contact infection. Secondly, because the flow resistance of the masks ensures that the air stays close to the head when breathing, speaking, singing, coughing and sneezing, thus protecting other people if they have sufficient distance from each other. However, if the distance rules cannot be observed and the risk of inhalation-based infection becomes high because many people in the vicinity are infectious and the air exchange rate is small, improved filtration efficiency masks are needed, to take full advantage of the three fundamental protective mechanisms these masks provide.", "title": "Fundamental protective mechanisms of face masks against droplet infections", "pid": "av1ev8ta", "bm25_score": 216.318603515625}, {"text": "The objective of this study was to investigate whether cotton mask worn by respiratory infection person could suppress respiratory droplet levels compared to medical mask. We recruited adult volunteers with confirmed influenza and suspected cases of coronavirus disease 2019 (COVID-19) to wear medical masks and self-designed triple-layer cotton masks in a regular bedroom and a car with air conditioning. Four 1-hour repeated measurements (two measurements for bedroom the others for car) of particles with a size range of 20-1000 nm measured by number concentrations (NC0.02-1), temperature and relatively humidity, and cough/sneeze counts per hour were conducted for each volunteer. The paired t-tests were used for within-group comparisons in a bedroom and in a car. The results showed that there was no significant difference in NC0.02-1 or cough/sneeze counts between volunteers with medical masks and cotton masks in a bedroom or a car. We concluded that the cotton mask could be a potential substitute for medical mask for respiratory infection person in microenvironment with air conditioning. Healthy people may daily use cotton mask in the community since cotton mask is washable and reusable.", "title": "Medical mask versus cotton mask for preventing respiratory droplet transmission in micro environments", "pid": "91zxeqwy", "bm25_score": 216.26734924316406}, {"text": "Background The pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), has become a serious worldwide public health emergency. This systematic review aims to summarize the available evidence regarding the role of face mask in community settings in slowing the spread of respiratory viruses such as SARS- CoV-2. Methods The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used for this review. A literature search using PUBMED, Google Scholar, and Cochrane database were performed using Medical subject heading (MeSH) words from the year 2000-2020. The articles focused on the use of masks and N95 respirators in healthcare workers were excluded. Results A total of 305 records were identified, out of which 14 articles were included in the review based upon quality and eligibility criteria. All the articles mentioned about the role of face masks in preventing the spread of respiratory viruses like influenza, SARS, and SARS-CoV-2, in the community or experimental setting. Studies also suggested that early initiation of face mask usage was more effective. Masks were also reported to be more effective in viruses that transmit easily from asymptomatic individuals, as is now known in SARS-CoV-2. Conclusion Theoretical, experimental, and clinical evidence suggested that usage of face masks in a general population offered significant benefit in preventing the spread of respiratory viruses especially in the pandemic situation, but its utility is limited by inconsistent adherence to mask usage.", "title": "The use of facemasks by the general population to prevent transmission of Covid 19 infection: A systematic review.", "pid": "f7rcijh4", "bm25_score": 216.26206970214844}, {"text": "As the COVID-19 pandemic progressed across the world, governments, international agencies, policymakers, and public health officials began recommending widespread use of nonmedical cloth masks to reduce the transmission of SARS-CoV-2. The authors of this article suggest that there is convincing evidence to support this recommendation.", "title": "Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach", "pid": "8je46886", "bm25_score": 216.26004028320312}, {"text": "Abstract The objective of this study was to investigate whether cotton mask worn by respiratory infection person could suppress respiratory droplet levels compared to medical mask. We recruited adult volunteers with confirmed influenza and suspected cases of coronavirus disease 2019 (COVID-19) to wear medical masks and self-designed triple-layer cotton masks in a regular bedroom and a car with air conditioning. Four 1-hour repeated measurements (two measurements for bedroom the others for car) of particles with a size range of 20–1000 nm measured by number concentrations (NC0.02–1), temperature and relatively humidity, and cough/sneeze counts per hour were conducted for each volunteer. The paired t-tests were used for within-group comparisons in a bedroom and in a car. The results showed that there was no significant difference in NC0.02–1 or cough/sneeze counts between volunteers with medical masks and cotton masks in a bedroom or a car. We concluded that the cotton mask could be a potential substitute for medical mask for respiratory infection person in microenvironment with air conditioning. Healthy people may daily use cotton mask in the community since cotton mask is washable and reusable.", "title": "Medical mask versus cotton mask for preventing respiratory droplet transmission in micro environments", "pid": "1w0dd54t", "bm25_score": 216.247314453125}, {"text": "", "title": "COVID-19 and non-traditional mask use: How do various materials compare in reducing the infection risk for mask wearers?", "pid": "imv1ygf6", "bm25_score": 216.2418670654297}, {"text": "Pandemics such as influenza, smallpox, and plague have caused the loss of hundreds of millions of lives and have occurred for many centuries. Fortunately, they have been largely eliminated by the use of vaccinations and drugs. More recently, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and now Coronavirus Disease 2019 (COVID-19) have arisen, and given the current absence of highly effective approved vaccines or drugs, brute-force approaches involving physical barriers are being used to counter virus spread. A major basis for physical protection from respiratory infections is eye, nose, and mouth protection. However, eye protection with goggles is problematic due to \"fogging\", while nose/mouth protection is complicated by the breathing difficulties associated with non-valved respirators. Here, we give a brief review of the origins and development of face masks and eye protection to counter respiratory infections on the basis of experiments conducted 100 years ago, work that was presaged by the first use of personal protective equipment, \"PPE\", by the plague doctors of the 17th Century. The results of the review lead to two conclusions: first, that eye protection using filtered eye masks be used to prevent ocular transmission; second, that new, pre-filtered, valved respirators be used to even more effectively block viral transmission.", "title": "COVID-19 and Other Pandemics: How Might They Be Prevented?", "pid": "ah29pm89", "bm25_score": 216.20465087890625}, {"text": "On January 8, 2020, a novel coronavirus was officially announced as the causative pathogen of coronavirus disease (COVID-19) by the Chinese Center for Disease Control and Prevention.On February 26, COVID-19 has been recognized in 34 countries, with a total of 80,239 laboratory-confirmed patients and 2700 deaths.Protecting healthcare workers from infectious hazards is paramount to ensuring their safety in delivering health care.In addition, being able to protect healthcare workers, constituting the front-line response against high-threat respiratory pathogens, such as severe acute respiratory syndrome coronavirus 2, is important for reducing secondary transmission in healthcare-associated outbreaks.Authors present a simple, reliable, and cheap protocol to produce a custom-made sterilizable filtering facepiece 2/3 masks for healthcare providers during pandemic COVID-19 emergency.", "title": "How to Produce Cheap and Easy Custom-Made Sterilizable Filtering Facepiece 2/3 Masks for Healthcare Providers During Pandemic COVID-19 Emergency", "pid": "2w05l8r6", "bm25_score": 216.20046997070312}, {"text": "Masks play a role in the protection of health-care workers (HCWs) from acquiring respiratory infections, including coronavirus disease 2019 (COVID-19) in health-care settings. This observational study was conducted among 382 HCWs in a tertiary care setting over a period of 1 month. Descriptive analysis was done to assess the rational and recommended use of masks/respirators during COVID-19 pandemic using a structured observation checklist as a survey tool. A total of 374 HCWs were included, 64.9% of whom were using face masks rationally as mentioned per risk area categorization with a predominance of triple-layered mask during all 4 weeks. Overall, 64.1% used masks correctly. Clear guidelines and strategies can help to increase the compliance of HCWs with rational use of face masks.", "title": "Rational use of face mask in a tertiary care hospital setting during COVID-19 pandemic: An observational study.", "pid": "t2e4bxsu", "bm25_score": 216.19699096679688}, {"text": "OBJECTIVES: To determine the risk of SARS-CoV-2 transmission by aerosols, to provide evidence on the rational use of masks, and to discuss additional measures important for the protection of healthcare workers from COVID-19. METHODS: Literature review and expert opinion. SHORT CONCLUSION: SARS-CoV-2, the pathogen causing COVID-19, is considered to be transmitted via droplets rather than aerosols, but droplets with strong directional airflow support may spread further than 2 m. High rates of COVID-19 infections in healthcare-workers (HCWs) have been reported from several countries. Respirators such as filtering face piece (FFP) 2 masks were designed to protect HCWs, while surgical masks were originally intended to protect patients (e.g., during surgery). Nevertheless, high quality standard surgical masks (type II/IIR according to European Norm EN 14683) appear to be as effective as FFP2 masks in preventing droplet-associated viral infections of HCWs as reported from influenza or SARS. So far, no head-to-head trials with these masks have been published for COVID-19. Neither mask type completely prevents transmission, which may be due to inappropriate handling and alternative transmission pathways. Therefore, compliance with a bundle of infection control measures including thorough hand hygiene is key. During high-risk procedures, both droplets and aerosols may be produced, reason why respirators are indicated for these interventions.", "title": "Risk of SARS-CoV-2 transmission by aerosols, the rational use of masks, and protection of healthcare workers from COVID-19", "pid": "9uxfxry4", "bm25_score": 216.17327880859375}, {"text": "", "title": "Masks and Coronavirus Disease 2019 (COVID-19)", "pid": "id8sfepi", "bm25_score": 216.1663818359375}, {"text": "Public health events caused by viruses pose a significant risk to humans worldwide. From December 2019 till now, the rampant novel 2019 coronavirus (SAR-CoV-2) has hugely impacted China and over world. Regarding a commendable means of protection, mask technology is relatively mature, though most of the masks cannot effectively resist the viral infections. The key material of the mask is a non-woven material, which makes the barrier of virus through filtration. Due to the lack of the ability to kill the viruses, masks are prone to cross-infection and become an additional source of infection after being discarded. If the filteration and antiviral effects can be simultaneously integrated into the mask, it will be more effcient, work for a longer time and create less difficulty in post-treatment. This mini-review presents the advances in antiviral materials, different mechanisms of their activity, and their potential applications in personal protective fabrics. Furthermore, the article addresses the future challenges and directions of mask technology.", "title": "Progress and Perspective of Antiviral Protective Material", "pid": "18crkfzj", "bm25_score": 216.16360473632812}, {"text": "Masks play a role in the protection of health-care workers (HCWs) from acquiring respiratory infections, including coronavirus disease 2019 (COVID-19) in health-care settings. This observational study was conducted among 382 HCWs in a tertiary care setting over a period of 1 month. Descriptive analysis was done to assess the rational and recommended use of masks/respirators during COVID-19 pandemic using a structured observation checklist as a survey tool. A total of 374 HCWs were included, 64.9% of whom were using face masks rationally as mentioned per risk area categorization with a predominance of triple-layered mask during all 4 weeks. Overall, 64.1% used masks correctly. Clear guidelines and strategies can help to increase the compliance of HCWs with rational use of face masks.", "title": "Rational use of face mask in a tertiary care hospital setting during COVID-19 pandemic: An observational study", "pid": "57zwd3y6", "bm25_score": 216.15525817871094}, {"text": "", "title": "Wearing face masks regardless of symptoms is crucial for preventing the spread of COVID-19 in hospitals", "pid": "st7c4v9v", "bm25_score": 216.1545867919922}, {"text": "", "title": "Physical distancing, face masks, and eye protection for prevention of COVID-19", "pid": "6y0vvogy", "bm25_score": 216.11941528320312}, {"text": "Background . Widespread use of masks in the general population is being used in many countries for Covid-19 . There has been reluctance on the part of the WHO and some governments to recommend this . Methodology . A basic model has been constructed to show the relative risk of aerosol from normal breathing in various situations together with the benefit from use of masks which is multiplicative . Results . Social distancing at 2 metres is validated but in confined areas is time limited and the use of masks in the absence of extremely good ventilation is important. Where social distancing is not possible at all times or an infectious person is in a confined area for a prolonged period there is a higher risk of infection requiring protection . Conclusions . The use of masks should be factored into models and used at an early stage as widespread use of more efficient masks could have a large impact on control and spread of infection . Public health planning requires stockpiling masks and encouraging everyone to have suitable masks in their household when supplies are normalised . The use of a cloth mask will be better than no protection at all .", "title": "A simple model to show the relative risk of viral aerosol infection and the benefit of wearing masks in different settings with implications for Covid-19 .", "pid": "sqr11fpv", "bm25_score": 216.1160125732422}, {"text": "", "title": "Role of Mask/Respirator Protection Against SARS-CoV-2", "pid": "sitxa2ul", "bm25_score": 216.11509704589844}, {"text": "", "title": "Role of mask/respirator protection against SARS-CoV-2", "pid": "4gdxnnj5", "bm25_score": 216.11509704589844}, {"text": "Respiratory infections may spread through droplets, airborne particles, and aerosols from infected individuals through coughing, sneezing, and speaking. In the case of Coronavirus Disease 2019 (COVID-19), droplet spread can occur from symptomatic as well as pre-symptomatic and asymptomatic persons. The U.S. Centers for Disease Control and Prevention (CDC) has therefore recently recommended home-made cloth face coverings for use by the general public in areas of significant community-based transmission. Because medical masks and N95 respirators are in short supply, these are to be reserved for healthcare workers. There is, however, little information on the effectiveness of home-made face coverings in reducing droplet dissemination. Here, we ascertained the performance of ten different fabrics, ranging from cotton to silk, in blocking high velocity droplets, using a 3-layered commercial medical mask as a benchmark material. We also assessed their breathability and ability to soak water. We reason that the materials should be as breathable as possible, without compromising blocking efficiency, to reduce air flow through the sides of the mask since such flow would defeat the purpose of the mask. We found that most home fabrics substantially block droplets, even as a single layer. With two layers, blocking performance can reach that of surgical mask without significantly compromising breathability. Furthermore, we observed that home fabrics are hydrophilic to varying degrees, and hence soak water. In contrast, medical masks are hydrophobic, and tend to repel water. Incoming droplets are thus soaked and 'held back' by home fabrics, which might offer an as of yet untapped and understudied advantage of home-made cloth masks. Overall, our study suggests that most double-layered cloth face coverings may help reduce droplet transmission of respiratory infections.", "title": "Performance of fabrics for home-made masks against spread of respiratory infection through droplets: a quantitative mechanistic study", "pid": "o71haprj", "bm25_score": 216.1083526611328}, {"text": "", "title": "Wearing masks and the fight against the novel coronavirus (COVID-19)", "pid": "s65ffpf1", "bm25_score": 216.10072326660156}, {"text": "", "title": "Masks and Coronavirus Disease 2019 (COVID-19).", "pid": "es8e165v", "bm25_score": 216.09828186035156}, {"text": "During the COVID-19 pandemic, there is no agreement, until the current date, about the recommendations of homemade face mask use for the general population, and one of the reasons is a lack of information about their real protective rule on spreading aerosols and viruses. This is a comparative study regarding the relative efficiencies of commercial respiratory masks (medical masks) and homemade fabric masks, which may guide authorities across the globe, following the 'Advice on the use of masks in the context of COVID-19', by the World Health Organization. We described two optical methodologies for charactering respiratory masks. It happens that the aerosol scattering coefficient is linear as a function of its concentration inside the mask chamber. Quantitative optical properties of scattering for a large batch fabrication of masks were demonstrated, making the mask N95 suitable for use as a reference standard.", "title": "Aerosol blocking assessment by different types of fabrics for homemade respiratory masks: spectroscopy and imaging study", "pid": "0lndg8s2", "bm25_score": 216.0732421875}, {"text": "BACKGROUND Conflicting recommendations exist related to which facial protection should be used by health care workers to prevent transmission of acute respiratory infections, including pandemic influenza. We performed a systematic review of both clinical and surrogate exposure data comparing N95 respirators and surgical masks for the prevention of transmissible acute respiratory infections. METHODS We searched various electronic databases and the grey literature for relevant studies published from January 1990 to December 2014. Randomized controlled trials (RCTs), cohort studies and case-control studies that included data on health care workers wearing N95 respirators and surgical masks to prevent acute respiratory infections were included in the meta-analysis. Surrogate exposure studies comparing N95 respirators and surgical masks using manikins or adult volunteers under simulated conditions were summarized separately. Outcomes from clinical studies were laboratory-confirmed respiratory infection, influenza-like illness and workplace absenteeism. Outcomes from surrogate exposure studies were filter penetration, face-seal leakage and total inward leakage. RESULTS We identified 6 clinical studies (3 RCTs, 1 cohort study and 2 case-control studies) and 23 surrogate exposure studies. In the meta-analysis of the clinical studies, we found no significant difference between N95 respirators and surgical masks in associated risk of (a) laboratory-confirmed respiratory infection (RCTs: odds ratio [OR] 0.89, 95% confidence interval [CI] 0.64-1.24; cohort study: OR 0.43, 95% CI 0.03-6.41; case-control studies: OR 0.91, 95% CI 0.25-3.36); (b) influenza-like illness (RCTs: OR 0.51, 95% CI 0.19-1.41); or (c) reported workplace absenteeism (RCT: OR 0.92, 95% CI 0.57-1.50). In the surrogate exposure studies, N95 respirators were associated with less filter penetration, less face-seal leakage and less total inward leakage under laboratory experimental conditions, compared with surgical masks. INTERPRETATION Although N95 respirators appeared to have a protective advantage over surgical masks in laboratory settings, our meta-analysis showed that there were insufficient data to determine definitively whether N95 respirators are superior to surgical masks in protecting health care workers against transmissible acute respiratory infections in clinical settings.", "title": "Effectiveness of N95 respirators versus surgical masks in protecting health care workers from acute respiratory infection: a systematic review and meta-analysis.", "pid": "iylmvmv3", "bm25_score": 216.05885314941406}, {"text": "Masks are widely discussed during the course of the ongoing COVID-19 pandemic. Most hospitals have implemented universal masking for their healthcare workers, and the Center for Disease Control currently advises even the general public to wear cloth masks when outdoors. The pertinent need for masks arises from plausible dissemination of the SARS-CoV-2 through close contacts, as well as the possibility of virus transmission from asymptomatic, pre-symptomatic, and mildly symptomatic individuals. Given current global shortages in personal protective equipment, the efficacy of various types of masks: N95 respirators, surgical masks, and cloth masks are researched. To accommodate limited supplies, techniques for extended use, reuse, and sterilization of masks are strategized. However, masks alone may not greatly slow down the COVID-19 pandemic unless they are coupled with adequate social distancing, diligent hand hygiene, and other proven preventive measures.", "title": "Comprehensive review of mask utility and challenges during the COVID-19 pandemic.", "pid": "3ttcfhm3", "bm25_score": 216.05609130859375}, {"text": "The main form of COVID-19 transmission is via oral-respiratory droplet contamination (droplet; very small drop of liquid) produced when individuals talk, sneeze or cough. In hospitals, health-care workers wear facemasks as a minimum medical droplet precaution to protect themselves. Due to the shortage of masks during the pandemic, priority is given to hospitals for their distribution. As a result, the availability/use of medical masks is discouraged for the public. However, given that asymptomatic individuals, not wearing masks within the public, can be highly contagious for COVID-19, prevention of environmental droplet contamination (EnDC) from coughing/sneezing/speech is fundamental to reducing transmission. As an immediate solution to promote public droplet safety, we assessed household textiles to quantify their potential as effective environmental droplet barriers (EDBs). The synchronized implementation of a universal community droplet reduction solution is discussed as a model against COVID-19. Using a bacterial-suspension spray simulation model of droplet ejection (mimicking a sneeze), we quantified the extent by which widely available clothing fabrics reduce the dispersion of droplets onto surfaces within 1.8m, the minimum distance recommended for COVID-19 social distancing. All textiles reduced the number of droplets reaching surfaces, restricting their dispersion to <30cm, when used as single layers. When used as double-layers, textiles were as effective as medical mask/surgical-cloth materials, reducing droplet dispersion to <10cm, and the area of circumferential contamination to ~0.3%. The synchronized implementation of EDBs as a community droplet reduction solution (i.e., face covers/scarfs/masks & surface covers) could reduce EnDC and the risk of transmitting or acquiring infectious respiratory pathogens, including COVID-19.", "title": "Textile Masks and Surface Covers - A 'Universal Droplet Reduction Model' Against Respiratory Pandemics", "pid": "t697xw4y", "bm25_score": 216.05325317382812}, {"text": "", "title": "The role of masks and respirator protection against SARS-CoV-2", "pid": "8w0cquhn", "bm25_score": 216.04611206054688}, {"text": "During the ongoing COVID-19 pandemic, healthcare professionals are at the forefront of managing the highly infectious coronavirus. As the most common route of transmission is via aerosols and droplet inhalation, it is critical for healthcare workers to have the correct personal protective equipment (PPE) including gowns, masks and goggles. Surgical masks are not effective in preventing the influenza and SARS, so they are unlikely to be able to resist contaminated aerosols from entering the respiratory system. Therefore, it is vital to use respirators which have been proven to offer better protection against droplets, aerosols and fluid penetration and which form a tight seal around the mouth and nose. Various types of respirators are used in healthcare settings, such as half-mask filtering facepiece respirators (FFRs) and powered air-purifying respirators (PAPRs). The most commonly used FFR is the N95 disposable respirator, which is tight fitting and has a 95% or above particle filtering efficiency for a median particle size of 0.3 µm. This review discusses respirators, their purpose, types, clinical efficiency and proper donning and doffing techniques.", "title": "Role of respirators in controlling the spread of novel coronavirus (COVID-19) amongst dental healthcare providers: a review", "pid": "gprvoecp", "bm25_score": 216.04171752929688}, {"text": "On January 8, 2020, a novel coronavirus was officially announced as the causative pathogen of coronavirus disease (COVID-19) by the Chinese Center for Disease Control and Prevention.On February 26, COVID-19 has been recognized in 34 countries, with a total of 80,239 laboratory-confirmed patients and 2700 deaths.Protecting healthcare workers from infectious hazards is paramount to ensuring their safety in delivering health care.In addition, being able to protect healthcare workers, constituting the front-line response against high-threat respiratory pathogens, such as severe acute respiratory syndrome coronavirus 2, is important for reducing secondary transmission in healthcare-associated outbreaks.Authors present a simple, reliable, and cheap protocol to produce a custom-made sterilizable filtering facepiece 2/3 masks for healthcare providers during pandemic COVID-19 emergency.", "title": "How to Produce Cheap and Easy Custom-Made Sterilizable Filtering Facepiece 2/3 Masks for Healthcare Providers During Pandemic COVID-19 Emergency.", "pid": "y5dalgsz", "bm25_score": 216.03927612304688}, {"text": "", "title": "What Type of Face Mask Is Appropriate for Everyone-Mask-Wearing Policy amidst COVID-19 Pandemic?", "pid": "4y2hi2e9", "bm25_score": 216.0251922607422}, {"text": "BACKGROUND: The novel coronavirus disease (COVID-19) has afflicted millions of people worldwide since its first case was reported in December 2019. Personal protective equipment (PPE) has been tailored accordingly, but as of April 2020, close to 10 000 health care workers in the United States have contracted COVID-19 despite wearing recommended PPE. As such, standard guidelines for PPE may be inadequate for the health care worker performing high-risk aerosolizing procedures such as endotracheal intubation. In this brief technical report, we describe the integration of an orthopedic hood cover as an item for full barrier protection against COVID-19 transmission. TECHNICAL DESCRIPTION: The Coronavirus Airway Task Force at Virginia Commonwealth University Medical Center approved this initiative and went live with the full barrier suit during the last week of March 2020. The PPE described in this report includes a Stryker T4 Hood, normally used in conjunction with the Stryker Steri-Shield T4 Helmet. Instead of the helmet, the hood is secured to the head via a baseball cap and binder clip. This head covering apparatus is to be used as an accessory to other PPE items that include an N95 mask, waterproof gown, and disposable gloves. The motor ventilation system is not used in order to prevent airborne viral entry into the hood. DISCUSSION: An advantage of the full barrier suit is an additional layer of droplet protection during intubation. The most notable disadvantage is the absence of a ventilation system within the hood covering. CONCLUSION: Modification of existing PPE may provide protection for health care workers during high-risk aerosolizing procedures such as endotracheal intubation. Although the integration of this medical equipment meets the immediate needs of an escalating crisis, further innovation is on the horizon. More research is needed to confirm the safety of modified PPE.", "title": "Utilization of an Orthopedic Hood as Personal Protective Equipment for Intubation of Coronavirus Patients: a Brief Technical Report", "pid": "l44xbgok", "bm25_score": 216.0128631591797}, {"text": "BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to personal protective equipment (PPE) shortages, requiring mask reuse or improvisation. We provide a review of medical-grade facial protection (surgical masks, N95 respirators and face shields) for healthcare workers, the safety and efficacy of decontamination methods, and the utility of alternative strategies in emergency shortages or resource-scarce settings. METHODS: We conducted a scoping review of PubMed and grey literature related to facial protection and potential adaptation strategies in the setting of PPE shortages (January 2000 to March 2020). Limitations included few COVID-19-specific studies and exclusion of non-English language articles. We conducted a narrative synthesis of the evidence based on relevant healthcare settings to increase practical utility in decision-making. RESULTS: We retrieved 5462 peer-reviewed articles and 41 grey literature records. In total, we included 67 records which met inclusion criteria. Compared with surgical masks, N95 respirators perform better in laboratory testing, may provide superior protection in inpatient settings and perform equivalently in outpatient settings. Surgical mask and N95 respirator conservation strategies include extended use, reuse or decontamination, but these strategies may result in inferior protection. Limited evidence suggests that reused and improvised masks should be used when medical-grade protection is unavailable. CONCLUSION: The COVID-19 pandemic has led to critical shortages of medical-grade PPE. Alternative forms of facial protection offer inferior protection. More robust evidence is required on different types of medical-grade facial protection. As research on COVID-19 advances, investigators should continue to examine the impact on alternatives of medical-grade facial protection.", "title": "Facial protection for healthcare workers during pandemics: a scoping review", "pid": "quwwani8", "bm25_score": 216.00430297851562}, {"text": "The current pandemic of COVID-19 has lead to conflicting opinions on whether wearing facemasks outside of health care facilities protects against the infection. To better understand the value of wearing facemasks we undertook a rapid systematic review of existing scientific evidence about development of respiratory illness, linked to use of facemasks in community settings. METHODS: We included all study designs. There were 31 eligible studies (including 12 RCTs). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention in 28 studies were performed. Results were reported by design, setting and type of face barrier in primary prevention, and by who wore the facemask (index patient or well contacts) in secondary prevention trials. The preferred outcome was influenza-like illness (ILI) but similar outcomes were pooled with ILI when ILI was unavailable. GRADE quality assessment was based on RCTs with support from observational studies. RESULTS: Where specific information was available, most studies reported about use of medical grade (surgical paper masks). In 3 RCTs, wearing a facemask may very slightly reduce the odds of developing ILI/respiratory symptoms, by around 6% (OR 0.94, 95% CI 0.75 to 1.19, I2 29%, low certainty evidence). Greater effectiveness was suggested by observational studies. When both house-mates and an infected household member wore facemasks the odds of further household members becoming ill may be modestly reduced by around 19% (OR 0.81, 95%CI 0.48 to 1.37, I 2 45%, 5 RCTs, low certainty evidence). The protective effect was very small if only the well person(OR 0.93, 95% CI 0.68 to 1.28, I2 11%, 2 RCTs, low uncertainty evidence) or the infected person wore the facemask (very low certainty evidence). DISCUSSION: Based on the RCTs we would conclude that wearing facemasks can be very slightly protective against primary infection from casual community contact, and modestly protective against household infections when both infected and uninfected members wear facemasks. However, the RCTs often suffered from poor compliance and controls using facemasks. Across observational studies the evidence in favour of wearing facemasks was stronger. We expect RCTs to under-estimate the protective effect and observational studies to exaggerate it. The evidence is not sufficiently strong to support widespread use of facemasks as a protective measure against COVID-19. However, there is enough evidence to support the use of facemasks for short periods of time by particularly vulnerable individuals when in transient higher risk situations. Further high quality trials are needed to assess when wearing a facemask in the community is most likely to be protective.", "title": "Facemasks and similar barriers to prevent respiratory illness such as COVID-19: A rapid systematic review", "pid": "844229sb", "bm25_score": 216.00315856933594}, {"text": "Pandemics such as influenza, smallpox, and plague have caused the loss of hundreds of millions of lives and have occurred for many centuries. Fortunately, they have been largely eliminated by the use of vaccinations and drugs. More recently, Severe Acute Respiratory Syndrome (SARS), Middle East Respiratory Syndrome (MERS), and now Coronavirus Disease 2019 (COVID-19) have arisen, and given the current absence of highly effective approved vaccines or drugs, brute-force approaches involving physical barriers are being used to counter virus spread. A major basis for physical protection from respiratory infections is eye, nose, and mouth protection. However, eye protection with goggles is problematic due to “fogging”, while nose/mouth protection is complicated by the breathing difficulties associated with non-valved respirators. Here, we give a brief review of the origins and development of face masks and eye protection to counter respiratory infections on the basis of experiments conducted 100 years ago, work that was presaged by the first use of personal protective equipment, “PPE”, by the plague doctors of the 17(th) Century. The results of the review lead to two conclusions: first, that eye protection using filtered eye masks be used to prevent ocular transmission; second, that new, pre-filtered, valved respirators be used to even more effectively block viral transmission.", "title": "COVID-19 and Other Pandemics: How Might They Be Prevented?", "pid": "9k2de2sd", "bm25_score": 215.9842529296875}, {"text": "", "title": "Masks and COVID-19", "pid": "e3icgsl9", "bm25_score": 215.97265625}, {"text": "", "title": "Face masks - a sustainable measure to mitigate COVID-19.", "pid": "n18gp3wj", "bm25_score": 215.96109008789062}, {"text": "", "title": "Mask wearing to complement social distancing and save lives during COVID-19.", "pid": "n63ecnfo", "bm25_score": 215.95558166503906}, {"text": "", "title": "Facial mask: A necessity to beat COVID-19", "pid": "nzpl38d0", "bm25_score": 215.95391845703125}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be transmitted via respiratory secretions. Since there are currently no specific therapeutics or vaccines available against the SARS-CoV-2, the commen nonpharmaceutical interventions (NPIs) are still the main measures to curb the COVID-19 epidemic. Face mask wearing is one important measure to suppress the pandemic. In order to know how efficient is face mask wearing in reducing the pandemic even with low efficiency non-professional face masks, we exploit physical abstraction to model the non-professional face masks made from cotton woven fabrics and characterize them by a parameter virus penetration rate (VPR){gamma}. Monte Carlo simulations exhibit that the effective reproduction number R of COVID-19 or similar pandemics can be approximately reduced by factor {gamma}4 with respect to the basic reproduction number R0,if the face masks with 70% <{gamma}< 90% are universally applied for the entire network. Furthermore, thought experiments and practical exploitation examples in country-level and city-level are enumerated and discussed to support our discovery in this study and indicate that the outbreak of a COVID-19 like pandemic can be even suppressed by the low efficiency non-professional face masks.", "title": "How Efficient Can Non-Professional MasksSuppress COVID-19 Pandemic?", "pid": "1yf1ae1d", "bm25_score": 215.95135498046875}, {"text": "Health professions preventing and controlling Coronavirus Disease 2019 are prone to skin and mucous membrane injury, which may cause acute and chronic dermatitis, secondary infection and aggravation of underlying skin diseases. This is a consensus of Chinese experts on protective measures and advice on hand-cleaning- and medical-glove-related hand protection, mask- and goggles-related face protection, UV-related protection, eye protection, nasal and oral mucosa protection, outer ear, and hair protection. It is necessary to strictly follow standards of wearing protective equipment and specification of sterilizing and cleaning. Insufficient and excessive protection will have adverse effects on the skin and mucous membrane barrier. At the same time, using moisturizing products is highly recommended to achieve better protection.", "title": "Consensus of Chinese experts on protection of skin and mucous membrane barrier for health-care workers fighting against coronavirus disease 2019", "pid": "2mf2f84q", "bm25_score": 215.9511260986328}, {"text": "In December 2019, transmission of the novel coronavirus (SARS-CoV-2) that causes coronavirus disease 2019(COVID-19) occurred in Wuhan, China1 .And later the virus began to be transmitted from person to person2 .Face masks are a type of personal protective equipment used to prevent the spread of respiratory infections，it may be effective at helping prevent transmission of respiratory viruses and bacteria3 .Here, we share a case of face masks are be used to prevent the transmission of COVID-19 infection.", "title": "COVID‐19: Face masks and human‐to‐human transmission", "pid": "wni08lks", "bm25_score": 215.94305419921875}, {"text": "Abstract Objective We compared the efficacy of medical masks (MM) and N95 respirators (N95) in preventing bacterial colonization/infection in healthcare workers (HCWs). Methods A cluster randomized clinical trial (RCT) of 1441 hospital HCWs randomized to medical masks or N95 respirators, and compared to 481 control HCWs, was performed in Beijing, China, during the winter season of 2008–2009. Participants were followed for development of clinical respiratory illness (CRI). Symptomatic subjects were tested for Streptococcus pneumoniae, Bordetella pertussis, Chlamydia pneumoniae, Mycoplasma pneumoniae or Haemophilus influenza type B by multiplex polymerase chain reaction (PCR). Results The rate of bacterial colonization was 2.8% in the N95 group (p=0.02), 5.3% among medical mask users (p<0.01) and 7.5% among the controls (p=0.16). N95 respirators were significantly protective (adjusted RR 0.34, 95% CI: 0.21–0.56) against bacterial colonization. Co-infections of two bacteria or a virus and bacteria occurred in up to 3.7% of HCWs, and were significantly lower in the N95 arm. Conclusions N95 respirators were significantly protective against bacterial colonization, co-colonization and viral-bacterial co-infection. We showed that dual respiratory virus or bacterial-viral co-infections can be reduced by the use of N95 respirators. This study has occupational health and safety implications for health workers.", "title": "Efficacy of face masks and respirators in preventing upper respiratory tract bacterial colonization and co-infection in hospital healthcare workers", "pid": "zsxkynim", "bm25_score": 215.92161560058594}, {"text": "We live in extraordinary times, where COVID-19 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different types of facial protection measures, including masks, needed both for the public and the healthcare workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air-purifying respirators (PAPR), and the skin health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID-19 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.", "title": "Facial protection in the era of COVID-19: A narrative review", "pid": "6n5gnow1", "bm25_score": 215.916259765625}, {"text": "Simple plastic face shields have many advantages compared to regular medical masks. They are easily cleaned for reuse and comfortable to wear. In light of the spreading COVID-19 pandemic, the potential of face shields as a substitution for medical masks, as a recommendation to the general population, was tested. Testing the efficacy of the protective equipment utilized a cough simulator that was carefully tuned to replicate human cough in terms of droplet size distribution and outlet velocity. The tested protective equipment was worn on a manikin head simulating human breathing. An Aerodynamic Particle Sizer (APS) was used to analyze the concentration and size distribution of small particles that reach the manikin head respiration pathways. Additionally, Water sensitive papers were taped over and under the tested protective equipment, and were subsequently photographed and analyzed. For droplets larger than 3m by diameter, the efficiency of shields to block cough droplets was found to be comparable to that of regular medical masks, with enhanced protection on face parts the mask does not cover. Additionally, for finer particles, of the order 0.3 to few microns, a shield was found to perform even better, blocking about 10 times more fine particles than the medical mask. This implies that for the general population that is not intendedly exposed to confirmed infected individuals, recommending the use of face shields as an alternative to medical masks should be considered.", "title": "Examining the protection efficacy of face shields against cough aerosol droplets using water sensitive papers", "pid": "5b9jytph", "bm25_score": 215.9100341796875}, {"text": "Mandates for mask use in public during the recent COVID-19 pandemic, worsened by global shortage of commercial supplies, have led to widespread use of homemade masks and mask alternatives. It is assumed that wearing such masks reduces the likelihood for an infected person to spread the disease, but many of these mask designs have not been tested in practice. We have applied a simple optical measurement method to evaluate the efficacy of masks to reduce the transmission of respiratory droplets during regular speech. We compare a variety of commonly available mask types and observe that some mask types approach the performance of standard surgical masks, while some mask alternatives, such as neck fleece or bandanas, offer very little protection. Our measurement setup is inexpensive and can be built and operated by non-experts, allowing for rapid evaluation of mask performance during speech, sneezing, or coughing.", "title": "Low-cost measurement of facemask efficacy for filtering expelled droplets during speech", "pid": "oyxxji7r", "bm25_score": 215.9051055908203}, {"text": "We live in extraordinary times, where COVID-19 pandemic has brought the whole world to a screeching halt. Tensions and contradictions that surround the pandemic ridden world include the availability, and the lack thereof, various facial protection measures to mitigate the viral spread. Here, we comprehensively explore the different type of facial protection measures, including masks, needed both for the pubic and the health care workers (HCW). We discuss the anatomy, the critical issues of disinfection and reusability of masks, the alternative equipment available for the protection of the facial region from airborne diseases, such as face shields and powered air purifying respirators (PAPR), and the skin-health impact of prolonged wearing of facial protection by HCW. Clearly, facial protection, either in the form of masks or alternates, appears to have mitigated the pandemic as seen from the minimal COVID-19 spread in countries where public mask wearing is strictly enforced. On the contrary, the healthcare systems, that appear to have been unprepared for emergencies of this nature, should be appropriately geared to handle the imbalance of supply and demand of personal protective equipment including face masks. These are two crucial lessons we can learn from this tragic experience.", "title": "Facial protection in the era of COVID-19: a narrative review", "pid": "uep2tfnu", "bm25_score": 215.89979553222656}, {"text": "During the ongoing COVID‐19 pandemic, healthcare professionals are at the forefront of managing the highly infectious coronavirus. As the most common route of transmission is via aerosols and droplet inhalation, it is critical for healthcare workers to have the correct personal protective equipment (PPE) including gowns, masks and goggles. Surgical masks are not effective in preventing the influenza and SARS, so they are unlikely to be able to resist contaminated aerosols from entering the respiratory system. Therefore, it is vital to use respirators which have been proven to offer better protection against droplets, aerosols and fluid penetration and which form a tight seal around the mouth and nose. Various types of respirators are used in healthcare settings, such as half‐mask filtering facepiece respirators (FFRs) and powered air‐purifying respirators (PAPRs). The most commonly used FFR is the N95 disposable respirator, which is tight fitting and has a 95% or above particle filtering efficiency for a median particle size of 0.3 µm. This review discusses respirators, their purpose, types, clinical efficiency and proper donning and doffing techniques.", "title": "Role of respirators in controlling the spread of novel coronavirus (COVID‐19) amongst dental healthcare providers: a review", "pid": "b27xeyy3", "bm25_score": 215.88153076171875}, {"text": "The medical community agrees that breathborne infectious materials can be spread with exhaled aerosols and that asymptomatic people, i.e., those showing no symptoms, could be unknowingly infectious. With the current worldwide pandemic of the respiratory coronavirus disease 2019 (COVID-19), various health bodies and governments are recommending that the population wear some form of mask or improvised facial covers while out in public in an effort to reduce the spread of disease . The general concept is that more accessible masks or mask-like materials (scarves, bandanas, etc.) could serve to reduce the amount of infectious aerosol from infected people, and reduce the viral load in the environment. This editorial addresses the underlying scientific rationale that such inexpensive or improvised could indeed serve to reduce the emissions of infectious aerosol by the mechanism of surface adhesion and particle kinetics in addition to the filtration effect.", "title": "The scientific rationale for the use of simple masks or improvised facial coverings to trap exhaled aerosols and possibly reduce the breathborne spread of COVID-19", "pid": "m17j5u0y", "bm25_score": 215.8690185546875}, {"text": "Background: There is paucity of evidence on the effectiveness of facemask use in COVID-19 in community settings. Objectives: We aimed to estimate the effectiveness of facemask use alone or along with hand hygiene in community settings in reducing the transmission of viral respiratory illness. Methods: We searched PubMed and Embase for randomized controlled trials on facemask use in community settings to prevent viral respiratory illnesses published up to April 25, 2020. Two independent reviewers were involved in synthesis of data. Data extraction and risk-of-bias assessment were done in a standard format from the selected studies. Outcome data for clinically diagnosed or self-reported influenza-like illness (ILI) was recorded from individual studies. Pooled effect size was estimated by random-effects model for \"facemask only versus control\" and \"facemask plus hand hygiene versus control.\" Results: Of the 465 studies from PubMed and 437 studies from Embase identified from our search, 9 studies were included in qualitative synthesis and 8 studies in quantitative synthesis. Risk of bias was assessed as low (n = 4), medium (n = 3), or high (n = 1) risk. Interventions included using a triple-layered mask alone or in combination with hand hygiene. Publication bias was not significant. There was no significant reduction in ILI either with facemask alone (n = 5, pooled effect size: -0.17; 95% confidence interval [CI]: -0.43-0.10; P = 0.23; I2 = 10.9%) or facemask with handwash (n = 6, pooled effect size: (n=6, pooled effect size: -0.09; 95% CI: -0.58 to 0.40; P = 0.71, I2 = 69.4%). Conclusion: : Existing data pooled from randomized controlled trials do not reveal a reduction in occurrence of ILI with the use of facemask alone in community settings.", "title": "Facemasks for prevention of viral respiratory infections in community settings: A systematic review and meta-analysis", "pid": "l77gla9f", "bm25_score": 215.85145568847656}, {"text": "Background There is paucity of evidence on the effectiveness of facemask use in COVID-19 in community settings. Objectives We aimed to estimate the effectiveness of facemask use alone or along with hand hygiene in community settings in reducing the transmission of viral respiratory illness. Methods We searched PubMed and Embase for randomized controlled trials on facemask use in community settings to prevent viral respiratory illnesses published up to April 25, 2020. Two independent reviewers were involved in synthesis of data. Data extraction and risk-of-bias assessment were done in a standard format from the selected studies. Outcome data for clinically diagnosed or self-reported influenza-like illness (ILI) was recorded from individual studies. Pooled effect size was estimated by random-effects model for \"facemask only versus control\" and \"facemask plus hand hygiene versus control.\" Results Of the 465 studies from PubMed and 437 studies from Embase identified from our search, 9 studies were included in qualitative synthesis and 8 studies in quantitative synthesis. Risk of bias was assessed as low (n = 4), medium (n = 3), or high (n = 1) risk. Interventions included using a triple-layered mask alone or in combination with hand hygiene. Publication bias was not significant. There was no significant reduction in ILI either with facemask alone (n = 5, pooled effect size: -0.17; 95% confidence interval [CI]: -0.43-0.10; P = 0.23; I2 = 10.9%) or facemask with handwash (n = 6, pooled effect size: (n=6, pooled effect size: -0.09; 95% CI: -0.58 to 0.40; P = 0.71, I2 = 69.4%). Conclusion : Existing data pooled from randomized controlled trials do not reveal a reduction in occurrence of ILI with the use of facemask alone in community settings.", "title": "Facemasks for prevention of viral respiratory infections in community settings: A systematic review and meta-analysis.", "pid": "9ncpsg7g", "bm25_score": 215.85000610351562}, {"text": "Coronavirus, the virus that caused the global pandemic at the beginning of 2020 and affected millions across the globe, presented as an enormous challenge to health care providers around the world. With increasing numbers of infected patients presenting daily, health care workers are struggling to take effective measures to protect themselves from transmission against the highly contagious coronavirus. This case helps us understand the implications of coronavirus-infected patients on the health care providers directly responsible for the management of these patients and the relative efficacy of different types of respiratory protective equipment mainly N95 masks and surgical masks in preventing the spread of infection among those at the front lines providing care.", "title": "COVID-19 and the Efficacy of Different Types of Respiratory Protective Equipment Used by Health Care Providers in a Health Care Setting", "pid": "xx5xbjqu", "bm25_score": 215.844482421875}]}
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Currently, strategies to deal with COVID-19 are purely supportive and preventative, aimed at reducing transmission. An effective and simple method for reducing transmission of infections in the public or healthcare settings is hand hygiene. Unfortunately, little is known regarding the efficacy of hand sanitizers against SARS-CoV-2. METHODS: In this review, an extensive literature search was performed to succinctly summarize the primary active ingredients and mechanisms of action of hand sanitizers, compare the effectiveness and compliance of gel and foam sanitizers, and predict whether alcohol and non-alcohol hand sanitizers would be effective against SARS-CoV-2. RESULTS: Most alcohol based hand sanitizers are effective at inactivating enveloped viruses, including coronaviruses. With what is currently known in the literature, one may not confidently suggest one mode of hand sanitizing delivery over the other. When hand washing with soap and water is unavailable, a sufficient volume of sanitizer is necessary to ensure complete hand coverage, and compliance is critical for appropriate hand hygiene. CONCLUSIONS: By extrapolating effectiveness of hand sanitizers on viruses of similar structure to SARS-CoV-2, this virus should be effectively inactivated with current hand hygiene products, though future research should attempt to determine this directly.", "title": "Hand Sanitizers: A Review of Ingredients, Mechanisms of Action, Modes of Delivery, and Efficacy Against Coronaviruses", "pid": "y777xosr", "bm25_score": 218.6791534423828}, {"text": "The World Health Organization (WHO) has declared a global health emergency over a new coronavirus. The new corona virus (SARS-CoV-2) has raised global attention with raising concerns of rapid spread from human-to-human. Like severe acute respiratory syndrome (SARS)-nCoV, 2019-nCoV can be passed directly from person to person by respiratory droplets, and may also be transmitted through contact and fomites.", "title": "Hand disinfection in the combat against Covid-19", "pid": "0macgbcn", "bm25_score": 218.53736877441406}, {"text": "The recent emergence of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 is a major burden for health care systems worldwide. It is important to address if the current infection control instructions based on active ingredients are sufficient. We therefore determined the virucidal activity of two alcohol-based hand rub solutions for hand disinfection recommended by the World Health Organization (WHO), as well as commercially available alcohols. Efficient SARS-CoV-2 inactivation was demonstrated for all tested alcohol-based disinfectants. These findings show the successful inactivation of SARS-CoV-2 for the first time and provide confidence in its use for the control of COVID-19. Importance The current COVID-19 outbreak puts a huge burden on the world’s health care systems. Without effective therapeutics or vaccines being available, effective hygiene measure are of utmost importance to prevent viral spreading. It is therefore crucial to evaluate current infection control strategies against SARS-CoV-2. We show the inactivation of the novel coronavirus for the first time and endorse the importance of disinfectant-based hand hygiene to reduce SARS-CoV-2 transmission.", "title": "Efficient inactivation of SARS-CoV-2 by WHO-recommended hand rub formulations and alcohols", "pid": "c1n994j6", "bm25_score": 218.25634765625}, {"text": "The World Health Organization (WHO) has declared a global health emergency over a new coronavirus. The new corona virus (SARS‐CoV‐2) has raised global attention with raising concerns of rapid spread from human‐to‐human. Like severe acute respiratory syndrome (SARS)‐nCoV, 2019‐nCoV can be passed directly from person to person by respiratory droplets, and may also be transmitted through contact and fomites.", "title": "Hand disinfection in the combat against Covid‐19", "pid": "t9ir627s", "bm25_score": 218.1480712890625}, {"text": "In-hospital transmission is one of the main routes of the 2019 novel coronavirus (SARS-CoV-2) spreading among health care workers (HCWs) who are the frontline fighters. However, coming into contact with COVID-19-positive patients is unavoidable. Therefore, hand hygiene is of utmost importance for the prevention of COVID-19 among HCWs. This purpose can be achieved by applying alcohol-based hand rubs, washing hands properly with soap and water, and applying other antiseptic agents. Nevertheless, regular hand hygiene could also be challenging, because water, detergents, and disinfectants may predispose HCWs to hand dermatitis. The current article reviews the risk factors for the development of hand dermatitis, with further focus on the most common agents used among HCWs. In addition, the risk of occupational hand dermatitis for each agent is evaluated to increase awareness of this common condition. Finally, some recommendations are discussed to reduce the effect of hand dermatitis on HCWs.", "title": "Hand Hygiene Among Health Care Workers During COVID-19 Pandemic: Challenges and Recommendations", "pid": "odfssrr6", "bm25_score": 217.86788940429688}, {"text": "In-hospital transmission is one of the main routes of the 2019 novel coronavirus (SARS-CoV-2) spreading among health care workers (HCWs) who are the frontline fighters. However, coming into contact with COVID-19-positive patients is unavoidable. Therefore, hand hygiene is of utmost importance for the prevention of COVID-19 among HCWs. This purpose can be achieved by applying alcohol-based hand rubs, washing hands properly with soap and water, and applying other antiseptic agents. Nevertheless, regular hand hygiene could also be challenging, because water, detergents, and disinfectants may predispose HCWs to hand dermatitis. The current article reviews the risk factors for the development of hand dermatitis, with further focus on the most common agents used among HCWs. In addition, the risk of occupational hand dermatitis for each agent is evaluated to increase awareness of this common condition. Finally, some recommendations are discussed to reduce the effect of hand dermatitis on HCWs.", "title": "Hand Hygiene Among Health Care Workers During COVID-19 Pandemic: Challenges and Recommendations.", "pid": "ji5pqh47", "bm25_score": 217.8633270263672}, {"text": "Infection control instructions call for use of alcohol-based hand rub solutions to inactivate severe acute respiratory syndrome coronavirus 2. We determined the virucidal activity of World Health Organization–recommended hand rub formulations, at full strength and multiple dilutions, and of the active ingredients. All disinfectants demonstrated efficient virus inactivation.", "title": "Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 by WHO-Recommended Hand Rub Formulations and Alcohols", "pid": "b0nkhsvv", "bm25_score": 217.83447265625}, {"text": "Infection control instructions call for use of alcohol-based hand rub solutions to inactivate severe acute respiratory syndrome coronavirus 2. We determined the virucidal activity of World Health Organization-recommended hand rub formulations, at full strength and multiple dilutions, and of the active ingredients. All disinfectants demonstrated efficient virus inactivation.", "title": "Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 by WHO-Recommended Hand Rub Formulations and Alcohols", "pid": "1v8wwn0d", "bm25_score": 217.81744384765625}, {"text": "Till date no medication or vaccine is available to cope with the COVID-19 infection and infection rate is increasing drastically across the globe. Only preventive measures and healthy life style with efficient immune system have been suggested by WHO to fight and stay safe from COVID-19. WHO recommended alcohol based hand sanitizers for frequent hand hygiene, which are mainly made up from ethanol, isopropyl alcohols, hydrogen peroxides in different combinations. These preparations may become toxic to human health and environment when misused. These chemicals have known toxic and hazardous impact on environment when released by evaporation. In early five months of 2020, American Association of Poison Control Center reported 9504 alcoholic hand sanitizer exposure cases in children under the age of 12 years and recognized that even a small amount of alcohol can cause alcohol poisoning in children that is responsible for confusion, vomiting and drowsiness, and in severe cases, respiratory arrest and death. Furthermore, frequent usage of said hand sanitizers has reported increased chance of antimicrobial resistance and chance of other viral diseases. Current review is designed with main objective to highlight the toxic and serious health risks to human health and environment by frequent using hand hygiene products with alcohols based formulations.", "title": "COVID-19 and frequent use of hand sanitizers; human health and environmental hazards by exposure pathways", "pid": "eevs62xf", "bm25_score": 217.59603881835938}, {"text": "With the beginning of the pandemic of COVID-19 throughout the world, the demand and consumption of hand sanitizers has increased, which had led to a sharp crunch in these products at all levels. This shortage has led to an increase in the prevalence of falsified alcohol-based hand sanitizers, including the illegal addition of methanol to hand sanitizers and the production of hand sanitizers with an alcohol concentration of less than 60%. These findings indicate that regulatory and public health bodies should take an active role in ensuring the safety and quality of antimicrobial products such as alcohol-based hand sanitizers at every stage of the products' lifecycle, including distribution, manufacture and import.", "title": "The pandemic of COVID-19 and its implications for the purity and authenticity of alcohol-based hand sanitizers: The health risks associated with falsified sanitizers and recommendations for regulatory and public health bodies", "pid": "uhhk4t7f", "bm25_score": 217.5709686279297}, {"text": "Abstract Till date no medication or vaccine is available to cope with the COVID-19 infection and infection rate is increasing drastically across the globe. Only preventive measures and healthy life style with efficient immune system have been suggested by WHO to fight and stay safe from COVID-19. WHO recommended alcohol based hand sanitizers for frequent hand hygiene, which are mainly made up from ethanol, isopropyl alcohols, hydrogen peroxides in different combinations. These preparations may become toxic to human health and environment when misused. These chemicals have known toxic and hazardous impact on environment when released by evaporation. In early five months of 2020, American Association of Poison Control Center reported 9504 alcoholic hand sanitizer exposure cases in children under the age of 12 years and recognized that even a small amount of alcohol can cause alcohol poisoning in children that is responsible for confusion, vomiting and drowsiness, and in severe cases, respiratory arrest and death. Furthermore, frequent usage of said hand sanitizers has reported increased chance of antimicrobial resistance and chance of other viral diseases. Current review is designed with main objective to highlight the toxic and serious health risks to human health and environment by frequent using hand hygiene products with alcohols based formulations.", "title": "COVID-19 and frequent use of hand sanitizers; human health and environmental hazards by exposure pathways", "pid": "hma2kvn2", "bm25_score": 217.43429565429688}, {"text": "The ongoing COVID-19 pandemic has made various challenges for communications all over the world. Nowadays hand hygiene practices with alcohol sanitizers are an unavoidable reality for many people, which cause skin dryness and flaking. The current short communication has been explained about monitoring the quality control of alcohol concentrations and hand rub formulation, which needs more attention and should consider meticulous in this crisis.", "title": "Hidden threat lurking behind the alcohol sanitizers in COVID-19 outbreak", "pid": "z6cda4o2", "bm25_score": 217.3834228515625}, {"text": "Abstract With the beginning of the pandemic of COVID-19 throughout the world, the demand and consumption of hand sanitizers has increased, which had led to a sharp crunch in these products at all levels. This shortage has led to an increase in the prevalence of falsified alcohol-based hand sanitizers, including the illegal addition of methanol to hand sanitizers and the production of hand sanitizers with an alcohol concentration of less than 60%. These findings indicate that regulatory and public health bodies should take an active role in ensuring the safety and quality of antimicrobial products such as alcohol-based hand sanitizers at every stage of the products’ lifecycle, including distribution, manufacture and import.", "title": "The pandemic of COVID-19 and its implications for the purity and authenticity of alcohol-based hand sanitizers: The health risks associated with falsified sanitizers and recommendations for regulatory and public health bodies", "pid": "20ipkh78", "bm25_score": 217.36624145507812}, {"text": "The ongoing COVID‐19 pandemic has made various challenges for communications all over the world. Nowadays hand hygiene practices with alcohol sanitizers are an unavoidable reality for many people, which cause skin dryness and flaking. The current short communication has been explained about monitoring the quality control of alcohol concentrations and hand rub formulation, which needs more attention and should consider meticulous in this crisis.", "title": "Hidden threat lurking behind the alcohol sanitizers in COVID‐19 outbreak", "pid": "hx8c0mxj", "bm25_score": 217.19180297851562}, {"text": "Water, sanitation, and hygiene (WASH) interventions remain to be important in the prevention of further spread of coronavirus disease-2019 (COVID-19). Basic hygiene interventions such as handwashing with water and soap (HWWS) when applied consistently will deactivate and remove the virus particles from the hands. Realizing the efforts that have been made by countries world over in controlling the COVID-19, this letter seeks to discuss how the available WASH services can be used in the fight against further spread of COVID-19. The letter highlights the challenges being faced by the current WASH services in middle- and low-income countries and suggests measures that can be employed to strengthen the WASH services in this period of the COVID-19 pandemic.", "title": "Tailoring of the ongoing water, sanitation and hygiene interventions for prevention and control of COVID-19", "pid": "5uc76djv", "bm25_score": 217.18324279785156}, {"text": "", "title": "Tainted hand sanitizer leads to outbreak of methanol toxicity during SARS-CoV-2 pandemic", "pid": "56sd6pnn", "bm25_score": 217.1309051513672}, {"text": "Hand hygiene is of utmost importance as it may be contaminated easily from direct contact with airborne microorganism droplets from coughs and sneezes. Particularly in situations like pandemic outbreak, it is crucial to interrupt the transmission chain of the virus by the practice of proper hand sanitization. It can be achieved with contact isolation and strict infection control tool like maintaining good hand hygiene in hospital settings and in public. The success of the hand sanitization solely depends on the use of effective hand disinfecting agents formulated in various types and forms such as antimicrobial soaps, water-based or alcohol-based hand sanitizer, with the latter being widely used in hospital settings. To date, most of the effective hand sanitizer products are alcohol-based formulations containing 62%-95% of alcohol as it can denature the proteins of microbes and the ability to inactivate viruses. This systematic review correlated with the data available in Pubmed, and it will investigate the range of available hand sanitizers and their effectiveness as well as the formulation aspects, adverse effects, and recommendations to enhance the formulation efficiency and safety. Further, this article highlights the efficacy of alcohol-based hand sanitizer against the coronavirus.", "title": "Hand Sanitizers: A Review on Formulation Aspects, Adverse Effects, and Regulations", "pid": "i0ll585x", "bm25_score": 217.1016845703125}, {"text": "Hand hygiene is of utmost importance as it may be contaminated easily from direct contact with airborne microorganism droplets from coughs and sneezes. Particularly in situations like pandemic outbreak, it is crucial to interrupt the transmission chain of the virus by the practice of proper hand sanitization. It can be achieved with contact isolation and strict infection control tool like maintaining good hand hygiene in hospital settings and in public. The success of the hand sanitization solely depends on the use of effective hand disinfecting agents formulated in various types and forms such as antimicrobial soaps, water-based or alcohol-based hand sanitizer, with the latter being widely used in hospital settings. To date, most of the effective hand sanitizer products are alcohol-based formulations containing 62%–95% of alcohol as it can denature the proteins of microbes and the ability to inactivate viruses. This systematic review correlated with the data available in Pubmed, and it will investigate the range of available hand sanitizers and their effectiveness as well as the formulation aspects, adverse effects, and recommendations to enhance the formulation efficiency and safety. Further, this article highlights the efficacy of alcohol-based hand sanitizer against the coronavirus.", "title": "Hand Sanitizers: A Review on Formulation Aspects, Adverse Effects, and Regulations", "pid": "d26y5291", "bm25_score": 217.0249786376953}, {"text": "", "title": "Ozone disinfectants like soclean CPAP sanitizer can be used to sterilize cloth and n95 masks in the protection against COVID-19", "pid": "2x2ewsp8", "bm25_score": 216.97525024414062}, {"text": "The coronavirus known as SARS-CoV-2, which causes COVID-19 disease, is presently responsible for a global pandemic wherein more than 3.5 million people have been infected and more than 250,000 killed to-date. There is currently no vaccine for COVID-19, leaving governments and public health agencies with little defense against the virus aside from advising or enforcing best practices for virus transmission prevention, which include hand-washing, physical distancing, use of face covers, and use of effective disinfectants. In this study, a novel iodine complex called CupriDyne® was assessed for its ability to inactivate SARS-CoV-2. CupriDyne was shown to be effective in inactivating the virus in a time-dependent manner, reducing virus titers by 99% (2 logs) after 30 minutes, and reducing virus titers to below the detection limit after 60 minutes. The novel iodine complex tested herein offers a safe and gentle alternative to conventional disinfectants for use on indoor and outdoor surfaces.", "title": "Efficacy of a novel iodine complex solution, CupriDyne, in inactivating SARS-CoV-2", "pid": "d8xtacyj", "bm25_score": 216.9400177001953}, {"text": "Since the onset of the COVID-19 pandemic, there has been an advisory for regular and thorough cleaning of hands besides other measures such as social distancing and self-isolation. The rationale for the same is to prevent the transfer of the virus from hands that have come in contact with fomites. While both alcohol-based hand rubs (ABHR) or washing with soap and water are claimed to have been effective, hand sanitizers have gained more popularity due to the ease of use. The increased frequency of ABHR use and the aerosols generated pose a potential threat to the skin and exposed mucosal surfaces, especially that of the eye due to the proximity of use. The adverse effects of alcohol in these sanitizers can be manifold. An allergic or inflammatory response can occur depending on the predisposing or preexisting conditions. This article describes the risks, underlying mechanisms, and preventive measures for sanitizer aerosol-driven ocular surface disease.", "title": "Sanitizer aerosol-driven ocular surface disease (SADOSD)-A COVID-19 repercussion?", "pid": "yjg54yyk", "bm25_score": 216.91378784179688}, {"text": "Objective: Social distancing and hand washing with soap and water have been advocated as the main proactive measures against the spread of coronavirus. We sought to find out what other alternative materials and methods would be used among populations without running water and who may not afford alcohol-based sanitizers. Results: We reviewed studies that reported use of sand, soil, ash, soda ash, seawater, alkaline materials, and sunlight as possible alternatives to handwashing with soap and water. We identified the documented mechanism of actions of these alternative wash methods on both inanimate surfaces and at cellular levels. The consideration of use of these alternative locally available in situations of unavailability of soap and water and alcohol-based sanitizers is timely in the face of coronavirus pandemic. Further randomized studies need to be carried out to evaluate the effectiveness of these alternatives in management of SARS-Cov-2.", "title": "Dry Taps? A Synthesis of Alternative “Wash” Methods in the Absence of Water and Sanitizers in the Prevention of Coronavirus in Low-Resource Settings", "pid": "nl55rm8o", "bm25_score": 216.85696411132812}, {"text": "Objective: Social distancing and hand washing with soap and water have been advocated as the main proactive measures against the spread of coronavirus. We sought to find out what other alternative materials and methods would be used among populations without running water and who may not afford alcohol-based sanitizers. Results: We reviewed studies that reported use of sand, soil, ash, soda ash, seawater, alkaline materials, and sunlight as possible alternatives to handwashing with soap and water. We identified the documented mechanism of actions of these alternative wash methods on both inanimate surfaces and at cellular levels. The consideration of use of these alternative locally available in situations of unavailability of soap and water and alcohol-based sanitizers is timely in the face of coronavirus pandemic. Further randomized studies need to be carried out to evaluate the effectiveness of these alternatives in management of SARS-Cov-2.", "title": "Dry Taps? A Synthesis of Alternative \"Wash\" Methods in the Absence of Water and Sanitizers in the Prevention of Coronavirus in Low-Resource Settings", "pid": "ojh3vgrb", "bm25_score": 216.83438110351562}, {"text": "Coronavirus disease 2019 (COVID-19) continues to spread globally, outpacing the capacity and resources of health systems worldwide. A therapeutic vaccine is not yet on the rise, and preventive measures are the current approach to restraint the transmission of cases. As the virus is highly contagious via respiratory route (droplets from infected persons, widely spread by coughing or sneezing) and via contact with contaminated surfaces, community transmission and spread can be decreased through the practice of regular and diligent hand hygiene. Frequent hand washing implies a prolonged exposure to water and other chemical or physical agents and may induce several pathophysiologic changes, such as epidermal barrier disruption, impairment of keratinocytes, the subsequent release of proinflammatory cytokines, activation of the skin immune system, and delayed-type hypersensitivity reactions. Adverse dermatologic effects, such as excessive skin dryness or even contact dermatitis (particularly the irritant subtype and, to a lesser extent, the allergic subtype), can occur, especially in individuals with a history of atopic dermatitis. These skin conditions are perfectly manageable, and applying a moisturizer immediately after washing hands or after using a portable hand sanitizer is the cornerstone in preventing the development of eczematous changes in the hands. In the current global context, the potential occurrence of these dermatological adverse events should in no way cause people to deviate from strict hand hygiene rules.", "title": "Frequent Hand Washing for COVID-19 Prevention Can Cause Hand Dermatitis: Management Tips", "pid": "irmwqjfh", "bm25_score": 216.8152313232422}, {"text": "The surgeon needs to have an inexpensive, available, non-toxic, and practical disinfectant that is effective in sanitizing against the CoVID-19 virus. The purpose of this paper is to review the evidence for using hypochlorous acid (HOCl) in the office setting on a daily basis. The methods used to assemble recommendations were to review the literature including evidence for this solution when used in different locations and industries other than the oral-maxillofacial clinic facility. The results indicate that this material can be used with a high predictability for disinfecting against the CoVID-19 virus.", "title": "Hypochlorous acid – a review", "pid": "joi5xr8o", "bm25_score": 216.721435546875}, {"text": "Background: Hand washing remains a key measure for intercepting the dispatch of the Coronavirus disease (COVID-19). However, hand washing must be perpetuated properly using soap and water for at least 20 seconds. In response to the current COVID-19 pandemic, various hospitals have imposed mandatory hand washing to everyone prior entering the facilities, and when leaving. This study aimed to assess the hand washing compliance among visitors of a university referral hospital. Methods: A non-participatory observational study was conducted in the main entrance of the hospital from April 27 to May 3, 2020, to measure hand washing compliance of its visitors. The quality of hand washing was assessed via direct observation for compliance with the recommended World Health Organization (WHO) core steps. Data were collected using Open Data Kit (ODK) mobile application. Results: A total of 1,282 hospital visitors were observed, of which 874(68.2%) were males. Full hand washing compliances were observed among 0.9% (95% CI: 0.4-1.4) of the visitors. Withal, there was no difference in the compliances between genders (0.9% vs 0.7%, P = 0.745). Conclusion: Despite the fact that proper hand washing with soap and water is proven to be one of the effective ways in preventing the spread of COVID-19, a significant number of hospital visitors did not practice standard hand washing procedures. Improvements in this measure are urgently needed in the face of the current COVID-19 pandemic.", "title": "Hand Washing Compliance and COVID-19: A Non-Participatory Observational Study among Hospital Visitors", "pid": "hzk2pl0w", "bm25_score": 216.7055206298828}, {"text": "As the COVID-19 pandemic continues to gain momentum around the world, several measures are being put in place to control its spread. One such effort includes the installation walkthrough sanitization gates to disinfect passersby and prevent cross infection. However, there is lack of clinical evidence on the effectiveness of these walkthrough gates to contain COVID-19. Moreover, there are potential public health concerns associated with these walkthrough gates. Spraying individuals with disinfectant chemicals is strongly discouraged by various health authorities around the globe because of their propensity for eye and skin irritation, bronchospasm following inhalation, and gastrointestinal effects such as nausea and vomiting. This article underscores that the risks associated with the use of these walkthrough gates overweigh any potential benefits. Health authorities must discourage their use and should focus efforts on other preventive measures such as social distancing, wearing masks, and hand hygiene to prevent the spread of COVID-19 among the general public.", "title": "Walkthrough Sanitization Gates for COVID-19: A Preventive Measure or Public Health Concern?", "pid": "b5xae518", "bm25_score": 216.66656494140625}, {"text": "The world is facing a medical crisis amid the CoViD-19 pandemic and the role of adequate hygiene and hand sanitisers is inevitable in controlling the spread of infection in public places and healthcare institutions. There has been a great surge in demand for hand sanitisation products leading to shortages in their supply. A consequent increase of substandard products in the market has raised safety concerns. This article, therefore, presents a critical review of hand sanitation approaches and products available on the market in light of the scientific evidence available to date. This review also provides a range of hand sanitisation product formulations, and manufacturing instructions to allow for extemporaneous preparations at the community and hospital pharmacies during this urgent crisis. In addition, this emergent situation is expected to continue, hence hand sanitisers will be in demand for an extended time, and the availability and purchase of substandard products on the market create an ongoing safety concern. Therefore, this article shall also provide various commercial organisations, interested in stepping forward the production and marketing of hand sanitisers, with a guide on the development of products of standardised ingredients and formulations.", "title": "Hand sanitisers amid CoViD-19: A critical review of alcohol-based products on the market and formulation approaches to respond to increasing demand.", "pid": "d6v5mkj7", "bm25_score": 216.57626342773438}, {"text": "The surge of patients in the pandemic of COVID-19 caused by the novel coronavirus SARS-CoV-2 may overwhelm the medical systems of many countries. Mask-wearing and handwashing can slow the spread of the virus, but currently, masks are in shortage in many countries, and timely handwashing is often impossible. In this study, the efficacy of three types of masks and instant hand wiping was evaluated using the avian influenza virus to mock the coronavirus. Virus quantification was performed using real-time reverse transcription-polymerase chain reaction. Previous studies on mask-wearing were reviewed. The results showed that instant hand wiping using a wet towel soaked in water containing 1.00% soap powder, 0.05% active chlorine, or 0.25% active chlorine from sodium hypochlorite removed 98.36%, 96.62%, and 99.98% of the virus from hands, respectively. N95 masks, medical masks, and homemade masks made of four-layer kitchen paper and one-layer cloth could block 99.98%, 97.14%, and 95.15% of the virus in aerosols. Medical mask-wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. With these data, we propose the approach of mask-wearing plus instant hand hygiene (MIH) to slow the exponential spread of the virus. This MIH approach has been supported by the experiences of seven countries in fighting against COVID-19. Collectively, a simple approach to slow the exponential spread of SARS-CoV-2 was proposed with the support of experiments, literature review, and control experiences.", "title": "Potential utilities of mask-wearing and instant hand hygiene for fighting SARS-CoV-2", "pid": "v0trjjni", "bm25_score": 216.54884338378906}, {"text": "The world is facing a medical crisis amid the CoViD-19 pandemic and the role of adequate hygiene and hand sanitisers is inevitable in controlling the spread of infection in public places and healthcare institutions. There has been a great surge in demand for hand sanitisation products leading to shortages in their supply. A consequent increase of substandard products in the market has raised safety concerns. This article, therefore, presents a critical review of hand sanitation approaches and products available on the market in light of the scientific evidence available to date. This review also provides a range of hand sanitisation product formulations, and manufacturing instructions to allow for extemporaneous preparations at the community and hospital pharmacies during this urgent crisis. In addition, this emergent situation is expected to continue, hence hand sanitisers will be in demand for an extended time, and the availability and purchase of substandard products on the market create an ongoing safety concern. Therefore, this article shall also provide various commercial organisations, interested in stepping forward the production and marketing of hand sanitisers, with a guide on the development of products of standardised ingredients and formulations.", "title": "Hand sanitisers amid CoViD-19: A critical review of alcohol-based products on the market and formulation approaches to respond to increasing demand", "pid": "rv2akbj8", "bm25_score": 216.53851318359375}, {"text": "The surge of patients in the pandemic of COVID‐19 caused by the novel coronavirus SARS‐CoV‐2 may overwhelm the medical systems of many countries. Mask‐wearing and handwashing can slow the spread of the virus, but currently, masks are in shortage in many countries, and timely handwashing is often impossible. In this study, the efficacy of three types of masks and instant hand wiping was evaluated using the avian influenza virus to mock the coronavirus. Virus quantification was performed using real‐time reverse transcription‐polymerase chain reaction. Previous studies on mask‐wearing were reviewed. The results showed that instant hand wiping using a wet towel soaked in water containing 1.00% soap powder, 0.05% active chlorine, or 0.25% active chlorine from sodium hypochlorite removed 98.36%, 96.62%, and 99.98% of the virus from hands, respectively. N95 masks, medical masks, and homemade masks made of four‐layer kitchen paper and one‐layer cloth could block 99.98%, 97.14%, and 95.15% of the virus in aerosols. Medical mask‐wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. With these data, we propose the approach of mask‐wearing plus instant hand hygiene (MIH) to slow the exponential spread of the virus. This MIH approach has been supported by the experiences of seven countries in fighting against COVID‐19. Collectively, a simple approach to slow the exponential spread of SARS‐CoV‐2 was proposed with the support of experiments, literature review, and control experiences.", "title": "Potential utilities of mask‐wearing and instant hand hygiene for fighting SARS‐CoV‐2", "pid": "2otax3zq", "bm25_score": 216.44454956054688}, {"text": "A novel virus named Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) emerged from Wuhan, China in late 2019. Since then, the virus has quickly spread worldwide, leading the World Health Organization to declare it as a pandemic; by the end of April 2020, the number of cases exceeded 3 million. Due to the high infectivity rate, SARS-CoV-2 is difficult to contain, making disinfectant protocols vital, especially for essential, highly trafficked areas such as hospitals, grocery stores, and delivery centers. According to the Centers for Disease Control and Prevention, best practices to slow the spread rely on good hand hygiene, including proper handwashing practices as well as the use of alcohol-based hand sanitizers. However, they provide warning against sanitizing products containing benzalkonium chloride (BAC), which has sparked concern in both the scientific community as well as the general public as BAC, a common quaternary ammonium compound (QAC), is ubiquitous in soaps and cleaning wipes as well as hospital sanitation kits. This viewpoint aims to highlight the outdated and incongruous data in the evaluation of BAC against the family of known coronaviruses and points to the need for further evaluation of the efficacy of QACs against coronaviruses.", "title": "Are Quaternary Ammonium Compounds, the Workhorse Disinfectants, Effective against Severe Acute Respiratory Syndrome-Coronavirus-2?", "pid": "9ksiyyqe", "bm25_score": 216.3792266845703}, {"text": "During global health emergencies such as the current COVID-19 pandemic, the decontamination of single-use personal protective equipment (PPE) becomes a necessary means to keep up with the growing demand from healthcare workers and patients alike. Many unverified methods are being considered, which can pose the risk of incomplete decontamination and lead to catastrophic results. Several factors come into play when determining the suitability of such methods including the quality of the decontamination technique, the targeted pathogen, cost, ease of installation and use, rate of sterilization, and the surface or material to be sterilized. The germicidal properties of ultraviolet-C are well known. This review will cover the most commonly described methods for the sterilization of N95 respirators, namely, ultraviolet germicidal irradiation, hydrogen peroxide vaporization, microwave-generated steaming, and dry heating. These techniques have been tested previously and have demonstrated efficacy in reducing or inactivating viral and bacterial pathogens, although testing against SARS-CoV-2 specifically has not been done. Moreover, it must be emphasized that proper disposal after a single use is still ideal under normal circumstances.", "title": "Ultraviolet-C and other methods of decontamination of filtering facepiece N-95 respirators during the COVID-19 pandemic.", "pid": "wc24ty89", "bm25_score": 216.3510284423828}, {"text": "Hand eczema, also known as hand dermatitis, often results from a combination of causes, including genetics (atopic constitution), irritating substances and contact allergens. The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19). As current evidence suggests that SARS-CoV-2 can be transmitted through contaminated hands, the World Health Organization recommends frequent handwashing with soap and water, or hand-rubbing with an alcohol based hand rub.", "title": "Hand Eczema Pandemic Caused by SARS-CoV-2 Hygiene Measures: The Setup of a Hand Eczema Helpline for Hospital Personnel.", "pid": "1disacfi", "bm25_score": 216.34439086914062}, {"text": "Decontamination using hand hygiene remains one of the most important and effective methods for reducing healthcare-associated infections and cross-infection between patients. In 1860, Florence Nightingale wrote that nurses should wash their hands frequently throughout the day, demonstrating an early awareness of the effectiveness of this simple procedure. The COVID-19 pandemic has demonstrated that effectively applied hand hygiene is a vital intervention that can be used to prevent the spread of disease. This article details the correct procedure required for effective hand hygiene and emphasises the need for nurses to keep up to date with evidence-based guidelines. The article also outlines the differences between hand decontamination using alcohol-based hand gels and soap and water, and the complex factors that can interfere with effective hand hygiene compliance.", "title": "Using effective hand hygiene practice to prevent and control infection.", "pid": "4jx0oq65", "bm25_score": 216.3028564453125}, {"text": "During global health emergencies such as the current COVID-19 pandemic, the decontamination of single-use personal protective equipment (PPE) becomes a necessary means to keep up with the growing demand from healthcare workers and patients alike. Many unverified methods are being considered, which can pose the risk of incomplete decontamination and lead to catastrophic results. Several factors come into play when determining the suitability of such methods including the quality of the decontamination technique, the targeted pathogen, cost, ease of installation and use, rate of sterilization, and the surface or material to be sterilized. The germicidal properties of ultraviolet-C are well known. This review will cover the most commonly described methods for the sterilization of N95 respirators, namely, ultraviolet germicidal irradiation, hydrogen peroxide vaporization, microwave-generated steaming, and dry heating. These techniques have been tested previously and have demonstrated efficacy in reducing or inactivating viral and bacterial pathogens, although testing against SARS-CoV-2 specifically has not been done. Moreover, it must be emphasized that proper disposal after a single use is still ideal under normal circumstances.", "title": "Ultraviolet-C and other methods of decontamination of filtering facepiece N-95 respirators during the COVID-19 pandemic", "pid": "t1xp9e23", "bm25_score": 216.2965087890625}, {"text": "Decontamination using hand hygiene remains one of the most important and effective methods for reducing healthcare-associated infections and cross-infection between patients. In 1860, Florence Nightingale wrote that nurses should wash their hands frequently throughout the day, demonstrating an early awareness of the effectiveness of this simple procedure. The COVID-19 pandemic has demonstrated that effectively applied hand hygiene is a vital intervention that can be used to prevent the spread of disease. This article details the correct procedure required for effective hand hygiene and emphasises the need for nurses to keep up to date with evidence-based guidelines. The article also outlines the differences between hand decontamination using alcohol-based hand gels and soap and water, and the complex factors that can interfere with effective hand hygiene compliance.", "title": "Using effective hand hygiene practice to prevent and control infection", "pid": "k5lz7ql7", "bm25_score": 216.22598266601562}, {"text": "In the setting of the coronavirus disease 2019 pandemic, efficient methods are needed to decontaminate shared portable devices and large open areas such as waiting rooms. We found that wheelchairs, portable equipment, and waiting room chairs were frequently contaminated with potential pathogens. After minimal manual precleaning of areas with visible soiling, application of a dilute sodium hypochlorite disinfectant using an electrostatic sprayer provided rapid and effective decontamination and eliminated the benign virus bacteriophage MS2 from inoculated surfaces.", "title": "Evaluation of an electrostatic spray disinfectant technology for rapid decontamination of portable equipment and large open areas in the era of SARS-CoV-2", "pid": "zpu4pyy5", "bm25_score": 216.19435119628906}, {"text": "In the setting of the coronavirus disease 2019 pandemic, efficient methods are needed to decontaminate shared portable devices and large open areas such as waiting rooms. We found that wheelchairs, portable equipment, and waiting room chairs were frequently contaminated with potential pathogens. After minimal manual pre-cleaning of areas with visible soiling, application of a dilute sodium hypochlorite disinfectant using an electrostatic sprayer provided rapid and effective decontamination and eliminated the benign virus bacteriophage MS2 from inoculated surfaces.", "title": "Evaluation of an Electrostatic Spray Disinfectant Technology for Rapid Decontamination of Portable Equipment and Large Open Areas in the Era of SARS-CoV-2", "pid": "j7pmb3mk", "bm25_score": 216.17782592773438}, {"text": "COVID-19 (SARS-CoV-2) is causing a huge concern to the global population due to its highly contagious properties. The SARS-CoV-2 is a new variant in the coronavirus family. The world is focussing on several methods to battle against this novel corona virus, including control of its spread. In this context, ARCI has quickly made efforts to develop disinfection systems including a UVC-based disinfection trolley, honeycomb air heater and a fogging chamber using UVC germicidal lamps, dry heat sterilization and HOCl-based chemical disinfectant to provide rapid and effective inactivation of microorganisms causing the pandemic. These systems have been successfully deployed at different hospitals for their validation.", "title": "Fight Against COVID-19: ARCI’s Technologies for Disinfection", "pid": "bq6ogxyq", "bm25_score": 216.15673828125}, {"text": "In order to prevent spread of COVID-19, World Health Organization (WHO) has specified that measures such as cleaning hands regularly with alcohol-based hand sanitizer or washing with soap and water, avoiding touching nose, eyes, mouth and social distancing should be followed by people. Another important measure for containing spread is by Testing–Testing and Testing. To conduct real-time reverse transcription polymerase chain reaction (rRT-PCR) test for diagnosing COVID-19. Possibility to test up to 2000 samples per day. For virus culturing for drug screening, convalescent plasma-derived therapy. To aid in the development of vaccine and development of diagnostic kits.", "title": "Mobile Virology Research and Diagnostic Laboratory (MVRDL: BSL-3) for COVID-19 Screening, Virus Culturing and Vaccine Development", "pid": "fjiffj86", "bm25_score": 216.15628051757812}, {"text": "The COVID-19 pandemic is posing a huge global health threat. To deal with this problem, in addition to research and work in the medical field, the main health measures being taken in the workplace and at home involve the establishment of safety protocols, which include distance measures, hygiene and the use of personal protective equipment, such as masks, etc. The WHO still does not recommend the use of masks for the general population. However, their successful use in China, South Korea and the Czech Republic has encouraged their widespread use, and the shortage that already existed. This has caused that companies and individuals are looking at the best way to reuse them, and to manufacture, homemade or not, of non-certified masks. This paper is based on two objectives: to consult the scientific literature to identify the main strategies for disinfecting them, and to determine the effectiveness of non-certified disposable masks. A rapid review has been conducted in which the main publications and other information available online have been analyzed. Results showed that the most promising methods are those that use hydrogen peroxide vapor, ultraviolet radiation, moist heat, dry heat and ozone gas. Soapy water, alcohol, bleach immersion, ethylene oxide, ionizing radiation, microwave, high temperature, autoclave or steam are not fully recommended. Regarding the effectiveness of surgical masks compared to PPE, the former have been seen to be slightly less effective than PPE. As for other types of masks the effectiveness of homemade or non-certified masks is very low.", "title": "Disposable masks: Disinfection and sterilization for reuse, and non-certified manufacturing, in the face of shortages during the COVID-19 pandemic", "pid": "lncsfohg", "bm25_score": 216.08169555664062}, {"text": "", "title": "Frequent handwashing amidst the COVID‐19 outbreak: prevention of hand irritant contact dermatitis and other considerations", "pid": "115fdhjz", "bm25_score": 216.02999877929688}, {"text": "", "title": "Rational hand hygiene during the coronavirus 2019 (COVID-19) pandemic", "pid": "f67jr495", "bm25_score": 216.02621459960938}, {"text": "Summary The novel human coronavirus SARS-CoV-2 has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described, probably via droplets but possibly also via contaminated hands or surfaces. In a recent review on the persistence of human and veterinary coronaviruses on inanimate surfaces it was shown that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days. Some disinfectant agents effectively reduce coronavirus infectivity within 1 minute such 62%–71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite. Other compounds such as 0.05%–0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. An effective surface disinfection may help to ensure an early containment and prevention of further viral spread.", "title": "Potential role of inanimate surfaces for the spread of coronaviruses and their inactivation with disinfectant agents", "pid": "80dfqjql", "bm25_score": 215.99978637695312}, {"text": "", "title": "The fight against COVID-19: disinfection protocol and turning over of CleanSpace(®) HALO™ in a Singapore Hospital", "pid": "xirncnh9", "bm25_score": 215.9828338623047}, {"text": "", "title": "Hand hygiene in preventing COVID-19 transmission.", "pid": "rq8sjc8q", "bm25_score": 215.97450256347656}, {"text": "", "title": "The fight against COVID-19: disinfection protocol and turning over of CleanSpace® HALO™ in a Singapore Hospital", "pid": "c3horjs4", "bm25_score": 215.9619140625}, {"text": "", "title": "Hand hygiene in preventing COVID-19 transmission", "pid": "0a8sp3iz", "bm25_score": 215.94642639160156}, {"text": "Alsace, in particular Haut-Rhin, is one of the main clusters of COVID-19 in France There has been a shortage of essential supplies in the area, especially alcohol-based hand sanitizer In this context, and in accordance with the decree dated March 6, 2020, our hospital management team asked us to start local production of alcohol-based handrub This was a real challenge: In one week, we had to implement the production of handrub to meet the needs of a 1,400-bed hospital The production had to comply with the French preparation guidelines and take place on specific premises, with qualified and calibrated equipment, by qualified staff, under the supervision of a pharmacist The other big challenge we faced was the supply of pharmaceutical raw and packaging materials During this particular critical period, all suppliers were out of stock Here, we describe the organizational set-up and the decisions made, e g , to use technical-grade ethanol before the publication of the decrees dated March 13 and March 23, 2020", "title": "Preparation of alcohol-based handrub in COVID-19 Alsatian cluster", "pid": "p5hvf569", "bm25_score": 215.93101501464844}, {"text": "The detection of SARS-CoV-2 in the saliva of patients with coronavirus disease (COVID-19) has made this biological fluid relevant in terms of the diagnosis and transmission of the infection (To et al, 2020a; Azzi et al, 2020a). As a result, the dental clinic is considered an environment of risk for dental healthcare personnel and their patients, particularly due to the potential transmission of the virus through droplets and aerosols (Peng et al, 2020).", "title": "Is povidone‐iodine mouthwash effective against SARS‐CoV‐2? First in vivo tests", "pid": "3lqqc7h9", "bm25_score": 215.91490173339844}, {"text": "The unprecedented pandemic of SARS-CoV-2 has created worldwide shortages of personal protective equipment, in particular respiratory protection such as N95 respirators. SARS-CoV-2 transmission is frequently occurring in hospital settings, with numerous reported cases of nosocomial transmission highlighting the vulnerability of healthcare workers. In general, N95 respirators are designed for single use prior to disposal. Here, we have analyzed four readily available and often used decontamination methods: UV, 70% ethanol, 70C heat and vaporized hydrogen peroxide for inactivation of SARS-CoV-2 on N95 respirators. Equally important we assessed the function of the N95 respirators after multiple wear and decontamination sessions.", "title": "Assessment of N95 respirator decontamination and re-use for SARS-CoV-2", "pid": "oam77j3m", "bm25_score": 215.88436889648438}, {"text": "The WHO has declared COVID-19 illness a global health concern which is caused by 2019-nCoV, causing severe respiratory tract infections in humans. Transmissibility among individual to individual have been reported through droplets and probably also via contaminated surfaces and hands. Human coronaviruses can persist on inanimate surfaces such as plastic, glass, fibers and metals up to nine days. 2019-nCoV remains infectious in air for 3 h and on inanimate surfaces such as cardboard, copper, plastic and steel up to 24, 4, 72 and 48 h respectively. Disinfectant activity of various biocidal agents against coronaviruses like ethanol (62–71%), sodium hypochlorite (0.1%) and hydrogen peroxide (0.5%) can be regarded effective against 2019-nCoV as well. As no vaccine and antiviral therapies have been discovered for 2019-nCoV, prevention of further spread will viable option to control the ongoing and future outbreaks.", "title": "Inanimate surfaces as potential source of 2019-nCoV spread and their disinfection with biocidal agents", "pid": "esvutpel", "bm25_score": 215.88258361816406}, {"text": "Disinfectants play a major role in the control of animal diseases by decontaminating the farm environment. We evaluated the virucidal efficacy of nine commonly used disinfectants on a nonporous surface contaminated experimentally with avian metapneumovirus (aMPV), avian influenza virus, or Newcastle disease virus (NDV). Phenolic compounds and glutaraldehyde were found to be the most effective against all three viruses. Quaternary ammonium compounds were effective against aMPV but not against the other two viruses. In addition, efficacy of commercially available hand sanitizers was evaluated on human fingers contaminated with aMPV and NDV. All three hand sanitizers tested were found to be effective against both viruses within 1 min of application on fingers.", "title": "Efficacy of disinfectants and hand sanitizers against avian respiratory viruses.", "pid": "lbu2xbqh", "bm25_score": 215.8765869140625}, {"text": "OBJECTIVE: The past 4 months, the emergence and spread of novel 2019 SARS-Cov-2 (COVID-19) has led to a global pandemic which is rapidly depleting supplies of personal protective equipment worldwide. There are currently over 1.6 million confirmed cases of COVID-19 worldwide which has resulted in more the 100,000 deaths. As these numbers grow daily, hospitals are being forced to reuse surgical masks in hopes of conserving their dwindling supply. Since COVID-19 will most likely have effects that last for many months, our nationwide shortage of masks poses a long term issue that must be addressed immediately. METHODS: Based on a previous study by Quan et al., a salt-based soaking strategy has been reported to enhance the filtration ability of surgical masks. We propose a similar soaking process which uses materials widely available in anyone's household. We tested this method of pretreating a variety of materials with a salt-based solution by a droplet test using fluorescently stained nanoparticles similar in size to the COVID-19 virus. RESULTS: In this study, we found that paper towels and surgical masks pretreated with the salt-based solution showed a noticeable increase in filtration of nanoparticles similar in size to the COVID-19 virus. We also show that the TWEEN20 used by Quan et al. is not a critical component for the solution, and using salt alone in solution still provides a dramatically increased level of protection. CONCLUSIONS: We believe this method will allow for healthcare workers to create a disposable added layer of protection to their surgical masks, N95s, or homemade masks by using household available products. Adoption of this method may play an essential role in ensuring the safety of healthcare workers during the COVID-19 pandemic and any pandemics that may arise in the future.", "title": "Pretreated household materials carry similar filtration protection against pathogens when compared with surgical masks", "pid": "8t0eks8g", "bm25_score": 215.86874389648438}, {"text": "The etiology of nosocomial infections, the frequency of contaminated hands with the different nosocomial pathogens, and the role of health care workers' hands during outbreaks suggest that a hand hygiene preparation should at least have activity against bacteria, yeasts, and coated viruses. The importance of efficacy in choosing the right hand hygiene product is reflected in the new Centers for Disease Control and Prevention guideline on hand hygiene (J. M. Boyce and D. Pittet, Morb. Mortal. Wkly. Rep. 51:1-45, 2002). The best antimicrobial efficacy can be achieved with ethanol (60 to 85%), isopropanol (60 to 80%), and n-propanol (60 to 80%). The activity is broad and immediate. Ethanol at high concentrations (e.g., 95%) is the most effective treatment against naked viruses, whereas n-propanol seems to be more effective against the resident bacterial flora. The combination of alcohols may have a synergistic effect. The antimicrobial efficacy of chlorhexidine (2 to 4%) and triclosan (1 to 2%) is both lower and slower. Additionally, both agents have a risk of bacterial resistance, which is higher for chlorhexidine than triclosan. Their activity is often supported by the mechanical removal of pathogens during hand washing. Taking the antimicrobial efficacy and the mechanical removal together, they are still less effective than the alcohols. Plain soap and water has the lowest efficacy of all. In the new Centers for Disease Control and Prevention guideline, promotion of alcohol-based hand rubs containing various emollients instead of irritating soaps and detergents is one strategy to reduce skin damage, dryness, and irritation. Irritant contact dermatitis is highest with preparations containing 4% chlorhexidine gluconate, less frequent with nonantimicrobial soaps and preparations containing lower concentrations of chlorhexidine gluconate, and lowest with well-formulated alcohol-based hand rubs containing emollients and other skin conditioners. Too few published data from comparative trials are available to reliably rank triclosan. Personnel should be reminded that it is neither necessary nor recommended to routinely wash hands after each application of an alcohol-based hand rub. Long-lasting improvement of compliance with hand hygiene protocols can be successful if an effective and accessible alcohol-based hand rub with a proven dermal tolerance and an excellent user acceptability is supplied, accompanied by education of health care workers and promotion of the use of the product.", "title": "Epidemiologic background of hand hygiene and evaluation of the most important agents for scrubs and rubs.", "pid": "btzrfs6g", "bm25_score": 215.86114501953125}, {"text": "OBJECTIVE: to perform a situational diagnosis of the behavior of health professionals concerning hand hygiene practices in highly-complex sectors. METHODS: this quantitative and retrospective study was based on reports (2016 and 2017) of Adult and Pediatric ICUs of a Federal hospital in Rio de Janeiro. RESULTS: one thousand two hundred fifty-eight opportunities for hand hygiene were analysed. The chance of professionals sanitizing hands in Pediatric ICUs is 41.61% higher than in Adult ICUs. Concerning proper hand hygiene, the medical team had a 39.44% lower chance than the nursing team. Others had a 30.62% lower chance when compared to the nursing team. The moment \"after contact with the patient\" presented 4.5275 times the chance in relation \"before contact with the patient\". CONCLUSION: in front of hand hygiene recommendations to control COVID-19, diagnostic assessment and previous analysis of the behavior of professionals proved to be positive.", "title": "Hand hygiene in high-complexity sectors as an integrating element in the combat of Sars-CoV-2", "pid": "56ibvpfy", "bm25_score": 215.84463500976562}, {"text": "Among the basic protective measures against COVID-19, the need to wash hands frequently and in a prolonged way using soap, and to regularly use alcohol-based hand sanitizers is well established for the whole population. Healthcare workers in general, and particularly those involved in the direct care of COVID-19 patients, have to wear personal protective equipment (PPE) daily for many hours and also accomplish general preventive measurements outside their work. Cutaneous adverse reactions can develop that need to be prevented, identified and therapeutically managed. According to the data reported by Lin et al 1 , based in the experience from healthcare workers in Wuhan, adverse skin reactions were reported in 74% of responders (n=376) to a general survey. The most commonly reported types of eruptions were skin dryness or desquamation (68.6%), papules or erythema (60.4%) and maceration (52,9%).", "title": "European Task Force on Contact Dermatitis statement on coronavirus 19 disease (COVID-19) outbreak and the risk of adverse cutaneous reactions.", "pid": "gfyup5aj", "bm25_score": 215.83544921875}, {"text": "Rapid transmission of the severe acute respiratory syndrome coronavirus 2 has led to the novel coronavirus disease 2019 (COVID-19) pandemic. The current emphasis is on preventive strategies such as social distancing, face mask, and hand washing. The technique of nasopharyngeal wash to prevent the virus from inhabiting and replicating in the nasal and pharyngeal mucosa has been suggested to be useful in reducing symptoms, transmission, and viral shedding in cases of viral acute respiratory tract infections. In rapid systematic review, we found studies showing some improvement in prevention and treatment of upper respiratory tract infections. We postulate that hypertonic saline gargles and nasal wash may be useful in prevention and for care of patients with COVID-19. The present evidence emphasizes the need of randomized controlled trials to evaluate the role and mechanism of nasopharyngeal wash in COVID-19.", "title": "Nasopharyngeal wash in preventing and treating upper respiratory tract infections: Could it prevent COVID-19?", "pid": "c2nkp1gq", "bm25_score": 215.8241424560547}, {"text": "Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus, SARS-COV-2 was declared a Public Health Emergency of International Concern (PHEIC) by the World Health Organization (WHO) in January 2020. Human-to-Human transmission occurs through close contact with an infected person or surfaces that are contaminated with droplets or secretions.", "title": "Povidone‐iodine gargle as a prophylactic intervention to interrupt the transmission of SARS‐CoV‐2", "pid": "pd78369r", "bm25_score": 215.81954956054688}, {"text": "Increased hand hygiene amongst the general public has been widely promoted as one of the most important non-pharmaceutical interventions for reducing transmission during the ongoing COVID-19 pandemic and is likely to continue to play a key role in long-term efforts to suppress transmission before a vaccine can be deployed. For other respiratory tract infections community hand hygiene interventions are supported by evidence from randomised trials, but information on how effectiveness in reducing transmission scales with achieved changes in hand hygiene behaviour is lacking. This information is of critical importance when considering the potential value of substantially enhancing community hand hygiene frequency to help suppress COVID-19. Here, we developed a simple model-based framework for understanding the key determinants of the effectiveness of changes in hand hygiene behaviour in reducing transmission and use it to explore the potential impact of interventions aimed at achieving large-scale population-wide changes in hand hygiene behaviour. Our analyses show that the effect of hand hygiene is highly dependent on the duration of viral persistence on hands and that hand washing needs to be performed very frequently or immediately after hand contamination events in order to substantially reduce the probability of infection. Hand washing at a lower frequency, such as every 30 minutes or with a delay of 15 minutes after contamination events, may be adequate to reduce the probability of infection when viral survival on hands is longer, such as when hands are contaminated with mucus. Immediate hand washing after contamination is more effective than hand washing at fixed-time intervals even when the total number of hand washing events is similar. This event-prompted hand washing strategy is consistently more effective than fixed-time strategy regardless of hand contamination rates and should be highlighted in hand hygiene campaigns.", "title": "The Potential Impact of Intensified Community Hand Hygiene Interventions on Respiratory tract Infections: A Modelling Study", "pid": "bgdr25z1", "bm25_score": 215.8119354248047}, {"text": "The COVID-19 pandemic has created a high demand on personal protective equipment, including disposable N95 masks. Given the need for mask reuse, we tested the feasibility of vaporized hydrogen peroxide (VHP), ultraviolet light (UV), and ethanol decontamination strategies on N95 mask integrity and the ability to remove the infectious potential of SARS-CoV-2. FIT test data showed functional degradation by both ethanol and UV decontamination to different degrees. VHP treated masks showed no significant change in function after two treatments. We also report a single SARS-CoV-2 virucidal experiment using Vero E6 cell infection. We hope our data will guide further research for evidenced-based decisions for disposable N95 mask reuse and help protect caregivers from SARS-CoV-2 and other pathogens.", "title": "Effect of various decontamination procedures on disposable N95 mask integrity and SARS-CoV-2 infectivity", "pid": "tq9kjozt", "bm25_score": 215.81072998046875}, {"text": "The SARS-CoV-2 outbreak causing the respiratory disease COVID-19 has left many chemists in academia without an obvious option to contribute to fighting the pandemic. Some of our recent experiences indicate that there are ways to overcome this dilemma. A three-pronged approach is proposed.", "title": "Thoughts on What Chemists Can Contribute to Fighting SARS-CoV-2 - A Short Note on Hand Sanitizers, Drug Candidates and Outreach", "pid": "uqxl4xux", "bm25_score": 215.80941772460938}, {"text": "", "title": "Does hand hygiene reduce SARS-CoV-2 transmission?", "pid": "kupm680z", "bm25_score": 215.80528259277344}, {"text": "", "title": "COVID-19 reinforces the importance of handwashing", "pid": "09w2yec8", "bm25_score": 215.7976837158203}, {"text": "Decontamination of N95 respirators has become critical to alleviate PPE shortages for healthcare workers in the current COVID-19 emergency. The factors that are considered for the effective reuse of these masks are the fit, filter efficiency and decontamination/disinfection level both for SARS-CoV-2, which is the causative virus for COVID-19, and for other organisms of concern in the hospital environment such as Staphylococcus aureus or Clostridium difficile. In its guidance entitled 'Recommendations for Sponsors Requesting EUAs for Decontamination and Bioburden Reduction Systems for Surgical Masks and Respirators During the Coronavirus Disease 2019 (COVID19) Public Health Emergency' (May 2020)[1], the FDA recommends a 6-log10 reduction in either the most resistant bacterial spores for the system or in a mycobacterium species to authorize the use of a decontamination method of N95 respirators for single or multiple users. While the goal is primarily inactivation against SARS-CoV-2, testing of decontamination methods against the virus may not always be available. For decontamination methods considered for only single users, the recommendation is a 6-log10 reduction in the infective virus concentration of 3 non-enveloped viruses or in the concentration of two Gram (+) and two Gram (-) bacteria. Based on these recommendations, we explored the efficacy of vaporized H2O2 (VHP) treatment of N95 respirators against surrogate viruses covering a wide range of disinfection resistance for emergency decontamination and reuse to alleviate PPE shortages for healthcare workers in the COVID-19 emergency.", "title": "Vaporized H2O2 decontamination against surrogate viruses for the reuse of N95 respirators in the COVID-19 emergency", "pid": "z22gaapb", "bm25_score": 215.7698211669922}, {"text": "BACKGROUND: Low-income countries have reduced health care system capacity and are therefore at risk of substantially higher COVID-19 case fatality rates than those currently seen in high-income countries. Handwashing is a key component of guidance to reduce transmission of the SARS-CoV-2 virus, responsible for the COVID-19 pandemic. Prior systematic reviews have indicated the effectiveness of handwashing to reduce transmission of respiratory viruses. In low-income countries, reduction of transmission is of paramount importance, but social distancing is challenged by high population densities and access to handwashing facilities with soap and water is limited. OBJECTIVES: Our objective was to estimate global access to handwashing with soap and water to inform use of handwashing in the prevention of COVID-19 transmission. METHODS: We utilized observational surveys and spatiotemporal Gaussian process regression modeling in the context of the Global Burden of Diseases, Injuries, and Risk Factors Study to estimate access to a handwashing station with available soap and water for 1,062 locations from 1990 to 2019. RESULTS: Despite overall improvements from 1990 {33.6% [95% uncertainty interval (UI): 31.5, 35.6] without access} to 2019, globally in 2019, 2.02 (95% UI: 1.91, 2.14) billion people, 26.1% (95% UI: 24.7, 27.7) of the global population, lacked access to handwashing with available soap and water. More than 50% of the population in sub-Saharan Africa and Oceania were without access to handwashing in 2019, and in eight countries, 50 million or more persons lacked access. DISCUSSION: For populations without handwashing access, immediate improvements in access or alternative strategies are urgently needed, and disparities in handwashing access should be incorporated into COVID-19 forecasting models when applied to low-income countries. https://doi.org/10.1289/EHP7200.", "title": "Global Access to Handwashing: Implications for COVID-19 Control in Low-Income Countries", "pid": "wfsq7vr5", "bm25_score": 215.76168823242188}, {"text": "COVID-19 is a disease with no proven pharmaceutical intervention and no proven vaccine. In such circumstances, prevention is all we have. The role of handwashing in the prevention of communicable diseases has been known for over a century, yet it remains severely neglected as a public health investment, to be periodically re-discovered during pandemic-scale infections. Over 26% of the global population has no access to a handwashing station in the home; for many low-income countries this proportion rises to over 50%. In other instances, the water is unaffordable or the supply has been shut off on account of unpaid bills. But when there is no water in the home or yard, or no mechanism for delivering enough water, good hand-washing is extremely difficult. Well before COVID-19, global cost-benefit analyses of water and sanitation investments, with benefits measured in time-savings as well as health, showed significant net benefits in all sub-regions of the developing world. This Viewpoint paper argues that, in the current crisis and its aftermath, it is imperative for governments and donors to prioritize and generously fund affordable, reliable, and accessible water services in underserved regions of the world. More than ever before, this is a foundational investment for health, dignity and development.", "title": "Viewpoint | Handwashing and COVID-19: Simple, right there…?", "pid": "xtv5tlsw", "bm25_score": 215.7607879638672}, {"text": "BACKGROUND: Low-income countries have reduced health care system capacity and are therefore at risk of substantially higher COVID-19 case fatality rates than those currently seen in high-income countries. Handwashing is a key component of guidance to reduce transmission of the SARS-CoV-2 virus, responsible for the COVID-19 pandemic. Prior systematic reviews have indicated the effectiveness of handwashing to reduce transmission of respiratory viruses. In low-income countries, reduction of transmission is of paramount importance, but social distancing is challenged by high population densities and access to handwashing facilities with soap and water is limited. OBJECTIVES: Our objective was to estimate global access to handwashing with soap and water to inform use of handwashing in the prevention of COVID-19 transmission. METHODS: We utilized observational surveys and spatiotemporal Gaussian process regression modeling in the context of the Global Burden of Diseases, Injuries, and Risk Factors Study to estimate access to a handwashing station with available soap and water for 1,062 locations from 1990 to 2019. RESULTS: Despite overall improvements from 1990 {33.6% [95% uncertainty interval (UI): 31.5, 35.6] without access} to 2019, globally in 2019, 2.02 (95% UI: 1.91, 2.14) billion people, 26.1% (95% UI: 24.7, 27.7) of the global population, lacked access to handwashing with available soap and water. More than 50% of the population in sub-Saharan Africa and Oceania were without access to handwashing in 2019, and in eight countries, 50 million or more persons lacked access. DISCUSSION: For populations without handwashing access, immediate improvements in access or alternative strategies are urgently needed, and disparities in handwashing access should be incorporated into COVID-19 forecasting models when applied to low-income countries. https://doi.org/10.1289/EHP7200", "title": "Global Access to Handwashing: Implications for COVID-19 Control in Low-Income Countries", "pid": "uynd63m5", "bm25_score": 215.7553253173828}, {"text": "", "title": "Rational hand hygiene during COVID-19 pandemic", "pid": "gdtm4d7w", "bm25_score": 215.74974060058594}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a severe, international shortage of N95 respirators, which are essential to protect health care providers from infection. Given the contemporary limitations of the supply chain, it is imperative to identify effective means of decontaminating, reusing, and thereby conserving N95 respirator stockpiles. To be effective, decontamination must result in sterilization of the N95 respirator without impairment of respirator filtration or user fit. Although numerous methods of N95 decontamination exist, none are universally accessible. In this work, we describe a microwave-generated steam decontamination protocol for N95 respirators for use in health care systems of all sizes, geographies, and means. Using widely available glass containers, mesh from commercial produce bags, a rubber band, and a 1,100-W commercially available microwave, we constructed an effective, standardized, and reproducible means of decontaminating N95 respirators. Employing this methodology against MS2 phage, a highly conservative surrogate for SARS-CoV-2 contamination, we report an average 6-log10 plaque-forming unit (PFU) (99.9999%) and a minimum 5-log10 PFU (99.999%) reduction after a single 3-min microwave treatment. Notably, quantified respirator fit and function were preserved, even after 20 sequential cycles of microwave steam decontamination. This method provides a valuable means of effective decontamination and reuse of N95 respirators by frontline providers facing urgent need.IMPORTANCE Due to the rapid spread of coronavirus disease 2019 (COVID-19), there is an increasing shortage of protective gear necessary to keep health care providers safe from infection. As of 9 April 2020, the CDC reported 9,282 cumulative cases of COVID-19 among U.S. health care workers (CDC COVID-19 Response Team, MMWR Morb Mortal Wkly Rep 69:477-481, 2020, https://doi.org/10.15585/mmwr.mm6915e6). N95 respirators are recommended by the CDC as the ideal method of protection from COVID-19. Although N95 respirators are traditionally single use, the shortages have necessitated the need for reuse. Effective methods of N95 decontamination that do not affect the fit or filtration ability of N95 respirators are essential. Numerous methods of N95 decontamination exist; however, none are universally accessible. In this study, we describe an effective, standardized, and reproducible means of decontaminating N95 respirators using widely available materials. The N95 decontamination method described in this work will provide a valuable resource for hospitals, health care centers, and outpatient practices that are experiencing increasing shortages of N95 respirators due to the COVID-19 pandemic.", "title": "Microwave-Generated Steam Decontamination of N95 Respirators Utilizing Universally Accessible Materials", "pid": "g9f97nfc", "bm25_score": 215.72299194335938}, {"text": "Coronavirus disease (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, is responsible for the 2020 global pandemic and characterized by high transmissibility and morbidity. Healthcare workers (HCWs) are at risk of contracting COVID-19, and this risk is mitigated through the use of personal protective equipment such as N95 Filtering Facepiece Respirators (FFRs). The high demand for FFRs is not currently met by global supply chains, potentially placing HCWs at increased exposure risk. Effective FFR decontamination modalities exist, which could maintain respiratory protection for HCWs in the midst of the current pandemic, through the decontamination and re-use of FFRs. Here, we present a locally-implemented ultraviolet-C germicidal irradiation (UVGI)-based FFR decontamination pathway, utilizing a home-built UVGI array assembled entirely with previously existing components available at our institution. We provide recommendations on the construction of similar systems, as well as guidance and strategies towards successful institutional implementation of FFR decontamination.", "title": "Homegrown Ultraviolet Germicidal Irradiation for Hospital-Based N95 Decontamination during the COVID-19 Pandemic", "pid": "zje20bzz", "bm25_score": 215.71783447265625}, {"text": "The SARS‐CoV‐2 outbreak causing the respiratory disease COVID‐19 has left many chemists in academia without an obvious option to contribute to fighting the pandemic. Some of our recent experiences indicate that there are ways to overcome this dilemma. A three‐pronged approach is proposed.", "title": "Thoughts on What Chemists Can Contribute to Fighting SARS‐CoV‐2 – A Short Note on Hand Sanitizers, Drug Candidates and Outreach", "pid": "kuwargnp", "bm25_score": 215.71697998046875}, {"text": "The 2019 Coronavirus epidemic, provisionally called 2019-nCoV, was first identified in Wuhan, China, in persons exposed to a seafood or wet market. There is an international push to contain the virus and prevent its spread. It is feasible that potentially infectious samples may be received in histopathology laboratories for diagnosis. This technical note presents disinfection procedures and histotechnology processes that should alleviate the risk of infection to laboratory staff. Using data obtained from similar coronaviruses, e.g. severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), experts are confident that 70% ethanol and 0.1% sodium hypochlorite should inactivate the virus. Formalin fixation and heating samples to 56oC, as used in routine tissue processing, were found to inactivate several coronaviruses and it is believed that 2019-nCoV would be similarly affected.", "title": "Coronavirus disinfection in histopathology.", "pid": "21stahui", "bm25_score": 215.67092895507812}, {"text": "The World Health Organization (WHO) recently released a press report highlighting the severe shortage of personal protective equipment (PPE) that is endangering healthcare workers worldwide during the COVID-19 pandemic.1 To meet this urgent need, healthcare institutions across the world have begun to utilize the germicidal properties of ultraviolet C (UVC) to decontaminate N95 respirators so that they can be reused.2 It is clearly crucial that the dose of UVC delivered is sufficient to kill any viable SARS-CoV-2, the causative virus of the COVID-19 pandemic, that may be present on the respirators.", "title": "The importance of the minimum dosage necessary for UVC decontamination of N95 respirators during the COVID‐19 pandemic", "pid": "hmdq2g3u", "bm25_score": 215.65985107421875}, {"text": "OBJECTIVE to perform a situational diagnosis of the behavior of health professionals concerning hand hygiene practices in highly-complex sectors. METHODS this quantitative and retrospective study was based on reports (2016 and 2017) of Adult and Pediatric ICUs of a Federal hospital in Rio de Janeiro. RESULTS one thousand two hundred fifty-eight opportunities for hand hygiene were analysed. The chance of professionals sanitizing hands in Pediatric ICUs is 41.61% higher than in Adult ICUs. Concerning proper hand hygiene, the medical team had a 39.44% lower chance than the nursing team. Others had a 30.62% lower chance when compared to the nursing team. The moment \"after contact with the patient\" presented 4.5275 times the chance in relation \"before contact with the patient\". CONCLUSION in front of hand hygiene recommendations to control COVID-19, diagnostic assessment and previous analysis of the behavior of professionals proved to be positive.", "title": "Hand hygiene in high-complexity sectors as an integrating element in the combat of Sars-CoV-2.", "pid": "xga0lncp", "bm25_score": 215.61837768554688}, {"text": "BACKGROUND: In the 2003 severe acute respiratory syndrome outbreak, finding viral nucleic acids on hospital surfaces suggested surfaces could play a role in spread in health care environments. Surface disinfection may interrupt transmission, but few data exist on the effectiveness of health care germicides against coronaviruses on surfaces. METHODS: The efficacy of health care germicides against 2 surrogate coronaviruses, mouse hepatitis virus (MHV) and transmissible gastroenteritis virus (TGEV), was tested using the quantitative carrier method on stainless steel surfaces. Germicides were o-phenylphenol/p-tertiary amylphenol) (a phenolic), 70% ethanol, 1:100 sodium hypochlorite, ortho-phthalaldehyde (OPA), instant hand sanitizer (62% ethanol), and hand sanitizing spray (71% ethanol). RESULTS: After 1-minute contact time, for TGEV, there was a log(10) reduction factor of 3.2 for 70% ethanol, 2.0 for phenolic, 2.3 for OPA, 0.35 for 1:100 hypochlorite, 4.0 for 62% ethanol, and 3.5 for 71% ethanol. For MHV, log(10) reduction factors were 3.9 for 70% ethanol, 1.3 for phenolic, 1.7 for OPA, 0.62 for 1:100 hypochlorite, 2.7 for 62% ethanol, and 2.0 for 71% ethanol. CONCLUSION: Only ethanol reduced infectivity of the 2 coronaviruses by >3-log(10) after 1 minute. Germicides must be chosen carefully to ensure they are effective against viruses such as severe acute respiratory syndrome coronavirus.", "title": "Inactivation of surrogate coronaviruses on hard surfaces by health care germicides", "pid": "yr1dq258", "bm25_score": 215.60910034179688}, {"text": "BACKGROUND: The need for protective masks greatly exceeds their global supply during the current COVID-19 pandemic. METHODS: We optimized the temperature used in the dry heat pasteurization method to destroy pathogens and decontaminate masks while retaining their filtering capacity. RESULTS: The current study showed that dry heat at both 60°C and 70°C for one hour could successfully kill six species of respiratory bacteria and one fungi species, and inactivate the H1N1 indicator virus. After being heated at 70°C for 1 h, 2 h, and 3 h, the N95 respirators and surgical face masks showed no changes in their shape and components. The filtering efficiency of bacterial aerosol for N95 respirators were 98%, 98%, and 97% after being heated for 1 h, 2 h, and 3 h, respectively, all of which were over the 95% efficiency required and similar to the value before being heated (99%). The filtering efficiency for surgical face masks was 97%, 97%, and 96% for 1 h, 2 h, and 3 h of heating, respectively, all of which were also similar to the value before being heated (97%). CONCLUSIONS: This method can be used at home and can resolve the current shortage of masks.", "title": "Decontamination of Surgical Face Masks and N95 Respirators by Dry Heat Pasteurization for One Hour at 70°C", "pid": "w4q75grn", "bm25_score": 215.59231567382812}, {"text": "Currently, the emergence of a novel human coronavirus, SARS-CoV-2, has become a global health concern causing severe respiratory tract infections in humans. Human-to-human transmissions have been described with incubation times between 2-10 days, facilitating its spread via droplets, contaminated hands or surfaces. We therefore reviewed the literature on all available information about the persistence of human and veterinary coronaviruses on inanimate surfaces as well as inactivation strategies with biocidal agents used for chemical disinfection, e.g. in healthcare facilities. The analysis of 22 studies reveals that human coronaviruses such as Severe Acute Respiratory Syndrome (SARS) coronavirus, Middle East Respiratory Syndrome (MERS) coronavirus or endemic human coronaviruses (HCoV) can persist on inanimate surfaces like metal, glass or plastic for up to 9 days, but can be efficiently inactivated by surface disinfection procedures with 62-71% ethanol, 0.5% hydrogen peroxide or 0.1% sodium hypochlorite within 1 minute. Other biocidal agents such as 0.05-0.2% benzalkonium chloride or 0.02% chlorhexidine digluconate are less effective. As no specific therapies are available for SARS-CoV-2, early containment and prevention of further spread will be crucial to stop the ongoing outbreak and to control this novel infectious thread.", "title": "Persistence of coronaviruses on inanimate surfaces and their inactivation with biocidal agents", "pid": "ssq0dwmn", "bm25_score": 215.5806427001953}, {"text": "", "title": "Ignaz Semmelweis—Handwashing Invention and COVID-19", "pid": "ckmjeokr", "bm25_score": 215.56094360351562}, {"text": "", "title": "COVID-19: Critical discussion on the applications and implications of chemicals in sanitizers and disinfectants", "pid": "5ir82dxi", "bm25_score": 215.55477905273438}, {"text": "A recent report described a sharp increase in calls to poison centers related to exposures to cleaners and disinfectants since the onset of the coronavirus disease 2019 (COVID-19) pandemic (1). However, data describing cleaning and disinfection practices within household settings in the United States are limited, particularly concerning those practices intended to prevent transmission of SARS-CoV-2, the virus that causes COVID-19. To provide contextual and behavioral insight into the reported increase in poison center calls and to inform timely and relevant prevention strategies, an opt-in Internet panel survey of 502 U.S. adults was conducted in May 2020 to characterize knowledge and practices regarding household cleaning and disinfection during the COVID-19 pandemic. Knowledge gaps were identified in several areas, including safe preparation of cleaning and disinfectant solutions, use of recommended personal protective equipment when using cleaners and disinfectants, and safe storage of hand sanitizers, cleaners, and disinfectants. Thirty-nine percent of respondents reported engaging in nonrecommended high-risk practices with the intent of preventing SARS-CoV-2 transmission, such as washing food products with bleach, applying household cleaning or disinfectant products to bare skin, and intentionally inhaling or ingesting these products. Respondents who engaged in high-risk practices more frequently reported an adverse health effect that they believed was a result of using cleaners or disinfectants than did those who did not report engaging in these practices. Public messaging should continue to emphasize evidence-based, safe practices such as hand hygiene and recommended cleaning and disinfection of high-touch surfaces to prevent transmission of SARS-CoV-2 in household settings (2). Messaging should also emphasize avoidance of high-risk practices such as unsafe preparation of cleaning and disinfectant solutions, use of bleach on food products, application of household cleaning and disinfectant products to skin, and inhalation or ingestion of cleaners and disinfectants.", "title": "Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention - United States, May 2020", "pid": "8766d0lw", "bm25_score": 215.552978515625}, {"text": "Background: Low-income countries have reduced health care system capacity and are therefore at risk of substantially higher COVID-19 case fatality rates than those currently seen in high-income countries. Handwashing is a key component of guidance to reduce transmission of the SARS-CoV-2 virus, responsible for the COVID-19 pandemic. Prior systematic reviews have indicated the effectiveness of handwashing to reduce transmission of respiratory viruses. In low-income countries, reduction of transmission is of paramount importance but social distancing is challenged by high population densities and handwashing access is limited. Objectives: To estimate global access to handwashing with soap and water to inform use of handwashing in the prevention of COVID-19 transmission. Methods: We utilized observational surveys and spatiotemporal gaussian process regression modeling in the context of the Global Burden of Diseases, Injuries, and Risk Factors Study, to estimate access to a handwashing station with available soap and water for 1062 locations from 1990 to 2019. Results: Despite overall improvements from 1990 (34.7% [95% uncertainty interval 32.5-36.7] without access) to 2019 globally, in 2019, 2.01 (1.89-2.13) billion people equal to 26.0% (24.4-27.6) of the global population lacked access to handwashing. More than 50% of the population in sub-Saharan Africa were without access to handwashing in 2019, while in eight countries, more than 50 million persons lacked access. Discussion: For populations without handwashing access, immediate improvements in access or alternative strategies are urgently needed, while disparities in handwashing access should be incorporated into COVID-19 forecasting models when applied to low-income countries.", "title": "Global access to handwashing: implications for COVID-19 control in low-income countries", "pid": "xyojgb8q", "bm25_score": 215.53323364257812}, {"text": "Health professions preventing and controlling Coronavirus Disease 2019 are prone to skin and mucous membrane injury, which may cause acute and chronic dermatitis, secondary infection and aggravation of underlying skin diseases. This is a consensus of Chinese experts on protective measures and advice on hand-cleaning- and medical-glove-related hand protection, mask- and goggles-related face protection, UV-related protection, eye protection, nasal and oral mucosa protection, outer ear, and hair protection. It is necessary to strictly follow standards of wearing protective equipment and specification of sterilizing and cleaning. Insufficient and excessive protection will have adverse effects on the skin and mucous membrane barrier. At the same time, using moisturizing products is highly recommended to achieve better protection.", "title": "Consensus of Chinese experts on protection of skin and mucous membrane barrier for health-care workers fighting against coronavirus disease 2019", "pid": "2mf2f84q", "bm25_score": 215.51531982421875}, {"text": "The 2019 Coronavirus epidemic, provisionally called 2019-nCoV, was first identified in Wuhan, China, in persons exposed to a seafood or wet market. There is an international push to contain the virus and prevent its spread. It is feasible that potentially infectious samples may be received in histopathology laboratories for diagnosis. This technical note presents disinfection procedures and histotechnology processes that should alleviate the risk of infection to laboratory staff. Using data obtained from similar coronaviruses, e.g. severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), experts are confident that 70% ethanol and 0.1% sodium hypochlorite should inactivate the virus. Formalin fixation and heating samples to 56oC, as used in routine tissue processing, were found to inactivate several coronaviruses and it is believed that 2019-nCoV would be similarly affected.", "title": "Coronavirus disinfection in histopathology", "pid": "90j5ymmr", "bm25_score": 215.50018310546875}, {"text": "", "title": "Back to the Basics: Diluted Bleach for COVID-19", "pid": "az8kgl8e", "bm25_score": 215.49407958984375}, {"text": "", "title": "Back to the basics: Diluted bleach for COVID-19", "pid": "2e5ppqub", "bm25_score": 215.49407958984375}, {"text": "", "title": "Hand hygiene and the novel coronavirus pandemic: the role of healthcare workers", "pid": "ksvbcwqb", "bm25_score": 215.49246215820312}, {"text": "", "title": "Hand hygiene and the novel coronavirus pandemic: The role of healthcare workers", "pid": "quu6b0b4", "bm25_score": 215.49246215820312}, {"text": "A recent report described a sharp increase in calls to poison centers related to exposures to cleaners and disinfectants since the onset of the coronavirus disease 2019 (COVID-19) pandemic (1). However, data describing cleaning and disinfection practices within household settings in the United States are limited, particularly concerning those practices intended to prevent transmission of SARS-CoV-2, the virus that causes COVID-19. To provide contextual and behavioral insight into the reported increase in poison center calls and to inform timely and relevant prevention strategies, an opt-in Internet panel survey of 502 U.S. adults was conducted in May 2020 to characterize knowledge and practices regarding household cleaning and disinfection during the COVID-19 pandemic. Knowledge gaps were identified in several areas, including safe preparation of cleaning and disinfectant solutions, use of recommended personal protective equipment when using cleaners and disinfectants, and safe storage of hand sanitizers, cleaners, and disinfectants. Thirty-nine percent of respondents reported engaging in nonrecommended high-risk practices with the intent of preventing SARS-CoV-2 transmission, such as washing food products with bleach, applying household cleaning or disinfectant products to bare skin, and intentionally inhaling or ingesting these products. Respondents who engaged in high-risk practices more frequently reported an adverse health effect that they believed was a result of using cleaners or disinfectants than did those who did not report engaging in these practices. Public messaging should continue to emphasize evidence-based, safe practices such as hand hygiene and recommended cleaning and disinfection of high-touch surfaces to prevent transmission of SARS-CoV-2 in household settings (2). Messaging should also emphasize avoidance of high-risk practices such as unsafe preparation of cleaning and disinfectant solutions, use of bleach on food products, application of household cleaning and disinfectant products to skin, and inhalation or ingestion of cleaners and disinfectants.", "title": "Knowledge and Practices Regarding Safe Household Cleaning and Disinfection for COVID-19 Prevention — United States, May 2020", "pid": "ydv0hc0m", "bm25_score": 215.4905242919922}, {"text": "The COVID-19 pandemic has caused a huge demand of alcohol-based hand rubs, medical gloves, face masks and gowns in healthcare and from the public. More and more hospitals face a serious shortage of these articles. We propose a risk-adapted approach to ensure adequate patient and healthcare worker safety for as long as possible.", "title": "COVID-19-associated shortage of alcohol-based hand rubs, face masks, medical gloves and gowns - proposal for a risk-adapted approach to ensure patient and healthcare worker safety", "pid": "dxx0ihcy", "bm25_score": 215.48782348632812}, {"text": "Background China reported the Novel Coronavirus at the end of the year 2019 which was, later on, declared a Pandemic by the WHO. Proper hand hygiene was identified as one of the simplest most cost effective Covid-19 control and prevention measures. It is therefore very important to understand the compliance of the community to hand hygiene. Method A descriptive cross-sectional study was conducted among the undergraduate students of Makerere University and residents of Katanga slum from 17th to 22nd of March, 2020. An interviewer guided questionnaire with questions on knowledge, attitude, practice, and barriers to hand hygiene was used in data collection. The collected data was analyzed using Microsoft office excel 2016 and STATA 15 software. A 95% confidence interval was used and statistical significance was P<0.05. Results Only 8.4% of the participants had good knowledge of hand hygiene. 11.7% of the university students had good knowledge compared to 0.9% of the Katanga residents. 29.0% of the participants had a good attitude while 50.1% had a moderate attitude to hand hygiene. University students were 6.3 times (OR: 6.3, 95%C1: (2.1 18.5), P=0.001) more likely to have good knowledge while Katanga residents were 3.6 times (OR: 3.6, 95%C1: (1.5 8.4), P=0.003) more likely to have good attitude to hand hygiene. Only 19.6% accomplished all the seven steps of handwashing. 38.4% of the participants still greeted by handshaking and 60.1% noted lack of soap as a barrier to hand hygiene and 62.9% reported having more than three barriers to hand hygiene. Participants that had been taught handwashing were more likely to have better hand hygiene knowledge and practice. Conclusion Despite a fair attitude, deficiency of knowledge coupled with many barriers such as Lack of soap hindered the Practice of proper hand hygiene. Public health involvement to promote hand hygiene must be promoted.", "title": "THE ERA OF CORONAVIRUS; KNOWLEDGE, ATTITUDE, PRACTICES, AND BARRIERS TO HAND HYGIENE AMONG MAKERERE UNIVERSITY STUDENTS AND KATANGA COMMUNITY RESIDENTS.", "pid": "e9yybglc", "bm25_score": 215.47503662109375}, {"text": "", "title": "Oral and Nasal Decontamination for COVID-19 Patients: More Harm Than Good?", "pid": "mkc6aift", "bm25_score": 215.4554443359375}, {"text": "", "title": "Oral and nasal decontamination for COVID-19 patients: more harm than good?", "pid": "3b10148o", "bm25_score": 215.4554443359375}, {"text": "Hands can be a vector for transmitting pathogenic microorganisms to foodstuffs and drinks, and to the mouths of susceptible hosts. Hand washing is the primary barrier to prevent transmission of enteric pathogens via cross-contamination from infected persons. Conventional hand washing involves the use of water, soap, and friction to remove dirt and microorganisms. The availability of hand sanitizing products for use when water and soap are unavailable has increased in recent years. The aim of this systematic review was to collate scientific information on the efficacy of hand sanitizers compared with washing hands with soap and water for the removal of foodborne pathogens from the hands of food handlers. An extensive literature search was carried out using three electronic databases: Web of Science, Scopus, and PubMed. Twenty-eight scientific publications were ultimately included in the review. Analysis of this literature revealed various limitations in the scientific information owing to the absence of a standardized protocol for evaluating the efficacy of hand products and variation in experimental conditions. However, despite conflicting results, scientific evidence seems to support the historical skepticism about the use of waterless hand sanitizers in food preparation settings. Water and soap appear to be more effective than waterless products for removal of soil and microorganisms from hands. Alcohol-based products achieve rapid and effective inactivation of various bacteria, but their efficacy is generally lower against nonenveloped viruses. The presence of food debris significantly affects the microbial inactivation rate of hand sanitizers.", "title": "Efficacy of Instant Hand Sanitizers against Foodborne Pathogens Compared with Hand Washing with Soap and Water in Food Preparation Settings: A Systematic Review.", "pid": "zyw3bpbr", "bm25_score": 215.4495391845703}, {"text": "BACKGROUND: Shortages of personal protective equipment (PPE) including N95 respirators are an urgent concern in the setting of the global COVID-19 pandemic. Decontamination of PPE could be useful to maintain adequate supplies, but there is uncertainty regarding the efficacy of decontamination technologies. METHODS: A modification of the American Society for Testing and Materials standard quantitative carrier disk test method (ASTM E-2197-11) was used to examine the effectiveness of 3 methods, including ultraviolet-C (UV-C) light, a high-level disinfection cabinet that generates aerosolized peracetic acid and hydrogen peroxide, and dry heat at 70°C for 30 minutes. We assessed the decontamination of 3 commercial N95 respirators inoculated with methicillin-resistant Staphylococcus aureus (MRSA) and bacteriophages MS2 and Phi6; the latter is an enveloped RNA virus used as a surrogate for coronaviruses. Three and 6 log(10) reductions on respirators were considered effective for decontamination and disinfection, respectively. RESULTS: UV-C administered as a 1-minute cycle in a UV-C box or a 30-minute cycle by a room decontamination device reduced contamination but did not meet criteria for decontamination of the viruses from all sites on the N95s. The high-level disinfection cabinet was effective for decontamination of the N95s and achieved disinfection with an extended 31-minute cycle. Dry heat at 70°C for 30 minutes was not effective for decontamination of the bacteriophages. CONCLUSIONS: UV-C could be useful to reduce contamination on N95 respirators. However, the UV-C technologies studied did not meet pre-established criteria for decontamination under the test conditions used. The high-level disinfection cabinet was more effective and met criteria for disinfection with an extended cycle.", "title": "Effectiveness of Ultraviolet-C Light and a High-Level Disinfection Cabinet for Decontamination of N95 Respirators", "pid": "k7sltus2", "bm25_score": 215.44773864746094}, {"text": "BACKGROUND: The need for protective masks greatly exceeds their global supply during the current COVID-19 pandemic. METHODS: We optimized the temperature used in the dry heat pasteurization method to destroy pathogens and decontaminate masks while retaining their filtering capacity. RESULTS: The current study showed that dry heat at both 60°C and 70°C for 1 hour could successfully kill 6 species of respiratory bacteria and one fungi species, and inactivate the H1N1 indicator virus. After being heated at 70°C for 1, 2, and 3 hours, the N95 respirators and surgical face masks showed no changes in their shape and components. The filtering efficiency of bacterial aerosol for N95 respirators were 98%, 98%, and 97% after being heated for 1, 2, and 3 hour, respectively, all of which were over the 95% efficiency required and similar to the value before being heated (99%). The filtering efficiency for surgical face masks was 97%, 97%, and 96% for 1, 2, and 3 hours of heating, respectively, all of which were also similar to the value before being heated (97%). CONCLUSIONS: This method can be used at home and can significantly resolve the current shortage of masks.", "title": "Decontamination of surgical face masks and N95 respirators by dry heat pasteurization for one hour at 70°C", "pid": "047asp3a", "bm25_score": 215.4312286376953}, {"text": "Many researchers are working on multiple aspects of the COVID-19 pandemic including disease detection, treatment, and vaccine development. It is expected that there will be a large increase in passenger traffic at airports and railway stations and other public places. This paper proposes one solution to reduce the transmission of the disease through fomites such as passenger luggage and packages at bus/train stations and airports in the country. A tunnel system similar to the X-ray machines used for passenger luggage at airports has been proposed for disinfection of fomites. The system consists of eight 36 W T8 TUV bulbs illuminating each square meter area of the fomites on a conveyor belt for 10 s. For the standard airline luggage dimensions, 24 such bulbs will be distributed evenly on all four sides of the tunnel. The entry and exit points on the conveyor are shielded from the UV-C light leakage by placing thin plastic (such as acrylic) curtains. An optional non-foaming soap solution spray system may be used as an additional disinfection step. The toxic sodium hypochlorite solutions are not used in this design. Non-foaming soap solutions which are very effective against coronavirus and are non-toxic and biodegradable may be used as an optional disinfectant. It is to be noted that while the disinfection systems are designed to effectively mitigate the threat of coronavirus on the passenger fomite surfaces, these are purely based on theoretical calculations and have not been tested with actual viral particles. However, considering the time-sensitive emergency with COVID-19 pandemic, these systems will be very useful even without rigorous campaign of testing.", "title": "An Automatic Disinfection System for Passenger Luggage at Airports and Train/Bus Stations", "pid": "g19nyrrf", "bm25_score": 215.42095947265625}, {"text": "INTRODUCTION: As of 22 June 2020, Severe Acute Respiratory Syndrome (SARS)-coronavirus (CoV)-2 has infected more than 8.95 million people worldwide, causing > 468,000 deaths. The virus is transmitted through respiratory droplets and physical contact from contaminated surfaces to the mucosa. Hand hygiene and oral decontamination among other measures are key to preventing the spread of the virus. We report the in vitro virucidal activity of topical and oral povidone-iodine (PVP-I) products against SARS-CoV-2. METHODS: Suspension assays were used to assess the virucidal activity of PVP-I against SARS-CoV-2. Products were tested at a contact time of 30 s for virucidal activity. Viral titres were calculated using the Spearman-Kärber method and reported as median tissue culture infectious dose (TCID50)/mL. RESULTS: All four products [antiseptic solution (PVP-I 10%), skin cleanser (PVP-I 7.5%), gargle and mouth wash (PVP-I 1%) and throat spray (PVP-I 0.45%)] achieved &#8805; 99.99% virucidal activity against SARS-CoV-2, corresponding to &#8805; 4 log10 reduction of virus titre, within 30 s of contact. CONCLUSION: This study provides evidence of rapid and effective virucidal activity of PVP-I against SARS-CoV-2. PVP-I-based products are widely available for medical and personal use for hand hygiene and oral decontamination, and could be readily integrated into coronavirus disease, COVID-19, infection control measures in hospital and community settings.", "title": "Povidone-Iodine Demonstrates Rapid In Vitro Virucidal Activity Against SARS-CoV-2, The Virus Causing COVID-19 Disease", "pid": "99hf7rlf", "bm25_score": 215.41873168945312}, {"text": "BACKGROUND: Health care-associated infections most commonly result from person-to-person transmission via the hands of health care workers. METHODS: We studied the efficacy of hand hygiene agents (n = 14) following 10-second applications to reduce the level of challenge organisms (Serratia marcescens and MS2 bacteriophage) from the hands of healthy volunteers using the ASTM-E-1174-94 test method. RESULTS: The highest log(10) reductions of S marcescens were achieved with agents containing chlorhexidine gluconate (CHG), triclosan, benzethonium chloride, and the controls, tap water alone and nonantimicrobial soap and water (episode 1 of hand hygiene, 1.60-2.01; episode 10, 1.60-3.63). Handwipes but not alcohol-based handrubs were significantly inferior from these agents after a single episode of hand hygiene, but both groups were significantly inferior after 10 episodes. After a single episode of hand hygiene, alcohol/silver iodide, CHG, triclosan, and benzethonium chloride were similar to the controls in reduction of MS2, but, in general, handwipes and alcohol-based handrubs showed significantly lower efficacy. After 10 episodes, only benzethonium chloride (1.33) performed as well as the controls (1.59-1.89) in the reduction of MS2. CONCLUSIONS: Antimicrobial handwashing agents were the most efficacious in bacterial removal, whereas waterless agents showed variable efficacy. Alcohol-based handrubs compared with other products demonstrated better efficacy after a single episode of hand hygiene than after 10 episodes. Effective hand hygiene for high levels of viral contamination with a nonenveloped virus was best achieved by physical removal with a nonantimicrobial soap or tap water alone.", "title": "Comparative efficacy of hand hygiene agents in the reduction of bacteria and viruses", "pid": "u93n11sw", "bm25_score": 215.40480041503906}]}
{"idx": 19, "qid": "20", "q_text": "are patients taking Angiotensin-converting enzyme inhibitors (ACE) at increased risk for COVID-19?", "qrels": {"000ajevz": 0, "6xntcvmb": 2, "01xdd8zf": 2, "04h53wjz": 2, "pl9ht0d0": 0, "08vsaov7": 2, "09a3tblt": 1, "09e5n5zd": 2, "oum6z3ab": 2, "0dl9cf7m": 2, "0dpv85od": 0, "qy4aupvr": 1, "0gier0lu": 2, "0h9wg03o": 1, "0j5828ah": 2, "0llgr357": 1, "0n1pea70": 1, "0nh58odf": 0, "0nwmoua3": 2, "0ojayw16": 0, "0pknmeip": 2, "0qkzd2w4": 1, "0rmuvb5i": 0, "0svdq020": 1, "0ti403i4": 0, "0tsefy6p": 2, "tsln2wup": 2, "0vhy44iq": 1, "0vlgfbar": 0, "0x02bmti": 2, "6i3nqrsp": 0, "0yumc7em": 2, "10l12wgu": 2, "11060ijh": 0, "118x15od": 2, "12o4zey2": 2, "13akn7dm": 2, "13jupb26": 0, "15jmiqrc": 2, "cussiba2": 1, "xf6r9ge9": 2, "1731se1k": 2, "17hyh3n5": 2, "190zxwwj": 0, "1915kvwk": 0, "tw6968h3": 2, "1a8uevk8": 1, "1aal6njl": 1, "1c47w4q5": 0, "1edsm58s": 2, "1f52iqjg": 2, "1f9kjtmm": 0, "1fdmmdll": 0, "1fp4ck88": 2, "9iitpj8u": 2, "1gf65b9j": 2, "1gnoo0us": 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been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes. We reviewed the available evidence, and have not found this to be the case. We recommend that patients on such medications should continue on them unless there is a clinical indication to stop their use.", "title": "A consensus statement on the use of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in relation to COVID-19 (corona virus disease 2019).", "pid": "z3l6eden", "bm25_score": 221.36907958984375}, {"text": "INTRODUCTION: There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. METHODS: Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. RESULTS: 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 - 0.88). A similar albeit not significant trend was observed for ACEI. CONCLUSION: ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2.", "title": "Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors", "pid": "bwg3tzx8", "bm25_score": 221.2509765625}, {"text": "In a large Israeli dataset of 14 520 individuals tested for SARS-CoV-2, angiotension-converting enzyme inhibitors and angiotensin-receptor blockers were not found to be associated with increased SARS-CoV-2 infection after adjusting for major confounders. Patients on these medications should not stop their medication prophylactically.", "title": "Angiotension-converting enzyme inhibitors and angiotensin-receptor blockers are not associated with increased risk of SARS-CoV-2 infection", "pid": "amgkcxaw", "bm25_score": 221.10206604003906}, {"text": "Intravenous infusions of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in experimental animals increase the numbers of angiotensin-converting enzyme 2 (ACE2) receptors in the cardiopulmonary circulation. ACE2 receptors serve as binding sites for SARS-CoV-2 virions in the lungs. Patients who take ACEIs and ARBS may be at increased risk of severe disease outcomes due to SARS-CoV-2 infections.", "title": "Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19", "pid": "240jc7l4", "bm25_score": 221.0341339111328}, {"text": "Concerns have been raised about the potential for renin-angiotensin system (RAS) inhibitors to upregulate expression of angiotensin-converting enzyme 2 (ACE2) and thus increase susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. Currently, there is no evidence that even if RAS inhibitors increase expression and activity of ACE2, that they would increase the risk of SARS-CoV-2 infection by facilitating greater viral entry or worsen outcomes in patients with COVID-19. At this time, there is no clinical evidence to suggest that treatment with RAS inhibitors should be discontinued in stable patients with COVID-19. In hospitalized patients with severe COVID-19, decisions about these medications should be based on clinical condition, including hemodynamic status and renal function.", "title": "Renin-angiotensin system inhibitors in COVID-19.", "pid": "paxcmex6", "bm25_score": 221.00625610351562}, {"text": "Abstract Introduction There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. Methods Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. Results 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 – 0.88). A similar albeit not significant trend was observed for ACEI. Conclusion ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2.", "title": "Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors:", "pid": "wxpfg25n", "bm25_score": 220.99392700195312}, {"text": "According to five new studies, therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) is not associated with an increased risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or with an increased risk of severe disease or in-hospital death among patients with COVID-19.", "title": "RAAS inhibitors do not increase the risk of COVID-19", "pid": "nxrg9fi6", "bm25_score": 220.86387634277344}, {"text": "Concerns have been raised about the potential for renin-angiotensin system (RAS) inhibitors to upregulate expression of angiotensin-converting enzyme 2 (ACE2) and thus increase susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) entry. Currently, there is no evidence that even if RAS inhibitors increase expression and activity of ACE2, that they would increase the risk of SARS-CoV-2 infection by facilitating greater viral entry or worsen outcomes in patients with COVID-19. At this time, there is no clinical evidence to suggest that treatment with RAS inhibitors should be discontinued in stable patients with COVID-19. In hospitalized patients with severe COVID-19, decisions about these medications should be based on clinical condition, including hemodynamic status and renal function.", "title": "Renin-angiotensin system inhibitors in COVID-19", "pid": "aqh90wmk", "bm25_score": 220.8544158935547}, {"text": "There has been a lot of speculation that patients with coronavirus disease 2019 (COVID-19) who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) may be at increased risk for adverse outcomes We reviewed the available evidence, and have not found this to be the case We recommend that patients on such medications should continue on them unless there is a clinical indication to stop their use", "title": "A consensus statement on the use of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in relation to COVID-19 (corona virus disease 2019)", "pid": "53107z56", "bm25_score": 220.8004150390625}, {"text": "Abstract: Background: The SARS-Cov2 virus binds to the ACE2 receptor for cell entry. It has been suggested that ACE-inhibitors, which are commonly used in patients with hypertension or diabetes and which raise ACE2 levels, may increase the risk of severe COVID-19 infection. Methods: We evaluated this hypothesis in an early cohort of 205 acute inpatients with COVID-19 at King's College Hospital and Princess Royal University Hospital, London, UK with the primary endpoint being death or transfer to a critical care unit for organ support within 7-days of symptom onset. Findings: 53 patients out of 205 patients reached the primary endpoint. Contrary to the hypothesis, treatment with ACE-inhibitors was associated with a reduced risk of rapidly deteriorating severe disease. There was a lower rate of death or transfer to a critical care unit within 7 days in patients on an ACE-inhibitor OR 0.29 (CI 0.10-0.75, p<0.01), adjusting for age, gender, comorbidities (hypertension, diabetes mellitus, ischaemic heart disease and heart failure). Interpretation: Although a small sample size, we do not see evidence for ACE-inhibitors increasing the short-term severity of COVID-19 disease and patients on treatment with ACE-inhibitors should continue these drugs during their COVID-19 illness. A potential beneficial effect needs to be explored as more data becomes available.", "title": "Treatment with ACE-inhibitors is associated with less severe disease with SARS-Covid-19 infection in a multi-site UK acute Hospital Trust", "pid": "60wcvkbn", "bm25_score": 220.57115173339844}, {"text": "Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin II type­1 receptor blockers (ARBs) are among the most widely prescribed drugs for the treatment of arterial hypertension, heart failure and chronic kidney disease. A number of studies, mainly in animals and not involving the lungs, have indicated that these drugs can increase expression of angiotensin-converting enzyme 2 (ACE2). ACE2 is the cell entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) that is currently battering the globe. This has led to the hypothesis that use of ACEIs and ARBs may increase the risk of developing severe COVID-19. In this point of view paper, possible scenarios regarding the impact of ACEI/ARB pharmacotherapy on COVID-19 are discussed in relation to the currently available evidence. Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV­2 infections. Thus, unless contraindicated, use of ACEIs/ARBs in COVID-19 patients should be continued in line with the recent recommendations of medical societies.", "title": "Renin-angiotensin system inhibition in COVID-19 patients", "pid": "3l1nru0l", "bm25_score": 220.53662109375}, {"text": "Background The effect of using Angiotensin-converting enzyme inhibitors (ACEIs) and Angiotensin-receptor blockers (ARBs) on the risk of coronavirus disease 2019 (COVID-19) is a topic of recent debate. Although studies have examined the potential association between them, the results remain controversial. This study aims to determine the true effect of ACEI/ARBs use on the risk of infection and clinical outcome of COVID-19. Methods Five electronic databases (PubMed, Web of science, Cochrane library, China National Knowledge Infrastructure database, medRxiv preprint server) were retrieved to find eligible studies. Meta-analysis was performed to examine the association between ACEI/ARBs use and the risk of infection and clinical outcome of COVID-19. Results 22 articles containing 157,328 patients were included. Use of ACEI/ARBs was not associated with increased risk of infection (Adjusted OR: 0.96, 95% CI: 0.91-1.01, I2=5.8%) or increased severity (Adjusted OR: 0.90, 95% CI: 0.77-1.05, I2=27.6%) of COVID-19. The use of ACEI/ARBs was associated with lower risk of death from COVID-19 (Adjusted OR: 0.66, 95% CI: 0.44-0.99, I2=57.9%). Similar results of reduced risk of death were also found for ACEI/ARB use in COVID-19 patients with hypertension (Adjusted OR: 0.36, 95% CI: 0.17-0.77, I2=0). Conclusion This study provides evidence that ACEI/ARBs use for COVID-19 patients does not lead to harmful outcomes and may even provide a beneficial role and decrease mortality from COVID-19. Clinicians should not discontinue ACEI/ARBs for patients diagnosed with COVID-19 if they are already on these agents. Keywords: COVID-19; Angiotensin-converting enzyme inhibitor; Angiotensin-receptor blockers; risk; systematic review; meta-analysis", "title": "Association between angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers use and the risk of infection and clinical outcome of COVID-19: a comprehensive systematic review and meta-analysis.", "pid": "7necpu7c", "bm25_score": 220.4989013671875}, {"text": "", "title": "Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19", "pid": "3ljfeizg", "bm25_score": 220.34405517578125}, {"text": "• There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation. • The level of ACE2 expression is not completely related with the risk of COVID-19 infection. • There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials. • It is not recommended that COVID-19 patients with hypertension or normal hypertensive patients at risk for exposure to stop using ACEI/ARB or change to other antihypertensive drugs.", "title": "Anti-RAS drugs and SARS-CoV-2 infection", "pid": "5y8cc5eb", "bm25_score": 220.2683563232422}, {"text": "AIMS: The SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. It has been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID-19 infection. METHODS AND RESULTS: We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID-19 at two hospitals with a multi-ethnic catchment population in London (UK). The mean age was 68 ± 17 years (57% male) and 74% of patients had at least one comorbidity. Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset. A total of 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co-morbidities, was 0.63 (95% confidence interval 0.47-0.84, P < 0.01). CONCLUSIONS: There was no evidence for increased severity of COVID-19 in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta-analyses and randomised clinical trials.", "title": "Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust", "pid": "aj1yup6a", "bm25_score": 220.26214599609375}, {"text": "•There is no enough evidence to indicate that ACEIs and ARBs result in ACE2 upregulation.•The level of ACE2 expression is not completely related with the risk of COVID-19 infection.•There is currently no evidence that ACEI/ARB increase risk for COVID-19 infection from clinical trials.•It is not recommended that COVID-19 patients with hypertension or normal hypertensive patients at risk for exposure to stop using ACEI/ARB or change to other antihypertensive drugs.", "title": "Anti-RAS drugs and SARS-CoV-2 infection", "pid": "z3w87lsj", "bm25_score": 220.258056640625}, {"text": "Angiotensin-converting enzyme (ACE) inhibitors (ACEIs) and angiotensin II type‑1 receptor blockers (ARBs) are among the most widely prescribed drugs for the treatment of arterial hypertension, heart failure and chronic kidney disease. A number of studies, mainly in animals and not involving the lungs, have indicated that these drugs can increase expression of angiotensin-converting enzyme 2 (ACE2). ACE2 is the cell entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19) that is currently battering the globe. This has led to the hypothesis that use of ACEIs and ARBs may increase the risk of developing severe COVID-19. In this point of view paper, possible scenarios regarding the impact of ACEI/ARB pharmacotherapy on COVID-19 are discussed in relation to the currently available evidence. Although further research on the influence of blood-pressure-lowering drugs, including those not targeting the renin-angiotensin system, is warranted, there are presently no compelling clinical data showing that ACEIs and ARBs increase the likelihood of contracting COVID-19 or worsen the outcome of SARS-CoV‑2 infections. Thus, unless contraindicated, use of ACEIs/ARBs in COVID-19 patients should be continued in line with the recent recommendations of medical societies.", "title": "Renin-angiotensin system inhibition in COVID-19 patients", "pid": "d9wfmvp8", "bm25_score": 220.22842407226562}, {"text": "BACKGROUND: The effect of chronic use of renin-angiotensin-aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19 related outcomes in hypertensive patients. METHODS: A single center study was conducted on 133 consecutive hypertensive subjects presenting to the Emergency Department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9th and 31st March 2020. RESULTS: All patients were grouped according to their chronic antihypertensive medications (ACEIs, N=40; ARBs, N=42; not on RAAS inhibitors, N=51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy and need for non-invasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared to the non-RAAS population (odds ratio [OR] 0.25, CI95% 0.09-0.66 p=0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI95% 0.17-1.83, p=0.341). CONCLUSIONS: Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID 19-related morbidity and mortality.", "title": "Use of RAAS inhibitors and risk of clinical deterioration in COVID-19: results from an Italian cohort of 133 hypertensives", "pid": "w2bhtu9f", "bm25_score": 220.216064453125}, {"text": "Importace: There is conflicting evidence about the role of angiotensin converting enzymes inhibitors (ACEIs) and angiotensin receptors blockers (ARBs) in the pathogenesis and outcome of patients infected with acute severe respiratory syndrome coronavirus 2 (SASR-CoV-2) virus and growing public concern. Methods: We systematically reviewed the literature and performed a meta-analysis using inverse variance random effect models including all studies that evaluate the role of ACEIs/ARBs and reported adjusted odds ratio. Results: Nine studies met our eligibility criteria that enrolled a population of 58615 patients infected with SASR-CoV-2. Prior use of ACEIs/ARBs were associated with significant reduction of inpatient mortality among infected patients with SASR-CoV-2, adjusted odds ratio from 4 studies 0.33, 95% confidence interval ( 0.22,0.49) with zero in between studies heterogeneity and with significant reduction of critical or fatal outcome , pooled adjusted odds ratio from 5 studies 0.32,95% confidence interval ( 0.22,0.46) with no in between studies heterogeneity. Conclusion: Our findings suggest that prior use ACEIs /ARBs is associated with a decreased risk of death or critical outcome among SASR-CoV-2 infected patients.This findings is limited by the observational nature of included studies.However, it provides a reassurance to the public not to stop prescribed ACEIs /ARBs due to fear of severe COVID-19. It also calls upon investigators and ethics committee to reconsider the ongoing randomized trials of discontinuation of these drugs.", "title": "Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Outcome of COVID-19 : A Systematic Review and Meta-analysis", "pid": "x90ifulu", "bm25_score": 220.18682861328125}, {"text": "Concerns have been raised regarding the safety of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease of 2019 (COVID-19), based on the hypothesis that such medications may raise expression of ACE2, the receptor for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). We conducted a literature review of studies (n = 12) in experimental animals and human subjects (n = 12) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses of ACEIs or ARBs than are typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.", "title": "Risks of ACE Inhibitor and ARB Usage in COVID-19: Evaluating the Evidence", "pid": "xnu55d2t", "bm25_score": 220.1669921875}, {"text": "The Corona Virus Disease 2019 (COVID-19) outbreak has rapidly spread throughout the world, accounting for significant morbidity and mortality. There is a concern that renin-angiotensin-aldosterone inhibitors increase susceptibility to COVID-19. Currently there are no clinical data demonstrating beneficial or adverse effects of these medications on COVID-19 outcomes. Renin-angiotensin-aldosterone inhibitors should be continued in patients in otherwise stable conditions who are at risk for or having COVID-19.", "title": "Renin-Angiotensin-Aldosterone Inhibitors and COVID-19", "pid": "sew2sx9v", "bm25_score": 220.12664794921875}, {"text": "Coronavirus disease 2019 (COVID-19) is a viral pandemic precipitated by the severe acute respiratory syndrome coronavirus 2. Since previous reports suggested that viral entry into cells may involve angiotensin converting enzyme 2, there has been growing concern that angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) use may exacerbate the disease severity. In this retrospective, single-center US study of adult patients diagnosed with COVID-19, we evaluated the association of ACEI/ARB use with hospital admission. Secondary outcomes included: ICU admission, mechanical ventilation, length of hospital stay, use of inotropes, and all-cause mortality. Propensity score matching was performed to account for potential confounders. Among 590 unmatched patients diagnosed with COVID-19, 78 patients were receiving ACEI/ARB (median age 63 years and 59.7% male) and 512 patients were non-users (median age 42 years and 47.1% male). In the propensity matched population, multivariate logistic regression analysis adjusting for age, gender and comorbidities demonstrated that ACEI/ARB use was not associated with hospital admission (OR 1.2, 95% CI 0.5-2.7, p = 0.652). CAD and CKD/ESRD remained independently associated with admission to hospital. All-cause mortality, ICU stay, need for ventilation, and inotrope use was not significantly different between the 2 study groups. In conclusion, among patients who were diagnosed with COVID-19, ACEI/ARB use was not associated with increased risk of hospital admission.", "title": "Angiotensin Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use Among Outpatients Diagnosed with COVID-19", "pid": "ps9xawlp", "bm25_score": 220.03240966796875}, {"text": "BACKGROUND: A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied. METHODS: We carried out a population-based case-control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients' clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression. RESULTS: Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex. CONCLUSIONS: In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.", "title": "Renin-Angiotensin-Aldosterone System Blockers and the Risk of Covid-19", "pid": "3twud97m", "bm25_score": 220.01068115234375}, {"text": "PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the aggressive coronavirus disease (COVID-19) pandemic. Recently, investigators have stipulated that COVID-19 patients receiving angiotensin-converting-enzyme inhibitors (ACEI) may be subject to poorer outcomes. This editorial presents the available evidence to guide treatment practices during this pandemic. RECENT FINDINGS: Recent studies from Wuhan cohorts provide valuable information about COVID-19. A cohort with 52 critically ill patients revealed cardiac injury in 12% of patients. Worse outcomes appear to be more prevalent in patients with hypertension and diabetes mellitus (DM), possibly due to overexpression of angiotensin-converting enzyme 2 (ACE2) receptor in airway alveolar epithelial cells. Investigators suspect that SARS-CoV-2 uses the ACE2 receptor to enter the lungs in a mechanism similar to SARS-CoV. Several hypotheses have been proposed to date regarding the net effect of ACEI/ARB on COVID-19 infections. Positive effects include ACE2 receptor blockade, disabling viral entry into the heart and lungs, and an overall decrease in inflammation secondary to ACEI/ARB. Negative effects include a possible retrograde feedback mechanism, by which ACE2 receptors are upregulated. Even though physiological models of SARS-CoV infection show a theoretical benefit of ACEI/ARB, these findings cannot be extrapolated to SARS-CoV-2 causing COVID-19. Major cardiology scientific associations, including ACC, HFSA, AHA, and ESC Hypertension Council, have rejected these correlation hypotheses. After an extensive literature review, we conclude that there is no significant evidence to support an association for now, but given the rapid evolvement of this pandemic, findings may change.", "title": "Outcomes in Patients with COVID-19 Infection Taking ACEI/ARB", "pid": "jt8i703w", "bm25_score": 219.97720336914062}, {"text": "PURPOSE OF REVIEW: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for the aggressive coronavirus disease (COVID-19) pandemic. Recently, investigators have stipulated that COVID-19 patients receiving angiotensin-converting-enzyme inhibitors (ACEI) may be subject to poorer outcomes. This editorial presents the available evidence to guide treatment practices during this pandemic. RECENT FINDINGS: Recent studies from Wuhan cohorts provide valuable information about COVID-19. A cohort with 52 critically ill patients revealed cardiac injury in 12% of patients. Worse outcomes appear to be more prevalent in patients with hypertension and diabetes mellitus (DM), possibly due to overexpression of angiotensin-converting enzyme 2 (ACE2) receptor in airway alveolar epithelial cells. Investigators suspect that SARS-CoV-2 uses the ACE2 receptor to enter the lungs in a mechanism similar to SARS-CoV. Several hypotheses have been proposed to date regarding the net effect of ACEI/ARB on COVID-19 infections. Positive effects include ACE2 receptor blockade, disabling viral entry into the heart and lungs, and an overall decrease in inflammation secondary to ACEI/ARB. Negative effects include a possible retrograde feedback mechanism, by which ACE2 receptors are upregulated. SUMMARY: Even though physiological models of SARS-CoV infection show a theoretical benefit of ACEI/ARB, these findings cannot be extrapolated to SARS-CoV-2 causing COVID-19. Major cardiology scientific associations, including ACC, HFSA, AHA, and ESC Hypertension Council, have rejected these correlation hypotheses. After an extensive literature review, we conclude that there is no significant evidence to support an association for now, but given the rapid evolvement of this pandemic, findings may change.", "title": "Outcomes in Patients with COVID-19 Infection Taking ACEI/ARB", "pid": "i073l1ww", "bm25_score": 219.9161834716797}, {"text": "Exposure to agents acting on the renin-angiotensin system was not associated to a risk increase of COVID-19 infection in two Italian matched case-control studies, one nested in hypertensive patients and the other in patients with cardiovascular diseases or diabetes.", "title": "Therapy with agents acting on the renin-angiotensin system and risk of SARS-CoV-2 infection.", "pid": "0yumc7em", "bm25_score": 219.90487670898438}, {"text": "Mackey and colleagues reported a systematic review that found high-certainty evidence that angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers are not associated with greater illness severity in patients with COVID-19. The editorialist discusses the findings and emphasizes that, unless further data show otherwise, clinicians should continue to prescribe these drugs for their standard indications in patients with COVID-19.", "title": "COVID-19 and Angiotensin-Converting Enzyme Inhibitor/Angiotensin-Receptor Blocker Therapy", "pid": "7ae0galy", "bm25_score": 219.9007110595703}, {"text": "Exposure to agents acting on the renin-angiotensin system was not associated to a risk increase of COVID-19 infection in two Italian matched case-control studies, one nested in hypertensive patients and the other in patients with cardiovascular diseases or diabetes.", "title": "Therapy with agents acting on the renin-angiotensin system and risk of SARS-CoV-2 infection", "pid": "2d8qyymo", "bm25_score": 219.89596557617188}, {"text": "The hypothesis has been proposed that patients COVID-19 positive, under anti-hypertensive treatment with angiotensin enzyme inhibitors or angiotensin receptor-blockers, might have a worse or a better clinical prognosis. This might be due to the fact that ACE2 is the receptor for the virus to enter human cells, but, on the contrary, that ACE2 expression is downregulated following SARS-1 infection, resulting in disproportionate activation of renin-angiotensin-aldosterone system and exacerbated pneumonia progression. However, no solid clinical data are available at the present moment to support or disprove such hypotheses. We announce in this letter that a large multicentre case-control study has been started in Italy that is the country with a very high impact of COVID-19 infection. We hope that our letter will encourage other clinical centres, even outside Italy, to join our study.", "title": "Controversial Relationship between Renin-Angiotensin System Inhibitors and Severity of COVID-19: Announcing a Large Multicentre Case-Control Study in Italy.", "pid": "pm5htiqb", "bm25_score": 219.8763885498047}, {"text": "BACKGROUND: The effect of chronic use of renin–angiotensin–aldosterone system (RAAS) inhibitors on the severity of COVID-19 infection is still unclear in patients with hypertension. We aimed to investigate the association between chronic use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) and COVID-19 related outcomes in hypertensive patients. METHODS: A single center study was conducted on 133 consecutive hypertensive subjects presenting to the Emergency Department with acute respiratory symptoms and/or fever who were diagnosed with COVID-19 infection between 9(th) and 31(st) March 2020. RESULTS: All patients were grouped according to their chronic antihypertensive medications (ACEIs, N=40; ARBs, N=42; not on RAAS inhibitors, N=51). There was no statistical difference between ACEIs and ARBs groups in terms of hospital admission rate, oxygen therapy and need for non-invasive ventilation. Patients chronically treated with RAAS inhibitors showed a significantly lower rate of admission to semi-intensive/intensive care units, when compared to the non-RAAS population (odds ratio [OR] 0.25, CI95% 0.09-0.66 p=0.006). Similarly, the risk of mortality was lower in the former group, although not reaching statistical significance (OR 0.56, CI95% 0.17-1.83, p=0.341). CONCLUSIONS: Our data suggest that chronic use of RAAS inhibitors does not negatively affect clinical course of COVID-19 in hypertensive patients. Further studies are needed to confirm this finding and determine whether RAAS inhibitors may have a protective effect on COVID 19-related morbidity and mortality.", "title": "Use of RAAS inhibitors and risk of clinical deterioration in COVID-19: results from an Italian cohort of 133 hypertensives", "pid": "82m84n4w", "bm25_score": 219.8697509765625}, {"text": "The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1-angiotensin II-angiotensin AT1 receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2-angiotensin(1-7)-angiotensin AT2 receptor and the ACE-2-angiotensin(1-7)-Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful.", "title": "Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients", "pid": "f48gflvs", "bm25_score": 219.8600616455078}, {"text": "Systemic arterial hypertension (referred to as hypertension herein) is a major risk factor of mortality worldwide, and its importance is further emphasized in the context of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to as COVID-19. Patients with severe COVID-19 infections commonly are older and have a history of hypertension. Almost 75% of patients who have died in the pandemic in Italy had hypertension. This raised multiple questions regarding a more severe course of COVID-19 in relation to hypertension itself as well as its treatment with renin-angiotensin system (RAS) blockers, e.g. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We provide a critical review on the relationship of hypertension, RAS, and risk of lung injury. We demonstrate lack of sound evidence that hypertension per se is an independent risk factor for COVID-19. Interestingly, ACEIs and ARBs may be associated with lower incidence and/or improved outcome in patients with lower respiratory tract infections. We also review in detail the molecular mechanisms linking the RAS to lung damage and the potential clinical impact of treatment with RAS blockers in patients with COVID-19 and a high cardiovascular and renal risk. This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues. In summary, a critical review of available evidence does not support a deleterious effect of RAS blockers in COVID-19 infections. Therefore, there is currently no reason to discontinue RAS blockers in stable patients facing the COVID-19 pandemic.", "title": "Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19", "pid": "69qefbbo", "bm25_score": 219.85751342773438}, {"text": "Importance The role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use. Objective To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation). Design, Setting, and Participants Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included. Exposures History of taking ACEIs or ARBs at the time of COVID-19 testing. Main Outcomes and Measures Results of COVID-19 testing in the entire cohort, number of patients requiring hospitalizations, intensive care unit admissions, and mechanical ventilation among those who tested positive. Results A total of 18 472 patients tested for COVID-19. The mean (SD) age was 49 (21) years, 7384 (40%) were male, and 12 725 (69%) were white. Of 18 472 patients who underwent COVID-19 testing, 2285 (12.4%) were taking either ACEIs or ARBs. A positive COVID-19 test result was observed in 1735 of 18 472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with COVID-19 test positivity (overlap propensity score-weighted odds ratio, 0.97; 95% CI, 0.81-1.15). Conclusions and Relevance This study found no association between ACEI or ARB use and COVID-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic. However, further study in larger numbers of hospitalized patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of COVID-19 severity.", "title": "Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19).", "pid": "pn4cz2bf", "bm25_score": 219.84487915039062}, {"text": "SARS-coronavirus 2 (SARS-CoV-2) enters the host-cells by binding the transmembraneous angiotensin converting enzyme 2 (ACE2) when causing coronavirus disease 2019 (COVID-19). The role of angiotensin converting enzyme inhibitors (ACE) and angiotensin II receptor blockers (ARB) in COVID-19 is debated. Several well-conducted observational studies show no increased risk from RAAS blockade in COVID-19 patients and are detailed in this brief review. The Swedish Society of Hypertension, Stroke and Vascular Medicine supports current recommendations that ongoing RAAS blockade should be maintained in patients with COVID-19.", "title": "[Hypertension, RAAS blockade and risk in COVID-19 patients].", "pid": "jyfcpsu6", "bm25_score": 219.82391357421875}, {"text": "The ACE2 receptor plays a central role in severe acute respiratory syndrome coronavirus 2 host cell entry and propagation. It has therefore been postulated that angiotensin converting enzyme inhibitors and angiotensin receptor blockers may upregulate ACE2 expression and thus increase susceptibility to infection. We suggest that alternative anti-hypertensive agents should be preferred among individuals who may be exposed to this increasingly common and potentially lethal virus.", "title": "Management of hypertension in COVID-19", "pid": "wdklinm2", "bm25_score": 219.7906036376953}, {"text": "Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.", "title": "Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019", "pid": "kxtxzt9f", "bm25_score": 219.76951599121094}, {"text": "Background: Effect of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) on outcomes in patients with coronavirus disease 2019 (COVID-19) is uncertain. Available evidence is limited to a few retrospective observational studies with small number of patients. Methods: We did a meta-analysis to assess the effect of ACEi/ARB in patients with COVID-19 on severity of disease, risk for hospitalisation, and death compared to those not on ACEi/ARB. We searched the Cochrane library, PubMed, Embase, ClinicalTrial.gov and medRxiv for studies published until 21.04.2020. Inclusion criteria included all studies with patients with confirmed COVID-19 either taking, or not taking, ACEi/ARB. Depending on degree of heterogeneity, fixed or random effect model was selected to calculate effect size (Odds ratio). Findings: Five studies were eligible for meta-analysis. These included 308 patients on ACEi/ARB, and 1172 not on ACEi/ARB. Compared to patients with COVID-19 not on ACEi/ARB, there was a statistically significant 44% reduction in odds of developing severe disease (OR: 0.56; 95% CI: 0.34-1.89, I2=68.15), and 62% reduction in odds of death (OR: 0.38; 95% CI: 0.19-0.74, I2=0.000) in those on ACEi/ARB. There was a non-significant 19% (OR 0.81; 95% CI: 0.42-1.55, I2: 0.000) reduction in odds of hospitalisation among those on ACEi/ARB. Interpretation: It is safe to use ACEi/ARB in patients with COVID-19 requiring these medications for associated comorbidities. Although limited by confounding factors typical of a meta-analysis of retrospective observational studies, our data suggests that use of these medications may reduce risk of developing severe disease and death. Funding Source: None", "title": "The effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers on death and severity of disease in patients with coronavirus disease 2019 (COVID-19): A meta-analysis", "pid": "dwcu6vyp", "bm25_score": 219.76454162597656}, {"text": "BACKGROUND: There is a controversy whether it is safe to continue renin-angiotensin system blockers in patients with coronavirus disease 2019 (COVID-19). We analyzed big data to investigate whether angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers have any significant effect on the risk of COVID-19. Population-based cohort study was conducted based on the prescription data from nationwide health insurance records. METHODS: We investigated the 1,374,381 residents aged &#8805; 40 years living in Daegu, the epicenter of the COVID-19 outbreak, between February and March 2020. Prescriptions of antihypertensive medication during the year before the outbreak were extracted from the National Health Insurance Service registry. Medications were categorized by types and stratified by the medication possession ratios (MPRs) of antihypertensive medications after controlling for the potential confounders. The risk of COVID-19 was estimated using a difference in difference analysis. RESULTS: Females, older individuals, low-income earners, and recently hospitalized patients had a higher risk of infection. Patients with higher MPRs of antihypertensive medications had a consistently lower risk of COVID-19 than those with lower MPRs of antihypertensive medications and non-users. Among patients who showed complete compliance, there was a significantly lower risk of COVID-19 for those prescribed angiotensin II receptor blockers (relative risk [RR], 0.751; 95% confidence interval [CI], 0.587-0.960) or calcium channel blockers (RR, 0.768; 95% CI, 0.601-0.980). CONCLUSION: Renin-angiotensin system blockers or other antihypertensive medications do not increase the risk of COVID-19. Patients should not stop antihypertensive medications, including renin-angiotensin system blockers, because of concerns of COVID-19.", "title": "Compliance of Antihypertensive Medication and Risk of Coronavirus Disease 2019: a Cohort Study Using Big Data from the Korean National Health Insurance Service", "pid": "7xzlcsbv", "bm25_score": 219.74349975585938}, {"text": "", "title": "Should Patients Receiving ACE Inhibitors or Angiotensin Receptor Blockers be Switched to Other Antihypertensive Drugs to Prevent or Improve Prognosis of Novel Coronavirus Disease 2019 (COVID-19)?", "pid": "09e5n5zd", "bm25_score": 219.72116088867188}, {"text": "In a rapid response published online by the British Medical Journal, Sommerstein and Gräni1 pushed forward the hypothesis that angiotensin-converting enzyme (ACE) inhibitors (ACE-Is) could act as a potential risk factor for fatal Corona virus disease 2019 (COVID-19) by up-regulating ACE2 This notion was quickly picked up by the lay press and sparked concerns among physicians and patients regarding the intake of inhibitors of the renin–angiotensin–aldosterone system (RAAS) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infected individuals 1 In this article, we try to shed light on what is known and unknown regarding the RAAS and SARS-CoV2 interaction We find translational evidence for diverse roles of the RAAS, which allows to formulate also the opposite hypothesis, i e that inhibition of the RAAS might be protective in COVID-19 [Truncated]", "title": "SARS-CoV2: should inhibitors of the renin–angiotensin system be withdrawn in patients with COVID-19? ;European Heart Journal ;Oxford Academic", "pid": "vzwsgfn9", "bm25_score": 219.72042846679688}, {"text": "The possible effects of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on COVID-19 disease severity have generated considerable debate. We performed a single-center, retrospective analysis of hospitalized adult COVID-19 patients in Wuhan, China, who had definite clinical outcome (dead or discharged) by February 15, 2020. Patients on anti-hypertensive treatment with or without ACEI/ARB were compared on their clinical characteristics and outcomes. The medical records from 702 patients were screened. Among the 101 patients with a history of hypertension and taking at least one anti-hypertensive medication, 40 patients were receiving ACEI/ARB as part of their regimen, and 61 patients were on antihypertensive medication other than ACEI/ARB. We observed no statistically significant differences in percentages of in-hospital mortality (28% vs. 34%, P = 0.46), ICU admission (20% vs. 28%, P = 0.37) or invasive mechanical ventilation (18% vs. 26%, P = 0.31) between patients with or without ACEI/ARB treatment. Further multivariable adjustment of age and gender did not provide evidence for a significant association between ACEI/ARB treatment and severe COVID-19 outcomes. Our findings confirm the lack of an association between chronic receipt of renin-angiotensin system antagonists and severe outcomes of COVID-19. Patients should continue previous anti-hypertensive therapy until further evidence is available.", "title": "Use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in context of COVID-19 outbreak: a retrospective analysis", "pid": "hfnqcw5d", "bm25_score": 219.72010803222656}, {"text": "Concerns have been raised regarding the safety of angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) in patients with coronavirus disease of 2019 (COVID‐19), based on the hypothesis that such medications may raise expression of ACE2, the receptor for severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). We conducted a literature review of studies (n = 12) in experimental animals and human subjects (n = 12) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses of ACEIs or ARBs than are typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID‐19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.", "title": "Risks of ACE Inhibitor and ARB Usage in COVID‐19: Evaluating the Evidence", "pid": "3ysa4twk", "bm25_score": 219.7195281982422}, {"text": "BACKGROUND: A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting–enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied. METHODS: We carried out a population-based case–control study in the Lombardy region of Italy. A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence. Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use. Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression. RESULTS: Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women. The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile. Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex. CONCLUSIONS: In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease. However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.", "title": "Renin–Angiotensin–Aldosterone System Blockers and the Risk of Covid-19", "pid": "1pahpghb", "bm25_score": 219.70303344726562}, {"text": "Coronavirus disease 2019 (COVID-19), which initially began in China, has spread to other countries of Asia, Europe, America, Africa and Oceania, with the number of confirmed cases and suspected cases increasing each day. According to recently published research, it was found that the majority of the severe cases were elderly, and many of them had at least one chronic disease, especially cardiovascular diseases. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are the most widely used drugs for cardiovascular diseases. The clinical effect of ACEIs/ARBs on patients with COVID-19 is still uncertain. This paper describes their potential role in the pathogenesis of COVID-19, which may provide useful in the advice of cardiologists and physicians.", "title": "Inhibitors of the renin-angiotensin system: The potential role in the pathogenesis of COVID-19.", "pid": "5a2zi2xp", "bm25_score": 219.69580078125}, {"text": "BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.", "title": "Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Covid-19", "pid": "fskfnmig", "bm25_score": 219.6857452392578}, {"text": "Background: controversy has arisen in the scientific community on whether the use of renin angiotensin system (RAS) inhibitors in the context of COVID-19 would be of benefit or harmful. A meta-analysis of eligible studies comparing the occurrence of severe and fatal COVID-19 in infected patients who were under treatment with angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) vs no treatment or other antihypertensives was conducted. Methods: PubMed, Google Scholar, the Cochrane Library, MedRxiv and BioRxiv were searched for relevant studies. Fixed-effect models or random-effect models were used depending on the heterogeneity between estimates. Results: a total of fifteen studies with 21,614 patients were included. The use of RAS inhibitors was associated with a non-significant 20% decreased risk of the composite outcome (death, admission to intensive care unit, mechanical ventilation requirement or progression to severe or critical pneumonia): RR 0.81 (95%CI: 0.63-1.04), p=0.10, I2=82%. In a subgroup analysis that included hypertensive subjects only, ACEI/ARB were associated with a 27% significant decrease in the risk of the composite outcome (RR 0.73 (95%CI: 0.56-0.96), p=0.02, I2=65%). Conclusion: the results of this pooled analysis suggest that the use of ACEI/ARB does not worsen the prognosis, and could even be protective in hypertensive subjects. Patients should continue these drugs during their COVID-19 illness.", "title": "Use of inhibitors of the renin angiotensin system and COVID-19 prognosis: a systematic review and meta-analysis", "pid": "lboa7rtn", "bm25_score": 219.67738342285156}, {"text": "Abstract Introduction and objective: A recent outbreak of Coronavirus disease 2019 (COVID-19) occurs in the worldwide. Angiotensin-converting enzyme 2 (ACE2) can mediate coronavirus entry into host cells. Therefore, renin-angiotensin system inhibitors (RASI) were suspected of contributing to the increase of coronavirus infection. We aimed to analyze the effects of RASI in COVID-19 patients with Hypertension. Patients and method: In this retrospective, single-center study, 27 COVID-19 patients with hypertension, who were admitted to the Shanghai Public Health Clinical Center from January 25, 2020 to January 31, 2020, were analyzed for clinical features, laboratory parameters, medications and the length of stay. All the patients were given antiviral and antihypertension treatment, of which 14 patients were treated with RASI and 13 patients without RASI. Results: Comparing the two groups, we did not found statistically significant differences in clinical symptoms and laboratory tests. Furthermore, cough was not aggravated. Conclusions: Through the analysis of this small sample, RASI could be deemed safe and effective to control high blood pressure of COVID-19 patients. Further analysis with a larger sampling size is required to explore the underlying mechanisms.", "title": "The effects of renin-angiotensin system inhibitors (RASI) in Corona Virus Disease (COVID-19) with Hypertension: A retrospective, single-center trial", "pid": "7vwxgm4r", "bm25_score": 219.6549530029297}, {"text": "Importance It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2. Objective To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19. Design, Setting, and Participants To examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020. Exposures ACEI/ARB use was defined as prescription fillings 6 months prior to the index date. Main Outcomes and Measures In the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis. Results In the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]). Conclusions and Relevance Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.", "title": "Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality.", "pid": "kc6dls2z", "bm25_score": 219.6395263671875}, {"text": "The prevalence of hypertension is high in patients affected by coronavirus disease 2019 (COVID-2019) and it appears to be related to an increased risk of mortality, as shown in many epidemiological studies. The angiotensin-converting enzyme (ACE) system is not uniformly expressed in all of the human races, and current differences could explain some of the geographical discrepancies in infection around the world. Furthermore, animal studies have shown that the ACE2 receptor is a potential pathway for host infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. As two-thirds of hypertensive patients take ACE inhibitors/angiotensin receptor blockers, several concerns have been raised about the detrimental role of current antihypertensive drugs in COVID-19. This report summarizes the recent evidence for and against the administration of ACE blockade in the COVID-19 era.", "title": "Hypertension prevalence in human coronavirus disease: the role of ACE system in infection spread and severity", "pid": "ih8oxr40", "bm25_score": 219.63665771484375}, {"text": "Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.", "title": "Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019", "pid": "7lonkj5p", "bm25_score": 219.63491821289062}, {"text": "Importance: The role of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB) in the setting of the coronavirus disease 2019 (COVID-19) pandemic is hotly debated. There have been recommendations to discontinue these medications, which are essential in the treatment of several chronic disease conditions, while, in the absence of clinical evidence, professional societies have advocated their continued use. Objective: To study the association between use of ACEIs/ARBs with the likelihood of testing positive for COVID-19 and to study outcome data in subsets of patients taking ACEIs/ARBs who tested positive with severity of clinical outcomes of COVID-19 (eg, hospitalization, intensive care unit admission, and requirement for mechanical ventilation). Design, Setting, and Participants: Retrospective cohort study with overlap propensity score weighting was conducted at the Cleveland Clinic Health System in Ohio and Florida. All patients tested for COVID-19 between March 8 and April 12, 2020, were included. Exposures: History of taking ACEIs or ARBs at the time of COVID-19 testing. Main Outcomes and Measures: Results of COVID-19 testing in the entire cohort, number of patients requiring hospitalizations, intensive care unit admissions, and mechanical ventilation among those who tested positive. Results: A total of 18 472 patients tested for COVID-19. The mean (SD) age was 49 (21) years, 7384 (40%) were male, and 12 725 (69%) were white. Of 18 472 patients who underwent COVID-19 testing, 2285 (12.4%) were taking either ACEIs or ARBs. A positive COVID-19 test result was observed in 1735 of 18 472 patients (9.4%). Among patients who tested positive, 421 (24.3%) were admitted to the hospital, 161 (9.3%) were admitted to an intensive care unit, and 111 (6.4%) required mechanical ventilation. Overlap propensity score weighting showed no significant association of ACEI and/or ARB use with COVID-19 test positivity (overlap propensity score-weighted odds ratio, 0.97; 95% CI, 0.81-1.15). Conclusions and Relevance: This study found no association between ACEI or ARB use and COVID-19 test positivity. These clinical data support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic. However, further study in larger numbers of hospitalized patients receiving ACEI and ARB therapy is needed to determine the association with clinical measures of COVID-19 severity.", "title": "Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19)", "pid": "v10tfut9", "bm25_score": 219.63180541992188}, {"text": "", "title": "Update Alert: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults", "pid": "22q41y93", "bm25_score": 219.62510681152344}, {"text": "Background: Concerns have been raised regarding the safety of Angiotensin Converting Enzyme Inhibitors (ACEIs) and Angiotensin Receptor Blockers (ARBs) in patients with COVID-19, based on the hypothesis that such medications may raise expression of ACE2, the receptor for SARS-CoV-2. Methods: We conducted a literature review of studies (n=12) in experimental animals and human subjects (n=11) and evaluated the evidence regarding the impact of administration of ACEIs and ARBs on ACE2 expression. We prioritized studies that assessed ACE2 protein expression data, measured directly or inferred from ACE2 activity assays. Results: The findings in animals are inconsistent with respect to an increase in ACE2 expression in response to treatment with ACEIs or ARBs. Control/sham animals show little to no effect in the plurality of studies. Those studies that report increases in ACE2 expression tend to involve acute injury models and/or higher doses than typically administered to patients. Data from human studies overwhelmingly imply that administration of ACEIs/ARBs does not increase ACE2 expression. Conclusion: Available evidence, in particular, data from human studies, does not support the hypothesis that ACEI/ARB use increases ACE2 expression and the risk of complications from COVID-19. We conclude that patients being treated with ACEIs and ARBs should continue their use for approved indications.", "title": "Dangers of ACE inhibitor and ARB usage in COVID-19: evaluating the evidence", "pid": "mgp38mdz", "bm25_score": 219.61866760253906}, {"text": "Potential but unconfirmed risk factors for coronavirus disease 2019 in adults and children may include hypertension, cardiovascular disease, and chronic kidney disease, as well as the medications commonly prescribed for these conditions, angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers. Coronavirus binding to angiotensin-converting enzyme 2, a crucial component of the renin-angiotensin-aldosterone system, underlies much of this concern. Children are uniquely impacted by the coronavirus but the reasons are unclear. This review will highlight the relationship of coronavirus disease 2019 with hypertension, use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers, and lifetime risk of cardiovascular disease from the pediatric perspective. We briefly summarize the renin-angiotensin-aldosterone system and comprehensively review the literature pertaining to the angiotensin-converting enzyme 2/angiotensin-(1-7) pathway in children and the clinical evidence for how angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers affect this important pathway. Given the importance of the angiotensin-converting enzyme 2/angiotensin-(1-7) pathway and the potential differences between adults and children, it is crucial that children are included in coronavirus-related research, as this may shed light on potential mechanisms for why children are at decreased risk of severe coronavirus disease 2019.", "title": "ACE2, COVID-19, and ACE Inhibitor and ARB Use during the Pandemic: The Pediatric Perspective.", "pid": "uu1jml2c", "bm25_score": 219.6184539794922}, {"text": "RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.", "title": "Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19", "pid": "h3xwg8uy", "bm25_score": 219.60946655273438}, {"text": "OBJECTIVE: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Renin-angiotensin-aldosterone-system (RAAS) inhibitors may increase the expression of angiotensin-converting enzyme 2, which is the receptor for SARSCoV-2 Spike protein. The consequences of using angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) during the COVID-19 pandemic are unknown. METHODS: A retrospective cohort study aiming to identify the odds of severe disease (defined as either hospitalization of &#8805;14 days, admission to the intensive care unit, or death) associated with exposure to ACEi or ARB was conducted. Adult patients (age &#8805;18 years) with COVID-19 admitted to the Istanbul Faculty of Medicine Corona Center between March 9 and May 11, 2020, were included. Chronic users of ACEi, ARB, or other antihypertensive drugs were matched according to age, sex, sick days before hospitalization, comorbidities, smoking, number of antihypertensive regimens, doxazosin use, furosemide use, and serum creatinine level. Odds ratios (OR) of having severe disease were calculated. RESULTS: In total, 611 patients were admitted with COVID-19, confirmed by either reverse-transcriptase polymerase chain reaction or computed tomography (CT). There were 363 males, and the age ranged from 18 to 98 years, with an average age of 57±15 years. Of these, 165 participants had severe disease (53 deaths, case fatality rate: 8.7%). Among those with hypertension (n=249), ARB exposure was compatible with decreased odds (OR=0.60, 95% CI: 0.27-1.36, p=0.31) of severe disease though not statistically significant, while ACEi exposure significantly reduced the risk of severe disease (OR=0.37, 95% CI: 0.15-0.87, p=0.03). ACEi exposure was associated with milder infiltrations seen on baseline CT, lower C-reactive protein and ferritin, higher monocytes, shorter hospitalization, and less requirement for specific empirical treatments (favipiravir and meropenem). CONCLUSION: Our data suggest that exposure to ACEi drugs may have favorable effects in the context of COVID-19 pneumonia.", "title": "Association between chronic ACE inhibitor exposure and decreased odds of severe disease in patients with COVID-19", "pid": "3qs8mnf1", "bm25_score": 219.60464477539062}, {"text": "There is current debate concerning the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II type 1 receptor blockers (ARBs), for hypertension management, during COVID-19 infection. Specifically, the suggestion has been made that ACE inhibitors or ARBs could theoretically contribute to infection via increasing ACE2 receptor expression and hence increase viral load. The ACE2 receptor is responsible for binding the SAR-CoV2 viral spike and causing COVID-19 infection. What makes the argument somewhat obtuse for ACE inhibitors or ARBs is that ACE2 receptor expression can be increased by compounds that activate or increase the expression of SIRT1. Henceforth common dietary interventions, vitamins and nutrients may directly or indirectly influence the cellular expression of the ACE2 receptor. There are many common compounds that can increase the expression of the ACE2 receptor including Vitamin C, Metformin, Resveratrol, Vitamin B3 and Vitamin D. It is important to acknowledge that down-regulation or blocking the cellular ACE2 receptor will likely be pro-inflammatory and may contribute to end organ pathology and mortality in COVID-19. In conclusion from the perspective of the ACE2 receptor, COVID-19 prevention and treatment are distinctly different. This letter reflects on this current debate and suggests angiotensin-converting enzyme inhibitors and ARBs are likely beneficial during COVID-19 infection for hypertensive and normotensive patients.", "title": "The angiotensin-converting enzyme 2 (ACE2) receptor in the prevention and treatment of COVID-19 are distinctly different paradigms", "pid": "ux844b25", "bm25_score": 219.59127807617188}, {"text": "With the capability of inducing elevated expression of ACE2, the cellular receptor for SARS-CoV-2, angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ARBs/ACEIs) treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the correlation of ARBs/ACEIs usage with the pathogenesis of COVID-19 in a retrospective, single-center study. 126 COVID-19 patients with preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine (HPHTCM) in Wuhan from January 5 to February 22, 2020 were retrospectively allocated to ARBs/ACEIs group (n=43) and non-ARBs/ACEIs group (n=83) according to their antihypertensive medication. 125 age- and sex-matched COVID-19 patients without hypertension were randomly selected as non-hypertension controls. In addition, the medication history of 1942 hypertension patients that were admitted to HPHTCM from November 1 to December 31, 2019 before COVID-19 outbreak were also reviewed for external comparison. Epidemiological, demographic, clinical and laboratory data were collected, analyzed and compared between these groups. The frequency of ARBs/ACEIs usage in hypertension patients with or without COVID-19 were comparable. Among COVID-19 patients with hypertension, those received either ARBs/ACEIs or non-ARBs/ACEIs had comparable blood pressure. However, ARBs/ACEIs group had significantly lower concentrations of CRP (p=0.049) and procalcitonin (PCT, p=0.008). Furthermore, much lower proportion of critical patients (9.3% vs 22.9%; p=0.061), and a lower death rate (4.7% vs 13.3%; p=0.216) were observed in ARBs/ACEIs group than non-ARBs/ACEIs group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACEIs in COVID-19 patients with preexisting hypertension.", "title": "Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors Usage is Associated with Improved Inflammatory Status and Clinical Outcomes in COVID-19 Patients With Hypertension", "pid": "mwttkclk", "bm25_score": 219.58631896972656}, {"text": "ACE2 is not only an enzyme that counters the effects of the renin-angiotensin-aldosterone system (RAAS) but is also the entry receptor for SARS-CoV-2, the virus of the Covid-19 pandemic. Some experimental data suggest that ACE inhibitors and ARBs increase ACE2 levels, thus raising concerns on their security in Covid-19 positive patients. However, some studies have shown protection by these drugs in lower tract respiratory infections and ARDS. The actual consensus is to continue the treatment with RAAS inhibitors, abrupt withdrawal, especially in patients with cardiac or renal conditions, being hazardous in terms of cardiovascular outcomes, except in patients hospitalized in intensive care with hemodynamic instability. This position statement is actually unanimous among all international learned societies.", "title": "[Renin-angiotensin-aldosterone blockers and Covic-19 infection : friends or enemies ?]", "pid": "eccv9401", "bm25_score": 219.56796264648438}, {"text": "Importance Data are lacking whether patients with hypertension who are taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have increased severity or risk of mortality during hospitalization for coronavirus disease 2019 (COVID-19). Objective To investigate the association between ACEIs/ARBs and severity of illness and mortality in patients with hypertension hospitalized for COVID-19 infection. Design, Setting, and Participants Retrospective, single-center case series of the 1178 hospitalized patients with COVID-19 infections at the Central Hospital of Wuhan, China, from January 15 to March 15, 2020. Main Outcomes and Measures COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction and epidemiologic, clinical, radiologic, laboratory, and drug therapy data were analyzed in all patients. The percentage of patients with hypertension taking ACEIs/ARBs was compared between those with severe vs nonsevere illness and between survivors vs nonsurvivors. Results Of the 1178 patients with COVID-19, the median age was 55.5 years (interquartile range, 38-67 years) and 545 (46.3%) were men. The overall in-hospital mortality was 11.0%. There were 362 patients with hypertension (30.7% of the total group; median age, 66.0 years [interquartile range, 59-73 years]; 189 [52.2%] were men), of whom 115 (31.8%) were taking ACEI/ARBs. The in-hospital mortality in the patients with hypertension was 21.3%. The percentage of patients with hypertension taking ACEIs/ARBs did not differ between those with severe and nonsevere infections (32.9% vs 30.7%; P = .65) nor did it differ between nonsurvivors and survivors (27.3% vs 33.0%; P = .34). Similar findings were observed when data were analyzed for patients taking ACEIs and those taking ARBs. Conclusions and Relevance This study provides clinical data on the association between ACEIs/ARBs and outcomes in patients with hypertension hospitalized with COVID-19 infections, suggesting that ACEIs/ARBs are not associated with the severity or mortality of COVID-19 in such patients. These data support current guidelines and societal recommendations for treating hypertension during the COVID-19 pandemic.", "title": "Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China.", "pid": "p10cya94", "bm25_score": 219.5673370361328}, {"text": "OBJECTIVE: The present short report summarizes some clinical characteristics of six patients affected by stroke while being on angiotensin-converting enzyme (ACE)2 inhibitors and angiotensin II receptor blockers (ARBs) before and during COVID-19. METHODS: Medical charts and images of six patients affected by stroke while being on ACE-Is and ARBs therapy before and during COVID-19 outbreak in Lombardy region, Italy, were reviewed. RESULTS: Three patients had a dural sinus thrombosis, whereas the remaining suffered by an arterial ischemia, which was a middle cerebral artery occlusion in one case, and a posterior-inferior cerebellar artery occlusion in the remaining two. All patients showed clinical features typical of SARS-CoV-2 infection and positive chest CT scan, and were treated with ACE-Is as needed. Hypercoagulability panel was negative in any case. A recovery was achieved in all cases, although in a variable manner. CONCLUSIONS: Whether or not and in which manner the pharmacomodulation of the renin-angiotensin system may had affect the clinical course of the reported six COVID-19 patients affected by stroke has to be still clarified. An urgent need of randomized clinical trials aimed to assess the safety profile and neuroprotective properties of ACE-Is and ARBs in COVID-19 patients diagnosed with stroke does exists.", "title": "Targeting of Renin-Angiotensin System In COVID-19 Patients Affected by Stroke: Emerging Concerns About Detrimental vs. Benefit Effect", "pid": "nur5901p", "bm25_score": 219.55848693847656}, {"text": "", "title": "Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection.", "pid": "5bgobcel", "bm25_score": 219.55264282226562}, {"text": "Importance: Data are lacking whether patients with hypertension who are taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have increased severity or risk of mortality during hospitalization for coronavirus disease 2019 (COVID-19). Objective: To investigate the association between ACEIs/ARBs and severity of illness and mortality in patients with hypertension hospitalized for COVID-19 infection. Design, Setting, and Participants: Retrospective, single-center case series of the 1178 hospitalized patients with COVID-19 infections at the Central Hospital of Wuhan, China, from January 15 to March 15, 2020. Main Outcomes and Measures: COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction and epidemiologic, clinical, radiologic, laboratory, and drug therapy data were analyzed in all patients. The percentage of patients with hypertension taking ACEIs/ARBs was compared between those with severe vs nonsevere illness and between survivors vs nonsurvivors. Results: Of the 1178 patients with COVID-19, the median age was 55.5 years (interquartile range, 38-67 years) and 545 (46.3%) were men. The overall in-hospital mortality was 11.0%. There were 362 patients with hypertension (30.7% of the total group; median age, 66.0 years [interquartile range, 59-73 years]; 189 [52.2%] were men), of whom 115 (31.8%) were taking ACEI/ARBs. The in-hospital mortality in the patients with hypertension was 21.3%. The percentage of patients with hypertension taking ACEIs/ARBs did not differ between those with severe and nonsevere infections (32.9% vs 30.7%; P = .65) nor did it differ between nonsurvivors and survivors (27.3% vs 33.0%; P = .34). Similar findings were observed when data were analyzed for patients taking ACEIs and those taking ARBs. Conclusions and Relevance: This study provides clinical data on the association between ACEIs/ARBs and outcomes in patients with hypertension hospitalized with COVID-19 infections, suggesting that ACEIs/ARBs are not associated with the severity or mortality of COVID-19 in such patients. These data support current guidelines and societal recommendations for treating hypertension during the COVID-19 pandemic.", "title": "Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China", "pid": "m6pth0tu", "bm25_score": 219.5465087890625}, {"text": "Aims: The question of interactions between the renin angiotensin aldosterone system drugs and the incidence and prognosis of COVID-19 infection has been raised by the medical community. We hypothesised that if patients treated with ACE inhibitors (ACEI) or AT1 receptor blockers (ARB) were more prone to SARS-CoV2 infection and had a worse prognosis than untreated patients, the prevalence of consumption of these drugs would be higher in patients with COVID-19 compared to the general population. Methods and results: We used a clinical epidemiology approach based on the estimation of standardised prevalence ratio (SPR) of consumption of ACEI and ARB in four groups of patients (including 187 COVID-19 positive) with increasing severity referred to the University hospital of Lille and in three French reference samples (the exhaustive North population (n=1,569,968), a representative sample of the French population (n=414,046), a random sample of Lille area (n=1,584)). The SPRs of ACEI and ARB did not differ as the severity of the COVID-19 patients increased, being similar to the regular consumption of these drugs in the North of France population with the same non-significant increase for both treatment (1.17 [0.83-1.67]). A statistically significant increase in the SPR of ARB (1.56 [1.02-2.39]) was observed in intensive care unit patients only. After stratification on obesity, this increase was limited to the high risk subgroup of obese patients. Conclusions: Our results strongly support the recommendation that ACEI and ARB should be continued in the population and in COVID-19 positive patients, reinforcing the position of several scientific societies.", "title": "ACE inhibitors, AT1 receptor blockers and COVID-19: clinical epidemiology evidences for a continuation of treatments. The ACER-COVID study", "pid": "6baw4hmt", "bm25_score": 219.54306030273438}, {"text": "The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1–angiotensin II–angiotensin AT(1) receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2–angiotensin(1-7)-angiotensin AT(2) receptor and the ACE-2–angiotensin(1-7)–Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful.", "title": "Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients", "pid": "6cxndab8", "bm25_score": 219.52215576171875}, {"text": "", "title": "Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection", "pid": "hl3g6778", "bm25_score": 219.50149536132812}, {"text": "BACKGROUND AND RATIONALE: Some studies of hospitalized patients suggested that the risk of death and/or severe illness due to COVID-19 is not associated with the use of angiotensin-converting enzyme inhibitors (ACEIs) and/or angiotensin II receptor type 1 blockers (ARBs). Nevertheless, some controversy still exists and there is limited information of the ACEIs/ARBs effect size on COVID-19 prognosis. AIM AND METHODS: We aimed to measure the effect of ACEIs and/or ARBs on COVID-19 severe clinical illness by a meta-analysis. Literature search included all studies published since the COVID-19 outbreak began (December 2019) until May 9, 2020. We analyzed information from studies that included tested COVID-19 patients with arterial hypertension as comorbidity prior to hospital admission and history of taking ACEIs, ARBs, or ACEIs/ARBs. RESULTS: We included 16 studies that involved 24,676 COVID-19 patients, and we compared patients with critical (n = 4134) vs. non-critical (n = 20,542) outcomes. The overall assessment by estimating random effects shows that the use of ACEIs/ARBs is not associated with higher risk of in-hospital-death and/or severe illness among hypertensive patients with COVID-19 infection. On the contrary, effect estimate shows an overall protective effect of RAAS inhibitors/blockers (ACEIs, ARBs, and/or ACEIs/ARBs) with ∼ 23 % reduced risk f death and/or critical disease (OR: 0.768, 95%CI: 0.651-0.907, p=0.0018). The use of ACEIs (OR:0.652, 95%CI:0.478-0.891, p=0.0072) but not ACEIs/ARBs (OR:0.867, 95%CI:0.638-1.179, p =NS) or ARBs alone (OR:0.810, 95%CI:0.629-1.044, p=NS) may explain the overall protection displayed by RAAS intervention combined. CONCLUSION: RAAS inhibitors might be associated with better COVID-19 prognosis.", "title": "Estimation of RAAS-Inhibitor effect on the COVID-19 outcome: A Meta-analysis", "pid": "npzzycis", "bm25_score": 219.49864196777344}, {"text": "COVID-19, which is caused by the single-stranded RNA severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has introduced significant therapeutic dilemmas in several areas. One of these is concern regarding the use of renin-angiotensin system (RAS) inhibitors. Dysfunction of the RAS has been observed in COVID-19 patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs), are associated with improved or worse clinical outcomes, remains unclear. RAS inhibitors are currently widely used in the treatment of hypertension. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with co-morbidities such as hypertension, coronary heart disease, and diabetes mellitus, particularly in the elderly. Therefore, several recently published research papers have focused on the management of hypertension during the COVID-19 pandemic, as this co-morbidity was found to be the most common in patients with coronavirus infections. SARS-CoV-2 viral surface protein is known to attach angiotensin converting enzyme-2 (ACE-2) on the cell membrane to facilitate viral entry into the cytoplasm. While the SARS-CoV-2 viral load remains the highest in upper respiratory tract of COVID-19 patients, it has also been reported in multiple sites in COVID-19, and patients not infrequently require the Intensive Care Units (ICU) admission. However, despite the theoretical concerns of possible increased ACE2 expression by RAS blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection, and indeed they have been shown to be beneficial in some animal studies. In this review we summarise the pathophysiology of the interaction between RAS, ACEIs/ARBs inhibitors and COVID-19, and conclude, on the basis of current data, that RAS blockade should be maintained during the current coronavirus pandemic.", "title": "Renin-angiotensin system inhibitors in management of hypertension during the COVID-19 pandemic.", "pid": "vv9ssqb8", "bm25_score": 219.49383544921875}, {"text": "Inhibitors of the Renin-Angiotensin-Aldosterone System (RAAS) notably Angiotensin-Converting Enzyme inhibitors (ACEi) or Angiotensin Receptor Blockers (ARB) have been scrutinised in hypertensive patients hospitalised with coronavirus disease 2019 (COVID-19) following some initial data they might adversely affect prognosis. With an increasing number of COVID-19 cases worldwide and the likelihood of a second wave of infection it is imperative to better understand the impact RAAS inhibitor use in antihypertensive covid positive hospitalised patients. A systematic review and meta-analysis of ACEi or ARB in patients admitted with COVID-19 was conducted. PubMed and Embase were searched and six studies were included in the meta-analysis. Pooled analysis demonstrated that 18.3% of the patients admitted with COVID-19 were prescribed ACEi/ARBs (0.183, CI 0.129 to 0.238, p<0.001). The use of RAAS inhibitors did not show any association with critical events (Pooled OR 0.833 CI 0.605 to 1.148, p=0.264) or death (Pooled OR 0.650, CI 0.356 to 1.187, p=0.161). In conclusion, our meta-analysis including critical events and mortality data on patients prescribed ACEi/ARB and hospitalised with COVID-19, found no evidence to associate ACEi/ARB with death or adverse events.", "title": "Impact of hospitalised patients with COVID-19 taking Renin-Angiotensin-Aldosterone System inhibitors: a systematic review and meta-analysis", "pid": "hc9ucl4a", "bm25_score": 219.46937561035156}, {"text": "COVID-19, which is caused by the single-stranded RNA severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), has introduced significant therapeutic dilemmas in several areas. One of these is concern regarding the use of renin-angiotensin system (RAS) inhibitors. Dysfunction of the RAS has been observed in COVID-19 patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type-1 receptor blockers (ARBs), are associated with improved or worse clinical outcomes, remains unclear. RAS inhibitors are currently widely used in the treatment of hypertension. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with co-morbidities such as hypertension, coronary heart disease, and diabetes mellitus, particularly in the elderly. Therefore, several recently published research papers have focused on the management of hypertension during the COVID-19 pandemic, as this co-morbidity was found to be the most common in patients with coronavirus infections. SARS-CoV-2 viral surface protein is known to attach angiotensin converting enzyme-2 (ACE-2) on the cell membrane to facilitate viral entry into the cytoplasm. While the SARS-CoV-2 viral load remains the highest in upper respiratory tract of COVID-19 patients, it has also been reported in multiple sites in COVID-19, and patients not infrequently require the Intensive Care Units (ICU) admission. However, despite the theoretical concerns of possible increased ACE2 expression by RAS blockade, there is no evidence that RAS inhibitors are harmful during COVID-19 infection, and indeed they have been shown to be beneficial in some animal studies. In this review we summarise the pathophysiology of the interaction between RAS, ACEIs/ARBs inhibitors and COVID-19, and conclude, on the basis of current data, that RAS blockade should be maintained during the current coronavirus pandemic.", "title": "Renin-angiotensin system inhibitors in management of hypertension during the COVID-19 pandemic", "pid": "wumtwdi5", "bm25_score": 219.4654541015625}, {"text": "Introduction: Angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor upregulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence but there is need for an updated systematic review of latest clinical studies. Methods: A search was conducted on PubMed, Google Scholar, EMBASE and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEI and/or ARB. Results: A total of eight studies were included in the review. There were conflicting findings reported in several studies as Meng J. et al, Liu Y. et al and Feng Y. reported that patients on ACE inhibitors/ARB had lower rates of severe outcomes whereas Richardson S. et al reported higher rates of invasive ventilation and intensive care unit (ICU) admissions in patients on ACE inhibitors/ARB as compared to non-users. However, Zhang P. et al found slightly higher rates of ICU admissions in patients on ACE inhibitors and ARB as compared to non-users. Similarly, there were conflicting results in the rate of mortality reported by the various clinical studies as well. Meng J. et al, Li J. et al and Zhang P. et al reported lower rates of mortality in ACE inhibitors/ARB users versus non-users whereas Guo J. et al reported higher rates of mortality in patients on ACE inhibitors/ARB as compared to non-users. Additionally, a large study conducted in New York by Richardson S. et al raised concerns with worse mortality outcomes in patients on ACEI/ ARB. Conclusion: It is concluded that ACEI and ARB should be continued in COVID-19 patients, albeit while exercising caution until larger clinical studies and randomized controlled trials confirm their safety. Additionally, the individual patient factors like ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.", "title": "A systematic review to evaluate the clinical outcomes in COVID -19 patients on angiotensin converting enzyme inhibitors or angiotensin receptor blockers", "pid": "a0asoy8j", "bm25_score": 219.4588165283203}, {"text": "BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in COVID-19 disease susceptibility, severity, and treatment is unclear. PURPOSE: To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment. DATA SOURCES: MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance. STUDY SELECTION: Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality. DATA EXTRACTION: Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence. DATA SYNTHESIS: Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case-control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19. LIMITATION: Half the studies were small and did not adjust for important confounding variables. CONCLUSION: High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: registration number pending).", "title": "Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults", "pid": "0nwmoua3", "bm25_score": 219.45811462402344}, {"text": "We have sparse knowledge of the effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the risk of COVID-19 infection and the progression of this disease. We systematically assessed these relationships. Unrestricted searches of the PubMed, Embase, and Cochrane Library databases were conducted, with an end date of May 9, 2020, to identify relevant studies that met predetermined inclusion criteria. Random-effects models were adopted to estimate the overall relative risk. Fourteen articles involving more than 19000 COVID-19 cases were included. Our results showed that ACEI/ARB exposure is not associated with a higher risk of COVID-19 infection (OR = 0.99; 95% CI, 0.95-1.04; P = 0.672). Among those with COVID-19 infection, ACEI/ARB exposure is not associated with a higher risk of severity (OR = 0.98; 95%CI 0.87-1.09; P = 0.69) or mortality (OR = 0.73, 95%CI 0.5-1.07; P = 0.111). However, ACEI/ARB exposure was associated with a lower risk of mortality compared those with non-ACEI/ARB antihypertensive drugs (OR = 0.48, 95% CI 0.29-0.81; P = 0.006). In conclusion, current evidence did not confirm previous concern regarding a harmful role of ACEI/ARB in COVID-19 patients. The present study support current professional society guidelines to not discontinue ACEIs or ARBs in the setting of the COVID-19 pandemic or COVID-19 patients.", "title": "ACEI/ARB Use and Risk of Infection or Severity or Mortality of COVID-19: A Systematic Review and Meta-analysis", "pid": "cvj1t0gi", "bm25_score": 219.4434051513672}, {"text": "In the recent coronavirus disease (COVID-19) outbreak, a higher proportion of patients with severe disease were found in older persons with comorbidities. This observation has been related to the use of drugs that can increase the cellular expression of angiotensin-converting enzyme 2 (ACE2) that has been recognized as target to which the virus bind to cells. Although this hypothesis is possible, it may also have other explanations which are discussed.", "title": "Is the ACE2 Overexpression a Risk Factor for COVID-19 Infection?", "pid": "9iitpj8u", "bm25_score": 219.43820190429688}, {"text": "", "title": "Angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers and risk of COVID 19: information from Bartter's and Gitelman's syndromes patients.", "pid": "2lxn4ceu", "bm25_score": 219.42709350585938}, {"text": "Coronavirus disease 2019 (COVID-19), which initially began in China, has spread to other countries of Asia, Europe, America, Africa and Oceania, with the number of confirmed cases and suspected cases increasing each day. According to recently published research, it was found that the majority of the severe cases were elderly, and many of them had at least one chronic disease, especially cardiovascular diseases. Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are the most widely used drugs for cardiovascular diseases. The clinical effect of ACEIs/ARBs on patients with COVID-19 is still uncertain. This paper describes their potential role in the pathogenesis of COVID-19, which may provide useful in the advice of cardiologists and physicians.", "title": "Inhibitors of the renin-angiotensin system: The potential role in the pathogenesis of COVID-19", "pid": "g4d4bdw0", "bm25_score": 219.40676879882812}, {"text": "INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor up-regulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence, but there is a need for an updated systematic review and meta-analysis of the latest clinical studies. METHODS AND RESULTS: A search was conducted on PubMed, Google Scholar, EMBASE, and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEIs and/or ARBs, and a meta-analysis was performed. A total of 16 studies were included for the review and meta-analysis. There were conflicting findings reported in the rates of severity and mortality in several studies. In a pooled analysis of four studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of developing severe disease vs. non-users [odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.41-1.58, I2=50.52, P-value = 0.53). In a pooled analysis of six studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of mortality as compared with non-users (OR = 0.86, 95% CI = 0.53-1.41, I2 = 79.12, P-value = 0.55). CONCLUSION: It is concluded that ACEIs and ARBs should be continued in COVID-19 patients, reinforcing the recommendations made by several medical societies. Additionally, the individual patient factors such as ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.", "title": "A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers", "pid": "lk7vkbav", "bm25_score": 219.40565490722656}, {"text": "This article reviews the correlation between angiotensin-converting enzyme 2 (ACE2) and severe risk factors for coronavirus disease 2019 (COVID-19) and the possible mechanisms. ACE2 is a crucial component of the renin-angiotensin system (RAS). The classical RAS ACE-Ang II-AT1R regulatory axis and the ACE2-Ang 1-7-MasR counter-regulatory axis play an essential role in maintaining homeostasis in humans. ACE2 is widely distributed in the heart, kidneys, lungs, and testes. ACE2 antagonizes the activation of the classical RAS system and protects against organ damage, protecting against hypertension, diabetes, and cardiovascular disease. Similar to SARS-CoV, SARS-CoV-2 also uses the ACE2 receptor to invade human alveolar epithelial cells. Acute respiratory distress syndrome (ARDS) is a clinical high-mortality disease, and ACE2 has a protective effect on this type of acute lung injury. Current research shows that the poor prognosis of patients with COVID-19 is related to factors such as sex (male), age (>60 years), underlying diseases (hypertension, diabetes, and cardiovascular disease), secondary ARDS, and other relevant factors. Because of these protective effects of ACE2 on chronic underlying diseases and ARDS, the development of spike protein-based vaccine and drugs enhancing ACE2 activity may become one of the most promising approaches for the treatment of COVID-19 in the future.", "title": "Organ-protective effect of angiotensin-converting enzyme 2 and its effect on the prognosis of COVID-19", "pid": "3d2kzqo2", "bm25_score": 219.4051513671875}, {"text": "The rapid spread of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease 2019 (COVID-19). Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for SARS-CoV-2 to enter host target cells. Given that angiotensin receptor blockers (ARBs) and an ACE inhibitor (ACEI) upregulated ACE2 expression in animal studies, the concern might arise regarding whether ARBs and ACEIs would increase the morbidity and mortality of COVID-19. On the other hand, animal data suggested a potential protective effect of ARBs against COVID-19 pneumonia because an ARB prevented the aggravation of acute lung injury in mice infected with SARS-CoV, which is closely related to SARS-CoV-2. Importantly, however, there is no clinical or experimental evidence supporting that ARBs and ACEIs either augment the susceptibility to SARS-CoV-2 or aggravate the severity and outcomes of COVID-19 at present. Until further data are available, it is recommended that ARB and ACEI medications be continued for the treatment of patients with cardiovascular disease and hypertension, especially those at high risk, according to guideline-directed medical therapy based on the currently available evidence.", "title": "Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors-lessons from available evidence and insights into COVID-19", "pid": "i5i2owvv", "bm25_score": 219.3948516845703}, {"text": "The effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) on the risk of COVID-19 infection and disease progression are yet to be investigated. The relationship between ACEI/ARB use and COVID-19 infection was systematically reviewed. To identify relevant studies that met predetermined inclusion criteria, unrestricted searches of the PubMed, Embase, and Cochrane Library databases were conducted. The search strategy included clinical date published until May 9, 2020. Twelve articles involving more than 19,000 COVID-19 cases were included. To estimate overall risk, random-effects models were adopted. Our results showed that ACEI/ARB exposure was not associated with a higher risk of COVID-19 infection (OR = 0.99; 95 % CI, 0-1.04; P = 0.672). Among those with COVID-19 infection, ACEI/ARB exposure was also not associated with a higher risk of having severe infection (OR = 0.98; 95 % CI, 0.87-1.09; P = 0.69) or mortality (OR = 0.73, 95 %CI, 0.5-1.07; P = 0.111). However, ACEI/ARB exposure was associated with a lower risk of mortality compared to those on non-ACEI/ARB antihypertensive drugs (OR = 0.48, 95 % CI, 0.29-0.81; P = 0.006). In conclusion, current evidence did not confirm the concern that ACEI/ARB exposure is harmful in patientswith COVID-19 infection. This study supports the current guidelines that discourage discontinuation of ACEIs or ARBs in COVID-19 patients and the setting of the COVID-19 pandemic.", "title": "ACEI/ARB use and risk of infection or severity or mortality of COVID-19: A systematic review and meta-analysis", "pid": "v8tfxd6a", "bm25_score": 219.38697814941406}, {"text": "Importance: It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2. Objective: To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19. Design, Setting, and Participants: To examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020. Exposures: ACEI/ARB use was defined as prescription fillings 6 months prior to the index date. Main Outcomes and Measures: In the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis. Results: In the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]). Conclusions and Relevance: Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.", "title": "Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality", "pid": "hn6wni8d", "bm25_score": 219.37322998046875}, {"text": "BACKGROUND: There is a controversy whether it is safe to continue renin-angiotensin system blockers in patients with coronavirus disease 2019 (COVID-19). We analyzed big data to investigate whether angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers have any significant effect on the risk of COVID-19. Population-based cohort study was conducted based on the prescription data from nationwide health insurance records. METHODS: We investigated the 1,374,381 residents aged ≥ 40 years living in Daegu, the epicenter of the COVID-19 outbreak, between February and March 2020. Prescriptions of antihypertensive medication during the year before the outbreak were extracted from the National Health Insurance Service registry. Medications were categorized by types and stratified by the medication possession ratios (MPRs) of antihypertensive medications after controlling for the potential confounders. The risk of COVID-19 was estimated using a difference in difference analysis. RESULTS: Females, older individuals, low-income earners, and recently hospitalized patients had a higher risk of infection. Patients with higher MPRs of antihypertensive medications had a consistently lower risk of COVID-19 than those with lower MPRs of antihypertensive medications and non-users. Among patients who showed complete compliance, there was a significantly lower risk of COVID-19 for those prescribed angiotensin II receptor blockers (relative risk [RR], 0.751; 95% confidence interval [CI], 0.587–0.960) or calcium channel blockers (RR, 0.768; 95% CI, 0.601–0.980). CONCLUSION: Renin-angiotensin system blockers or other antihypertensive medications do not increase the risk of COVID-19. Patients should not stop antihypertensive medications, including renin-angiotensin system blockers, because of concerns of COVID-19.", "title": "Compliance of Antihypertensive Medication and Risk of Coronavirus Disease 2019: a Cohort Study Using Big Data from the Korean National Health Insurance Service", "pid": "pnk1tt3w", "bm25_score": 219.3700408935547}, {"text": "There are plausible mechanisms by which angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of COVID-19 infection or affect disease severity. To examine the association between these medications and COVID-19 infection or hospitalization, we conducted a retrospective cohort study within a US integrated healthcare system. Among people aged [≥]18 years enrolled in the health plan for at least 4 months as of 2/29/2020, current ACEI and ARB use was identified from pharmacy data, and the estimated daily dose was calculated and standardized across medications. COVID-19 infections were identified through 6/14/2020 from laboratory and hospitalization data. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals. Among 322,044 individuals, 720 developed COVID-19 infection. Among people using ACEI/ARBs, 183/56,105 developed COVID-19 (3.3 per 1000 individuals) compared with 537/265,939 without ACEI/ARB use (2.0 per 1000), yielding an adjusted OR of 0.94 (95% CI 0.75-1.16). For use of < 1 defined daily dose vs. nonuse, the adjusted OR for infection was 0.89 (95% CI 0.62-1.26); for 1 to < 2 defined daily doses, 0.97 (95% CI 0.71-1.31); and for [≥]2 defined daily doses, 0.94 (95% CI 0.72-1.23). The OR was similar for ACEIs and ARBs and in subgroups by age and sex. 29% of people with COVID-19 infection were hospitalized; the adjusted OR for hospitalization in relation to ACEI/ARB use was 0.92 (95% CI 0.54-1.57), and there was no association with dose. These findings support current recommendations that individuals on these medications continue their use.", "title": "Renin-angiotensin-aldosterone system inhibitors and COVID-19 infection or hospitalization: a cohort study", "pid": "01xdd8zf", "bm25_score": 219.3687744140625}, {"text": "", "title": "Angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers and risk of COVID 19: information from Bartter's and Gitelman's syndromes patients", "pid": "zmc70464", "bm25_score": 219.36277770996094}, {"text": "The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown. COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors. We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood. In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs. This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.", "title": "Renin-angiotensin system inhibitors improve the clinical outcomes of COVID-19 patients with hypertension", "pid": "wz28xxhn", "bm25_score": 219.36160278320312}, {"text": "Abstract A new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was discovered in December 2019 in Wuhan, China; the virus escalated rapidly and on March 11, 2020, the World Health Organization declared it a pandemic.Emerging data suggests that older patients with COVID-19 associated with other comorbid conditions such as diabetes, hypertension, heart and lung diseases are particularly more susceptible, compared to general populations, and have higher mortality. It is not yet clear whether this increased association of high blood pressure with COVID-19 and the increased risk of mortality are directly related to high blood pressure or other associated comorbidities, or to antihypertensive treatment.Although the underlying pathogenic mechanism linking hypertension and severity of COVID-19 infection remains to be elucidated, it has been hypothesized that excessive activation of the renin-angiotensin system (RAS) could contribute to the progression of COVID-19 related lung injury.Concern about whether angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors may have deleterious effects on morbidity and mortality in patients with COVID-19 is based on speculation that these drugs would increase the regulation of angiotensin II converting enzyme (ACE2), a receptor for SARS-CoV-2, which would increase viral load and lung damage.Recent studies are consistent with the recommendations of scientific societies that propose avoiding the suspension or change of antihypertensive medication, as there is no evidence that shows that these can be taken as risk factors for severity or mortality from COVID-19.", "title": "Inhibidores de la enzima convertidora de angiotensina y antagonistas del receptor de angiotensina II: ¿Aumentan el riesgo de padecer COVID-19?", "pid": "ynias4ga", "bm25_score": 219.361328125}, {"text": "Potential but unconfirmed risk factors for coronavirus disease 2019 (COVID-19) in adults and children may include hypertension, cardiovascular disease, and chronic kidney disease, as well as the medications commonly prescribed for these conditions, ACE (angiotensin-converting enzyme) inhibitors, and Ang II (angiotensin II) receptor blockers. Coronavirus binding to ACE2 (angiotensin-converting enzyme 2), a crucial component of the renin-angiotensin-aldosterone system, underlies much of this concern. Children are uniquely impacted by the coronavirus, but the reasons are unclear. This review will highlight the relationship of COVID-19 with hypertension, use of ACE inhibitors and Ang II receptor blockers, and lifetime risk of cardiovascular disease from the pediatric perspective. We briefly summarize the renin-angiotensin-aldosterone system and comprehensively review the literature pertaining to the ACE 2/Ang-(1-7) pathway in children and the clinical evidence for how ACE inhibitors and Ang II receptor blockers affect this important pathway. Given the importance of the ACE 2/Ang-(1-7) pathway and the potential differences between adults and children, it is crucial that children are included in coronavirus-related research, as this may shed light on potential mechanisms for why children are at decreased risk of severe COVID-19.", "title": "ACE2 (Angiotensin-Converting Enzyme 2), COVID-19, and ACE Inhibitor and Ang II (Angiotensin II) Receptor Blocker Use During the Pandemic: The Pediatric Perspective", "pid": "ohj6misb", "bm25_score": 219.3546905517578}, {"text": "SARS-CoV-2 is spreading rapidly all over the world. The case fatality rate seems higher in cardiovascular disease and hypertension. Other comorbidities do not seem to confer the same risk, therefore the understanding of the relationship between infection and cardiovascular system could be a crucial point for the fight against the virus. A great interest is currently directed towards the angiotensin 2 converting enzyme (ACE 2) which is the SARS-CoV-2 receptor and creates important connections between the virus replication pathway, the cardiovascular system and blood pressure. All cardiovascular conditions share an imbalance of the renin angiotensin system (RAAS) in which ACE 2 plays a central role. In the last few days, much confusion has appeared about the management of therapy with angiotensin converting enzyme inhibitors (ACE-i) and angiotensin receptor blockers (ARBs) in infected patients and in those at risk of critical illness in case of infection. In this article we will try to reorder the major opinions currently emerging on this topic.", "title": "Relationship between ACE-inhibitors, ARBs and SARS-CoV-2 infection: where are we?", "pid": "43th3c20", "bm25_score": 219.34783935546875}, {"text": "", "title": "Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non–COVID-19 Sepsis but Carries a Moderately Increased Risk of Death", "pid": "3n2nji8l", "bm25_score": 219.34701538085938}, {"text": "Background. Medical editorials have suggested that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) should not be given to people with arterial hypertension during the coronavirus disease 2019 (COVID-19) pandemic because of a potential increased risk of worse clinical outcomes and that calcium channel blockers (CCBs) should be used as an alternative. Methods Using a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zheijang, China we have tested the role of usage of ACEIs, ARBs, CCBs and other medications on risk and severity of COVID 19. Analyses were adjusted for age, sex and BMI and for presence of relevant comorbidities. Findings: Higher BMI, diabetes and cardio/ cerebrovascular disease as independent risk factors for the development of COVID-19. Individuals with hypertension taking CCBs had significantly increased risk [odds ratio (OR)= 1.67 (95% CI 1.2-2.9)) of manifesting symptoms of COVID-19 whereas those taking ARBs and diuretics had significantly lower disease risk (OR=0.24; 95%CI 0.17-0.34 and OR=0.32; 95%CI 0.19-0.57 respectively). Other antihypertensive drugs were not associated with increased risk of severe or critical form of the infection. Use of glucocorticoids was significantly associated with a severe/critical form of COVID-19 (OR= 7.56; 95%CI 1.17-48.93). Interpretation: we found no evidence to alter ARBs or ACEIs therapy in the context of the pandemic. Patients on corticosteroids with COVID-19 are at higher risk of developing a severe form of COVID-19and therefore should be monitored closely.", "title": "Role of Drugs Affecting the Renin-Angiotensin-Aldosterone System on Susceptibility and Severity of COVID-19: A Large Case-Control Study from Zheijang Province, China.", "pid": "llzfc1r7", "bm25_score": 219.34136962890625}, {"text": "Systemic arterial hypertension (referred to as hypertension herein) is a major risk factor of mortality worldwide, and its importance is further emphasized in the context of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to as COVID-19. Patients with severe COVID-19 infections commonly are older and have a history of hypertension. Almost 75% of patients who have died in the pandemic in Italy had hypertension. This raised multiple questions regarding a more severe course of COVID-19 in relation to hypertension itself as well as its treatment with renin–angiotensin system (RAS) blockers, e.g. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We provide a critical review on the relationship of hypertension, RAS, and risk of lung injury. We demonstrate lack of sound evidence that hypertension per se is an independent risk factor for COVID-19. Interestingly, ACEIs and ARBs may be associated with lower incidence and/or improved outcome in patients with lower respiratory tract infections. We also review in detail the molecular mechanisms linking the RAS to lung damage and the potential clinical impact of treatment with RAS blockers in patients with COVID-19 and a high cardiovascular and renal risk. This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues. In summary, a critical review of available evidence does not support a deleterious effect of RAS blockers in COVID-19 infections. Therefore, there is currently no reason to discontinue RAS blockers in stable patients facing the COVID-19 pandemic.", "title": "Hypertension, the renin–angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19: European Society of Hypertension COVID-19 Task Force Review of Evidence", "pid": "y4h95kb4", "bm25_score": 219.33836364746094}, {"text": "ABSTRACT Hypertension emerged from early reports as a potential risk factor for worse outcomes for persons with coronavirus disease 2019 (COVID-19). Among the putative links between hypertension and COVID-19 is a key counter-regulatory component of the renin-angiotensin system (RAS): angiotensin-converting enzyme 2 (ACE2). ACE2 facilitates entry of SARS-CoV-2, the virus responsible for COVID-19, into host cells. Since RAS inhibitors have been suggested to increase ACE2 expression, healthcare providers and patients have grappled with the decision of whether to discontinue these medications during the COVID-19 pandemic. However, experimental models of analogous viral pneumonias suggest RAS inhibitors may exert protective effects against acute lung injury. We review how RAS and ACE2 biology may affect outcomes in COVID-19 through pulmonary and other systemic effects. In addition, we briefly detail the data for and against continuation of RAS inhibitors in persons with COVID-19 and summarize the current consensus recommendations from select specialty organizations.", "title": "COVID-19 and Hypertension: The Role of ACE2 and the Renin-Angiotensin System", "pid": "4ined9rx", "bm25_score": 219.335693359375}, {"text": "BACKGROUND: The role of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in COVID-19 disease susceptibility, severity, and treatment is unclear. PURPOSE: To evaluate, on an ongoing basis, whether use of ACEIs or ARBs either increases risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or is associated with worse COVID-19 disease outcomes, and to assess the efficacy of these medications for COVID-19 treatment. DATA SOURCES: MEDLINE (Ovid) and Cochrane Database of Systematic Reviews from 2003 to 4 May 2020, with planned ongoing surveillance for 1 year; the World Health Organization database of COVID-19 publications and medRxiv.org through 17 April 2020; and ClinicalTrials.gov to 24 April 2020, with planned ongoing surveillance. STUDY SELECTION: Observational studies and trials in adults that examined associations and effects of ACEIs or ARBs on risk for SARS-CoV-2 infection and COVID-19 disease severity and mortality. DATA EXTRACTION: Single-reviewer abstraction confirmed by another reviewer, independent evaluation by 2 reviewers of study quality, and collective assessment of certainty of evidence. DATA SYNTHESIS: Two retrospective cohort studies found that ACEI and ARB use was not associated with a higher likelihood of receiving a positive SARS-CoV-2 test result, and 1 case–control study found no association with COVID-19 illness in a large community (moderate-certainty evidence). Fourteen observational studies, involving a total of 23 565 adults with COVID-19, showed consistent evidence that neither medication was associated with more severe COVID-19 illness (high-certainty evidence). Four registered randomized trials plan to evaluate ACEIs and ARBs for treatment of COVID-19. LIMITATION: Half the studies were small and did not adjust for important confounding variables. CONCLUSION: High-certainty evidence suggests that ACEI or ARB use is not associated with more severe COVID-19 disease, and moderate-certainty evidence suggests no association between use of these medications and positive SARS-CoV-2 test results among symptomatic patients. Whether these medications increase the risk for mild or asymptomatic disease or are beneficial in COVID-19 treatment remains uncertain. PRIMARY FUNDING SOURCE: None. (PROSPERO: registration number pending)", "title": "Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults: A Living Systematic Review", "pid": "z22a5yzo", "bm25_score": 219.33206176757812}, {"text": "AIMS: The SARS‐Cov2 virus binds to the ACE2 receptor for cell entry. It has been suggested that ACE‐inhibitors (ACEi) and Angiotensin‐2 Blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID19 infection. METHODS AND RESULTS: We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID19 at two hospitals with a multi‐ethnic catchment population in London (UK). The mean age was 68 ± 17 years (57% male) and 74% of patients had at least 1 comorbidity. 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21‐days of symptom onset. 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio (OR) for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co‐morbidities, was 0.63 (CI 0.47–0.84, p < 0.01). CONCLUSIONS: There was no evidence for increased severity of COVID19 disease in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta‐analyses and randomised clinical trials. This article is protected by copyright. All rights reserved.", "title": "ACE‐inhibitors and Angiotensin‐2 Receptor Blockers are not associated with severe SARS‐COVID19 infection in a multi‐site UK acute Hospital Trust", "pid": "akancd4c", "bm25_score": 219.30929565429688}, {"text": "Background: Angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) have anti-inflammatory effects. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane protein angiotensin-converting enzyme 2 (ACE2), which is increased by ARB/ACEI treatment, as a cell entry receptor. Therefore, the use of ARBs/ACEIs for COVID-19 remains controversial. Methods: A retrospective case-control study was conducted using COVID-19 patients previously diagnosed with hypertension before COVID-19 onset. The primary outcome was severe infection or all-cause mortality. Cases included ARB/ACEI use for 30 days or longer during the 6 months before COVID-19 onset. Primary controls included antihypertensive use other than ARBs/ACEIs (narrow control); secondary controls included all other hypertension patients (broad control). We investigated ARB/ACEI association with outcomes in general and by subgroups (age, sex, and presence of diabetes) using logistic regression models with propensity score matching. Findings: Of 234427 suspected COVID-19 patients we screened, 1585 hypertension patients were analyzed. In the 892 cases, 428 narrow controls, and 693 broad controls, severe infection or death occurred in 8.6%, 22.2%, and 16.7%, respectively. ARB/ACEI use was associated with a reduced risk of severe infection or death relative to the narrow control group (adjusted odds ratio [aOR] 0.43, 95% confidence interval [CI] 0.28-0.65) and broad control group (aOR 0.49, 95% CI 0.33-0.71). The association was smaller for newly diagnosed hypertension patients (aOR 0.11, 95% CI 0.03-0.42 compared to narrow control group). ARB/ACEI protective effects against severe infection or death were significantly observed in male and diabetic patients. Interpretation: ARB/ACEI use was associated with a lower risk of severe infection or mortality compared to other antihypertensives or ARB/ACEI nonuse.", "title": "ARB/ACEI use and severe COVID-19: a nationwide case-control study", "pid": "vla7tt6s", "bm25_score": 219.30844116210938}, {"text": "INTRODUCTION: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) share their target receptor site with the SARS-CoV-2 virus, that may cause ACE2 receptor up-regulation which raised concerns regarding ACEI and ARB use in COVID-19 patients. However, many medical professional societies recommended their continued use given the paucity of clinical evidence, but there is a need for an updated systematic review and meta-analysis of the latest clinical studies. METHODS AND RESULTS: A search was conducted on PubMed, Google Scholar, EMBASE, and various preprint servers for studies comparing clinical outcomes and mortality in COVID-19 patients on ACEIs and/or ARBs, and a meta-analysis was performed. A total of 16 studies were included for the review and meta-analysis. There were conflicting findings reported in the rates of severity and mortality in several studies. In a pooled analysis of four studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of developing severe disease vs. non-users [odds ratio (OR) = 0.81, 95% confidence interval (CI): 0.41–1.58, I(2)=50.52, P-value = 0.53). In a pooled analysis of six studies, there was a statistically non-significant association of ACEI/ARB use with lower odds of mortality as compared with non-users (OR = 0.86, 95% CI = 0.53–1.41, I(2) = 79.12, P-value = 0.55). CONCLUSION: It is concluded that ACEIs and ARBs should be continued in COVID-19 patients, reinforcing the recommendations made by several medical societies. Additionally, the individual patient factors such as ACE2 polymorphisms which might confer higher risk of adverse outcomes need to be evaluated further.", "title": "A systematic review and meta-analysis to evaluate the clinical outcomes in COVID-19 patients on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers", "pid": "s4ty52kb", "bm25_score": 219.29859924316406}, {"text": "BACKGROUND: There is concern about the potential of an increased risk related to medications that act on the renin–angiotensin–aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2). METHODS: We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive. Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class. A difference of at least 10 percentage points was prespecified as a substantial difference. RESULTS: Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness. A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness. There was no association between any single medication class and an increased likelihood of a positive test. None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive. CONCLUSIONS: We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.", "title": "Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Covid-19", "pid": "oapjfamm", "bm25_score": 219.29649353027344}, {"text": "", "title": "Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non-COVID-19 Sepsis but Carries a Moderately Increased Risk of Death", "pid": "9anoehl3", "bm25_score": 219.27761840820312}, {"text": "The rapid spread of a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to an ongoing pandemic of coronavirus disease 2019 (COVID-19). Recently, angiotensin-converting enzyme 2 (ACE2) has been shown to be a functional receptor for SARS-CoV-2 to enter host target cells. Given that angiotensin receptor blockers (ARBs) and an ACE inhibitor (ACEI) upregulated ACE2 expression in animal studies, the concern might arise regarding whether ARBs and ACEIs would increase the morbidity and mortality of COVID-19. On the other hand, animal data suggested a potential protective effect of ARBs against COVID-19 pneumonia because an ARB prevented the aggravation of acute lung injury in mice infected with SARS-CoV, which is closely related to SARS-CoV-2. Importantly, however, there is no clinical or experimental evidence supporting that ARBs and ACEIs either augment the susceptibility to SARS-CoV-2 or aggravate the severity and outcomes of COVID-19 at present. Until further data are available, it is recommended that ARB and ACEI medications be continued for the treatment of patients with cardiovascular disease and hypertension, especially those at high risk, according to guideline-directed medical therapy based on the currently available evidence.", "title": "Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors—lessons from available evidence and insights into COVID-19", "pid": "6u623i0w", "bm25_score": 219.26824951171875}, {"text": "The novel coronavirus 2019 (COVID-19) infected patients by binding human ACE2, leading to severe pneumonia and highly mortality rate in patients. At present, there is no definite and effective treatment for COVID-19. ACE2 plays an important role in the RAS, and the imbalance between ACE/Ang II/AT1R pathway and ACE2/Ang (1-7)/Mas receptor pathway in the RAS system will lead to multi-system inflammation. Increased ACE and Ang II are poor prognostic factors for severe pneumonia. Animal studies have shown that RAS inhibitors could effectively relieve symptoms of acute severe pneumonia and respiratory failure. The binding of COVID-19 and ACE2 resulted in the exhaustion of ACE2, and then ACE2/Ang (1-7)/Mas receptor pathway was inhibited. The balance of the RAS system was broken, and this would lead to the exacerbation of acute severe pneumonia. Therefore, we speculate that ACEI and AT1R inhibitors could be used in patients with COVID-19 pneumonia under the condition of controlling blood pressure, and might reduce the pulmonary inflammatory response and mortality.", "title": "[Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia].", "pid": "5fbcjhqj", "bm25_score": 219.2664794921875}]}
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deaths in the United States were related to motor vehicles. A Healthy People 2010 objective calls for reducing the rate of deaths related to motor vehicles to 9.2 per 100,000 population from a baseline of 15.6 in 1998. To assess progress toward the Healthy People objective and to examine characteristics of motor vehicle--related death rates, CDC analyzed data from the National Vital Statistics System (NVSS) for the period 1999--2005. This report summarizes the results of that analysis, which determined that, during 1999--2005, although annual age-adjusted motor vehicle--related death rates overall were nearly unchanged (range: 15.2--15.7 per 100,000 population), substantial differences were observed by state, U.S. Census region, sex, race, and age group. Among states, the average annual death rate ranged from 7.9 per 100,000 population in Massachusetts to 31.9 in Mississippi. Among regions, the rate ranged from 9.8 per 100,000 population in the Northeast to 19.5 in the South. The rate for men (21.7 per 100,000 population) was more than double the rate for women (9.4); the rate for American Indians/Alaska Natives (27.2) was nearly twice the rate for whites (15.7) and blacks (15.2), and the rate for persons aged 15--24 years (26.8) was 74% higher than the average annual rate overall (15.4). Additional analysis and research to determine the causes of geographic and demographic variations in motor vehicle--related deaths might result in more effective targeted interventions among the states, regions, and populations at greatest risk.", "title": "Motor vehicle-related death rates--United States, 1999-2005.", "pid": "yjt2g95o", "bm25_score": 214.6726837158203}, {"text": "Cancer is the fourth most common cause of death (after unintentional injury, homicide, and suicide) among persons aged 1-19 years in the United States. Because recent childhood cancer mortality has not been well characterized in terms of temporal, demographic, and geographic trends, CDC analyzed cancer death rates among children (defined as aged 0-14 years) and adolescents (defined as aged 15-19 years) for the period 1990-2004 by sex, age group, race, ethnicity, U.S. Census region, and primary cancer site/leading diagnosis, using the most recent data available from the National Vital Statistics System (NVSS). This report describes the results of that analysis, which indicated that, overall, age-adjusted childhood cancer death rates decreased significantly during 1990-2004 among both sexes, both age groups, all races (except American Indians/Alaska Natives [AI/ANs]), Hispanics, non-Hispanics, and all U.S. Census regions. However, decreases in death rates varied among U.S. Census regions and between Hispanics and non-Hispanics. Eliminating racial/ethnic health disparities is one of the overarching goals of Healthy People 2010. Further research is needed to understand geographic and ethnic disparities in childhood cancer death rates. Moreover, cancer prevention and intervention measures should be designed to reach populations that are underserved and at high risk.", "title": "Trends in childhood cancer mortality--United States, 1990-2004.", "pid": "0falsc4z", "bm25_score": 214.032958984375}, {"text": "BACKGROUND Detailed assessments of mortality patterns, particularly age-specific mortality, represent a crucial input that enables health systems to target interventions to specific populations. Understanding how all-cause mortality has changed with respect to development status can identify exemplars for best practice. To accomplish this, the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) estimated age-specific and sex-specific all-cause mortality between 1970 and 2016 for 195 countries and territories and at the subnational level for the five countries with a population greater than 200 million in 2016. METHODS We have evaluated how well civil registration systems captured deaths using a set of demographic methods called death distribution methods for adults and from consideration of survey and census data for children younger than 5 years. We generated an overall assessment of completeness of registration of deaths by dividing registered deaths in each location-year by our estimate of all-age deaths generated from our overall estimation process. For 163 locations, including subnational units in countries with a population greater than 200 million with complete vital registration (VR) systems, our estimates were largely driven by the observed data, with corrections for small fluctuations in numbers and estimation for recent years where there were lags in data reporting (lags were variable by location, generally between 1 year and 6 years). For other locations, we took advantage of different data sources available to measure under-5 mortality rates (U5MR) using complete birth histories, summary birth histories, and incomplete VR with adjustments; we measured adult mortality rate (the probability of death in individuals aged 15-60 years) using adjusted incomplete VR, sibling histories, and household death recall. We used the U5MR and adult mortality rate, together with crude death rate due to HIV in the GBD model life table system, to estimate age-specific and sex-specific death rates for each location-year. Using various international databases, we identified fatal discontinuities, which we defined as increases in the death rate of more than one death per million, resulting from conflict and terrorism, natural disasters, major transport or technological accidents, and a subset of epidemic infectious diseases; these were added to estimates in the relevant years. In 47 countries with an identified peak adult prevalence for HIV/AIDS of more than 0·5% and where VR systems were less than 65% complete, we informed our estimates of age-sex-specific mortality using the Estimation and Projection Package (EPP)-Spectrum model fitted to national HIV/AIDS prevalence surveys and antenatal clinic serosurveillance systems. We estimated stillbirths, early neonatal, late neonatal, and childhood mortality using both survey and VR data in spatiotemporal Gaussian process regression models. We estimated abridged life tables for all location-years using age-specific death rates. We grouped locations into development quintiles based on the Socio-demographic Index (SDI) and analysed mortality trends by quintile. Using spline regression, we estimated the expected mortality rate for each age-sex group as a function of SDI. We identified countries with higher life expectancy than expected by comparing observed life expectancy to anticipated life expectancy on the basis of development status alone. FINDINGS Completeness in the registration of deaths increased from 28% in 1970 to a peak of 45% in 2013; completeness was lower after 2013 because of lags in reporting. Total deaths in children younger than 5 years decreased from 1970 to 2016, and slower decreases occurred at ages 5-24 years. By contrast, numbers of adult deaths increased in each 5-year age bracket above the age of 25 years. The distribution of annualised rates of change in age-specific mortality rate differed over the period 2000 to 2016 compared with earlier decades: increasing annualised rates of change were less frequent, although rising annualised rates of change still occurred in some locations, particularly for adolescent and younger adult age groups. Rates of stillbirths and under-5 mortality both decreased globally from 1970. Evidence for global convergence of death rates was mixed; although the absolute difference between age-standardised death rates narrowed between countries at the lowest and highest levels of SDI, the ratio of these death rates-a measure of relative inequality-increased slightly. There was a strong shift between 1970 and 2016 toward higher life expectancy, most noticeably at higher levels of SDI. Among countries with populations greater than 1 million in 2016, life expectancy at birth was highest for women in Japan, at 86·9 years (95% UI 86·7-87·2), and for men in Singapore, at 81·3 years (78·8-83·7) in 2016. Male life expectancy was generally lower than female life expectancy between 1970 and 2016, and the gap between male and female life expectancy increased with progression to higher levels of SDI. Some countries with exceptional health performance in 1990 in terms of the difference in observed to expected life expectancy at birth had slower progress on the same measure in 2016. INTERPRETATION Globally, mortality rates have decreased across all age groups over the past five decades, with the largest improvements occurring among children younger than 5 years. However, at the national level, considerable heterogeneity remains in terms of both level and rate of changes in age-specific mortality; increases in mortality for certain age groups occurred in some locations. We found evidence that the absolute gap between countries in age-specific death rates has declined, although the relative gap for some age-sex groups increased. Countries that now lead in terms of having higher observed life expectancy than that expected on the basis of development alone, or locations that have either increased this advantage or rapidly decreased the deficit from expected levels, could provide insight into the means to accelerate progress in nations where progress has stalled. FUNDING Bill & Melinda Gates Foundation, and the National Institute on Aging and the National Institute of Mental Health of the National Institutes of Health.", "title": "Global, regional, and national under-5 mortality, adult mortality, age-specific mortality, and life expectancy, 1970-2016: a systematic analysis for the Global Burden of Disease Study 2016.", "pid": "eet3v4cs", "bm25_score": 214.02810668945312}, {"text": "Currently (mid May 2020), most active cases of COVID-19 are found in Europe and North America while it is still in the initial phases in Africa. As COVID-19 mortality occurs mainly in elderly and as Africa has a comparably young population, the death rates should be lower than on other continents. We calculated standardised mortality ratios (SMR) using age-specific case fatality rates for COVID-19 and the age structure of the population of Africa and of other continents. Compared to a European or Northern American population, the standardised mortality ratio was only 0.22 and 0.25, respectively, corresponding to reduction of deaths rates to a quarter. Compared to the Asian and Latin American & Caribbean population, the SMR was 0.43 and 0.44, respectively, corresponding to half the death rate for Africa. It is useful to quantify the isolated effect of the African age-structure on potential COVID-19 mortality for illustrative and communication purposes, keeping in mind the importance of public health measures that have been shown to be effective in reducing cases and deaths. The different aspect of age pyramids of a European and an African population are striking and the potential implications for the pandemic are often discussed but rarely quantified.", "title": "The potential effect of the African population age structure on COVID-19 mortality", "pid": "vzmn6zep", "bm25_score": 213.89996337890625}, {"text": "The growing number of series on COVID-19 deaths classified by age and sex, released by national health authorities, has allowed us to compute age and sex patterns of its mortality, based on 183,619 deaths from Western Europe and the USA. We highlight the specific age schedule of COVID-19 mortality and its pronounced excess male mortality and we then apply these COVID-19 death rates to world populations, in 2020. Our results underscore that considerable variations exist between world regions, as concerns the potential impact of COVID-19 mortality, because of their demographic structures. When compared to younger countries in Sub-Saharan Africa, the vulnerability to COVID-19 mortality is shown to be 17 times higher in several industrialized countries of East Asia and Europe. There is a high correlation (r2= .44) between demographic vulnerability to COVID-19 mortality and current COVID-19 death rates.", "title": "COVID-19 death rates by age and sex and the resulting mortality vulnerability of countries and regions in the world", "pid": "cysj93kv", "bm25_score": 213.49266052246094}, {"text": "This study investigates the contribution of population age structure to mortality from Covid-19 in the UK by geographical units. We project death rates at various spatial scales by applying data on age-specific fatality rates to the area's population by age and sex. Our analysis shows a significant variation in the projected death rates between the constituent countries of the UK, between its regions and within regions. First, Scotland and Wales have higher projected fatality levels from Covid-19 than England, whereas Northern Ireland has lower rate. Second, the infection fatality rates are projected to be substantially higher in small towns and rural areas than those in large urban areas. Third, our analysis shows that within urban regions there are also 'pockets' of high projected death rates. Overall, the areas with high and low fatality rates tend to cluster because of the high residential separation of different population age-groups in the UK. Our analysis also reveals that the Welsh-, Gaelic- and Cornish-speaking communities with relatively old populations are likely to experience heavy population losses if the virus spreads widely across the UK.", "title": "The Contribution of Age Structure to the Number of Deaths from Covid-19 in the UK by Geographical Units", "pid": "vpakh3jk", "bm25_score": 213.43133544921875}, {"text": "The objective of study was to evaluate the incidence and mortality rates of disasters and mass casualty incidents (MCIs) over the past 10 yr in the administrative system of Korea administrative system and to examine their relationship with population characteristics. This was a population-based cross-sectional study. We calculated the nationwide incidence, as well as the crude mortality and injury incidence rates, of disasters and MCIs. The data were collected from the administrative database of the National Emergency Management Agency (NEMA) and from provincial fire departments from January 2000 to December 2009. A total of 47,169 events were collected from the NEMA administrative database. Of these events, 115 and 3,079 cases were defined as disasters and MCIs that occurred in Korea, respectively. The incidence of technical disasters/MCIs was approximately 12.7 times greater than that of natural disasters/MCIs. Over the past 10 yr, the crude mortality rates for disasters and MCIs were 2.36 deaths per 100,000 persons and 6.78 deaths per 100,000 persons, respectively. The crude injury incidence rates for disasters and MCIs were 25.47 injuries per 100,000 persons and 152 injuries per 100,000 persons, respectively. The incidence and mortality of disasters/MCIs in Korea seem to be low compared to that of trend around the world.", "title": "Incidence and Mortality Rates of Disasters and Mass Casualty Incidents in Korea: A Population-Based Cross-Sectional Study, 2000-2009", "pid": "ysyz3grd", "bm25_score": 213.41014099121094}, {"text": "Different ways of calculating mortality ratios during epidemics can yield widely different results, particularly during the COVID-19 pandemic. We formulate both a survival probability model and an associated infection duration-dependent SIR model to define individual- and population-based estimates of dynamic mortality ratios. The key parameters that affect the dynamics of the different mortality estimates are the incubation period and the length of time individuals were infected before confirmation of infection. We stress that none of these ratios are accurately represented by the often misinterpreted case fatality ratio (CFR), the number of deaths to date divided by the total number of infected cases to date. Using available data on the recent SARS-CoV-2 outbreaks and simple assumptions, we estimate and compare the different dynamic mortality ratios and highlight their differences. Informed by our modeling, we propose a more systematic method to determine mortality ratios during epidemic outbreaks and discuss sensitivity to confounding effects and errors in the data.", "title": "Why estimating population-based case fatality rates during epidemics may be misleading", "pid": "embnko1q", "bm25_score": 213.2524871826172}, {"text": "Although much progress has been made to uncover age-specific mortality patterns of the 1918 influenza pandemic in populations around the world, more studies in different populations are needed to make sense of the heterogeneous death impact of this pandemic. We assessed the absolute and relative magnitudes of 3 pandemic waves in the city of Madrid, Spain, between 1918 and 1920, on the basis of age-specific all-cause and respiratory excess death rates. Excess death rates were estimated using a Serfling model with a parametric bootstrapping approach to calibrate baseline death levels with quantified uncertainty. Excess all-cause and pneumonia and influenza mortality rates were estimated for different pandemic waves and age groups. The youngest and oldest persons experienced the highest excess mortality rates, and young adults faced the highest standardized mortality risk. Waves differed in strength; the peak standardized mortality risk occurred during the herald wave in spring 1918, but the highest excess rates occurred during the fall and winter of 1918/1919. Little evidence was found to support a “W”-shaped, age-specific excess mortality curve. Acquired immunity may have tempered a protracted fall wave, but recrudescent waves following the initial 2 outbreaks heightened the total pandemic mortality impact.", "title": "Age-Specific Excess Mortality Patterns During the 1918–1920 Influenza Pandemic in Madrid, Spain", "pid": "36fljyl2", "bm25_score": 213.19949340820312}, {"text": "BACKGROUND Since Macao's return of sovereignty to China in December 1999, the life style of Macao residents has changed. The aim of this study was to investigate changes of death patterns in Macao residents from 1986 to 2006 in order to identify the trends and patterns of major public health problems, which could provide the guidance for developing public health policies. METHODS A retrospective study was conducted for this investigation. Research data were collected from official websites and statistical yearbooks and classified by the International Classification of Diseases (ICD)-9. RESULTS It was observed that mortality from the three major causes of (1) infectious, maternal and childhood diseases, (2) chronic non-communicable diseases, and (3) injury and poisoning were 17.7, 298.2 and 26.0 per 100 000, respectively. The largest decrease in death rate over the 21-year study-period was from infectious, maternal and childhood diseases (62.5%). The highest mortality rate was ischemic heart diseases (37.0%). The largest increase in mortality rate was lung cancer (46.9%). CONCLUSIONS Mortality rate of Macao residents progressively decreased, but the constituent ratio of death from chronic non-communicable diseases was increasing. The mortality rate of lung cancer was clearly ascending, so emphasis should be put on tertiary prevention in future.", "title": "Changes in main causes of death in Macao residents from 1986 - 2006.", "pid": "eb7deut6", "bm25_score": 213.19467163085938}, {"text": "A variety of predisposing factors have been associated with serious illness and death from COVID-19. Understanding the distribution of risks associated with these factors by local communities can provide important opportunities for targeting interventions. We characterize the distribution of risk for COVID-19 mortality for populations at large across 442 US cities, by utilizing recently published estimates of risk associated with age, gender, ethnicity, social deprivation and 12 health conditions from a very large UK-based study, combined with the information available on prevalence and co-occurrence of these factors in the US through a variety of population-based public databases. We estimate that across all the cities, an underlying weighted risk-score can identify a total of approximately 12.65 million, 4.09 million and 1.34 million individuals who are at 2-, 5- and 10-fold higher risk, respectively, compared to the average risk for the US population. The percentage of population which exceed the respective risk thresholds varies across the cities in the range (1st-99th percentile), 3.6%-20.1%, 0.7%-8.0% and 0.1%-3.2%, respectively. The percentage of deaths within a city that are expected to occur above these risk-thresholds varies in the range of 20.1%-53.5%, 8.5%-38.2% and 2.9%-25.4%, respectively. Our analysis can provide guidance to national and local policy makers regarding resources needed to protect the most vulnerable populations in these communities, and how much utility such interventions may have in reducing the total population burden of death.", "title": "Estimating the Size of High-risk Populations for COVID-19 Mortality across 442 US Cities", "pid": "9n9irx70", "bm25_score": 213.1481170654297}, {"text": "Background: South Korea was among the first countries to report a case of the novel coronavirus (COVID-19) outside of China. As of 22 March, 2020, South Korea reported 8897 confirmed cases of and 104 deaths from COVID-19. Methods: We collected the number of laboratory-confirmed cases and deaths in South Korea from the World Health Organization (as of 21 March, 2020) and case distribution and fatality rates by age from the Korean Center for Disease Control and Prevention (as of 22 March, 2020). We estimated population-level mortality rates by fitting a negative binomial regression model with the number of deaths as the outcome and population by age as an offset. We then calculated the age-standardized death rate (ASDR) based on the current COVID-19 figures and for alternative scenarios of increased prevalence. Findings: The COVID-19 population-level mortality rate (per 100,000 person-years) increased with age: from 0.1 deaths among 30-39 year olds to 9.5 deaths among ≥80 year olds. The ASDR (per 100,000 person-years) was 0.8 deaths. The ASDR would increase to 52.0 deaths at a 1% prevalence (becoming the third leading cause of death) and 155.9 deaths at 3% prevalence (becoming the leading cause of death). Interpretation: Currently, the population-level mortality burden of COVID-19 in South Korea, as measured by the ASDR, was relatively low compared to other causes of death partly due to the low prevalence of COVID-19. If the prevalence increases from another outbreak, the mortality burden could increase substantially and surpass other leading causes.", "title": "Population-Level Mortality Rates from Novel Coronavirus (COVID-19) in South Korea", "pid": "lizwiate", "bm25_score": 213.13458251953125}, {"text": "Objective: We undertook this study to explore the role of important determinants affecting global COVID-19 incidence and mortality taking multifactorial disease dynamics into consideration. Design: Secondary data as on March 28, 2020 were obtained for 97 countries. Association of COVID-19 cumulative incidence and mortality measures were assessed with ten indictors representing health system characteristics, climate, demography, promptness of international travel restriction and population movement using Generalized Linear Modelling. Main outcome measures: Country-specific COVID-19 cumulative incidence, cumulative cause-specific mortality and case fatality rate. Results: Significant inter-country variation in incidence and mortality rates were observed. Five variables were found to be associated with cumulative incidence: testing rate per 1000 population ({beta} = 0.119, p < 0.01), UHC index ({beta} = 0.043, p = 0.04), percentage elderly population ({beta} = 0.122, p < 0.01), percentage below-poverty line population ({beta} = -0.048, p < 0.01) and disability adjusted life years due to NCDs ({beta} = -0.013, p < 0.01). Case fatality rate was observed to be associated with testing rate per 1000 population ({beta} = -0.058, p = 0.03) and population density ({beta} = 0.002, p = 0.02), while the cumulative cause-specific mortality was associated with only percentage elderly population ({beta} = 0.096, p = 0.04) in the country. Conclusions: Health system response, population susceptibility and demography were the most important factors determining the progression. Policy response should focus towards increasing testing, primarily targeting high population density areas. Health system strengthening and reduction in population risk factors should be long term goals for a better response to such epidemics.", "title": "Determinants of COVID-19 incidence and mortality: A cross-country analysis", "pid": "u72yj5kx", "bm25_score": 213.06063842773438}, {"text": "Different estimation methods produce diverging accounts of racial/ethnic disparities in COVID-19 mortality in the United States. The Center for Disease Control's decision to present the racial/ethnic distribution of COVID-19 deaths at the state level alongside the weighted racial/ethnic distribution of the counties within each state reporting those death -- in effect, a geographic adjustment -- makes it seem that Whites have the highest death rates. Age adjustment procedures used by others, including the New York City Department of Health and Mental Hygiene, lead to the opposite conclusion that Blacks and Hispanics are dying from COVID-19 at higher rates than Whites. In this paper, we use indirect standardization methods to adjust per capita death rates for both age and geography simultaneously, avoiding the one-sided adjustment procedures currently in use. Using CDC data, we find age-and-place-adjusted COVID-19 death rates are 80% higher for Blacks and over 50% higher for Hispanics, relative to Whites, on a national level. State-specific estimates show wide variation in mortality disparities. Comparison with nonepidemic mortality reveals potential roles for preexisting health disparities and differential rates of infection and care.", "title": "Improved measurement of racial/ethnic disparities in COVID-19 mortality in the United States", "pid": "fyna1euk", "bm25_score": 213.05137634277344}, {"text": "Background: Since partial oxygen pressure decreases as altitude increases, environmental hypoxia could worsen COVID-19 patient's hypoxemia. We compared COVID-19 mortality at different altitudes. Methods: Retrospective analysis of population-level data on COVID-19 deaths in the U.S. (1,016 counties) and Mexico (567 municipalities). Mixed-model Poisson regression analysis of the association between altitude and COVID-19 mortality using individual-level data from 40,168 Mexican subjects with COVID-19, adjusting for multiple covariates. Results: Between January 20 and April 13, 2020, mortality rates were higher in U.S. counties located at [≥]2,000 m elevation vs. those located below 1,500 m (12.3 vs. 3.2 per 100,000; P<0.001). In Mexico, between March 13 and May 13, 2020, mortality rates were higher in municipalities located at [≥]2,000 m vs. <1,500 m (5.3 vs. 3.9 per 100,000; P<0.001). Among Mexican subjects <65 years old, the risk of death was 36% higher in those living at [≥]2,000 m vs. <1,500 m (adjusted incidence rate ratio: 1.36; 95% CI, 1.05-1.78; P=0.022). Among men, the risk of death was 31% higher at [≥]2,000 m vs. <1,500 m (adjusted IRR: 1.31; 95% CI, 1.03-1.66; P=0.025). No association was found among women. Conclusion: Altitude is associated with COVID-19 mortality in men younger than 65 years.", "title": "Mortality Attributed to COVID-19 in High-Altitude Populations", "pid": "k1a2f2d2", "bm25_score": 213.01068115234375}, {"text": "BACKGROUND: On March 13, 2020, the World Health Organization declared COVID-19 a pandemic. Shortly after that, it was reported that mortality rates in New York City (NYC), the epicenter of the pandemic in the United States, were found to be significantly higher in black and Hispanic populations. OBJECTIVES: The aim of this article is to evaluate the mortality rates in NYC among the different ethnic groups and the different boroughs as they relate to the obesity rates to see whether this issue merits further evaluation. SETTING: NYC. METHODS: COVID-19 data were obtained from the official New York authorities in relation to total number of cases in the different boroughs of NYC. Age-adjusted COVID-19-related mortality rates of the different ethnic groups were also obtained. These data were cross-compared with historic community health data on obesity rates previously published and also obesity rates among the different ethnic groups in NYC. RESULTS: The 2 NYC boroughs that have the highest mortality rates are the Bronx (6%) and Brooklyn (5.4%). Both the Bronx and Brooklyn were also found to have the highest obesity rates at 32% and 27%, respectively. The 2 ethnic groups with the highest obesity rates (Hispanic and black) were also found to have the highest age-adjusted mortality rates per 100,000 compared with the other ethnic groups (22.8% and 19.8%, respectively). CONCLUSIONS: The Hispanic and black populations in NYC seem to be disproportionately affected by the COVID-19 pandemic because of the higher incidence of mortality rates. Obesity may have played a role in the high incidence of mortality in those ethnic groups.", "title": "Are black and Hispanic persons disproportionately affected by COVID-19 because of higher obesity rates?", "pid": "na4izro0", "bm25_score": 212.96685791015625}, {"text": "Summary Background This study was conducted in Kunming, the capital of Yunnan, a poor province in south-west China experiencing rapid economic growth. The study examined the short-term trend in premature mortality burden from common causes of death in a suburban region between 1998 and 2003. Methods Years of life lost (YLL) per 1000 population and mortality rate per 100,000 population were calculated from medical death certificates, and broken down by cause of death, sex and year without age weighting but with a discounting rate of 3%. Results Non-communicable diseases contributed over 80% of all causes of YLL, with a slightly increasing trend. The combined rate for communicable, maternal, prenatal and nutritional deficiencies declined from 4.7 to 2.4 per 1000 population. Remarkably, declining trends in YLL were also seen for chronic obstructive pulmonary disease, drug use and road traffic accidents, whereas increasing trends were seen for ischaemic heart disease (IHD) and liver cancer (males). The YLL rate for stroke, self-inflicted injuries, lung cancer and stomach cancer fluctuated over time. Conclusions The region should focus on further control of IHD and liver cancer.", "title": "Changing pattern of premature mortality burden over 6 years of rapid growth of the economy in suburban south-west China: 1998–2003", "pid": "lf90j7mm", "bm25_score": 212.95497131347656}, {"text": "BACKGROUND AND AIMS: COVID-19 disease has been associated with disproportionate mortality amongst world population. We try to elucidate various reasons for lower mortality rate in the Indian subcontinent due to COVID-19 pandemic. METHOD: We carried out a comprehensive review of the literature using suitable keywords such as 'COVID-19', 'Pandemics', 'disease outbreaks' and 'India' on the search engines of PubMed, SCOPUS, Google Scholar and Research Gate in the month of May 2020 during the current COVID-19 pandemic and assessed mortality data. RESULTS: The mortality observed in Indian and south Asian subcontinent is lower than in the west. Multifactorial reasons indicated for this differential mortality due to COVID-19 have been described in the current literature. CONCLUSIONS: The effects of COVID-19 on the health of racial and ethnic minority groups are still emerging with disproportionate burden of illness and death amongst some black and ethnic minority groups. Overall the current COVID-19 related mortality appears to be lower in the health and resource challenged populous Indian subcontinent. Further scientific studies would be helpful to understand this disparity in mortality due to COVID-19 in the world population.", "title": "Differential mortality in COVID-19 patients from India and western countries", "pid": "v4yto9p3", "bm25_score": 212.94955444335938}, {"text": "BACKGROUND AND AIMS: COVID-19 disease has been associated with disproportionate mortality amongst world population. We try to elucidate various reasons for lower mortality rate in the Indian subcontinent due to COVID-19 pandemic. METHOD: We carried out a comprehensive review of the literature using suitable keywords such as ‘COVID-19’, ‘Pandemics’, ‘disease outbreaks’ and ‘India’ on the search engines of PubMed, SCOPUS, Google Scholar and Research Gate in the month of May 2020 during the current COVID-19 pandemic and assessed mortality data. RESULTS: The mortality observed in Indian and south Asian subcontinent is lower than in the west. Multifactorial reasons indicated for this differential mortality due to COVID-19 have been described in the current literature. CONCLUSIONS: The effects of COVID-19 on the health of racial and ethnic minority groups are still emerging with disproportionate burden of illness and death amongst some black and ethnic minority groups. Overall the current COVID-19 related mortality appears to be lower in the health and resource challenged populous Indian subcontinent. Further scientific studies would be helpful to understand this disparity in mortality due to COVID-19 in the world population.", "title": "Differential mortality in COVID-19 patients from India and western countries", "pid": "q3pqo3iu", "bm25_score": 212.93310546875}, {"text": "BACKGROUND 258 million people reside outside their country of birth; however, to date no global systematic reviews or meta-analyses of mortality data for these international migrants have been done. We aimed to review and synthesise available mortality data on international migrants. METHODS In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, and Google Scholar databases for observational studies, systematic reviews, and randomised controlled trials published between Jan 1, 2001, and March 31, 2017, without language restrictions. We included studies reporting mortality outcomes for international migrants of any age residing outside their country of birth. Studies that recruited participants exclusively from intensive care or high dependency hospital units, with an existing health condition or status, or a particular health exposure were excluded. We also excluded studies limited to maternal or perinatal outcomes. We screened studies using systematic review software and extracted data from published reports. The main outcomes were all-cause and International Classification of Diseases, tenth revision (ICD-10) cause-specific standardised mortality ratios (SMRs) and absolute mortality rates. We calculated summary estimates using random-effects models. This study is registered with PROSPERO, number CRD42017073608. FINDINGS Of the 12 480 articles identified by our search, 96 studies were eligible for inclusion. The studies were geographically diverse and included data from all global regions and for 92 countries. 5464 mortality estimates for more than 15·2 million migrants were included, of which 5327 (97%) were from high-income countries, 115 (2%) were from middle-income countries, and 22 (<1%) were from low-income countries. Few studies included mortality estimates for refugees (110 estimates), asylum seekers (144 estimates), or labour migrants (six estimates). The summary estimate of all-cause SMR for international migrants was lower than one when compared with the general population in destination countries (0·70 [95% CI 0·65-0·76]; I2=99·8%). All-cause SMR was lower in both male migrants (0·72 [0·63-0·81]; I2=99·8%) and female migrants (0·75 [0·67-0·84]; I2=99·8%) compared with the general population. A mortality advantage was evident for refugees (SMR 0·50 [0·46-0·54]; I2=89·8%), but not for asylum seekers (1·05 [0·89-1·24]; I2=54·4%), although limited data was available on these groups. SMRs for all causes of death were lower in migrants compared with the general populations in the destination country across all 13 ICD-10 categories analysed, with the exception of infectious diseases and external causes. Heterogeneity was high across the majority of analyses. Point estimates of all-cause age-standardised mortality in migrants ranged from 420 to 874 per 100 000 population. INTERPRETATION Our study showed that international migrants have a mortality advantage compared with general populations, and that this advantage persisted across the majority of ICD-10 disease categories. The mortality advantage identified will be representative of international migrants in high-income countries who are studying, working, or have joined family members in these countries. However, our results might not reflect the health outcomes of more marginalised groups in low-income and middle-income countries because little data were available for these groups, highlighting an important gap in existing research. Our results present an opportunity to reframe the public discourse on international migration and health in high-income countries. FUNDING Wellcome Trust, National Institute for Health Research, Medical Research Council, Alliance for Health Policy and Systems Research, Department for International Development, Fogarty International Center, Grand Challenges Canada, International Development Research Centre Canada, Inter-American Institute for Global Change Research, National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Mental Health, Swiss National Science Foundation, World Diabetes Foundation, UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, and European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group Research Funding for the ESCMID Study Group for Infections in Travellers and Migrants.", "title": "Global patterns of mortality in international migrants: a systematic review and meta-analysis.", "pid": "ppwviewr", "bm25_score": 212.92041015625}, {"text": "Using data from the WHO's Situation Report on the COVID-19 pandemic from 21 January 2020 to 30 March 2020 along with other health, demographic, and macroeconomic indicators from the WHO's Application Programming Interface and the World Bank's Development Indicators, this paper explores the death rates of infected persons and their possible associated factors. Through the panel analysis, we found consistent results that healthcare system conditions, particularly the number of hospital beds and medical staff, have played extremely important roles in reducing death rates of COVID-19 infected persons. In addition, both the mortality rates due to different non-communicable diseases (NCDs) and rate of people aged 65 and over were significantly related to the death rates. We also found that controlling international and domestic travelling by air along with increasingly popular anti-COVID-19 actions (i.e., quarantine and social distancing) would help reduce the death rates in all countries. We conducted tests for robustness and found that the Driscoll and Kraay (1998) method was the most suitable estimator with a finite sample, which helped confirm the robustness of our estimations. Based on the findings, we suggest that preparedness of healthcare systems for aged populations need more attentions from the public and politicians, regardless of income level, when facing COVID-19-like pandemics.", "title": "COVID-19: A relook at healthcare systems and aged populations", "pid": "t1ggb2cj", "bm25_score": 212.91702270507812}, {"text": "Background: Current reporting of Covid-19 mortality data by race and ethnicity across the United States could bias our understanding of population-mortality disparities. Moreover, stark differences in age distribution by race and ethnicity groups are seldom accounted for in analyses. Methods: To address these gaps, we conducted a cross-sectional study using publicly-reported Covid-19 mortality data to assess the quality of race and ethnicity data (Black, Latinx, white), and estimated age-adjusted disparities using a random effects meta-analytic approach. Results: We found only 28 states, and NYC, reported race and ethnicity-stratified Covid-19 mortality along with large variation in the percent of missing race and ethnicity data by state. Aggregated relative risk of death estimates for Black compared to the white population was 3.57 (95% CI: 2.84-4.48). Similarly, Latinx population displayed 1.88 (95% CI: 1.61-2.19) times higher risk of death than white patients. Discussion: In states providing race and ethnicity data, we identified significant population-level Covid-19 mortality disparities. We demonstrated the importance of adjusting for age differences across population groups to prevent underestimating disparities in younger population groups. The availability of high-quality and comprehensive race and ethnicity data is necessary to address factors contributing to inequity in Covid-19 mortality.", "title": "Racial and Ethnic Disparities in Population Level Covid-19 Mortality", "pid": "7kevqevo", "bm25_score": 212.89456176757812}, {"text": "It is generally expected that in developing countries the epidemiological transition, with improved health and lower mortality rates, will eventually lead to a demographic transition with lower fertility rates. The reductions in mortality characterising the epidemiological transition are often associated with controlling the infectious diseases within populations, which leaves the chronic diseases associated with old age, cancer and heart disease dominating the causes of death. However, if the demographic transition does not occur quickly, populations can grow rapidly, creating an increased potential for spread of infectious disease. These infectious diseases could, in turn, increase death rates amongst young people and reverse the epidemiological transition. The relationship between population growth, size and infection depends upon the changes in contact pattern associated with there being more people. If facilities can keep pace with growth, then the increase in contact rates can be kept to a minimum, and the potential reversal in the epidemic transition prevented. This makes development a crucial adjunct to population growth if the global community is not to be increasingly exposed to pandemics of infectious disease. Here we review the epidemiological and demographic theory which relates population growth and infectious disease.", "title": "The Impact of Population Growth on the Epidemiology and Evolution of Infectious Diseases", "pid": "61norte8", "bm25_score": 212.85606384277344}, {"text": "In this article, we analyse the factors that determine the fatality rates across 29 economies spread across both the developing and developed world. Recent emerging literature and expert opinions in popular media have indicated various factors that may explain cross-country difference in fatality rates. These factors range from access to public health infrastructure, BCG vaccination policies, demographic structure, restrictive policy interventions and the weather. In addition, articles are examining different kinds of fatality rates that can be explained. Progressing beyond fragmented databases and anecdotal evidence, we have developed a database for such factors, have explored various econometric models to test the explanatory power of these factors in explaining several kinds of fatality rates. Based on available data, our study reveals that factors such as public health system, population age structure, poverty level and BCG vaccination are powerful contributory factors in determining fatality rates. Interactions between factors such as poverty level and BCG vaccination provide interesting insights into the complex interplay of factors. Our analysis suggests that poor citizens’ access to the public healthcare system are worse in many countries irrespective of whether they are developed or developing countries.", "title": "Why Do COVID-19 Fatality Rates Differ Across Countries? An Explorative Cross-country Study Based on Select Indicators", "pid": "98n6ycwe", "bm25_score": 212.84902954101562}, {"text": "Purpose: To estimate influenza-associated excess mortality rates (EMRs) in Chongqing from 2012 to 2018.Methods: We obtained weekly mortality data for all-cause and four underlying causes of death (circulatory and respiratory disease (CRD), pneumonia and influenza (P&I), chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IDH)), and influenza surveillance data, from 2012 to 2018. A negative-binomial regression model was used to estimate influenza-associated EMRs in two age groups (<65 years and &#8805;65 years).Results: It was estimated that an annual average of 10025 influenza-associated deaths occurred in Chongqing, corresponding to 5.2% of all deaths. The average EMR for all-cause death associated with influenza was 33.5 (95% confidence interval (CI): 31.5-35.6) per 100 000 persons, and in separate cause-specific models we attributed 24.7 (95% CI: 23.3-26.0), 0.8 (95% CI: 0.7-0.8), 8.5 (95% CI: 8.1-9.0) and 5.0 (95% CI: 4.7-5.3) per 100 000 persons EMRs to CRD, P&I, COPD and IDH, respectively. The estimated EMR for influenza B virus was 20.6 (95% CI: 20.3-21.0), which was significantly higher than the rates of 5.3 (95% CI: 4.5-6.1) and 7.5 (95% CI: 6.7-8.3) for A(H3N2) and A(H1N1) pdm09 virus, respectively. The estimated EMR was 152.3 (95% CI: 136.1-168.4) for people aged &#8805;65 years, which was significantly higher than the rate for those aged <65 years (6.8, 95% CI: 6.3-7.2).Conclusions: Influenza was associated with substantial EMRs in Chongqing, especially among elderly people. Influenza B virus caused a relatively higher excess mortality impact compared with A(H1N1)pdm09 and A(H3N2). It is advisable to optimize future seasonal influenza vaccine reimbursement policy in Chongqing to curb disease burden.", "title": "Mortality burden from seasonal influenza in Chongqing, China, 2012-2018", "pid": "bwoot89o", "bm25_score": 212.84188842773438}, {"text": "BACKGROUND Inclusion health focuses on people in extremely poor health due to poverty, marginalisation, and multimorbidity. We aimed to review morbidity and mortality data on four overlapping populations who experience considerable social exclusion: homeless populations, individuals with substance use disorders, sex workers, and imprisoned individuals. METHODS For this systematic review and meta-analysis, we searched MEDLINE, Embase, and the Cochrane Library for studies published between Jan 1, 2005, and Oct 1, 2015. We included only systematic reviews, meta-analyses, interventional studies, and observational studies that had morbidity and mortality outcomes, were published in English, from high-income countries, and were done in populations with a history of homelessness, imprisonment, sex work, or substance use disorder (excluding cannabis and alcohol use). Studies with only perinatal outcomes and studies of individuals with a specific health condition or those recruited from intensive care or high dependency hospital units were excluded. We screened studies using systematic review software and extracted data from published reports. Primary outcomes were measures of morbidity (prevalence or incidence) and mortality (standardised mortality ratios [SMRs] and mortality rates). Summary estimates were calculated using a random effects model. FINDINGS Our search identified 7946 articles, of which 337 studies were included for analysis. All-cause standardised mortality ratios were significantly increased in 91 (99%) of 92 extracted datapoints and were 11·86 (95% CI 10·42-13·30; I2=94·1%) in female individuals and 7·88 (7·03-8·74; I2=99·1%) in men. Summary SMR estimates for the International Classification of Diseases disease categories with two or more included datapoints were highest for deaths due to injury, poisoning, and other external causes, in both men (7·89; 95% CI 6·40-9·37; I2=98·1%) and women (18·72; 13·73-23·71; I2=91·5%). Disease prevalence was consistently raised across the following categories: infections (eg, highest reported was 90% for hepatitis C, 67 [65%] of 103 individuals for hepatitis B, and 133 [51%] of 263 individuals for latent tuberculosis infection), mental health (eg, highest reported was 9 [4%] of 227 individuals for schizophrenia), cardiovascular conditions (eg, highest reported was 32 [13%] of 247 individuals for coronary heart disease), and respiratory conditions (eg, highest reported was 9 [26%] of 35 individuals for asthma). INTERPRETATION Our study shows that homeless populations, individuals with substance use disorders, sex workers, and imprisoned individuals experience extreme health inequities across a wide range of health conditions, with the relative effect of exclusion being greater in female individuals than male individuals. The high heterogeneity between studies should be explored further using improved data collection in population subgroups. The extreme health inequity identified demands intensive cross-sectoral policy and service action to prevent exclusion and improve health outcomes in individuals who are already marginalised. FUNDING Wellcome Trust, National Institute for Health Research, NHS England, NHS Research Scotland Scottish Senior Clinical Fellowship, Medical Research Council, Chief Scientist Office, and the Central and North West London NHS Trust.", "title": "Morbidity and mortality in homeless individuals, prisoners, sex workers, and individuals with substance use disorders in high-income countries: a systematic review and meta-analysis.", "pid": "h9gfyeb8", "bm25_score": 212.82809448242188}, {"text": "Since the beginning of the SARS-CoV-2/COVID-19 epidemic in China, elderly and multimorbid subjects showed a higher mortality rate. However, other factors could influence the mortality and the spread of contagion such as the population density. An archival research based on the Italian data stratified by region was performed in order to quantify the association between the population density, ageing index, number of positive cases, number of deaths, case-fatality rate, and medical equipment (gloves, masks, and ventilators). Results showed a significant positive linear relationship between the population density and cases, deaths, and case-fatality rate. No correlation with the ageing index was shown. Furthermore, we found a significant positive correlation between the number of medical supplies and population density, cases, and deaths. However, the medical supplies did not show any correlation with the case-fatality rate. Taken together, these findings suggest that the population density and the lack of medical equipment are key factors explaining morbidity and mortality of COVID-19 in Italy.", "title": "SARS-CoV-2 in Italy: Population Density correlates with Morbidity and Mortality.", "pid": "3t8636xa", "bm25_score": 212.82778930664062}, {"text": "The relationship between log cumulative number of patients (X) and that of deaths (Y) in an epidemic follows the equation logY = klogX - klogN(0), where k is a constant determining the slope and N(0) is the value of X when Y = 1. Diseases with k = 1 are Ebola hemorrhagic fever, avian influenza H5N1, cholera, and hand, foot, and mouth disease; those with k > 1 are the influenza H1N1 2009 pandemic in countries other than Mexico and the SARS epidemic in some countries; and those with k < 1 include the influenza H1N1 2009 pandemic in Mexico. Epidemics with k > 1 can be simulated by postulating two subpopulations (normal population [NP] and vulnerable population [VP]), where the epidemic proceeds at higher speed and at higher mortality in VP than in NP. Epidemics with k < 1 can be simulated by postulating coexisting high virulence virus (HVV) and low virulence virus (LVV), with the former being propagated at slower speed and with a higher mortality rate than the latter. An epidemic with k > 1 was simulated using parameters that are fractions of subpopulations NP or VP from the total population (f) and NP- or VP-specific patient multiplication (M) and mortality (D) rates. An epidemic with k < 1 was simulated using parameters that are fractions of HVV- or LVV-infected human populations (f), and HVV- or LVV-specific M and D.", "title": "On case-fatality rate: review and hypothesis.", "pid": "h0plbvg3", "bm25_score": 212.80807495117188}, {"text": "", "title": "Clarification of Mortality Rate and Data in Abstract, Results, and Table 2", "pid": "r086n6hq", "bm25_score": 212.80551147460938}, {"text": "", "title": "Clarification of Mortality Rate and Data in Abstract, Results, and Table 2.", "pid": "op16ufhz", "bm25_score": 212.80352783203125}, {"text": "COVID-19 death rates vary strikingly across Europe. The death rate in Spain, for example, is greater than the death rate in Germany by more than a factor of ten. Few if any epidemiological indicators distinguish the countries of Europe by such a vast margin. Evidence on age-specific case-fatality rates (deaths over observed infections) and age-specific death rates (deaths over population) indicate that COVID-19 disproportionately afflicts the elderly and frail, suggesting that the share of elderly population (≥ 65 years of age) in a country ought to be a strong predictor of the COVID-19 death rate. However, the COVID-19 death rate and the share of elderly population are statistically uncorrelated (r = 0.163, p = 0.399). Share of population ≥ 65 years of age is confounded by mortality selection, as well as other demographic dynamics. By contrast, elderly longevity or life expectancy at 65 more effectively captures population survival and the accumulation of age-related frailty in society. We find a strong statistical relationship between the COVID-19 death rate (r = 0.839, p < .001) and elderly longevity, and a moderately strong relationship between the date of epidemic timing and elderly longevity (r = −0.634, p < .001). These relationships are robust to the inclusion of statistical controls for international tourism inflow and hospital bed capacity. While the countries of Europe vary meaningfully in healthcare system capacity and in the timing and intensity of non-pharmaceutical interventions, the striking variation in COVID-19 death rates across these countries is statistically and intuitively associated with elderly survival and consequent frailty.", "title": "The Longevity-Frailty Hypothesis: Evidence from COVID-19 Death Rates in Europe", "pid": "9p0dsyqx", "bm25_score": 212.79364013671875}, {"text": "Since the beginning of the SARS-CoV-2/COVID-19 epidemic in China, elderly and multimorbid subjects showed a higher mortality rate. However, other factors could influence the mortality and the spread of contagion such as the population density. An archival research based on the Italian data stratified by region was performed in order to quantify the association between the population density, ageing index, number of positive cases, number of deaths, case-fatality rate, and medical equipment (gloves, masks, and ventilators). Results showed a significant positive linear relationship between the population density and cases, deaths, and case-fatality rate. No correlation with the ageing index was shown. Furthermore, we found a significant positive correlation between the number of medical supplies and population density, cases, and deaths. However, the medical supplies did not show any correlation with the case-fatality rate. Taken together, these findings suggest that the population density and the lack of medical equipment are key factors explaining morbidity and mortality of COVID-19 in Italy.", "title": "SARS-CoV-2 in Italy: Population Density correlates with Morbidity and Mortality", "pid": "2e90esx8", "bm25_score": 212.77671813964844}, {"text": "Mortality statistics due to COVID-19 worldwide are compared, by adjusting for the size of the population and the stage of the pandemic. Data from the European Centre for Disease Control and Prevention, and Our World in Data websites were used. Analyses are based on number of deaths per one million inhabitants. In order to account for the stage of the pandemic, the baseline date was defined as the day in which the 10th death was reported. The analyses included 78 countries and territories which reported 10 or more deaths by April 9. On day 10, India had 0.06 deaths per million, Belgium had 30.46 and San Marino 618.78. On day 20, India had 0.27 deaths per million, China had 0.71 and Spain 139.62. On day 30, four Asian countries had the lowest mortality figures, whereas eight European countries had the highest ones. In Italy and Spain, mortality on day 40 was greater than 250 per million, whereas in China and South Korea, mortality was below 4 per million. Mortality on day 10 was moderately correlated with life expectancy, but not with population density. Asian countries presented much lower mortality figures as compared to European ones. Life expectancy was found to be correlated with mortality.", "title": "Worldwide differences in COVID-19-related mortality.", "pid": "inhxonsk", "bm25_score": 212.77059936523438}, {"text": "Although testing is widely regarded as critical to fighting the Covid-19 pandemic, what measure and level of testing best reflects successful infection control remains unresolved. Our aim was to compare the sensitivity of two testing metrics--population testing number and testing coverage--to population mortality outcomes and identify a benchmark for testing adequacy with respect to population mortality and capture of potential disease burden. This ecological study aggregated publicly available data through April 12 on testing and outcomes related to COVID-19 across 36 OECD (Organization for Economic Development) countries and Taiwan. All OECD countries and Taiwan were included in this population-based study as a proxy for countries with highly developed economic and healthcare infrastructure. Spearman correlation coefficients were calculated between the aforementioned metrics and following outcome measures: deaths per 1 million people, case fatality rate, and case proportion of critical illness. Fractional polynomials were used to generate scatter plots to model the relationship between the testing metrics and outcomes. Testing coverage, but not population testing number, was highly correlated with population mortality (rs= -0.79, P=5.975e-09 vs rs =- 0.3, P=0.05) and case fatality rate (rs= -0.67, P=9.067e-06 vs rs = -0.21, P=0.20). A testing coverage threshold of 15-45 signified adequate testing: below 15, testing coverage was associated with exponentially increasing population mortality, whereas above 45, increased testing did not yield significant incremental mortality benefit. Testing coverage was better than population testing number in explaining country performance and can be used as an early and sensitive indicator of testing adequacy and disease burden. This may be particularly useful as countries consider re-opening their economies.", "title": "Correlation of population mortality of COVID-19 and testing coverage: a comparison among 36 OECD countries and Taiwan", "pid": "3jmxamtj", "bm25_score": 212.76016235351562}, {"text": "Background: The coronavirus 2019 (COVID-19) pandemic has been spread-ing globally for months, yet the infection fatality ratio of the disease is still uncertain. This is partly because of inconsistencies in testing and death reporting standards across countries. Our purpose is to provide accurate estimates which do not rely on testing and death count data directly but only use population level statistics. Methods: We collected demographic and death records data from the Italian Institute of Statistics. We focus on the area in Italy that experienced the initial outbreak of COVID-19 and estimated a Bayesian model fitting age-stratified mortality data from 2020 and previous years. We also assessed the sensitivity of our estimates to alternative assumptions on the proportion of population infected. Findings: We estimate an overall infection fatality rate of 1.29% (95% credible interval [CrI] 0.89 - 2.01), as well as large differences by age, with a low infection fatality rate of 0.05% for under 60 year old (CrI 0-.19) and a substantially higher 4.25% (CrI 3.01-6.39) for people above 60 years of age. In our sensitivity analysis, we found that even under extreme assumptions, our method delivered useful information. For instance, even if only 10% of the population were infected, the infection fatality rate would not rise above 0.2% for people under 60. Interpretation: Our empirical estimates based on population level data show a sharp difference in fatality rates between young and old people and firmly rule out overall fatality ratios below 0.5% in populations with more than 30% over 60 years old.", "title": "An empirical estimate of the infection fatality rate of COVID-19 from the first Italian outbreak", "pid": "86l1xixa", "bm25_score": 212.75694274902344}, {"text": "We aimed to clarify if the infection and death rate by COVID-19 differ among gender in the top 50 countries with the highest death rates. Also, we investigated if secondary variables such as HDI, number of hospital beds, average age, temperature, percentage of elderly, smoker and obesity are contributing to the variability observed among countries. Meta-analyses and meta-regressions approaches were applied to official public data reported by the Word Health Organization and governments until May, 2020. A random effect model was used for the meta-analysis and heterogeneity was calculated by I2 statistic. There was not significative difference between men and women to be infected by COVID-19 (P = 0.42), though a significative difference was observed for death rate (P < 0.0001). High heterogeneity was observed among countries. For both infection and death rates this variability was mainly explained by the HDI (42.3% and 54.2%), average age (40.9% and 40.3%) and temperature (30.1% and 39.3%). Man are dying more than women around the word by COVID-19. Countries with highest HDI present less difference between sexes. These results reinforce that public politics promoting social isolation, health care and general well-being of the population are key factors in combating COVID-19.", "title": "Are men dying more than women by COVID-19?", "pid": "0ekb6c8e", "bm25_score": 212.75485229492188}, {"text": "Mortality statistics due to COVID-19 worldwide are compared, by adjusting for the size of the population and the stage of the pandemic. Data from the European Centre for Disease Control and Prevention, and Our World in Data websites were used. Analyses are based on number of deaths per one million inhabitants. In order to account for the stage of the pandemic, the baseline date was defined as the day in which the 10th death was reported. The analyses included 78 countries and territories which reported 10 or more deaths by April 9. On day 10, India had 0.06 deaths per million, Belgium had 30.46 and San Marino 618.78. On day 20, India had 0.27 deaths per million, China had 0.71 and Spain 139.62. On day 30, four Asian countries had the lowest mortality figures, whereas eight European countries had the highest ones. In Italy and Spain, mortality on day 40 was greater than 250 per million, whereas in China and South Korea, mortality was below 4 per million. Mortality on day 10 was moderately correlated with life expectancy, but not with population density. Asian countries presented much lower mortality figures as compared to European ones. Life expectancy was found to be correlated with mortality.", "title": "Worldwide differences in COVID-19-related mortality", "pid": "xwpqae0r", "bm25_score": 212.7481689453125}, {"text": "The demographic factors have a substantial impact on the overall casualties caused by the COVID-19. In this study, the spatial association between the key demographic variables and COVID-19 cases and deaths were analyzed using the spatial regression models. Total 13 (for COVID-19 case factor) and 8 (for COVID-19 death factor) key variables were considered for the modelling. Total five spatial regression models such as Geographically weighted regression (GWR), Spatial Error Model (SEM), Spatial Lag Model (SLM), Spatial Error_Lag model (SEM_SLM), and Ordinary Least Square (OLS) were performed for the spatial modelling and mapping of model estimates. The local R2 values, which suggesting the influences of the selected demographic variables on overall casualties caused by COVID-19, was found highest in Italy and the UK. The moderate local R2 was observed for France, Belgium, Netherlands, Ireland, Denmark, Norway, Sweden, Poland, Slovakia, and Romania. The lowest local R2 value for COVID-19 cases was accounted for Latvia and Lithuania. Among the 13 variables, the highest local R2 was calculated for total population (R2 = 0.92), followed by death crude death rate (R2 = 0.9), long time illness (R2 = 0.84), population with age>80 (R2 = 0.59), employment (R2 = 0.46), life expectancy at 65 (R2 = 0.34), crude birth rate (R2 = 0.31), life expectancy (R2 = 0.31), Population with age 65-80 (R2 = 0.29), Population with age 15-24 (R2 = 0.27), Population with age 25-49 (R2 = 0.27), Population with age 0-14 (R2 = 0.23), and Population with age 50-65 (R2 = 0.23), respectively.", "title": "The overall mortality caused by COVID-19 in the European region is highly associated with demographic composition: A spatial regression-based approach", "pid": "pil10k4i", "bm25_score": 212.7401123046875}, {"text": "For COVID-19 the Infection Fatality Rate or IFR - a crucial variable in epidemiological modeling - is difficult to estimate because many cases are asymptomatic and the overall infection rate is generally not known. Circumstances in the Italian provinces of Milano, Bergamo, Brescia, and Lodi allow estimation of lower bounds for age- and sex-specific all-cause excess mortality (a proxy for IFR) since anecdotal reports indicate some towns were close to fully infected. Using data from ISTAT on mortality from January 1 through April 15 for 2020 and the three preceding years, I estimate excess mortality by sex and age categories (0-14, 15-54, 55-64, 65-74, and 75+ years) while controlling for town-specific mortality that proxies for town-specific infection rate. The 99th percentile from the tail of the town distribution gives a lower-bound estimate for COVID-19 mortality. The overall population-weighted mortality at the 99th percentile is 1.09 percent (95% CI 1.06-1.14). The age- and sex-specific rates vary considerably: for men age 65-74 the estimate is 2.10 percent (95% CI 1.94-2.28) which is 3.5-times higher than men 55-64 and 2.7-times higher than women 65-74.", "title": "Estimating Lower Bounds for COVID-19 Mortality from Northern Italian Towns", "pid": "0ie6tkgm", "bm25_score": 212.71762084960938}, {"text": "OBJECTIVE: To provide estimates of the relative rate of COVID-19 death in people <65 years old versus older individuals in the general population, the absolute risk of COVID-19 death at the population level during the first epidemic wave, and the proportion of COVID-19 deaths in non-elderly people without underlying diseases in epicenters of the pandemic. ELIGIBLE DATA: Cross-sectional survey of countries and US states with at least 800 COVID-19 deaths as of April 24, 2020 and with information on the number of deaths in people with age <65. Data were available for 14 countries (Belgium, Canada, France, Germany, India, Ireland, Italy, Mexico, Netherlands, Portugal, Spain, Sweden, Switzerland, UK) and 13 US states (California, Connecticut, Florida, Georgia, Illinois, Indiana, Louisiana, Maryland, Massachusetts, Michigan, New Jersey, New York, Pennsylvania). We also examined available data on COVID-19 deaths in people with age <65 and no underlying diseases. MAIN OUTCOME MEASURES: Proportion of COVID-19 deaths in people <65 years old; relative mortality rate of COVID-19 death in people <65 versus ≥65 years old; absolute risk of COVID-19 death in people <65 and in those ≥80 years old in the general population as of June 17, 2020; absolute COVID-19 mortality rate expressed as equivalent of mortality rate from driving a motor vehicle. RESULTS: Individuals with age <65 account for 4.5–11.2% of all COVID-19 deaths in European countries and Canada, 8.3–22.7% in the US locations, and were the majority in India and Mexico. People <65 years old had 30- to 100-fold lower risk of COVID-19 death than those ≥65 years old in 11 European countries and Canada, 16- to 52-fold lower risk in US locations, and less than 10-fold in India and Mexico. The absolute risk of COVID-19 death as of June 17, 2020 for people <65 years old in high-income countries ranged from 10 (Germany) to 349 per million (New Jersey) and it was 5 per million in India and 96 per million in Mexico. The absolute risk of COVID-19 death for people ≥80 years old ranged from 0.6 (Florida) to 17.5 per thousand (Connecticut). The COVID-19 mortality rate in people <65 years old during the period of fatalities from the epidemic was equivalent to the mortality rate from driving between 4 and 82 miles per day for 13 countries and 5 states, and was higher (equivalent to the mortality rate from driving 106–483 miles per day) for 8 other states and the UK. People <65 years old without underlying predisposing conditions accounted for only 0.7–3.6% of all COVID-19 deaths in France, Italy, Netherlands, Sweden, Georgia, and New York City and 17.7% in Mexico. CONCLUSIONS: People <65 years old have very small risks of COVID-19 death even in pandemic epicenters and deaths for people <65 years without underlying predisposing conditions are remarkably uncommon. Strategies focusing specifically on protecting high-risk elderly individuals should be considered in managing the pandemic.", "title": "Population-level COVID-19 mortality risk for non-elderly individuals overall and for non-elderly individuals without underlying diseases in pandemic epicenters", "pid": "f3eogz0n", "bm25_score": 212.71519470214844}, {"text": "Background. Inequalities and burden of comorbidities of the Coronavirus disease 2019 (COVID-19) vary importantly inside the countries. We aimed to analyze the Municipality-level factors associated with a high COVID-19 mortality rate of in Mexico. Methods. We retrieved information from 142,643 cumulative confirmed symptomatic cases and 18,886 deaths of COVID-19 as of June 20th, 2020 from the publicly available database of the Ministry of Health of Mexico. Public official data of the most recent census and surveys of the country were used to adjust a negative binomial regression model with the quintiles (Q) of the distribution of sociodemographic and health outcomes among 2,457 Municipality-level. Expected Mortality Rates (EMR), Incidence Rate Ratios (IRR) and 95% Confidence Intervals are reported. Results. Factors associated with high MR of COVID-19, relative to Quintile 1 (Q1), were; diabetes prevalence (Q4, IRR=2.60), obesity prevalence (Q5, IRR=1.93), diabetes mortality rate (Q5, IRR=1.58), proportion of indigenous population (Q2, IRR=1.68), proportion of economically active population (Q5, IRR=1.50), density of economic units that operate essential activities (Q4, IRR=1.54) and population density (Q5, IRR=2.12). We identified 1,351 Municipality-level without confirmed COVID-19 deaths, of which, 202 had nevertheless high (Q4, Mean EMR= 8.0 deaths per 100,000) and 82 very high expected COVID-19 mortality (Q5, Mean EMR= 13.8 deaths per 100,000). Conclusion. This study identified 1,351 Municipality-level of Mexico that, in spite of not having confirmed COVID-19 deaths yet, share characteristics that could eventually lead to a high mortality scenario later in the epidemic and warn against premature easing of mobility restrictions. Local information should be used to reinforce strategies of prevention and control of outbreaks in communities vulnerable to COVID-19. Keywords: COVID-19; risk factors; social determinants; health determinants; Municipality-level; counties.", "title": "Municipality- level predictors of COVID-19 mortality in Mexico: a cautionary tale", "pid": "9o81djzl", "bm25_score": 212.70376586914062}, {"text": "There has been great concern in the UK that people from the BAME (Black And Minority Ethnic) community have a far higher risk of dying from Covid19 than those of other ethnicities. However, the overall fatalities data from the Government's ONS (Office of National Statistics) most recent report on deaths by religion shows that Jews (very few of whom are classified as BAME) have a much higher risk than those of religions (Hindu, Sikh, Muslim) with predominantly BAME people. This apparently contradictory result is, according to the ONS statistical analysis, implicitly explained by age as the report claims that, when 'adjusted for age' Muslims have the highest fatality risk. However, the report fails to provide the raw data to support this. There are many factors other than just age that must be incorporated into any analysis of the observed data before making definitive conclusions about risk based on religion/ethnicity. We propose the need for a causal model for this. If we discount unknown genetic factors, then religion and ethnicity have NO impact at all on a person's Covid19 death risk once we know their age, underlying medical conditions, work/living conditions, and extent of social distancing.", "title": "A Note on UK Covid19 death rates by religion: which groups are most at risk?", "pid": "4aool4q0", "bm25_score": 212.70291137695312}, {"text": "It is well known that statistics using cumulative data are insensitive to changes. World Health Organization (WHO) estimates of fatality rates are of the above type, which may not be able to reflect the latest changes in fatality due to treatment or government policy in a timely fashion. Here, the authors propose an estimate of a real-time fatality rate based on a chain multinomial model with a kernel function. It is more accurate than the WHO estimate in describing fatality, especially earlier in the course of an epidemic. The estimator provides useful information for public health policy makers for understanding the severity of the disease or evaluating the effects of treatments or policies within a shorter time period, which is critical in disease control during an outbreak. Simulation results showed that the performance of the proposed estimator is superior to that of the WHO estimator in terms of its sensitivity to changes and its timeliness in reflecting the severity of the disease.", "title": "A Chain Multinomial Model for Estimating the Real-Time Fatality Rate of a Disease, with an Application to Severe Acute Respiratory Syndrome", "pid": "uy25ll4p", "bm25_score": 212.69549560546875}, {"text": "CoViD-19 deaths to population size ratios fail to account for well-documented age and sex differences in CoViD-19 mortality. To assess trends across populations for which CoViD-19 deaths might not be available by age and sex, an indirect age-and-sex adjustment can still be performed. The corresponding Comparative CoViD-19 Mortality Ratio (CCMR) only requires population age and sex compositions. To compare CoViD-19 and overall mortality levels, the Crude Death Rate (CDR) and life expectancy at birth for recent calendar years are the most widely available overall mortality indicators. Readily comparable to an annual CDR, a Crude CoViD-19 Death Rate (CCDR) can be calculated for periods of any duration. CoViD-19-induced declines in projected life expectancy at birth for 2020 can also be calculated from existing life tables. We calculate the CCMR and CCDR for the period from their first CoViD-19 death to the present using US age and sex data and current estimates of CoViD-19 deaths in 166 Countries whose population composition is available from the UN, 28 Provinces in China, the 50 United States and DC. Across these 245 populations, 14 States and 11 Countries have CCMR values above 1—the US value by construction. Most affected to date, the period CCDR in New York exceeds its CDR for the most recent year available (7.83 per thousand in 2017). We also calculate CCMR and CCDR values corresponding to projections for the 50 States and DC, and for 49 countries, for which we can additionally calculate reductions in 2020 life expectancy at birth using UN life tables. This suggests life-expectancy reductions between .5 and 1 year for 7 European Countries, 3 South-American Countries and the US. The .55 reduction in the U.S. amounts to nearly twice the largest single-year decline induced by HIV/AIDS (−.3 between 1992 and 1993) or the total decline induced by opioid overdoses (also −.3 between 2014 and 2017), and would bring US life expectancy at birth down to its lowest level since 2008. As current CoViD-19 death counts likely underestimate the total increase in deaths and current projections do not account for possible new infection waves later this year, the impact on 2020 life expectancies at birth should be expected to exceed these figures.", "title": "Beyond Deaths per Capita: Three CoViD-19 Mortality Indicators for Temporal and International Comparisons", "pid": "peg0m87x", "bm25_score": 212.691162109375}, {"text": "Objectives: Mortality from Covid-19 is monitored in detail both within as well as between countries with different strategies against the virus. However, death counts and relative risks based on crude numbers can be misleading. Instead, age specific death rates should be used for comparability. Given the difficulty of ascertainment of Covid-19 specific deaths, excess all-cause mortality is currently more appropriate for comparisons. By estimating age- and sex-specific death rates we aim to get more accurate estimates of the excess mortality attributed to Covid-19, as well as the difference between men and women in Sweden. Design: We make use of Swedish register data about total weekly deaths, total population at risk, and estimate age- and sex-specific weekly death rates for 2020 and the 5 previous years. The data is provided by Statistics Sweden. Results: From the first week of April and onwards, the death rates at all ages above 60 are higher than those in previous years in Sweden. Persons above age 80 are dis-proportionally more affected, and men suffer higher levels of excess mortality than women at all ages with 75% higher death rates for males and 50% higher for females. Current excess mortality corresponds to a decline in remaining life expectancy of 3 years for men and 2 years for women. Conclusion: The Covid-19 pandemic has so far had a clear and consistent effect on total mortality in Sweden, with male death rates being comparably more affected. What consequences the pandemic will eventually have on mortality and life expectancy will depend on the progression of the pandemic, the extent that some of the deaths would have occurred in the absence of the pandemic, only somewhat later, the consequences for other health conditions, as well as the health care sector at large.", "title": "EXCESS MORTALITY FROM COVID-19. WEEKLY EXCESS DEATH RATES BY AGE AND SEX FOR SWEDEN.", "pid": "0o3wjvpx", "bm25_score": 212.68655395507812}, {"text": "Purpose: To estimate influenza-associated excess mortality rates (EMRs) in Chongqing from 2012 to 2018.Methods: We obtained weekly mortality data for all-cause and four underlying causes of death (circulatory and respiratory disease (CRD), pneumonia and influenza (P&I), chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IDH)), and influenza surveillance data, from 2012 to 2018. A negative-binomial regression model was used to estimate influenza-associated EMRs in two age groups (<65 years and ≥65 years).Results: It was estimated that an annual average of 10025 influenza-associated deaths occurred in Chongqing, corresponding to 5.2% of all deaths. The average EMR for all-cause death associated with influenza was 33.5 (95% confidence interval (CI): 31.5-35.6) per 100 000 persons, and in separate cause-specific models we attributed 24.7 (95% CI: 23.3-26.0), 0.8 (95% CI: 0.7-0.8), 8.5 (95% CI: 8.1-9.0) and 5.0 (95% CI: 4.7-5.3) per 100 000 persons EMRs to CRD, P&I, COPD and IDH, respectively. The estimated EMR for influenza B virus was 20.6 (95% CI: 20.3-21.0), which was significantly higher than the rates of 5.3 (95% CI: 4.5-6.1) and 7.5 (95% CI: 6.7-8.3) for A(H3N2) and A(H1N1) pdm09 virus, respectively. The estimated EMR was 152.3 (95% CI: 136.1-168.4) for people aged ≥65 years, which was significantly higher than the rate for those aged <65 years (6.8, 95% CI: 6.3-7.2).Conclusions: Influenza was associated with substantial EMRs in Chongqing, especially among elderly people. Influenza B virus caused a relatively higher excess mortality impact compared with A(H1N1)pdm09 and A(H3N2). It is advisable to optimize future seasonal influenza vaccine reimbursement policy in Chongqing to curb disease burden.", "title": "Mortality burden from seasonal influenza in Chongqing, China, 2012-2018.", "pid": "3o75m5oq", "bm25_score": 212.684326171875}, {"text": "Governments around the world must rapidly mobilize and make difficult policy decisions to mitigate the coronavirus disease 2019 (COVID-19) pandemic. Because deaths have been concentrated at older ages, we highlight the important role of demography, particularly, how the age structure of a population may help explain differences in fatality rates across countries and how transmission unfolds. We examine the role of age structure in deaths thus far in Italy and South Korea and illustrate how the pandemic could unfold in populations with similar population sizes but different age structures, showing a dramatically higher burden of mortality in countries with older versus younger populations. This powerful interaction of demography and current age-specific mortality for COVID-19 suggests that social distancing and other policies to slow transmission should consider the age composition of local and national contexts as well as intergenerational interactions. We also call for countries to provide case and fatality data disaggregated by age and sex to improve real-time targeted forecasting of hospitalization and critical care needs.", "title": "Demographic science aids in understanding the spread and fatality rates of COVID-19", "pid": "haiuzuha", "bm25_score": 212.67735290527344}, {"text": "Background: Initial reports suggest that ethnic minorities may be experiencing more severe clinical outcomes of coronavirus disease 2019 (COVID19) infections. We therefore assessed the association between ethnic composition, income deprivation and COVID19 mortality rates in England. Methods: We performed a cross-sectional ecological analysis across upper tier local authorities in England. We assessed the association between the proportion of the population from Black, Asian and Minority Ethnic (BAME) backgrounds, income deprivation and COVID19 mortality rates using negative binomial regression models, whilst adjusting for population density, proportion of the population aged 50-79 and 80+ years, and the duration of the epidemic in each area. Findings: Local authorities with a greater proportion of residents from ethnic minority backgrounds had statistically significantly higher COVID19 mortality rates, as did local authorities with a greater proportion of residents experiencing deprivation relating to low income. After adjusting for income deprivation and other covariates, each percentage point increase in the proportion of the population from BAME backgrounds was associated with a 1% increase in the COVID19 mortality rate [IRR=1.01, 95%CI 1.01 to 1.02]. Each percentage point increase in the proportion of the population experiencing income deprivation was associated with a 2% increase in the COVID19 mortality rate [IRR=1.02, 95%CI 1.01 to 1.04]. Interpretation: This study provides evidence that both income deprivation and ethnicity are associated with greater COVID19 mortality. To reduce these inequalities governments need to target effective control measures at these disadvantaged communities, ensuring investment of resources reflects their greater need and vulnerability to the pandemic. Funding: National Institute of Health Research; Medical Research Council", "title": "Inequalities in COVID19 mortality related to ethnicity and socioeconomic deprivation", "pid": "kxsfyjdg", "bm25_score": 212.6505126953125}, {"text": "We perform a counterfactual time series analysis using two different Data Science methods applied to 2020 mortality data reported from towns in Italy, with data from the previous five years as control. We find an excess mortality that is correlated in time with the COVID-19 reported death rate time series. Our analysis shows good agreement with reported COVID-19 mortality for age<70 years, but an excess in total mortality increasing with age above 70 years, suggesting there is a large population of predominantly old people missing from the official fatality statistics. We estimate that the number of COVID-19 deaths in Italy is 52,000 ± 2000 as of April 18 2020, more than a factor of 2 higher than the official number. The Population Fatality Rate (PFR) has reached 0.22% in the most affected region of Lombardia and 0.57% in the most affected province of Bergamo,which constitutes a lower bound to the Infection Fatality Rate (IFR). We estimate PFR as a function of age, finding a steep age dependence: in Lombardia (Bergamo province) 0.6% (1.7%) of the total population in age group 70-79 died, 1.6% (4.6%) in age group 80-89, and 3.41% (10.2%) in the age group above 90. We combine this with the Test Positivity Rate to estimate the lower bound of 0.84% on the IFR for Lombardia. We observe IFR to trace the Yearly Mortality Rate (YMR) above 60 years, which can be used to estimate the IFR for other regions in the world. We predict an IFR lower bound of 0.5% for NYC and 26% of total COVID-19 mortality arising from the population below 65 years, in agreement with the existing data and several times higher than Lombardia. Combining PFR with the Princess Diamond cruise ship IFR for ages above 70 we estimate the infection rates(IR) of regions in Italy, which peak in Lombardia at 23% (12%-41%, 95% c.l.), and for provinces in Bergamo at 67% (33%-100%, 95% c.l.). This suggests that Bergamo may have reached herd immunity, and that the number of infected people greatly exceeds the number of positive tests, by a factor of 35 in Lombardia.", "title": "Total COVID-19 Mortality in Italy: Excess Mortality and Age Dependence through Time-Series Analysis", "pid": "vg96f35h", "bm25_score": 212.6390838623047}, {"text": "All measures of health status are ultimately derived from observations of individuals. At the field level we have such measures as self-assessed health status, report of a specific disease, record of a particular death, or an individual’s test on a biomarker, such as blood pressure or serum cholesterol. The observations for individuals are combined and summarized to represent subnational geographic areas, demographic or socioeconomic groups within countries, or national populations. The summary measures, whether they are percentages, averages, or rates, apply to groups. A problem arises when the measures that are based on groups are assumed to represent individuals. The analysis becomes especially problematic when the units analyzed are geographic areas and inferences are being made about individuals from the analysis for these geographic areas.", "title": "Health Inequalities, General Trends in Mortality and Morbidity, and Associated Factors", "pid": "cqlt5mq2", "bm25_score": 212.63385009765625}, {"text": "The Covid-19 pandemic brings major new challenges to health services resulting from the lack of a vaccine and from the enormous resources it can consume over a prolonged period. The available control measures are currently limited to quarantining, contact tracking-and-tracing and social distancing. Disease transmission to health care workers is common and deaths among clinical and nursing staff have been reported in the UK (where serious concerns about the availability of personal protective equipment - PPE - have been raised) and elsewhere; particularly in Lombardy, where General Practitioners (Medici di Base) have died in disproportionate numbers.", "title": "Mortality rates from COVID-19 in Spain and Italy, Lessons for the UK!", "pid": "do444pph", "bm25_score": 212.63153076171875}, {"text": "In 2001, heart disease accounted for approximately 29.0% of deaths among U.S. residents; 16.8% of those deaths occurred among persons aged <65 years. Although mortality rates from heart disease have decreased, the decline has not been uniform for all populations. One of the two overall national health objectives for 2010 is to eliminate health disparities among different segments of the U.S. population. To better understand these disparities, CDC analyzed death certificate data for premature deaths from heart disease occurring in 2001. This report summarizes the results of that analysis, which indicated that the proportion of premature heart disease deaths varied by state and was higher among blacks, American Indians/Alaska Natives (AI/ANs), Asians/Pacific Islanders (A/PIs), and Hispanics. Reducing premature death from heart disease and eliminating disparities will require preventing, detecting, treating, and controlling risk factors for heart disease in young and middle-aged adults.", "title": "Disparities in premature deaths from heart disease--50 States and the District of Columbia, 2001.", "pid": "03q86e1d", "bm25_score": 212.62928771972656}, {"text": "Governments around the world must rapidly mobilize and make difficult policy decisions to mitigate the COVID-19 pandemic. Because deaths have been concentrated at older ages, we highlight the important role of demography, particularly how the age structure of a population may help explain differences in fatality rates across countries and how transmission unfolds. We examine the role of age structure in deaths thus far in Italy and South Korea and illustrate how the pandemic could unfold in populations with similar population sizes but different age structures, showing a dramatically higher burden of mortality in countries with older versus younger populations. This powerful interaction of demography and current age-specific mortality for COVID-19 suggests that social distancing and other policies to slow transmission should consider both the age composition of local and national contexts as well as the social connectedness of older and younger generations. We also call for countries to provide case and fatality data disaggregated by age and sex to improve real-time targeted nowcasting.", "title": "Demographic science aids in understanding the spread and fatality rates of COVID-19", "pid": "gv8wlo06", "bm25_score": 212.62435913085938}, {"text": "The current COVID‐19 outbreak has raised many questions, amongst them the higher mortality rates in men and the low overall mortality rates in Germany compared to other European countries. Here the authors explore some of the reasons behind both these phenomena and outline what we can learn from them for the future.", "title": "Male mortality and the German response: lessons from COVID‐19", "pid": "2vxnmiyj", "bm25_score": 212.62380981445312}, {"text": "Abstract Background: The SARS-CoV-2 virus has spread all over the world infecting more than 3,585,936 people from over 210 countries and caused more than 245,803 deaths worldwide. We report the first epidemiological, socio-demographic, and clinical findings for the first 9,468 confirmed COVID-19 cases in Ecuador. Methods: We conducted a descriptive cross-sectional analysis of 9,468 COVID-19 confirmed cases in Ecuador from 27 February to 18 April 2020. The overall incidence, mortality, and case fatality rate was computed according to the entire population at risk living in a canton or a province. Disability adjusted life years, attack and crude mortality rates as well as relative risk and odds ratios were computed as an outcome. Results: Since the first case reported in Ecuador on 27 Feb 2020, at least 9,468 positive COVID-19 cases of which 474 deaths were officially registered over a 54-day period. Men accounted for 55.40% (n = 5, 247) of the overall cases with an incidence rate of 60.5 per 100,000 while women accounted for 44.60 % (n = 4, 221) representing 47.2 per 100,000. The mortality rate per canton showed that cantons with a lower attack rate had higher mortality rates. Coastal cantons have a lower attack rate than the highlands and living above >2,500 m seems to be linked with a lower risk of dying (RR: 0.63 [CI 95% 0.50 - 0.79]). Fatigue was reported in 53.2% of the patients, followed by headache (43%), dry cough (41.7%), ageusia (37.1%) and anosmia (36.1%). Conclusion: This study is the first of its kind in Ecuador. The results of this analysis show that men are at higher risk of dying from COVID-19 than women, which increases as with age and the presence of comorbidities. Areas with better testing capabilities reported lower CFR% and mortality, additionally cantons located above 2,500 m have lower attack and mortality rates although the risk of dying is greater among highlanders. Keywords: COVID-19; SARS-CoV-2; Ecuador; Epidemiology; Latin America", "title": "Epidemiological, socio-demographic and clinical features of the early phase of the COVID-19 epidemic in Ecuador", "pid": "rrohv3to", "bm25_score": 212.62109375}, {"text": "Background: Health disparities were often overlooked during the emerging epidemic. Objectives: This study examined geographic differences in the rates of health care use and deaths among elderly patients. Methods: Based on individual patient records, multivariate Poisson and logistic models were used to calculate adjusted incidences of COVID-19 and probabilities of emergency department (ED) visits, hospitalizations and deaths. Results: Of 8,203 elderly patients, 11% died. Elderly people living in small metropolitan areas were half as likely to be diagnosed with COVID-19. Elderly female patients living in small metropolitan areas had much lower rates of ED visits (23% vs. 34%; Odds Ratio (OR): 0.58; 95%confidence interval (CI): 0.41-0.81; p=0.002) and hospitalizations (22% vs. 31%; OR: 0.62; 95%CI: 0.44 - 0.87; p=0.006) than those living in large metropolitan areas. Furthermore, those living in non-metropolitan areas were more likely to be hospitalized than those living in large metropolitan areas (44% vs. 33%; OR: 1.46; 95%CI: 1.07-1.99; p=0.016), especially among elderly men (51% vs. 35%; OR:1.86; 95%CI: 1.18-2.93; p=0.008). Finally, there was a significant linear trend in hospitalization rates among elderly male patients (p for trend = 0.01). Conclusions: Profound health disparities exist in the time of emerging epidemic.", "title": "Did elderly people living in small towns or rural areas suffer heavier disease burden during the COVID-19 epidemic?", "pid": "m71rwh67", "bm25_score": 212.62094116210938}, {"text": "INTRODUCTION: On March 13, 2020 the WHO declared COVID-19 a pandemic. Shortly after that, it was reported that mortality rates in New York City (NYC), the epicenter of the pandemic in the United States, were found to be significantly higher in African American and Hispanics. The aim of this manuscript is to evaluate the mortality rates in NYC among the different ethnic groups and the different boroughs as it relates to the obesity rates to see whether this issue merits further evaluation. METHODS: COVID-19 data was obtained from the official New York (NY) authorities in relation to total number of cases in the different boroughs of NYC. Age adjusted COVID-19 related mortality rates of the different ethnic groups were also obtained. This data was cross compared to historic community health data on obesity rates previously published and also obesity rates among the different ethnic groups in NYC. RESULTS: The two NYC boroughs that have the highest mortality rates are The Bronx (6%) and Brooklyn (5.4%). Both The Bronx and Brooklyn were also found to have the highest obesity rates 32% and 27% respectively. The two ethnic groups with the highest obesity rates (Hispanics and African Americans) were also found to have the highest age adjusted mortality rates per 100,000 compared to the other ethnic groups (22.8% and 19.8% respectively). CONCLUSION: Hispanics and African Americans in NYC seem to be disproportionately affected by the COVID-19 pandemic because of the higher incidence of mortality rates. Obesity may have played a role in the high incidence of mortality in those ethnic groups.", "title": "Are African American and Hispanics Disproportionately Affected by COVID-19 Because of Higher Obesity Rates?", "pid": "fvkr77sf", "bm25_score": 212.58316040039062}, {"text": "Background The role of health-related disparities including sociodemographic, environmental, and critical care capacity in the COVID-19 pandemic are poorly understood. In the present study, we characterized vulnerable populations located in areas at higher risk of COVID-19 related mortality and low critical healthcare capacity in the U.S. Methods Using Bayesian multilevel analysis and small area disease risk mapping, we assessed the spatial variation of COVID-19 related mortality risk for the U.S. in relation with healthcare disparities including race, ethnicity, poverty, air quality, and critical healthcare capacity. Results Overall, highly populated, regional air hub areas, and minorities had an increased risk of COVID-19 related mortality. We found that with an increase of only 1 ug/m3 in long term PM2.5 exposure, the COVID-19 mortality rate increased by 13%. Counties with major air hubs had 18% increase in COVID-19 related death compared to counties with no airport connectivity. Sixty-eight percent of the counties with high COVID-19 related mortality risk were also counties with lower critical care capacity than national average. These counties were primary located at the North- and South-Eastern regions of the country. Conclusion The existing disparity in health and environmental risk factors that exacerbate the COVID-19 related mortality, along with the regional healthcare capacity, determine the vulnerability of populations to COVID-19 related mortality. The results from this study can be used to guide the development of strategies for the identification and targeting preventive strategies in vulnerable populations with a higher proportion of minority groups living in areas with poor air quality and low healthcare capacity.", "title": "Identification of Vulnerable Populations and Areas at Higher Risk of COVID-19 Related Mortality in the U.S.", "pid": "0j6a5xqc", "bm25_score": 212.57493591308594}, {"text": "BACKGROUND: New York City emerged as an epicenter of the coronavirus disease 2019 (COVID-19) pandemic. OBJECTIVE: To describe the clinical characteristics and risk factors associated with mortality in a large patient population in the USA. DESIGN: Retrospective cohort study. PARTICIPANTS: 6493 patients who had laboratory-confirmed COVID-19 with clinical outcomes between March 13 and April 17, 2020, who were seen in one of the 8 hospitals and/or over 400 ambulatory practices in the New York City metropolitan area MAIN MEASURES: Clinical characteristics and risk factors associated with in-hospital mortality. KEY RESULTS: A total of 858 of 6493 (13.2%) patients in our total cohort died: 52/2785 (1.9%) ambulatory patients and 806/3708 (21.7%) hospitalized patients. Cox proportional hazard regression modeling showed an increased risk of in-hospital mortality associated with age older than 50 years (hazard ratio [HR] 2.34, CI 1.47-3.71), systolic blood pressure less than 90 mmHg (HR 1.38, CI 1.06-1.80), a respiratory rate greater than 24 per min (HR 1.43, CI 1.13-1.83), peripheral oxygen saturation less than 92% (HR 2.12, CI 1.56-2.88), estimated glomerular filtration rate less than 60 mL/min/1.73m2 (HR 1.80, CI 1.60-2.02), IL-6 greater than 100 pg/mL (HR 1.50, CI 1.12-2.03), D-dimer greater than 2 mcg/mL (HR 1.19, CI 1.02-1.39), and troponin greater than 0.03 ng/mL (HR 1.40, CI 1.23-1.62). Decreased risk of in-hospital mortality was associated with female sex (HR 0.84, CI 0.77-0.90), African American race (HR 0.78 CI 0.65-0.95), and hydroxychloroquine use (HR 0.53, CI 0.41-0.67). CONCLUSIONS: Among patients with COVID-19, older age, male sex, hypotension, tachypnea, hypoxia, impaired renal function, elevated D-dimer, and elevated troponin were associated with increased in-hospital mortality and hydroxychloroquine use was associated with decreased in-hospital mortality.", "title": "Risk Factors for Mortality in Patients with COVID-19 in New York City", "pid": "ciqhdft3", "bm25_score": 212.56227111816406}, {"text": "Using the Irish experience of the Spanish flu, we demonstrate that pandemic mortality statistics are sensitive to the demographic composition of a country. We build a new demographic database for Ireland's 32 counties with vital statistics on births, ageing, migration and deaths. We then show how age-at-death statistics in 1918 and 1919 should be reinterpreted in light of these data. Our new estimates suggest the very young were most impacted by the flu. New studies of the economic impact of Influenza-18 must better control for demographic factors if they are to yield useful policy-relevant results. Covid-19 mortality statistics must go through a similar procedure so policymakers can better target their public health interventions.", "title": "Death, Demography and the Denominator:New Influenza-18 Mortality Estimates for Ireland", "pid": "hyz6fwt9", "bm25_score": 212.558837890625}, {"text": "Different ways of calculating mortality ratios during epidemics have yielded very different results, particularly during the current COVID-19 pandemic. We formulate both a survival probability model and an associated infection duration-dependent SIR model to define individual- and population-based estimates of dynamic mortality ratios. The key parameters that affect the dynamics of the different mortality estimates are the incubation period and the time individuals were infected before confirmation of infection. We stress that none of these ratios are accurately represented by the often misinterpreted case fatality ratio (CFR), the number of deaths to date divided by the total number of confirmed infected cases to date. Using data on the recent SARS-CoV-2 outbreaks, we estimate and compare the different dynamic mortality ratios and highlight their differences. Informed by our modeling, we propose more systematic methods to determine mortality ratios during epidemic outbreaks and discuss sensitivity to confounding effects and uncertainties in the data.", "title": "Why case fatality ratios can be misleading: individual- and population-based mortality estimates and factors influencing them", "pid": "1tc6i94v", "bm25_score": 212.55287170410156}, {"text": "Internationally, health authorities and governments are warning older people that they are at a higher risk of more serious and possible fatal illness associated with COVID-19. Mortality data from Oxford COVID-19 Evidence Service (25/3/20) indicates a risk of mortality of 3.6% for people in their 60s, which increases to 8.0% and 14.8% for people in their 70s and over 80s. Therefore, the global recommendation for older populations includes social isolation, which involves staying at home and avoiding contact with other people, possibly for an extended period of time, currently estimated to be between three and four months. Older populations in this current context, refers to people over 70 years, and 50 years in some particularly vulnerable Indigenous populations.", "title": "Older people and COVID-19: Isolation, risk and ageism.", "pid": "vare9x8g", "bm25_score": 212.54188537597656}, {"text": "Pandemics tend to have higher occurrence (morbidity) in younger individuals but higher mortality for the elderly. The higher rate of mortality of COVID-19 in elderly individuals has been discussed in many reports. However, this pandemic is a double-edged sword as this comment shows higher morbidity rates in elderly as well. This is shown by comparing the age distribution of cases in China and South Korea to the relative populations. In every case, the relative number of elderly contracting the virus is far higher than the proportion of elderly in the population. This is unlike past pandemics and shows that aging populations are at an even higher risk than the perceived age dependent rates may imply.", "title": "On Determining the Age Distribution of COVID-19 Pandemic", "pid": "ldv9hsv1", "bm25_score": 212.54151916503906}, {"text": "This paper highlights the relevance of age-specific hazard rates in explaining the age variation in “value of statistical life” (VSL) figures. The analysis—which refers to a stated preference framework—contributes to the ongoing discussion of whether benefits resulting from reduced mortality risk should be valued differently depending on the age of the beneficiaries. By focussing on a life-threatening environmental phenomenon I show that the consideration of the individual’s age-specific hazard rate is important. If a particular risk affects all individuals regardless of their age so that their hazard rate is age-independent, VSL is rather constant for people at different age; if hazard rate varies with age, VSL estimates are sensitive to age. The results provide an explanation for the mixed outcomes in empirical studies and illustrate in which cases an adjustment to age may or may not be justified. Efficient provision of live-saving measures requires that such differences to be taken into account.", "title": "Age effects in monetary valuation of reduced mortality risks: the relevance of age-specific hazard rates", "pid": "um9kefk4", "bm25_score": 212.53550720214844}, {"text": "Objective: To model how known COVID-19 comorbidities will affect mortality rates and the age distribution of mortality in a large lower middle income country (India), as compared with a high income country (England), and to identify which health conditions drive any differences. Design: Modelling study. Setting: England and India. Participants: 1,375,548 respondents aged 18 to 99 to the District Level Household Survey-4 and Annual Health Survey in India. Additional information on health condition prevalence on individuals aged 18 to 99 was obtained from the Health Survey for England and the Global Burden of Diseases, Risk Factors, and Injuries Studies (GBD). Main outcome measures: The primary outcome was the proportional increase in age-specific mortality in each country due to the prevalence of each COVID-19 mortality risk factor (diabetes, hypertension, obesity, chronic heart disease, respiratory illness, kidney disease, liver disease, and cancer, among others). The combined change in overall mortality and the share of deaths under 60 from the combination of risk factors was estimated in each country. Results: Relative to England, Indians have higher rates of diabetes (10.6% vs. 8.5%), chronic respiratory disease (4.8% vs. 2.5%), and kidney disease (9.7% vs. 5.6%), and lower rates of obesity (4.4% vs. 27.9%), chronic heart disease (4.4% vs. 5.9%), and cancer (0.3% vs. 2.8%). Population COVID-19 mortality in India relative to England is most increased by diabetes (+5.4%) and chronic respiratory disease (+2.3%), and most reduced by obesity (-9.7%), cancer (-3.2%), and chronic heart disease (-1.9%). Overall, comorbidities lower mortality in India relative to England by 9.7%. Accounting for demographics and population health explains a third of the difference in share of deaths under age 60 between the two countries. Conclusions: Known COVID-19 health risk factors are not expected to have a large effect on aggregate mortality or its age distribution in India relative to England. The high share of COVID-19 deaths from people under 60 in low- and middle-income countries (LMICs) remains unexplained. Understanding mortality risk associated with health conditions prevalent in LMICs, such as malnutrition and HIV/AIDS, is essential for understanding differential mortality. Keywords: COVID-19, India, low- and middle-income countries, comorbidity", "title": "The COVID-19 mortality effects of underlying health conditions in India: a modelling study", "pid": "ekaqbruo", "bm25_score": 212.53463745117188}, {"text": "We used a regression model to examine the impact of influenza on death rates in tropical Singapore for the period 1996–2003. Influenza A (H3N2) was the predominant circulating influenza virus subtype, with consistently significant and robust effect on mortality rates. Influenza was associated with an annual death rate from all causes, from underlying pneumonia and influenza, and from underlying circulatory and respiratory conditions of 14.8 (95% confidence interval 9.8–19.8), 2.9 (1.0–5.0), and 11.9 (8.3–15.7) per 100,000 person-years, respectively. These results are comparable with observations in the United States and subtropical Hong Kong. An estimated 6.5% of underlying pneumonia and influenza deaths were attributable to influenza. The proportion of influenza-associated deaths was 11.3 times higher in persons age >65 years than in the general population. Our findings support the need for influenza surveillance and annual influenza vaccination for at-risk populations in tropical countries.", "title": "Influenza-associated Deaths in Tropical Singapore", "pid": "suw7yov6", "bm25_score": 212.52755737304688}, {"text": "", "title": "Morbidity and mortality.", "pid": "7sddz7ck", "bm25_score": 212.52731323242188}, {"text": "Introduction Non-specific effects of vaccines have gained increasing interest during the Covid-19 pandemic. In particular, population use of BCG vaccine has been associated with improved outcomes. This study sought to determine the association of population use of BCG, adult pneumococcal and adult seasonal influenza vaccination with Covid-19 mortality when adjusted for a number of confounding variables. Methods: Using publicly available data, mortality adjusted for the timeframe of crisis, population size and population characteristics was calculated. The primary analysis was the relationship between each of the day 15 and day 30 standardised mortality rates and BCG, adult pneumococcal and influenza vaccination scores using unadjusted measures and with adjustment for population structure and case fatality rates. Secondary analyses were measures of case increases and mortality increases from day 15 to day 30 for each of the relative vaccination scores. Finally, we also analysed the peak Z score reflecting increases in total mortality from historical averages reported by EuroMOMO (Euromomo.eu), Results: Following adjustment for the effects of population size, median age, population density, the proportion of population living in an urban setting, life-expectancy, the elderly dependency ratio (or proportion over 65 years), net migration, days from day 1 to lockdown and case-fatality rate, only BCG vaccination score remained significantly associated with Covid-19 mortality at day 30. In the best fit model, BCG vaccination score was associated with a 64% reduction in log(10) mortality per 10 million population (OR 0.362 reduction [95% CI 0.188 to 0.698]), following adjustment for population size, median age, density, urbanization, elderly dependency ratio, days to lockdown, yearly migration and case fatality rate. Conclusion BCG vaccine was associated with reduced mortality rates in level 4 countries while adult pneumococcal and adult seasonal influenza vaccines were not when adjusted for a number of confounding variables. A number of trials are ongoing to determine if BCG is protective against severe Covid-19 infection.", "title": "Association of Bacille Calmette-Guerin (BCG), Adult Pneumococcal and Adult Seasonal Influenza Vaccines with Covid-19 Adjusted Mortality Rates in Level 4 European countries", "pid": "leu2hygk", "bm25_score": 212.52113342285156}, {"text": "The purpose of this paper is to review the major sources of data on mortality, morbidity and health in Europe and in other developed regions in order to examine their potential for analysing mortality and morbidity levels and trends. The review is primarily focused on routinely collected information covering a whole country. No attempt is made to draw up an inventory of sources by country; the paper deals instead with the pros and cons of each source for mortality and morbidity studies in demography. While each source considered separately can already yield useful, though partial, results, record linkage among data sources can significantly improve the analysis. Record linkage can also lead to the detection of possible causal associations that could eventually be confirmed. More generally, Big Data can reveal changing mortality and morbidity trends and patterns that could lead to preventive measures being taken rather than more costly curative ones.", "title": "Mortality, morbidity and health in developed societies: a review of data sources", "pid": "cs9zddms", "bm25_score": 212.51235961914062}, {"text": "BACKGROUND: The 16 Southern Africa Development Community (SADC) countries remain the epicentre of the HIV/AIDS epidemic with the largest number of people living with HIV/AIDS. Anti-retroviral treatment (ART) has improved survival and prevention of mother-to-child transmission (PMTCT) of HIV, but the disease remains a serious cause of mortality. We conducted a descriptive epidemiological analysis of HIV/AIDS burden for the 16 SADC countries using secondary data from the Global Burden of Diseases, Injuries and Risk Factor (GBD) Study. METHODS: The GBD study is a systematic, scientific effort by the Institute for Health Metrics and Evaluation (IHME) to quantify the comparative magnitude of health loss due to diseases, injuries, and risk factors by age, sex, and geographies for specific points in time. We analyzed the following outcomes: mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to HIV/AIDS for SADC. Input data for GBD was extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service utilisation, disease notifications, and other sources. Country- and cause-specific HIV/AIDS-related death rates were calculated using the Cause of Death Ensemble model (CODEm) and spatiotemporal Gaussian process regression (ST-GPR). Deaths were multiplied by standard life expectancy at each age-group to calculate YLLs. Cause-specific mortality was estimated using a Bayesian meta-regression modelling tool, DisMod-MR. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases to calculate YLDs. Crude and age-adjusted rates per 100,000 population and changes between 1990 and 2017 were determined for each country. RESULTS: In 2017, HIV/AIDS caused 336,175 deaths overall in SADC countries, and more than 20 million DALYs. This corresponds to a 3-fold increase from 113,631 deaths (6,915,170 DALYs) in 1990. The five leading countries with the proportion of deaths attributable to HIV/AIDS in 2017 were Botswana at the top with 28.7% (95% UI; 23.7–35.2), followed by South Africa 28.5% (25.8–31.6), Lesotho, 25.1% (21.2–30.4), eSwatini 24.8% (21.3–28.6), and Mozambique 24.2% (20.6–29.3). The five countries had relative attributable deaths that were at least 14 times greater than the global burden of 1.7% (1.6–1.8). Similar patterns were observed with YLDs, YLLs, and DALYs. Comoros, Seychelles and Mauritius were on the lower end, with attributable proportions less than 1%, below the global proportion. CONCLUSIONS: Great progress in reducing HIV/AIDS burden has been achieved since the peak but more needs to be done. The post-2005 decline is attributed to PMTCT of HIV, resources provided through the US President’s Emergency Plan For AIDS Relief (PEPFAR), and behavioural change. The five countries with the highest burden of HIV/AIDS as measured by proportion of death attributed to HIV/AIDS and age-standardized mortaility rate were Botswana, South Africa, Lesotho, eSwatini, and Mozambique. SADC countries should cooperate, work with donors, and embrace the UN Fast-Track approach, which calls for frontloading investment from domestic or other sources to prevent and treat HIV/AIDS. Robust tracking, testing, and early treatment are required, as well as refinement of individual treatment strategies for transient individuals in the region.", "title": "Burden and changes in HIV/AIDS morbidity and mortality in Southern Africa Development Community Countries, 1990–2017", "pid": "hs9cfdsu", "bm25_score": 212.50689697265625}, {"text": "Age-adjusted mortality rates for coronary heart disease (CHD) have declined steadily in the United States since the 1960s. Multiple factors likely have contributed to this decline in CHD deaths, including greater control of risk factors, resulting in declining incidence of CHD, and improved treatment. Greater control of risk factors and declining incidence can reduce CHD prevalence, whereas improved treatment that results in lower mortality rates and more persons living with CHD can increase prevalence. To estimate state-specific CHD prevalence and recent trends by age, sex, race/ethnicity, and education, CDC analyzed data from Behavioral Risk Factor Surveillance System (BRFSS) surveys for the period 2006-2010. This report summarizes the results of that analysis, which determined that, although self-reported CHD prevalence declined overall, substantial differences in prevalence existed by age, sex, race/ethnicity, education, and state of residence. These data can enable state and national health agencies to monitor CHD prevalence as a measure of progress toward meeting the Healthy People 2020 objective to reduce the U.S. rate of CHD deaths 20% from the 2007 baseline.", "title": "Prevalence of coronary heart disease--United States, 2006-2010.", "pid": "puzk6p4v", "bm25_score": 212.47911071777344}, {"text": "There has been extensive speculation on the apparent differences in mortality between countries reporting on the confirmed cases and deaths due to Covid-19. A number of explanations have been suggested, but there is no clear evidence about how apparent fatality rates may be expected to vary with the different testing regimes, admission policies and other variables. An individual patient simulation model was developed to address this question. Parameters and sensitivity analysis based upon recent international data sources for Covid-19 and results were averaged over 100 iterations for a simulated cohort of over 500,000 patients. Different testing regimes for Covid-19 were considered; testing admitted patients only, various rates of community testing of symptomatic cases and active contact-tracing and screening. In the base case analysis, apparent mortality ranged from 10.5% under a policy of testing only admitted patients to 0.4% with intensive contact tracing and community testing. These findings were sensitive to assumptions regarding admission rates and the rate of spread, with more selective admission policies and suppression of spread increasing the apparent mortality and the potential for apparent mortality rates to exceed 18% under some circumstances. Under all scenarios the proportion of patients tested in the community had the greatest impact on apparent mortality. Whilst differences in mortality due to health service and demographic factors cannot be excluded, the current international differences in reported mortality are all consistent with differences in practice regarding screening, community testing and admission policies.", "title": "Explaining national differences in the mortality of Covid-19: individual patient simulation model to investigate the effects of testing policy and other factors on apparent mortality.", "pid": "gkd1h8yi", "bm25_score": 212.47811889648438}, {"text": "The true infection rate of COVID-19 and the infection fatality rate in the whole population have been estimated for each country. The estimate well coincided with local surveys. The fact that several tens of times, or more, of identified cases are already infected might require reconsideration of the strategy.", "title": "Estimation of the true infection rate and infection fatality rate of COVID-19 in the whole population of each country", "pid": "yjny2xcf", "bm25_score": 212.46319580078125}, {"text": "Covid-19 deaths and positive cases show a remarkable heterogeneity across countries which cannot be easily explained on the basis of similarities or differences in the quality of healthcare, access to healthcare, testing facilities, or preventive measures such as lockdowns. Here we show that there is a distinct correlation between the mortality level and the infection level across countries, which can explain the mortality levels for a wide spectrum of countries. This implies that the number of deaths per 100 infected individuals is approximately the same across diverse countries and can be estimated from the slope of the mortality level-infection level plot. The correlation presented here can potentially be combined with estimates of infection spread to forecast future mortality levels and therefore future needs in terms of healthcare and other resources. Tracking of an individual locations temporal path on this plot can potentially serve as a visual assessment of the nature of the epidemic. Methods presented here are not specific to the current epidemic. This is a preliminary report and uses data from a single source at a single time-point to demonstrate the capability of such an analysis.", "title": "Correlating Covid-19 mortality and infection levels", "pid": "svk4cstf", "bm25_score": 212.42990112304688}, {"text": "Objective To estimate the infection fatality rate of coronavirus disease 2019 (COVID-19) from data of seroprevalence studies. Methods Population studies with sample size of at least 500 and published as peer-reviewed papers or preprints as of May 12, 2020 were retrieved from PubMed, preprint servers, and communications with experts. Studies on blood donors were included, but studies on healthcare workers were excluded. The studies were assessed for design features and seroprevalence estimates. Infection fatality rate was estimated from each study dividing the number of COVID-19 deaths at a relevant time point by the number of estimated people infected in each relevant region. Correction was also attempted accounting for the types of antibodies assessed. Results Twelve studies were identified with usable data to enter into calculations. Seroprevalence estimates ranged from 0.113% to 25.9% and adjusted seroprevalence estimates ranged from 0.309% to 33%. Infection fatality rates ranged from 0.03% to 0.50% and corrected values ranged from 0.02% to 0.40%. Conclusions The infection fatality rate of COVID-19 can vary substantially across different locations and this may reflect differences in population age structure and case-mix of infected and deceased patients as well as multiple other factors. Estimates of infection fatality rates inferred from seroprevalence studies tend to be much lower than original speculations made in the early days of the pandemic.", "title": "The infection fatality rate of COVID-19 inferred from seroprevalence data", "pid": "po32j519", "bm25_score": 212.4238739013672}, {"text": "There is established and consistent findings from epidemiologic studies, among individuals, that religion— broadly assessed through frequency of attending worship services—is associated with lower all-cause and cause-specific mortality attributed to suicide, alcohol, cardiovascular disease and cancer. Religious norms, social support, character, virtue, compassion, love, generosity, and religious community are among some mechanisms purported to explain lower mortality, on aggregate. The religious ecology or characteristics of religion within an area or geographic level (e.g., county, ZIP-code, country), has been linked with overall and cause-specific mortality, but directions of findings are mixed. Mechanisms to explain the links between the religious ecology and mortality included social integration, civic engagement, and social control. The manuscript (SSM-D-19-03928R2) adds a fresh and timely perspective by investigating another mechanism: investment in local healthcare spending. The study found some support of an indirect association from county-level religious denominational composition, through investments in health spending, on Black and White all-cause mortality rates. Should society or government invest finances in religious institutions to indirectly improve population health? This work adds evidence to debate that question. Future work on the topic will need to address several conceptual and methodological challenges. Conceptually, is investigating the market share of religious denominations (i.e., % Catholics vs % Protestants) relevant today given diversity in population and declining trends of worship attendance? Is mortality the most relevant for moving policy or should the focus be on well-being? Methodologically, are there alternate observable measures religious investments/spending in the local economy? Mechanisms, challenges, and opportunities for social epidemiology research on this topic are discussed.", "title": "Is investing in religious institutions a viable pathway to reduce mortality in the population?", "pid": "l42w2jyk", "bm25_score": 212.41766357421875}, {"text": "As reporting of COVID‐19 at the US state level has become more granular, many states have reported a higher proportion of deaths among African‐Americans. In our study, we assessed state level data on race, population density, age, obesity rates, insurance data, GDP, per capita healthcare resources (hospital‐beds/ventilators per‐capita), median household income and high‐school graduation rates. We report a higher death rate among states with a greater proportion of African‐American residents despite adjusting for case rates and state‐level factors. To the best of our knowledge this is the first study looking at state level data (from across the US) and mortality with COVID‐19. This article is protected by copyright. All rights reserved.", "title": "Differences in race and other state‐level characteristics and associations with mortality from COVID‐19 infection", "pid": "rxgnrrx8", "bm25_score": 212.4169464111328}, {"text": "Homicide disproportionately affects persons aged 10-24 years in the United States and consistently ranks in the top three leading causes of death in this age group, resulting in approximately 4,800 deaths and an estimated $9 billion in lost productivity and medical costs in 2010. To investigate trends in homicide among persons aged 10-24 years for the period 1981-2010, CDC analyzed National Vital Statistics System data on deaths caused by homicide of persons in this age group and examined trends by sex, age, race/ethnicity, and mechanism of injury. This report describes the results of that analysis, which indicated that homicide rates varied substantially during the study period, with a sharp rise from 1985 to 1993 followed by a decline that has slowed since 1999. During the period 2000-2010, rates declined for all groups, although the decline was significantly slower for males compared with females and for blacks compared with Hispanics and persons of other racial/ethnic groups. By mechanism of injury, the decline for firearm homicides from 2000 to 2010 was significantly slower than for nonfirearm homicides. The homicide rate among persons aged 10-24 years in 2010 was 7.5 per 100,000, the lowest in the 30-year study period. Primary prevention strategies remain critical, particularly among groups at increased risk for homicide.", "title": "Homicide rates among persons aged 10-24 years - United States, 1981-2010.", "pid": "fpz3aikk", "bm25_score": 212.4124755859375}, {"text": "ABSTRACT Objective: Analyze a set of indicators to understand the variability of the evolution and impact of the COVID-19 epidemic in a set of selected countries. Method: Ecological study of a group of countries with more than 200 reported cases. Demographic variables, health expenditure variables, and variables about characteristics of health services were included as explanatory variables. and incidence, mortality and fatality rates have been analyzed as response variables. In addition, a relative fatality index has been created. Data are from international organizations. Spearman's correlation coefficient was used to estimate the magnitude of the associations. Results: Number of tests and of medical professionals are associated with a higher incidence rate. Mortality and case fatality rate are not associated with demographic, health expenditure, or health services variables. Conclusion: Differences suggest a general underestimation of the magnitude of the epidemic. Improvement of case identification and effectiveness of epidemiological surveillance systems is necessary.", "title": "Letalidad del COVID-19: ausencia de patrón epidemiológico", "pid": "earli6ww", "bm25_score": 212.41162109375}, {"text": "Background/Purpose Controversy exists in the literature regarding whether dentists with multiple occupational exposures suffer from premature mortality. A cohort mortality study was conducted to evaluate the survival outcome and determine if potential exposure to harmful agents leads to premature mortality among dentists. Methods Using the Life Table Analysis System, we calculated standardized mortality ratios (SMRs) for a cohort of 11,700 dentists affiliated with the Taiwan Dental Association. These dentists were followed from 1985–2009. Reference rates were derived from cause-, gender-, and age-specific mortality rates of the general population of Taiwan and 18,664 Taiwanese internists, who were considered to be more socioeconomically proximal to dentists. A Cox proportional hazard model was also constructed to determine multiple risk factors associated with mortality. Results Compared with the general population, dentists in Taiwan consistently demonstrated reduced from all-cause mortality. However, compared with internists, significant and excess mortality were observed in dentists for overall mortality (SMR=1.13; 95% confidence interval [CI]=1.00–1.26), drowning (SMR=6.62; 95% CI=2.15–15.45), and heart diseases (SMR=1.66; 95% CI=1.22–2.21). After adjusting for other risk factors, the Cox model showed an increased hazard ratio of 1.17 (95% CI=1.01–1.37) for dentists. Conclusion Taiwanese dentists demonstrated significant elevated SMRs for overall causes, drowning, and heart diseases. Careful precaution should be taken to reduce these trends. Future studies are also needed for in-depth exploration of the mechanisms regarding how professional stress and exposure contribute to the increased risk of mortality in Taiwanese dentists.", "title": "Mortality among dentists in Taiwan, 1985–2009", "pid": "lr4l368z", "bm25_score": 212.41012573242188}, {"text": "BACKGROUND: Extraordinary infection control measures limited access to medical care in the Greater Toronto Area during the 2003 Severe Acute Respiratory Syndrome (SARS) outbreak. The objective of this study was to determine if the period of these infection control measures was associated with changes in overall population mortality due to causes other than SARS. METHODS: Observational study of death registry data, using Poisson regression and interrupted time-series analysis to examine all-cause mortality rates (excluding deaths due to SARS) before, during, and after the SARS outbreak. The population of Ontario was grouped into the Greater Toronto Area (N = 2.9 million) and the rest of Ontario (N = 9.3 million) based upon the level of restrictions on delivery of clinical services during the SARS outbreak. RESULTS: There was no significant change in mortality in the Greater Toronto Area before, during, and after the period of the SARS outbreak in 2003 compared to the corresponding time periods in 2002 and 2001. The rate ratio for all-cause mortality during the SARS outbreak was 0.99 [95% Confidence Interval (CI) 0.93–1.06] compared to 2002 and 0.96 [95% CI 0.90–1.03] compared to 2001. An interrupted time series analysis found no significant change in mortality rates in the Greater Toronto Area associated with the period of the SARS outbreak. CONCLUSION: Limitations on access to medical services during the 2003 SARS outbreak in Toronto had no observable impact on short-term population mortality. Effects on morbidity and long-term mortality were not assessed. Efforts to contain future infectious disease outbreaks due to influenza or other agents must consider effects on access to essential health care services.", "title": "Population mortality during the outbreak of Severe Acute Respiratory Syndrome in Toronto", "pid": "ou3wj4rz", "bm25_score": 212.4082489013672}, {"text": "", "title": "Covid-19: death rate is 0.66% and increases with age, study estimates.", "pid": "gs9nvs5h", "bm25_score": 212.4056854248047}, {"text": "We assessed late mortality in 854 individuals who had survived 2 or more years after autologous hematopoietic cell transplantation (HCT) for hematologic malignancies. Median age at HCT was 36.5 years, and median length of follow-up was 7.6 years. Overall survival was 68.8% +/- 1.8% at 10 years, and the cohort was at a 13-fold increased risk for late death (standardized mortality ratio [SMR] = 13.0) when compared with the general population. Mortality rates approached those of the general population after 10 years among patients at standard risk for relapse at HCT (SMR = 1.1) and in patients undergoing transplantation for acute myeloid leukemia (AML; SMR = 0.9). Relapse of primary disease (56%) and subsequent malignancies (25%) were leading causes of late death. Relapse-related mortality was increased among patients with Hodgkin disease (HD; relative risk [RR] = 3.6), non-Hodgkin lymphoma (NHL; RR = 2.1), and acute lymphoblastic leukemia (ALL; RR = 6.5). Total body irradiation (RR = 0.6) provided a protective effect. Nonrelapse-related mortality was increased after carmustine (RR = 2.3) and with use of peripheral blood stem cells (RR = 2.4). Survivors were more likely to report difficulty in holding jobs (RR = 9.4) and in obtaining health (RR = 7.7) or life insurance (RR = 8.4) when compared with siblings. Although mortality rates approach that of the general population after 10 years in certain subgroups, long-term survivors of autologous HCT continue to face challenges affecting their health and well-being.", "title": "Late mortality in survivors of autologous hematopoietic-cell transplantation: report from the Bone Marrow Transplant Survivor Study.", "pid": "xr4flvzx", "bm25_score": 212.3907470703125}, {"text": "Background. Quantitative estimates of the global burden of the 1957 influenza pandemic are lacking. Here we fill this gap by modeling historical mortality statistics. Methods. We used annual rates of age- and cause-specific deaths to estimate pandemic-related mortality in excess of background levels in 39 countries in Europe, the Asia-Pacific region, and the Americas. We modeled the relationship between excess mortality and development indicators to extrapolate the global burden of the pandemic. Results. The pandemic-associated excess respiratory mortality rate was 1.9/10 000 population (95% confidence interval [CI], 1.2–2.6 cases/10 000 population) on average during 1957–1959. Excess mortality rates varied 70-fold across countries; Europe and Latin America experienced the lowest and highest rates, respectively. Excess mortality was delayed by 1–2 years in 18 countries (46%). Increases in the mortality rate relative to baseline were greatest in school-aged children and young adults, with no evidence that elderly population was spared from excess mortality. Development indicators were moderate predictors of excess mortality, explaining 35%–77% of the variance. Overall, we attribute 1.1 million excess deaths (95% CI, .7 million–1.5 million excess deaths) globally to the 1957–1959 pandemic. Conclusions. The global mortality rate of the 1957–1959 influenza pandemic was moderate relative to that of the 1918 pandemic but was approximately 10-fold greater than that of the 2009 pandemic. The impact of the pandemic on mortality was delayed in several countries, pointing to a window of opportunity for vaccination in a future pandemic.", "title": "Global Mortality Impact of the 1957–1959 Influenza Pandemic", "pid": "ao5676lc", "bm25_score": 212.388427734375}, {"text": "Objective: Severity of the coronavirus disease 2019 (covid-19) has been assessed in terms of absolute mortality in SARS-CoV-2 positive cohorts. An assessment of mortality relative to mortality in the general population is presented. Design: Retrospective population-based study. Setting: Individual information on symptomatic confirmed SARS-CoV-2 patients and subsequent deaths from any cause were compared to the all-cause mortality in the Swiss population of 2018. Starting February 23, 2020, mortality in covid-19 patients was monitored for 80 days and compared to the population mortality observed in the same time-of-year starting February 23, 2018. Participants: 5 160 595 inhabitants of Switzerland aged 35 to 95 without covid-19 (general population in spring 2018) and 20 769 persons tested positively for covid-19 (spring 2020). Measurements: Sex- and age-specific mortality rates were estimated using Cox proportional hazards models. Absolute probabilities of death were predicted and risk was assessed in terms of relative mortality by taking the ratio between the sex- and age-specific absolute mortality in covid19 patients and the corresponding mortality in the 2018 general population. Results: A confirmed SARS-CoV-2 infection substantially increased the probability of death across all patient groups, ranging from nine (6 to 15) times the population mortality in 35-year old infected females to a 53-fold increase (46 to 59) for 95 year old infected males. The highest relative risks were observed among males and older patients. The magnitude of these effects was smaller compared to increases observed in absolute mortality risk. Male covid-19 patients exceeded the population hazard for males (hazard ratio 1.20, 1.00 to 1.44). Each additional year of age increased the population hazard in covid-19 patients (hazard ratio 1.04, 1.03 to 1.05). Limitations: Information about the distribution of relevant comorbidities was not available on population level and the associated risk was not quantified. Conclusions: Health care professionals, decision makers, and societies are provided with an additional population-adjusted assessment of covid-19 mortality risk. In combination with absolute measures of risk, the relative risks presented here help to develop a more comprehensive understanding of the actual impact of covid-19.", "title": "Relative Coronavirus Disease 2019 Mortality: A Swiss Population-based Study", "pid": "92ipp5ge", "bm25_score": 212.38690185546875}, {"text": "Introduction With the pandemic of COVID-19, the number of confirmed cases and related deaths are increasing in the US. We aimed to understand the potential impact of health and demographic factors on the infection and mortality rates of COVID-19 at the population level. Methods We collected total number of confirmed cases and deaths related to COVID-19 at the county level in the US from January 21, 2020 to April 23, 2020. We extracted health and demographic measures for each US county. Multivariable linear mixed effects models were used to investigate potential correlations of health and demographic characteristics with the infection and mortality rates of COVID-19 in US counties. Results Our models showed that several health and demographic factors were positively correlated with the infection rate of COVID-19, such as low education level and percentage of Black. In contrast, several factors, including percentage of smokers and percentage of food insecure, were negatively correlated with the infection rate of COVID-19. While the number of days since first confirmed case and the infection rate of COVID-19 were negatively correlated with the mortality rate of COVID-19, percentage of elders (65 and above) and percentage of rural were positively correlated with the mortality rate of COVID-19. Conclusions At the population level, health and demographic factors could impact the infection and mortality rates of COVID-19 in US counties.", "title": "Health and Demographic Impact on COVID-19 Infection and Mortality in US Counties", "pid": "632r6uqe", "bm25_score": 212.38491821289062}, {"text": "BACKGROUND The various epidemiological indicators used to communicate the impact of COVID-19 have different strengths and limitations. METHODS We conducted a selective literature review to identify the indicators used and to derive appropriate definitions. We calculated crude and age-adjusted indicators for selected countries. RESULTS The proportion of deaths (case fatality proportion [CFP]; number of deaths/ total number of cases) is commonly used to estimate the severity of a disease. If the CFP is used for purposes of comparison, the existence of heterogeneity in the detection and registration of cases and deaths has to be taken into account. In the early phase of an epidemic, when case numbers rise rapidly, the CFP suffers from bias. For these reasons, variants have been proposed: the \"confirmed CFP\" (number of deaths/total number of confirmed cases), and the \"delay-adjusted CFP,\" which considers the delay between infection with the disease and death from the disease. The indicator mortality (number of deaths/total population) has at first sight the advantage of being based on a defined denominator, the total population. During the outbreak of a disease, however, the cumulative deaths rise while the total population remains stable. The phase of the epidemic therefore has to be considered when using this indicator. In this context, R0 and R(t) are important indicators. R0 estimates the maximum rate of spread of a disease in a population, while R(t) describes the dynamics of the epidemic at a given time. Age-adjusted analysis of the CFP shows that the differences between countries decrease but do not dis - appear completely. If the test strategies depend on age or symptom severity, however, the bias cannot be entirely eliminated. CONCLUSION Various indicators of the impact of the COVID-19 epidemic at population level are used in daily communication. Considering the relevance of the pandemic and the importance of relevant communications, however, the strengths and the limitations of each parameter must be considered carefully.", "title": "Epidemiological Measures in the Context of the COVID-19 Pandemic.", "pid": "338d8gme", "bm25_score": 212.38302612304688}, {"text": "BACKGROUND: The coronavius disease 2019 (COVID-9) caused by the severe acute respiratory syndrome coronavirus 2 reached Spain by 31 January 2020, in April 2020, the Comunidad de Madrid suffered one of the world's highest crude mortality rate ratios. This study aimed to detect risk factors for mortality in patients with COVID-19. METHODS: Our cohort were all consecutive adult patients with laboratory-confirmed COVID-19 at a secondary hospital in Madrid, March 3-16, 2020. Clinical and laboratory data came from electronic clinical records and were compared between survivors and non-survivors, with outcomes followed up until April 4. Univariable and multivariable logistic regression methods allowed us to explore risk factors associated with in-hospital death. FINDINGS: The cohort comprised 562 patients with COVID-19. Clinical records were available for evaluation for 392 patients attended at the emergency department of our hospital, of whom 199 were discharged, 85 remained hospitalized and 108 died during hospitalization. Among 311 of the hospitalized patients, 34.7% died. Of the 392 patients with records, the median age was 71.5 years (50.6-80.7); 52.6% were men. 252 (64.3%) patients had a comorbidity, hypertension being the most common: 175 (44.6%), followed by other cardiovascular disease: 102 (26.0%) and diabetes: 97 (24.7%). Multivariable regression showed increasing odds of in-hospital death associated with age over 65 (odds ratio 8.32, 95% CI 3.01-22.96; p<0.001), coronary heart disease (2.76, 1.44-5.30; 0.002), and both lower lymphocyte count (0.34, 0.17-0.68; 0.002) and higher LDH (1.25, 1.05-1.50; 0.012) per 1-unit increase and per 100 units respectively. INTERPRETATION: COVID-19 was associated in our hospital at the peak of the pandemic with a crude mortality ratio of 19.2% and a mortality ratio of 34.7% in admitted patients, considerably above most of the ratios described in the Chinese series. These results leave open the question as to which factors, epidemiological or intrinsically viral, apart from age and comorbidities, can explain this difference in excess mortality. FUNDING: None.", "title": "Prevalence and risk factors for mortality related to COVID-19 in a severely affected area of Madrid, Spain", "pid": "hj4wd5lc", "bm25_score": 212.37933349609375}, {"text": "ABSTRACT Objectives Initial data on Covid-19 infection has pointed out a special vulnerability of elderly people. Design we performed a meta-analysis with available national reports at May 7th 2020 from China, Italy, Spain, United Kingdom and New York State. Analyses were performed by a random effects model and sensitivity analyses were performed for the identification of potential sources of heterogeneity. Setting and Participants: covid-19 positive patients reported in literature and national reports. Measures all-cause mortality by age. Results A total of 611,1583 subjects were analyzed and 141,745 (23.2%) had age ≥80. The percentage of octogenarians was different in the 5 registries being the lowest in China (3.2%) and the highest and the highest in UK and New York State. The overall mortality rate was 12.10% and it varied widely between countries being the lowest in China (3.1%) and the highest in UK (20.8%) and New York State (20.99%). Mortality was <1.1% in patients with age <50 and it increased exponentially after that age in the 5 national registries. As expected, the highest mortality rate was observed in patients ≥80 years old. All age groups had significantly higher mortality compared to the inmediatelly younger age group. The largest increase in mortality risk was observed in patients with age 60-69 compared to 50-59 (OR: 3.13 95% CI 2.61-3.76). Conclusions and implications this metanalysis with more than half-million of Covid-19 patients from different countries highlights the determinant effect of age on mortality with the relevant thresholds on age >50 and, especially, >60. Elderly patients should be priorized in the implementation of preventive measures.", "title": "The effect of age on mortality in patients with Covid-19: a metanalysis with 611,583 subjects", "pid": "6cgajmb8", "bm25_score": 212.37698364257812}, {"text": "Previous studies have found large variations in the COVID-19 infection fatality rate (IFR). This study hypothesized that IFR would be influenced by COVID-19 epidemic intensity. We tested the association between epidemic intensity and IFR using serological results from a recent large SARS-CoV-2 serosurvey (N = 60,983) in 19 Spanish regions. The infection fatality rate for Spain as a whole was 1.15% and varied between 0.13% and 3.25% in the regions (median 1.07%, IQR 0.69-1.32%). The IFR by region was positively associated with SARS-CoV-2 seroprevalence (rho = 0.54; p = 0.0162), cases/100,000 (rho = 0.75; p = 0.002), hospitalizations/100,000 (rho = 0.78; p = 0.0001), mortality/100,000 (rho = 0.77; p = 0.0001) and case fatality rate (rho = 0.49; p = 0.0327). These results suggest that the SARS-CoV-2 IFR is not fixed. The Spanish regions with more rapid and extensive spread of SARS-CoV-2 had higher IFRs. These findings are compatible with the theory that slowing the spread of COVID-19 down reduces the IFR and case fatality rate via preventing hospitals from being overrun, and thus allowing better and lifesaving care.", "title": "COVID-19 Infection Fatality Rate Associated with Incidence-A Population-Level Analysis of 19 Spanish Autonomous Communities", "pid": "6fa8fana", "bm25_score": 212.37673950195312}, {"text": "Previous studies have found large variations in the COVID-19 infection fatality rate (IFR). This study hypothesized that IFR would be influenced by COVID-19 epidemic intensity. We tested the association between epidemic intensity and IFR using serological results from a recent large SARS-CoV-2 serosurvey (N = 60,983) in 19 Spanish regions. The infection fatality rate for Spain as a whole was 1.15% and varied between 0.13% and 3.25% in the regions (median 1.07%, IQR 0.69–1.32%). The IFR by region was positively associated with SARS-CoV-2 seroprevalence (rho = 0.54; p = 0.0162), cases/100,000 (rho = 0.75; p = 0.002), hospitalizations/100,000 (rho = 0.78; p = 0.0001), mortality/100,000 (rho = 0.77; p = 0.0001) and case fatality rate (rho = 0.49; p = 0.0327). These results suggest that the SARS-CoV-2 IFR is not fixed. The Spanish regions with more rapid and extensive spread of SARS-CoV-2 had higher IFRs. These findings are compatible with the theory that slowing the spread of COVID-19 down reduces the IFR and case fatality rate via preventing hospitals from being overrun, and thus allowing better and lifesaving care.", "title": "COVID-19 Infection Fatality Rate Associated with Incidence—A Population-Level Analysis of 19 Spanish Autonomous Communities", "pid": "gvtsneoy", "bm25_score": 212.3737335205078}, {"text": "This article examines how the epidemiologic transition and the reduction of the urban mortality penalty gave rise to the current mortality regime of the United States and demonstrates how the 1918 influenza pandemic signaled its advent. This article approaches those issues through the analysis of urban-rural mortality differentials from 1890 to 1930. Until 1910, infectious diseases dwarfed degenerative diseases in leading causes of death, and generally, the more urban the location was, the higher infectious disease and overall death rates were—a direct relationship. But by 1930, degenerative diseases had eclipsed infectious diseases, and infectious disease mortality had ceased to differ between cities and rural areas. The 1918 influenza pandemic broke out toward the end of these changes, and the larger the city was, the lower influenza and overall death rates were in that year—an inverse relationship. Such gradations characterized a new mortality regime emerging in the late 1910s and foreshadowed urban-rural mortality differentials in 1930 among persons aged 45 years or older, the group whose high rates of degenerative disease death would symbolize that regime. Thus, intertwined changes in the late 19th and early 20th centuries—a shift in leading causes of death from infectious diseases to degenerative diseases and a concomitant shift from a direct relationship to an inverse relationship between urban environment and mortality—produced the current mortality regime of the United States.", "title": "The Rise of the Current Mortality Pattern of the United States, 1890–1930", "pid": "iultl80s", "bm25_score": 212.37062072753906}, {"text": "Different ways of calculating mortality during epidemics have yielded very different results, particularly during the current COVID-19 pandemic. For example, the \"CFR\" has been interchangeably called the case fatality ratio, case fatality rate, and case fatality risk, often without standard mathematical definitions. The most commonly used CFR is thecase fatality ratio, typically constructed using the estimated number of deaths to date divided by the estimated total number of confirmed infected cases to date. How does this CFR relate to an infected individual's probability of death? To explore such issues, we formulate both a survival probability model and an associated infection duration-dependent SIR model to define individual- and population-based estimates of dynamic mortality measures to show that neither of these are directly represented by the case fatality ratio. The key parameters that affect the dynamics of different mortality estimates are the incubation period and the time individuals were infected before confirmation of infection. Using data on the recent SARS-CoV-2 outbreaks, we estimate and compare the different dynamic mortality estimates and highlight their differences. Informed by our modeling, we propose more systematic methods to determine mortality during epidemic outbreaks and discuss sensitivity to confounding effects and uncertainties in the data such as undertesting and heterogeneous populations.", "title": "Why case fatality ratios can be misleading: individual- and population-based mortality estimates and factors influencing them", "pid": "zf0bboc1", "bm25_score": 212.3642578125}, {"text": "", "title": "Mortality rate and gender differences in COVID-19 patients dying in Italy: A comparison with other countries.", "pid": "0c21csjz", "bm25_score": 212.34793090820312}, {"text": "The Infection Fatality Rate (IFR) for COVID-19 is a poorly known, yet crucial, aspect of the disease. Counting only current deaths in a region and assuming everyone in that region is infected provides an absolute lower bound on the IFR. Using this estimator for New York City, Lombardy and Madrid yields strong bounds on the average IFR in overwhelmed health systems. Their combined 35,152 deaths implies IFR > 0.14% averaged over 25.1 million people. This is the best-case scenario and conclusively demonstrates that COVID-19 is more deadly than influenza. The actual value of the average COVID-19 IFR is likely to be higher than this bound.", "title": "Strict Lower Bound on the COVID-19 Fatality Rate in Overwhelmed Healthcare Systems", "pid": "cmjzst9v", "bm25_score": 212.33702087402344}, {"text": "Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015–2019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID–19 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.", "title": "How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy", "pid": "t9qdiz7n", "bm25_score": 212.33575439453125}, {"text": "Epidemiological studies suggest that age distribution of a population has a non-trivial effect on how morbidity rates, mortality rates and case fatality rates (CFR) vary when there is an epidemic or pandemic. We look at the empirical evidence from a large cohort of countries to see the sensitivity of Covid-19 data to their respective median ages. The insights that emerge could be used to control for age structure effects while investigating other factors like cross-protection, co-morbidities, etc.", "title": "Covid-19 and Population Age Structure", "pid": "arfz6224", "bm25_score": 212.3341064453125}, {"text": "This study aims to ascertain the long-term epidemic trends of malaria and evaluates the probability of achieving the eradication goal by 2020 in China. Data on malaria incidence and deaths were extracted from the China Information System for Disease Control and Prevention. The epidemic trends by sex, age and spatial distribution and predictions of malaria were estimated by using Joinpoint and Poisson regressions. From 1950 to 2016, 227 668 374 malaria cases were reported in China, with an annualised average incidence of 337.02 (336.98–337.07, 95% confidence interval (CI)) per 100 000 population. The incidence decreased with an average annual per cent change (AAPC) of −11.4% (−16.6 to −6.0). There were 36 085 malaria deaths, with an annualised average mortality of 0.534 (0.529–0.540) per 1 000 000 population. The mortality decreased with an AAPC of −8.7% (−13.7 to −3.4). The predicted number of malaria cases and deaths for 2020 is 2 562 and 10, respectively, and zero for indigenous cases. The disease burden of malaria dramatically decreased in China. Though, the goal of malaria elimination is realistic by 2020 in China, routine clinical and entomological surveillance should be continually conducted, especially for the cross-border areas and imported malaria cases.", "title": "Malaria in China: a longitudinal population-based surveillance study", "pid": "k9wlfrmx", "bm25_score": 212.3332061767578}, {"text": "Objective. Scrutiny of COVID-19 mortality in Belgium over the period 8 March-9 May 2020 (Weeks 11-19), using number of deaths per million, infection fatality rates, and the relation between COVID-19 mortality and excess death rates. Data. Publicly available COVID-19 mortality (2020); overall mortality (2009-2020) data in Belgium and demographic data on the Belgian population; data on the nursing home population; results of repeated sero-prevalence surveys in March-April 2020. Statistical methods. Reweighing, missing-data handling, rate estimation, visualization. Results. Belgium has virtually no discrepancy between COVID-19 reported mortality (confirmed and possible cases) and excess mortality. There is a sharp excess death peak over the study period; the total number of excess deaths makes April 2020 the deadliest month of April since WWII, with excess deaths far larger than in early 2017 or 2018, even though influenza-induced January 1951 and February 1960 number of excess deaths were similar in magnitude. Using various sero-prevalence estimates, infection fatality rates (IFRs; fraction of deaths among infected cases) are estimated at 0.38-0.73% for males and 0.20-0.39% for females in the non-nursing home population (non-NHP), and at 0.79-1.52% for males and 0.88-1.31% for females in the entire population. Estimates for the NHP range from 38 to 73% for males and over 22 to 37% for females. The IFRs rise from nearly 0% under 45 years, to 4.3% and 13.2% for males in the non-NHP and the general population, respectively, and to 1.5% and 11.1% for females in the non-NHP and general population, respectively. The IFR and number of deaths per million is strongly influenced by extensive reporting and the fact that 66.0% of the deaths concerned NH residents. At 764 (our re-estimation of the figure 735, presented by \"Our World in Data\"), the number of COVID-19 deaths per million led the international ranking on May 9, 2020, but drops to 262 in the non-NHP. The NHP is very specific: age-related increased risk; highly prevalent comorbidities that, while non-fatal in themselves, exacerbate COVID-19; larger collective households that share inadvertent vectors such as caregivers and favor clustered outbreaks; initial lack of protective equipment, etc. High-quality health care countries have a relatively older but also more frail population [1], which is likely to contribute to this result.", "title": "Belgian Covid-19 Mortality, Excess Deaths, Number of Deaths per Million, and Infection Fatality Rates (8 March - 9 May 2020)", "pid": "qzb8a22l", "bm25_score": 212.32821655273438}, {"text": "Objective: Overall mortality is a relevant indicator of the population burden during an epidemic. It informs on both undiagnosed cases and on the effects of health system disruption. Methods: We aimed at evaluating the extent of the total death excess during the COVID-19 epidemic in Italy. Data from 4433 municipalities providing mortality reports until April 15th, 2020 were included for a total of 34.5 million residents from all Italian regions. Data were analyzed by region, sex and age, and compared to expected from 2015-2019. Results: In both genders, overall mortality was stable until February 2020 and abruptly increased from March 1st onwards. Within the municipalities studied, 77,339 deaths were observed in the period between March 1st to April 15th, 2020, in contrast to the 50,822.6 expected. The rate ratio was 1.11 before age 60 and 1.55 afterwards. Both sexes were affected. The excess was greater in the regions most affected by COVID-19 but always exceeded the deaths attributed to COVID-19. The extrapolation to the total Italian population suggests an excess of 45,033 deaths in the study period, while the number of COVID-19 deaths was 21,046. Conclusion: Our paper shows a large death excess during the COVID-19 epidemic in Italy; greater than the number attributed to it. Possible causes included both the undetected cases and the disruption of the Health Service organization. Timely monitoring of overall mortality based on unbiased nationwide data is an essential tool for epidemic control.", "title": "How Large Was the Mortality Increase Directly and Indirectly Caused by the COVID-19 Epidemic? An Analysis on All-Causes Mortality Data in Italy", "pid": "ekxz577j", "bm25_score": 212.3218231201172}]}
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It has been spread to more than 100 countries and more than 1 million patients have been confirmed. Although coronavirus causes severe respiratory infections in human, accumulating data have demonstrated cardiac complications and poor outcome in patients with coronavirus disease 2019. A large percent of patients have underlying cardiovascular disease and they are at a high risk of developing cardiac complications. We review the basics of the virus, the clinical manifestation, and the possible mechanisms of cardiac complications in patients with coronavirus disease 2019. Before the effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.", "title": "Coronavirus disease 2019 (COVID-19) and cardiovascular complications", "pid": "v3qgqfwr", "bm25_score": 219.8557891845703}, {"text": "The coronavirus disease-2019 (COVID-19) has become a global pandemic. It has spread to more than 100 countries, and more than 1 million cases have been confirmed. Although coronavirus causes severe respiratory infections in humans, accumulating data have demonstrated cardiac complications and poor outcome in patients with COVID-19. A large percent of patients have underlying cardiovascular disease, and they are at a high risk of developing cardiac complications. The basics of the virus, the clinical manifestations, and the possible mechanisms of cardiac complications in patients with COVID-19 are reviewed. Before an effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.", "title": "Coronavirus Disease-2019 (COVID-19) and Cardiovascular Complications", "pid": "wkp58iov", "bm25_score": 219.80911254882812}, {"text": "In December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2). Although coronavirus disease (COVID-19) clinical manifestations are mainly respiratory, major cardiac complications are being reported. Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2-receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others. Studies evaluating patients with COVID-19 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon. Besides, drugs currently used to treat the COVID-19 are known to prolong the QT interval and can have a proarrhythmic propensity. This review focus on COVID-19 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS-CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.", "title": "Cardiac and arrhythmic complications in patients with COVID-19", "pid": "rmio55bx", "bm25_score": 218.96022033691406}, {"text": "BACKGROUND: The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. OBJECTIVE: This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. DISCUSSION: The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. CONCLUSIONS: Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "title": "Cardiovascular complications in COVID-19", "pid": "hl225efn", "bm25_score": 218.8544921875}, {"text": "Abstract Background The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. Objective This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. Discussion The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. Conclusions Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "title": "Cardiovascular complications in COVID-19", "pid": "mbbnk3la", "bm25_score": 218.76107788085938}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has shown an association with acute myocardial injury, cardiomyopathy, and myocarditis. Individuals with myocardial involvement in association with the coronavirus disease 2019 (COVID-19) may be at increased risk of developing severe illness. Cardiomyopathies are a heterogeneous group of diseases of the myocardium associated with mechanical and/or electrical dysfunction that usually exhibit inappropriate ventricular hypertrophy or dilation and are due to a variety of causes that frequently are genetic. It has been primarily divided into three subsets: genetic, mixed, and acquired cardiomyopathy. We anticipate that, because of the high inflammatory response, other cardiovascular complications may also occur in COVID-19 patients with severe symptoms. This review explores new information as it pertains to COVID-19 and cardiac complications.", "title": "A Review of Cardiac Complications in Coronavirus Disease 2019", "pid": "u6vq5ohr", "bm25_score": 218.73500061035156}, {"text": "The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to more than 187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, myocarditis) and secondary (myocardial injury/biomarker elevation, heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a \"Heart-Lung\" team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.", "title": "Approach to Acute Cardiovascular Complications in COVID-19 Infection.", "pid": "mol4s3iz", "bm25_score": 218.45993041992188}, {"text": "In December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2). Although coronavirus disease (COVID‐19) clinical manifestations are mainly respiratory, major cardiac complications are being reported. Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2‐receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others. Studies evaluating patients with COVID‐19 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon. Besides, drugs currently used to treat the COVID‐19 are known to prolong the QT interval and can have a proarrhythmic propensity. This review focus on COVID‐19 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS‐CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.", "title": "Cardiac and arrhythmic complications in patients with COVID‐19", "pid": "xhum1ykr", "bm25_score": 218.40972900390625}, {"text": "Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now a global pandemic with the highest number of affected individuals in the modern era. Not only is the infection inflicting significant morbidity and mortality, but there has also been a significant strain to the health care system and the economy. COVID-19 typically presents as viral pneumonia, occasionally leading to acute respiratory distress syndrome (ARDS) and death. However, emerging evidence suggests that it has a significant impact on the cardiovascular (CV) system by direct myocardial damage, severe systemic inflammatory response, hypoxia, right heart strain secondary to ARDS and lung injury, and plaque rupture secondary to inflammation. Primary cardiac manifestations include acute myocarditis, myocardial infarction, arrhythmia, and abnormal clotting. Several consensus documents have been released to help manage CV disease during this pandemic. In this review, we summarize key cardiac manifestations, their management, and future implications.", "title": "COVID-19 Pandemic: Cardiovascular Complications and Future Implications", "pid": "1vcpq06y", "bm25_score": 218.3054962158203}, {"text": "The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to more than 187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, myocarditis) and secondary (myocardial injury/biomarker elevation, heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a \"Heart-Lung\" team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.", "title": "Approach to Acute Cardiovascular Complications in COVID-19 Infection", "pid": "gs45hgch", "bm25_score": 218.1995849609375}, {"text": "The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to >187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, and myocarditis) and secondary (myocardial injury/biomarker elevation and heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a Heart-Lung team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.", "title": "Approach to Acute Cardiovascular Complications in COVID-19 Infection", "pid": "sw0xtwno", "bm25_score": 218.1770477294922}, {"text": "PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. SUMMARY: Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.", "title": "Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty", "pid": "lfjud2aq", "bm25_score": 218.16757202148438}, {"text": "PURPOSE OF REVIEW: COronaVirus Disease 2019 (COVID-19) has spread at unprecedented speed and scale into a global pandemic with cardiovascular risk factors and complications emerging as important disease modifiers. We aim to review available clinical and biomedical literature on cardiovascular risks of COVID-19. RECENT FINDINGS: SARS-CoV2, the virus responsible for COVID-19, enters the cell via ACE2 expressed in select organs. Emerging epidemiological evidence suggest cardiovascular risk factors are associated with increased disease severity and mortality in COVID-19 patients. Patients with a more severe form of COVID-19 are also more likely to develop cardiac complications such as myocardial injury and arrhythmia. The true incidence of and mechanism underlying these events remain elusive. Cardiovascular diseases appear intricately linked with COVID-19, with cardiac complications contributing to the elevated morbidity/mortality of COVID-19. Robust epidemiologic and biologic studies are urgently needed to better understand the mechanism underlying these associations to develop better therapies.", "title": "Cardiovascular Risks in Patients with COVID-19: Potential Mechanisms and Areas of Uncertainty", "pid": "ejsqsn59", "bm25_score": 218.0003204345703}, {"text": "PURPOSE OF REVIEW: Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. While cardiac injury has been demonstrated in critically ill COVID-19 patients, the mechanism of injury remains unclear. Here, we review our current knowledge of the biology of SARS-CoV-2 and the potential mechanisms of myocardial injury due to viral toxicities and host immune responses. RECENT FINDINGS: A number of studies have reported an epidemiological association between history of cardiac disease and worsened outcome during COVID infection. Development of new onset myocardial injury during COVID-19 also increases mortality. While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensin-converting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome. Potential treatments for reducing viral infection and excessive immune responses are also discussed. COVID patients with cardiac disease history or acquire new cardiac injury are at an increased risk for in-hospital morbidity and mortality. More studies are needed to address the mechanism of cardiotoxicity and the treatments that can minimize permanent damage to the cardiovascular system.", "title": "Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response", "pid": "6f8la6sw", "bm25_score": 217.99423217773438}, {"text": "BACKGROUND: Respiratory complications have been well remarked in the novel coronavirus disease (SARS-CoV-2/COVID-19), yet an emerging body of research indicates that cardiac involvement may be implicated in poor outcomes for these patients. AIMS: This review seeks to gather and distill the existing body of literature that describes the cardiac implications of COVID-19. MATERIALS AND METHODS: The English literature was reviewed for papers dealing with the cardiac effects of COVID-19. RESULTS: Notably, COVID-19 patients with pre-existing cardiovascular disease are counted in greater frequency in intensive care unit settings, and ultimately suffer greater rates of mortality. Other studies have noted cardiac presentations for COVID-19, rather than respiratory, such as acute pericarditis and left ventricular dysfunction. In some patients there has been evidence of acute myocardial injury, with correspondingly increased serum troponin I levels. With regard to surgical interventions, there is a dearth of data describing myocardial protection during cardiac surgery for COVID-19 patients. Although some insights have been garnered in the study of cardiovascular diseases for these patients, these insights remain fragmented and have yet to cement clear guidelines for actionable clinical practice. CONCLUSION: While some information is available, further studies are imperative for a more cohesive understanding of the cardiac pathophysiology in COVID-19 patients to promote more informed treatment and, ultimately, better clinical outcomes.", "title": "Cardiac involvement in COVID-19 patients: Risk factors, predictors, and complications: A review", "pid": "0ec1cu8q", "bm25_score": 217.97962951660156}, {"text": "PURPOSE OF REVIEW: Coronavirus disease of 2019 (COVID-19) is a cause of significant morbidity and mortality worldwide. While cardiac injury has been demonstrated in critically ill COVID-19 patients, the mechanism of injury remains unclear. Here, we review our current knowledge of the biology of SARS-CoV-2 and the potential mechanisms of myocardial injury due to viral toxicities and host immune responses. RECENT FINDINGS: A number of studies have reported an epidemiological association between history of cardiac disease and worsened outcome during COVID infection. Development of new onset myocardial injury during COVID-19 also increases mortality. While limited data exist, potential mechanisms of cardiac injury include direct viral entry through the angiotensin-converting enzyme 2 (ACE2) receptor and toxicity in host cells, hypoxia-related myocyte injury, and immune-mediated cytokine release syndrome. Potential treatments for reducing viral infection and excessive immune responses are also discussed. SUMMARY: COVID patients with cardiac disease history or acquire new cardiac injury are at an increased risk for in-hospital morbidity and mortality. More studies are needed to address the mechanism of cardiotoxicity and the treatments that can minimize permanent damage to the cardiovascular system.", "title": "Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response", "pid": "xkg0ylz8", "bm25_score": 217.97288513183594}, {"text": "The infection caused by severe acute respiratory syndrome coronavirus-2, or COVID-19, can result in myocardial injury, heart failure, and arrhythmias. In addition to the viral infection itself, investigational therapies for the infection can interact with the cardiovascular system. As cardiologists and cardiovascular service lines will be heavily involved in the care of patients with COVID-19, our division organized an approach to manage these complications, attempting to balance resource utilization and risk to personnel with optimal cardiovascular care. The model presented can provide a framework for other institutions to organize their own approaches and can be adapted to local constraints, resource availability, and emerging knowledge.", "title": "A care pathway for the cardiovascular complications of COVID-19: Insights from an institutional response", "pid": "38ltcpcw", "bm25_score": 217.94277954101562}, {"text": "Patients with pre-existing cardiovascular disease and risk factors are more likely to experience adverse outcomes associated with the novel coronavirus disease-2019 (COVID-19). Additionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome. As the spread of the virus increases exponentially, many patients will require medical care either for COVID-19 related or traditional cardiovascular issues. While the COVID-19 pandemic is dominating the attention of the healthcare system, there is an unmet need for a standardized approach to deal with COVID-19 associated and other traditional cardiovascular issues during this period. We provide consensus guidance for the management of various cardiovascular conditions during the ongoing COVID-19 pandemic with the goal of providing the best care to all patients and minimizing the risk of exposure to frontline healthcare workers.", "title": "Management of Cardiovascular Disease During Coronavirus Disease (COVID-19) Pandemic", "pid": "scddzn5t", "bm25_score": 217.91848754882812}, {"text": "Coronavirus disease 2019 (COVID-19) has caused a devastating global pandemic and continues to overwhelm the health-care facilities and shatter the economies of countries worldwide. Although it primarily affects the lungs, it shares a strong interplay with the cardiovascular system. The presence of underlying cardiovascular disease and its risk factors (diabetes, hypertension) predispose the patients to increased severity and mortality associated with COVID-19. On the other hand, COVID-19 itself leads to various cardiovascular complications, which increase its associated morbidity and mortality in affected patients. It is, therefore, prudent to review the rapidly evolving data in this field and understand the mechanisms behind the cardiovascular involvement of this lethal disease.", "title": "Cardiovascular comorbidities and complications associated with coronavirus disease 2019", "pid": "o6a30irm", "bm25_score": 217.88262939453125}, {"text": "Community-acquired pneumonia (CAP) remains a global health problem with significant morbidity and mortality. Much recent published literature about the infection has indicated that a substantial number of patients with CAP, particularly those ill enough to be admitted to hospital, will suffer a cardiovascular event. While these may include events such as deep venous thrombosis and stroke, most of the events involve the heart and include the occurrence of an arrhythmia (most commonly atrial fibrillation), new onset or worsening of heart failure and acute myocardial infarction. While such cardiac events may occur, for example, in all-cause CAP and CAP due to influenza virus infection, and more recently described with the SARS-CoV-2 pandemic, a significant amount of research work has been investigating the pathogenic mechanisms of these cardiac events in patients with CAP due to Streptococcus pneumoniae (pneumococcus) and, more recently, COVID-19 infections. Such research has identified a number of mechanisms by which these microorganisms may cause cardiovascular events. Importantly, these cardiac events appear not only to be associated with in-hospital mortality, but they also appear to contribute to longer-term mortality of patients with CAP, even after their discharge from hospital. This review will focus initially on studies of cardiovascular events in all-cause CAP and pneumococcal CAP, excluding COVID-19 infection, and then address similar issues in the latter infection.", "title": "Cardiac complications in community-acquired pneumonia and COVID-19", "pid": "k0kud80s", "bm25_score": 217.84616088867188}, {"text": "Background: Since the outbreak of the Coronavirus Disease 2019 (COVID-19) in China, respiratory manifestations of the disease have been observed. However, as a fatal comorbidity, acute myocardial injury (AMI) in COVID-19 patients has not been previously investigated in detail. We investigated the clinical characteristics of COVID-19 patients with AMI and determined the risk factors for AMI in them. Methods: We analyzed data from 53 consecutive laboratory-confirmed and hospitalized COVID-19 patients (28 men, 25 women; age, 19-81 years). We collected information on epidemiological and demographic characteristics, clinical features, routine laboratory tests (including cardiac injury biomarkers), echocardiography, electrocardiography, imaging findings, management methods, and clinical outcomes. Results: Cardiac complications were found in 42 of the 53 (79.25%) patients: tachycardia (n=15), electrocardiography abnormities (n=11), diastolic dysfunction (n=20), elevated myocardial enzymes (n=30), and AMI (n=6). All the six AMI patients were aged >60 years; five of them had two or more underlying comorbidities (hypertension, diabetes, cardiovascular diseases, and chronic obstructive pulmonary disease). Novel coronavirus pneumonia (NCP) severity was higher in the AMI patients than in patients with non-definite AMI (p<0.001). All the AMI patients required care in intensive care unit; of them, three died, two remain hospitalized. Multivariate analyses showed that C-reactive protein (CRP) levels, NCP severity, and underlying comorbidities were the risk factors for cardiac abnormalities in COVID-19 patients. Conclusions: Cardiac complications are common in COVID-19 patients. Elevated CRP levels, underlying comorbidities, and NCP severity are the main risk factors for cardiac complications in COVID-19 patients.", "title": "Acute Myocardial Injury of Patients with Coronavirus Disease 2019", "pid": "jg6v644y", "bm25_score": 217.84397888183594}, {"text": "The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. Meanwhile, COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Up-to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs. In this context, special attention should be given towards COVID-19 patients with concurrent cardiovascular diseases, and special cardiovascular attention is warranted for treatment of COVID-19.", "title": "SARS-CoV-2 and cardiovascular complications: From molecular mechanisms to pharmaceutical management", "pid": "ye7yxtd3", "bm25_score": 217.72817993164062}, {"text": "The coronavirus disease 2019 (COVID-19), elicited by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, is a pandemic public health emergency of global concern. Other than the profound severe pulmonary damage, SARS-CoV-2 infection also leads to a series of cardiovascular abnormalities, including myocardial injury, myocarditis and pericarditis, arrhythmia and cardiac arrest, cardiomyopathy, heart failure, cardiogenic shock, and coagulation abnormalities. Meanwhile, COVID-19 patients with preexisting cardiovascular diseases are often at a much higher risk of increased morbidity and mortality. Up–to-date, a number of mechanisms have been postulated for COVID-19-associated cardiovascular damage including SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) activation, cytokine storm, hypoxemia, stress and cardiotoxicity of antiviral drugs. In this context, special attention should be given towards COVID-19 patients with concurrent cardiovascular diseases, and special cardiovascular attention is warranted for treatment of COVID-19.", "title": "SARS-CoV-2 and Cardiovascular Complications: from Molecular Mechanisms to Pharmaceutical Management", "pid": "5fn1nfpf", "bm25_score": 217.65028381347656}, {"text": "In face of the pandemic of the novel coronavirus disease 2019 (COVID-19), the management of patients with cardiovascular risk factors and/or disease is challenging. The cardiovascular complications evidenced in patients with COVID-19 derive from several mechanisms, ranging from direct viral injury to complications secondary to the inflammatory and thrombotic responses to the infection. The proper care of patients with COVID-19 requires special attention to the cardiovascular system aimed at better outcomes.", "title": "The Heart and COVID-19: What Cardiologists Need to Know.", "pid": "7icw3be3", "bm25_score": 217.641845703125}, {"text": "BACKGROUND: Respiratory complications have been well remarked in the novel coronavirus disease (SARS‐CoV‐2/COVID‐19), yet an emerging body of research indicates that cardiac involvement may be implicated in poor outcomes for these patients. AIMS: This review seeks to gather and distill the existing body of literature that describes the cardiac implications of COVID‐19. MATERIALS AND METHODS: The English literature was reviewed for papers dealing with the cardiac effects of COVID‐19. RESULTS: Notably, COVID‐19 patients with pre‐existing cardiovascular disease are counted in greater frequency in intensive care unit settings, and ultimately suffer greater rates of mortality. Other studies have noted cardiac presentations for COVID‐19, rather than respiratory, such as acute pericarditis and left ventricular dysfunction. In some patients there has been evidence of acute myocardial injury, with correspondingly increased serum troponin I levels. With regard to surgical interventions, there is a dearth of data describing myocardial protection during cardiac surgery for COVID‐19 patients. Although some insights have been garnered in the study of cardiovascular diseases for these patients, these insights remain fragmented and have yet to cement clear guidelines for actionable clinical practice. CONCLUSION: While some information is available, further studies are imperative for a more cohesive understanding of the cardiac pathophysiology in COVID‐19 patients to promote more informed treatment and, ultimately, better clinical outcomes.", "title": "Cardiac involvement in COVID‐19 patients: Risk factors, predictors, and complications: A review", "pid": "qsy2kex1", "bm25_score": 217.6373291015625}, {"text": "Various cardiovascular complications have been reported in patients with coronavirus disease 2019. Common complications include acute myocardial injury, myocarditis, arrhythmia, pericarditis, heart failure, and shock. We present a case of cor pulmonale diagnosed with serial point of care ultrasound. Given the current shortage of personal protective equipment (PPE) and high infectivity of this virus, we acknowledge the utility of this tool in obtaining important clinical information while minimizing exposure and PPE consumption.", "title": "Novel Coronavirus-Induced Right Ventricular Failure and Point of Care Echocardiography: A Case Report", "pid": "fmum9fe5", "bm25_score": 217.63673400878906}, {"text": "Today the modern world is facing an unprecedented health crisis. The COVID‐19 pandemic is putting extensive strain on health care systems, hospitals and medical workers worldwide. Epidemiological data are emerging that COVID‐19 patients with cardiac risk factors or pre‐existing cardiac conditions are at increased risk for complications and mortality from COVID‐19. As we just begin to understand the pathophysiology underlying the disease, the involvement of the heart, whether through direct myocardial infection and damage or due to cardiac complications, is already evident.", "title": "Emerging cardiological issues during the COVID‐19 pandemic", "pid": "6p39cx2e", "bm25_score": 217.5819091796875}, {"text": "ABSTRACT Patients with pre-existing cardiovascular disease and risk factors are more likely to experience adverse outcomes associated with the novel coronavirus disease-2019 (COVID-19). Additionally, consistent reports of cardiac injury and de novo cardiac complications, including possible myocarditis, arrhythmia, and heart failure in patients without prior cardiovascular disease or significant risk factors, are emerging, possibly due to an accentuated host immune response and cytokine release syndrome. As the spread of the virus increases exponentially, many patients will require medical care either for COVID-19 related or traditional cardiovascular issues. While the COVID-19 pandemic is dominating the attention of the healthcare system, there is an unmet need for a standardized approach to deal with COVID-19 associated and other traditional cardiovascular issues during this period. We provide consensus guidance for the management of various cardiovascular conditions during the ongoing COVID-19 pandemic with the goal of providing the best care to all patients and minimizing the risk of exposure to frontline healthcare workers.", "title": "Management of Cardiovascular Disease During Coronavirus Disease (COVID-19) Pandemic", "pid": "ynt2koko", "bm25_score": 217.47129821777344}, {"text": "Aims To explore the epidemiological and clinical features of 2019 novel coronavirus(2019-nCoV)-infected patients with cardiac injury . Methods and results Data were collected from patients medical records, and we defined cardiac injury according to cardiac biomarker troponin I level > 0.03>ug/L. Among the 291 patients, 15 (5.2%) showed evidence of cardiac injury. Of 16 hospitalized patients with cardiac injury, the median age was 62 years, and 11/15 (73.3%) were men. Underlying cardiovascular diseases in some patients were hypertension (n=7, 46.6%), coronary heart disease (n=3, 20%) and diabetes (n=3, 20%). The most common symptoms at illness onset in patients with cardiac injury were fever (n=11, 73.3%), cough (n=7, 46.7%), headache or fatigue (n=5, 33.3%) and dyspnoea (n=4, 26.6%). These patients had higher systolic pressures, and lower lymphocyte counts and platelet counts, compared with patients without cardiac injury, respectively. Bilateral infiltrates on chest X-ray and elevated C-reactive protein occurred in all patients with cardiac injury. Compared with patients without cardiac injury, patients with cardiac injury were more likely to develop acute respiratory distress syndrome (73.3%), and receive mechanical ventilation (53.4%), continuous renal replacement therapy (33.3%), extracorporeal membrane oxygenation (26.7%) and vasopressor therapy (26.7%) and be admitted to the intensive care unit (73.3%). One patient died during the study. Conclusion Cardiac injury is a common condition among patients infected with 2019-nCoV.Compared with patients without cardiac injury, the clinical outcomes of patients with cardiac injury are relatively worse. Keywords: 2019-nCoV, Cardiac injury, Clinical features", "title": "Clinical features and outcomes of 2019 novel coronavirus-infected patients with cardiac injury", "pid": "qbxx6yae", "bm25_score": 217.45086669921875}, {"text": "The novel coronavirus disease (COVID-19) pandemic has already caused more than 300,000 deaths worldwide. Several studies have elucidated the central role of cardiovascular complications in the disease course. Herein, we provide a concise review of current knowledge regarding the involvement of cardiovascular system in the pathogenesis and prognosis of COVID-19. We summarize data from 21 studies involving in total more than 21,000 patients from Asia, Europe and the USA indicating that severe disease is associated with the presence of myocardial injury, heart failure and arrhythmias. Additionally, we present the clinical and laboratory differences between recovered and deceased patients highlighting the importance of cardiac manifestations. For the infected patients, underlying cardiovascular comorbidities and especially existing cardiovascular disease seem to predispose to the development of cardiovascular complications, which are in turn associated with higher mortality rates. We provide mechanistic insights into the underlying mechanisms including direct myocardial damage by the virus and the consequences of the hyperinflammatory syndrome developed later in the disease course. Finally, we summarize current knowledge on therapeutic modalities and recommendations by scientific societies and experts regarding the cardiovascular management of COVID-19 patients.", "title": "Involvement of Cardiovascular System As The Critical Point in Coronavirus Disease 2019 (COVID-19) Prognosis and Recovery", "pid": "fzmrvjtl", "bm25_score": 217.35997009277344}, {"text": "Coronavirus disease (COVID-19) is a serious illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The symptoms of the disease range from asymptomatic to mild respiratory symptoms and even potentially life-threatening cardiovascular and pulmonary complications. Cardiac complications include acute myocardial injury, arrhythmias, cardiogenic shock and even sudden death. Furthermore, drug interactions with COVID-19 therapies may place the patient at risk for arrhythmias, cardiomyopathy and sudden death. In this review, we summarise the cardiac manifestations of COVID-19 infection and propose a simplified algorithm for patient management during the COVID-19 pandemic.", "title": "SARS-CoV-2 Infection and Cardiovascular Disease: COVID-19 Heart", "pid": "0376d6vf", "bm25_score": 217.237060546875}, {"text": "", "title": "COVID-19 pandemic and cardiovascular complications: what have we learned so far?", "pid": "i7yul1c1", "bm25_score": 217.2069091796875}, {"text": "Patients with cardiovascular risk factors or established cardiovascular disease have an increased risk of developing coronavirus disease 19 and have a worse outcome when infected, but translating this notion into effective action is challenging. At present it is unclear whether cardiovascular therapies may reduce the likelihood of infection, or improve the survival of infected patients. Given the crucial importance of this issue for clinical cardiologists and all specialists dealing with coronavirus disease 19, we tried to recapitulate the current evidence and provide some practical recommendations.", "title": "Cardiovascular disease and COVID-19: les liaisons dangereuses", "pid": "hzq8pkr5", "bm25_score": 217.18727111816406}, {"text": "Abstract Coronavirus disease (COVID-19) pandemic has so far involved 184 countries and more than 2.79 million patients worldwide. Over the past three months, it has attributed to more than 196, 000 deaths, with more than 50, 000 deaths in the United States alone. Pulmonary manifestations are predominant and have been well identified. Cardiac involvement is also common. Acute cardiac injury, the most common cardiac manifestation of this disease can be seen in patients even without prior cardiac comorbidities. Established cardiovascular risk factors such as diabetes mellitus, hypertension, and coronary artery disease predispose to cardiac injury, the severity of illness and mortality. Non-ischemic myocardial injury secondary to cytokine storm is thought to be the predominant mechanism of acute cardiac injury associated with COVID-19. Multiple mechanisms and processes contribute to cardiac injury resulting in a poor outcome. Some of these are not clearly understood. Clinical and diagnostic details of cardiovascular involvement in these patients are mostly limited to biochemical markers. Multiple therapeutic agents have been tried with questionable efficacy and without clinical evidence. Interactions of comorbidities, cardiovascular drugs, the cardiac effect of therapeutic agents on the illness continue to be under investigation. With an increasing number of patients, newer promising therapies, and ongoing clinical trials, the exact mechanisms and extent to which these risk factors contribute to outcomes will be clearer in the future.", "title": "A review of cardiac manifestations and predictors of outcome in patients with COVID – 19", "pid": "lbt57ccs", "bm25_score": 217.15167236328125}, {"text": "BACKGROUND Many patients with COVID-19 have pre-existing cardiovascular (CV) co-morbidities or develop acute heart damage during the course of the disease. OBJECTIVES To study the risk of COVID-19 infection in the presence of preexisting CV diseases and to describe new CV manifestations during COVID-19. METHODS A \"scoping review\" was carried out via PubMed, to synthesize the results of research currently published on this subject. RESULTS Patients with cardiovascular disease were at greater risk of developing COVID-19, especially in its severe form. These patients were five to ten times more at risk of death. Cardiac manifestations, de novo, were dominated by acute myocardial damage, defined by a significant elevation of cardiac troponins. These occurred in 7 to 17% of hospitalized patients. The presence of a new heart lesion in patients with COVID-19 was consistently associated with a poor prognosis. CONCLUSION Given the enormous cardiovascular challenge posed by the COVID-19 pandemic and the prognostic impact of heart damage, additional research at a high level of evidence will be necessary.", "title": "COVID-19 and Cardiovascular diseases. Scoping review study.", "pid": "x4093iad", "bm25_score": 217.128662109375}, {"text": "Coronavirus disease (COVID-19) pandemic has so far involved 184 countries and more than 2.79 million patients worldwide. Over the past three months, it has attributed to more than 196,000 deaths, with more than 50,000 deaths in the United States alone. Pulmonary manifestations are predominant and have been well identified. Cardiac involvement is also common. Acute cardiac injury, the most common cardiac manifestation of this disease can be seen in patients even without prior cardiac comorbidities. Established cardiovascular risk factors such as diabetes mellitus, hypertension, and coronary artery disease predispose to cardiac injury, the severity of illness and mortality. Non-ischemic myocardial injury secondary to cytokine storm is thought to be the predominant mechanism of acute cardiac injury associated with COVID-19. Multiple mechanisms and processes contribute to cardiac injury resulting in a poor outcome. Some of these are not clearly understood. Clinical and diagnostic details of cardiovascular involvement in these patients are mostly limited to biochemical markers. Multiple therapeutic agents have been tried with questionable efficacy and without clinical evidence. Interactions of comorbidities, cardiovascular drugs, the cardiac effect of therapeutic agents on the illness continue to be under investigation. With an increasing number of patients, newer promising therapies, and ongoing clinical trials, the exact mechanisms and extent to which these risk factors contribute to outcomes will be clearer in the future.", "title": "A review of cardiac manifestations and predictors of outcome in patients with COVID - 19", "pid": "bus1nb6t", "bm25_score": 217.104248046875}, {"text": "", "title": "Cardiac Troponin-I may be a predictor of complications and mortality in COVID-19 patients.", "pid": "n2atn6nf", "bm25_score": 217.10035705566406}, {"text": "", "title": "The role of pre-existing chronic disease in cardiac complications from SARS-CoV-2 infection: A systematic review and meta-analysis", "pid": "xdk07uc5", "bm25_score": 217.09088134765625}, {"text": "", "title": "Cardiovascular complications in COVID-19: A systematic review and meta-analysis.", "pid": "t5zdmken", "bm25_score": 217.05332946777344}, {"text": "Respiratory symptoms, especially the development of severe acute respiratory distress syndrome, dominate the discussion and initial concerns of the population and health professionals. However, the cardiovascular system is greatly affected by these conditions and is often responsible for complications and mortality of these patients. In order to show the cardiovascular implications in patients infected with COVID-19 and the importance of social isolation as an alternative to curb the spread of the disease, a literature review was carried out based on 37 articles, in English, Portuguese and Spanish, available on Scielo and PubMed. The findings showed that cardiac complications associated with COVID-19 infection are similar to those produced by: severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and influenza. However, COVID-19 has a much greater and faster contamination and, unlike influenza, there is no vaccine or treatment available yet. In view of this, social isolation becomes a tool that can reduce and flatten the curve of cases and thus protect the people at higher risk, decreasing the chances of serious conditions related to the disease, potential deaths and the collapse of the country's health system.", "title": "Cardiovascular Implications in Patients Infected with Covid-19 and the Importance of Social Isolation to Reduce Dissemination of the Disease.", "pid": "0nyj1sbm", "bm25_score": 217.05279541015625}, {"text": "Introduction: Cardiac complications of COVID-19 are potentially life-threatening. The occurrence of myocardial injury in the context of COVID-19 is multifactorial and has generated increasing interest. Methods: A systematic review with meta-analysis of the literature was performed. MEDLINE and EMBASE were searched. Two independente reviewers evaluated the selected manuscripts for the outcome myocardial injury, defined by troponin elevation above the 99th percentile. Study heterogeneity and risk of bias were evaluated. Results: Eight studies, with a total of 1229 patients, were included. The frequency of myocardial injury was 16% (95% CI: 9% - 27%). The heterogeneity among studies was high (93%). Conclusions: Myocardial injury may occur in patients with COVID-19, with a frequency of 16% among current studies. Continuous research is needed to update these findings, as the pandemic evolves, and to define the implications of myocardial injury in the context of this infection.", "title": "Acute cardiac injury in patients with COVID-19", "pid": "wvxybca4", "bm25_score": 217.0479736328125}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide. Not just respiratory complications such as pneumonia and acute respiratory distress syndrome, cardiac manifestations have drawn attention due to the increased risk of mortality and morbidity related to SARS-CoV-2 infections. The mechanisms of the cardiac injury related to SARS-CoV-2 infections have been direct cardiac injury caused by angiotensin converting enzyme 2, hypoxemia, microvascular damage, and a systemic inflammatory response. Stress induced cardiomyopathy in a critically ill condition and acute coronary syndrome due to a vulnerable plaque rupture with coagulopathy can finally lead to acute heart failure with further cardiac manifestations. When dealing with the highly contagious viral disease-related cardiac manifestations, we should carefully apply the diagnostic and therapeutic methods to achieve the best therapeutic results without adding any risk of disease transmission.", "title": "Updates of Cardiovascular Manifestations in COVID-19: Korean Experience to Broaden Worldwide Perspectives", "pid": "43i56hfu", "bm25_score": 217.03514099121094}, {"text": "We present a case series of three patients with COVID-19 who developed arterial vascular complications, one who developed an acute CVA, one who developed popliteal artery occlusion and one who developed both during their hospital course. We present a case series of three patients admitted to Northwell Plainview Hospital in Plainview, New York with COVID-19 as confirmed by PCR. The clinical disease course of COVID-19 has been well documented in China and Europe and most recently, the United States. Publications highlighting the non-respiratory complications of COVID-19 have been limited.[1, 2] Acute cardiac injury and arrhythmia in the ICU have been described as major complications of COVID-19.[3] A few publications have highlighted the incidence of venous thromboembolic complications in COVID-19.[4, 5].", "title": "Arterial thromboembolic complications in COVID‐19 in low‐risk patients despite prophylaxis", "pid": "01yzk0au", "bm25_score": 217.0295867919922}, {"text": "COVID-2019 disease mainly affects the respiratory tract and can progress in severe cases to pneumonia, acute respiratory distress syndrome and multi-organ failure. Patients with prior cardiovascular disease are at higher risk of developing an infection and progressing to a severe form of the disease. Also, due to the growing number of infected cases, it is clear that, in addition to the typical respiratory symptoms caused by the infection, some patients suffer from cardiovascular damage. This condition can, in fact, cause significant myocardial damage, which worsens the disease and affects the prognosis. Based on the results of currently published research, it seems important to discuss the manifestations and characteristics of myocardial damage induced by COVID-19 and its impact on patient prognosis.", "title": "[COVID-19 andcardiovascular diseases].", "pid": "w996v6od", "bm25_score": 217.01797485351562}, {"text": "", "title": "Cardiovascular complications in COVID-19: A systematic review and meta-analysis", "pid": "bmsw715l", "bm25_score": 217.01568603515625}, {"text": "Up to 20-30% of patients hospitalized with coronavirus disease (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment for COVID-19 may affect convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk for cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19 associated cardiac injury is needed. The type of testing, and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of \"post-COVID-19 Cardiac Syndrome\".", "title": "COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors", "pid": "bsqpkjcj", "bm25_score": 217.01426696777344}, {"text": "", "title": "Severe Acute Respiratory Syndrome Coronavirus-2 Cardiovascular Complications: Implications for Cardiothoracic Anesthesiology.", "pid": "nkcp20lx", "bm25_score": 217.00613403320312}, {"text": "Up to 20-30% of patients hospitalized with coronavirus disease (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment for COVID-19 may affect convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk for cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19 associated cardiac injury is needed. The type of testing, and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of “post-COVID-19 Cardiac Syndrome”", "title": "COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors", "pid": "3tna1y5o", "bm25_score": 216.97714233398438}, {"text": "", "title": "Cardiac considerations in patients with COVID-19.", "pid": "zfs45uvp", "bm25_score": 216.97364807128906}, {"text": "BACKGROUND: Many patients with COVID-19 have pre-existing cardiovascular (CV) co-morbidities or develop acute heart damage during the course of the disease. OBJECTIVES: To study the risk of COVID-19 infection in the presence of preexisting CV diseases and to describe new CV manifestations during COVID-19. METHODS: A \"scoping review\" was carried out via PubMed, to synthesize the results of research currently published on this subject. RESULTS: Patients with cardiovascular disease were at greater risk of developing COVID-19, especially in its severe form. These patients were five to ten times more at risk of death. Cardiac manifestations, de novo, were dominated by acute myocardial damage, defined by a significant elevation of cardiac troponins. These occurred in 7 to 17% of hospitalized patients. The presence of a new heart lesion in patients with COVID-19 was consistently associated with a poor prognosis. CONCLUSION: Given the enormous cardiovascular challenge posed by the COVID-19 pandemic and the prognostic impact of heart damage, additional research at a high level of evidence will be necessary.", "title": "COVID-19 and Cardiovascular diseases. Scoping review study", "pid": "20zujaha", "bm25_score": 216.96665954589844}, {"text": "Coronavirus disease of 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading rapidly the world over. The disease was declared “pandemic” by the World Health Organization. An approved therapy for patients with COVID-19 has yet to emerge; however, there are some medications used in the treatment of SARS-CoV-2 infection globally including hydroxychloroquine, remdesivir, dexamethasone, protease inhibitors, and anti-inflammatory agents. Patients with underlying cardiovascular disease are at increased risk of mortality and morbidity from COVID-19. Moreover, patients with chronic stable states and even otherwise healthy individuals might sustain acute cardiovascular problems due to COVID-19 infection. This article seeks to review the latest evidence with a view to explaining possible pharmacotherapies for the cardiovascular complications of COVID-19 including acute coronary syndrome, heart failure, myocarditis, arrhythmias, and venous thromboembolism, as well as possible interactions between these medications and those currently administered (or under evaluation) in the treatment of COVID-19.", "title": "Cardiovascular Complications of COVID-19: Pharmacotherapy Perspective", "pid": "qvsoinfy", "bm25_score": 216.95901489257812}, {"text": "", "title": "Cardiac Troponin-I may be a predictor of complications and mortality in COVID-19 patients", "pid": "dzr7dfcu", "bm25_score": 216.9343719482422}, {"text": "Since its origin in China, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become a pandemic and spread to 209 countries. As coronavirus disease 2019 (COVID-19) is a very rapidly emerging disease, organ-specific studies related to it have been reported. Apart from respiratory findings, some studies have highlighted inflammatory consequences in the heart, kidney, and/or liver as well. Cardiac involvement in COVID-19 seems to be a result of an inflammatory storm in response to the infection. Moreover, direct viral invasion of cardiomyocytes, as well as a myocardial injury due to oxidative stress, may account for acute cardiac injury in COVID-19. Nevertheless, the mechanism of heart injury in COVID-19 is not clear yet. However, multiple studies that highlight the clinical features, laboratory findings, and prognosis of acute myocardial injury (AMI) in COVID-19-affected individuals have been published. In this review, we have summarized the findings of all those studies as well as the clinical features and management of cardiac injury discussed by some case reports.", "title": "Cardiac Manifestations of Coronavirus Disease 2019 (COVID-19): A Comprehensive Review", "pid": "qmp2tqtb", "bm25_score": 216.89019775390625}, {"text": "", "title": "Guidance for Health Care Providers on Management of Cardiovascular Complications in Patients Suspected or Confirmed with COVID 19 Virus Infection.", "pid": "o8mn467d", "bm25_score": 216.83592224121094}, {"text": "It has been pointed out that the second paragraph of the section \"Treatments for SARS-CoV-2 Infection\" contains an error. The original article has been corrected.", "title": "Correction to: Cardiovascular Complications in Patients with COVID-19: Consequences of Viral Toxicities and Host Immune Response", "pid": "cx6w1rh9", "bm25_score": 216.82974243164062}, {"text": "BACKGROUND: In this systematic review and meta-analysis, we aimed to explore the association between cardiac injury and mortality, the need for intensive care unit (ICU) care, acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19) in patients with COVID-19 pneumonia. METHODS: We performed a comprehensive literature search from several databases. Definition of cardiac injury follows that of the included studies, which includes highly sensitive cardiac troponin I (hs-cTnl) >99th percentile.The primary outcome was mortality, and the secondary outcomes were ARDS, the need for ICU care, and severe COVID-19. ARDS and severe COVID-19 were defined per the World Health Organization (WHO) interim guidance of severe acute respiratory infection (SARI) of COVID-19. RESULTS: There were a total of 2389 patients from 13 studies. This meta-analysis showed that cardiac injury was associated with higher mortality (RR 7.95 [5.12, 12.34], p < 0.001; I2: 65%). Cardiac injury was associated with higher need for ICU care (RR 7.94 [1.51, 41.78], p = 0.01; I2: 79%), and severe COVID-19 (RR 13.81 [5.52, 34.52], p < 0.001; I2: 0%). The cardiac injury was not significant for increased risk of ARDS (RR 2.57 [0.96, 6.85], p = 0.06; I2: 84%). The level of hs-cTnI was higher in patients with primary + secondary outcome (mean difference 10.38 pg/mL [4.44, 16.32], p = 0.002; I2: 0%). CONCLUSION: Cardiac injury is associated with mortality, need for ICU care, and severity of disease in patients with COVID-19.", "title": "Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis", "pid": "8txb9563", "bm25_score": 216.82090759277344}, {"text": "Coronavirus disease 2019 (COVID-19) has been declared a pandemic on 11 March 2020 by the WHO Despite being mainly a respiratory virus, cardiac complications have been described These range from sudden cardiac death to subtle diastolic dysfunction after recovery from COVID-19 The commonest cardiac presentation to date is acute heart failure resulting from biventricular or left ventricular hypokinesis and elevation of cardiac troponins It has been shown that COVID-19 downregulates angiotensin-converting enzyme-2, which has protective effects on the endothelium and cardiomyocytes It has also been proven that COVID-19 induces a state of hypercytokinaemia, some cytokines such as interleukin-1 and interleukin-6 have an injurious effect on the myocardium and endothelium, respectively Such pathogenic mechanisms might play a crucial role in induction of cardiomyocyte injury and impaired myocardial perfusion probably through coronary endothelial dysfunction The understanding and linking of such mechanisms might help in tailoring drug repurposing for treatment or prophylaxis of COVID-19 cardiovascular complications Received 6 April 2020 Accepted 14 April 2020 Correspondence to Antoine Fakhry AbdelMassih, MD, Pediatrics’ Department, Pediatric Cardiology unit, Cairo University Children Hospital, Faculty of Medicine, Cairo University, Kasr Al Ainy Street, Cairo 12411, Egypt, E-mail: antoine abdelmassih@kasralainy edu eg © 2020Wolters Kluwer Health Lippincott Williams Wilkins", "title": "Possible molecular and paracrine involvement underlying the pathogenesis of COVID-19 cardiovascular complications", "pid": "tkbctdyj", "bm25_score": 216.81814575195312}, {"text": "", "title": "Severe Acute Respiratory Syndrome Coronavirus-2 Cardiovascular Complications: Implications for Cardiothoracic Anesthesiology", "pid": "v56dkhc7", "bm25_score": 216.81414794921875}, {"text": "Although coronavirus disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system. Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes. However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain. Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19. Potential contributors to acute cardiac injury in the setting of COVID-19 include (1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; (2) acute coronary syndrome due to acute atherothrombosis in a virally induced thrombotic and inflammatory milieu; (3) microvascular dysfunction due to diffuse microthrombi or vascular injury; (4) stress-related cardiomyopathy (Takotsubo syndrome); (5) nonischemic myocardial injury due to a hyperinflammatory cytokine storm; or (6) direct viral cardiomyocyte toxicity and myocarditis. Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19. Practitioners should be vigilant for cardiovascular complications of COVID-19. Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, D-dimer, and inflammatory biomarkers. Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative nonischemic causes of injury, integrating the level of suspicion for COVID-19.", "title": "A current review of COVID-19 for the cardiovascular specialist", "pid": "umhj7nk7", "bm25_score": 216.80517578125}, {"text": "Coronavirus diseases 2019 (COVID-19) has become a worldwide pandemic affecting people at high risk and particularly at advanced age, cardiovascular and pulmonary disease. As cardiovascular patients are at high risk but also have dyspnea and fatigue as leading symptoms, prevention, diagnostics and treatment in these patients are important to provide adequate care for those with or without COVID-19 but most importantly when comorbid cardiovascular conditions are present. Severe COVID-19 with acute respiratory distress (ARDS) is challenging as patients with elevated myocardial markers such as troponin are at enhanced high risk for fatal outcomes. As angiotensin-converting enzyme 2 (ACE2) is regarded as the viral receptor for cell entry and as the Coronavirus is downregulating this enzyme, which provides cardiovascular and pulmonary protection, there is ongoing discussions on whether treatment with cardiovascular drugs, which upregulate the viral receptor ACE2 should be modified. As most of the COVID-19 patients have cardiovascular comorbidities like hypertension, diabetes, coronary artery disease and heart failure, which imposes a high risk on these patients, cardiovascular therapy should not be modified or even withdrawn. As cardiac injury is a common feature of COVID-19 associated ARDS and is linked with poor outcomes, swift diagnostic management and specialist care of cardiovascular patients in the area of COVID-19 is of particular importance and deserves special attention.", "title": "Coronavirus Disease 2019 (COVID-19) and its implications for cardiovascular care: expert document from the German Cardiac Society and the World Heart Federation", "pid": "0zkwn7hi", "bm25_score": 216.7954559326172}, {"text": "In patients with COVID-19, myocardial injury is prevalent and is associated with an adverse prognosis and increased mortality, according to two retrospective cohort studies from China and the USA.", "title": "Myocardial injury in patients with COVID-19", "pid": "jwu0az6g", "bm25_score": 216.79510498046875}, {"text": "Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, covid-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of covid-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.", "title": "Cardiovascular manifestations and treatment considerations in covid-19", "pid": "873txs85", "bm25_score": 216.79452514648438}, {"text": "Abstract Although Coronavirus Disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system. Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes. However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain. Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19. Potential contributors to acute cardiac injury in the setting of COVID-19 include 1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; 2) acute coronary syndrome due to acute atherothrombosis in a virally-induced thrombotic and inflammatory milieu; 3) microvascular dysfunction due to diffuse microthrombi or vascular injury; 4) stress-related cardiomyopathy (Takotsubo syndrome); 5) non-ischemic myocardial injury due to a hyperinflammatory cytokine storm; or 6) direct viral cardiomyocyte toxicity and myocarditis. Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19. Practitioners should be vigilant for cardiovascular complications of COVID-19. Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, d-dimer, and inflammatory biomarkers. Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative non-ischemic causes of injury, integrating the level of suspicion for COVID-19.", "title": "A current review of COVID-19 for the cardiovascular specialist", "pid": "dm9nefdg", "bm25_score": 216.7652587890625}, {"text": "As the coronavirus disease 2019 (COVID-19) pandemic evolves, more complications associated with the disease come to surface. Thus far, there is limited information available on the etiology, clinical outcomes, and management options for cardiovascular complications caused by COVID-19. This review focuses on literature published in year 2020 on the virus-induced cardiovascular damage with intention to better understand pathophysiology of this process, its impact on clinical outcomes, and available therapies. Literature review shows that severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) acts through angiotensin-converting enzyme 2 (ACE-2) receptors and causes cardiac injury by direct damage to the cardiomyocytes, systemic inflammation, fibrosis, interferon and cytokine-mediated immune response, coronary plaque destabilization, and hypoxia. Comorbidities, especially underling heart disease, make patients more predisposed to severe cardiovascular damage. COVID-19 patients who develop myocardial injury have a higher mortality rate compared to those who do not. During the pandemic, percutaneous coronary intervention (PCI) should remain the standard of care for patients with ST segment elevation myocardial infarction (STEMI). On the other hand, in order to limit healthcare worker exposure, patients with non-ST segment elevation myocardial infarction (NSTEMI) should be managed with stabilization strategies if hemodynamically stable. Monitoring hospitalized COVID-19 patients with high sensitivity troponin can help screen for severe complications and detect them early. Use of multiple investigational drugs with uncertain cardiac safety profiles in COVID-19 patients requires continuous cardiac monitoring. Notch signaling pathway therapy along with anti-viral agents, interleukin-6 inhibitors, and convalescent serum are possible treatment options to better control the inflammatory state that drives the cardiac damage.", "title": "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)-Induced Cardiovascular Syndrome: Etiology, Outcomes, and Management", "pid": "q82gkygd", "bm25_score": 216.76132202148438}, {"text": "The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients. First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death. Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. Third, therapies under investigation for COVID-19 may have cardiovascular side effects. Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions. Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission. We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.", "title": "Cardiovascular Considerations for Patients, Health Care Workers, and Health Systems During the COVID-19 Pandemic", "pid": "e9k6pnr3", "bm25_score": 216.74803161621094}, {"text": "OBJECTIVE COVID-19 is a disease with high mortality, and risk factors for worse clinical outcome have not been well-defined yet. The aim of this study is to delineate the prognostic importance of presence of concomitant cardiac injury on admission in patients with COVID-19. METHODS For this multi-center retrospective study, data of consecutive patients who were treated for COVID-19 between 20 March and 20 April 2020 were collected. Clinical characteristics, laboratory findings and outcomes data were obtained from electronic medical records. In-hospital clinical outcome was compared between patients with and without cardiac injury. RESULTS A total of 607 hospitalized patients with COVID-19 were included in the study; the median age was 62.5 ± 14.3 years, and 334 (55%) were male. Cardiac injury was detected in 150 (24.7%) of patients included in the study. Mortality rate was higher in patients with cardiac injury (42% vs. 8%; P < 0.01). The frequency of patients who required ICU (72% vs. 19%), who developed acute kidney injury (14% vs. 1%) and acute respiratory distress syndrome (71%vs. 18%) were also higher in patients with cardiac injury. In multivariate analysis, age, coronary artery disease (CAD), elevated CRP levels, and presence of cardiac injury [odds ratio (OR) 10.58, 95% confidence interval (CI) 2.42-46.27; P < 0.001) were found to be independent predictors of mortality. In subgroup analysis, including patients free of history of CAD, presence of cardiac injury on admission also predicted mortality (OR 2.52, 95% CI 1.17-5.45; P = 0.018). CONCLUSION Cardiac injury on admission is associated with worse clinical outcome and higher mortality risk in COVID-19 patients including patients free of previous CAD diagnosis.", "title": "Prognostic significance of cardiac injury in COVID-19 patients with and without coronary artery disease.", "pid": "z8ywyb1t", "bm25_score": 216.74742126464844}, {"text": "There has been the need to make major modifications to the way cardiology is practised in light of the COVID-19 pandemic. There has also been the need to recognise the complex cardiovascular manifestations and complications of COVID-19. In this article we provide guidance on the management of cardiac patients without COVID-19 in the current pandemic as well as patients with cardiac disease and COVID-19 and patients with cardiac complications of COVID-19. There is also a focus on indications and interpretation of commonly performed cardiac investigations in the setting of COVID-19. References are included from a number of specialist societies and groups.", "title": "SARS-CoV-2 pandemic and the cardiovascular system: What the non-cardiologist needs to know.", "pid": "8ysfaww2", "bm25_score": 216.738037109375}, {"text": "The COVID-19 pandemic has emerged as a serious global threat causing a large number of fatalities and putting enormous strain on the health care resources across the world. This has resulted in preferentially triaging the coronavirus infected patients and placing others, especially cardiovascular patients at increased risk for adverse complications. The effective management of cardiac patients in the hospital environment during this COVID-19 pandemic has emerged as a real challenge. We try to address this issue and also highlight the interplay between COVID-19 and cardiovascular diseases. We hereby review the available literature and emerging guidelines about cardiovascular implications related to COVID-19 which will have a bearing on the patient care, health care professionals and cardiac centres.", "title": "COVID-19 pandemic and the impact on the cardiovascular disease patient care", "pid": "5gd0q8yq", "bm25_score": 216.73170471191406}, {"text": "OBJECTIVE: COVID-19 is a disease with high mortality, and risk factors for worse clinical outcome have not been well-defined yet. The aim of this study is to delineate the prognostic importance of presence of concomitant cardiac injury on admission in patients with COVID-19. METHODS: For this multi-center retrospective study, data of consecutive patients who were treated for COVID-19 between 20 March and 20 April 2020 were collected. Clinical characteristics, laboratory findings and outcomes data were obtained from electronic medical records. In-hospital clinical outcome was compared between patients with and without cardiac injury. RESULTS: A total of 607 hospitalized patients with COVID-19 were included in the study; the median age was 62.5 ± 14.3 years, and 334 (55%) were male. Cardiac injury was detected in 150 (24.7%) of patients included in the study. Mortality rate was higher in patients with cardiac injury (42% vs. 8%; P < 0.01). The frequency of patients who required ICU (72% vs. 19%), who developed acute kidney injury (14% vs. 1%) and acute respiratory distress syndrome (71%vs. 18%) were also higher in patients with cardiac injury. In multivariate analysis, age, coronary artery disease (CAD), elevated CRP levels, and presence of cardiac injury [odds ratio (OR) 10.58, 95% confidence interval (CI) 2.42-46.27; P < 0.001) were found to be independent predictors of mortality. In subgroup analysis, including patients free of history of CAD, presence of cardiac injury on admission also predicted mortality (OR 2.52, 95% CI 1.17-5.45; P = 0.018). CONCLUSION: Cardiac injury on admission is associated with worse clinical outcome and higher mortality risk in COVID-19 patients including patients free of previous CAD diagnosis.", "title": "Prognostic significance of cardiac injury in COVID-19 patients with and without coronary artery disease", "pid": "dxfyfhnd", "bm25_score": 216.73094177246094}, {"text": "BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) could cause virulent infection leading to Corona Virus Disease 2019 (COVID-19)-related pneumonia as well as multiple organ injuries. HYPOTHESIS: COVID-19 infection may result in cardiovascular manifestations leading to worse clinical outcome. METHODS: Fifty four severe and critical patients with confirmed COVID-19 were enrolled. Risk factors predicting the severity of COVID-19 were analyzed. RESULTS: Of the 54 patients (56.1 ± 13.5 years old, 66.7% male) with COVID-19, 39 were diagnosed as severe and 15 as critical cases. The occurrence of diabetes, the level of D-dimer, inflammatory and cardiac markers in critical cases were significantly higher. Troponin I (TnI) elevation occurred in 42.6% of all the severe and critical patients. Three patients experienced hypotension at admission and were all diagnosed as critical cases consequently. Hypotension was found in one severe case and seven critical cases during hospitalization. Sinus tachycardia is the most common type of arrythmia and was observed in 23 severe patients and all the critical patients. Atrioventricular block and ventricular tachycardia were observed in critical patients at end stage while bradycardia and atrial fibrillation were less common. Mild pericardial effusion was observed in one severe case and five critical cases. Three critical cases suffered new onset of heart failure. Hypotension during treatment, severe myocardial injury and pericardial effusion were independent risk factors predicting the critical status of COVID-19 infection. CONCLUSION: This study has systemically observed the impact of COVID-19 on cardiovascular system, including myocardial injury, blood pressure, arrythmia and cardiac function in severe and critical cases. Monitoring of vital signs and cardiac function of COVID-19 patients and applying potential interventions especially for those with hypotension during treatment, severe myocardial injury or pericardial effusion, is of vital importance.", "title": "Cardiovascular manifestations in severe and critical patients with COVID-19", "pid": "x9qxnybj", "bm25_score": 216.7151336669922}, {"text": "Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has recently evolved as a pandemic disease. Although the respiratory system is predominantly affected, cardiovascular complications have been frequently identified, including acute myocarditis, myocardial infarction, acute heart failure, arrhythmias and venous thromboembolic events. Pericardial disease has been rarely reported. We present a case of acute life-threatening cardiac tamponade caused by a small pericardial effusion in a mechanically ventilated patient with severe COVID-19 associated pneumonia. The patient presented acute circulatory collapse with hemodynamic features of cardiogenic or obstructive shock. Bedside echocardiography permitted prompt diagnosis and life-saving pericardiocentesis. Further investigation revealed no other apparent cause of pericardial effusion except for SARS-CoV-2 infection. Cardiac tamponade may complicate COVID-19 and should be included in the differential diagnosis of acute hemodynamic deterioration in mechanically ventilated COVID-19 patients.", "title": "Acute Life-threatening Cardiac Tamponade in a Mechanically Ventilated Patient with COVID-19 Pneumonia", "pid": "p7iraa2k", "bm25_score": 216.71188354492188}, {"text": "Over the past few months, health systems worldwide have been put to the test with the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Even though the leading clinical manifestations of the SARS-CoV-2 infection involve the respiratory tract, there is a non-negligible risk of systemic involvement leading to the onset of multi-organ failure with fatal consequences. Since the onset of COVID-19, patients with underlying cardiovascular disease have been at increased risk of poor clinical outcomes with higher death rates. Moreover, the occurrence of new-onset cardiac complications is not uncommon among patients hospitalised for COVID-19. Of importance, a significant portion of COVID-19 patients present with myocardial injury. Herein, the authors discuss the mechanisms leading to myocardial and microvascular injury in SARS-CoV-2 infection and their clinical implications.", "title": "Myocardial and Microvascular Injury Due to Coronavirus Disease 2019", "pid": "uo88b0mk", "bm25_score": 216.70791625976562}, {"text": "The COVID-19 pandemic has emerged as a serious global threat causing a large number of fatalities and putting enormous strain on the health care resources across the world. This has resulted in preferentially triaging the coronavirus infected patients and placing others, especially cardiovascular patients at increased risk for adverse complications. The effective management of cardiac patients in the hospital environment during this COVID-19 pandemic has emerged as a real challenge. We try to address this issue and also highlight the interplay between COVID-19 and cardiovascular diseases. We hereby review the available literature and emerging guidelines about cardiovascular implications related to COVID-19 which will have a bearing on the patient care, health care professionals and cardiac centres.", "title": "COVID-19 pandemic and the impact on the cardiovascular disease patient care.", "pid": "nj0ue2c2", "bm25_score": 216.70591735839844}, {"text": "", "title": "Guidance for Health Care Providers on Management of Cardiovascular Complications in Patients Suspected or Confirmed with COVID 19 Virus Infection", "pid": "tdjdlnrk", "bm25_score": 216.6853790283203}, {"text": "BACKGROUND: COVID-19 infection may cause severe respiratory distress and is associated with increased morbidity and mortality. Impaired cardiac function and/or pre-existing cardiovascular disease may be associated with poor prognosis. In the present study, we report a comprehensive cardiovascular characterization in the first consecutive collective of patients that was admitted and treated at the University Hospital of Tübingen, Germany. METHODS: 123 consecutive patients with COVID-19 were included. Routine blood sampling, transthoracic echocardiography and electrocardiography were performed at hospital admission. RESULTS: We found that impaired left-ventricular and right-ventricular function as well as tricuspid regurgitation > grade 1 were significantly associated with higher mortality. Furthermore, elevated levels of myocardial distress markers (troponin-I and NT pro-BNP) were associated with poor prognosis in this patient collective. CONCLUSION: Impaired cardiac function is associated with poor prognosis in COVID-19 positive patients. Consequently, treatment of these patients should include careful guideline-conform cardiovascular evaluation and treatment. Thus, formation of a competent Cardio-COVID-19 team may represent a major clinical measure to optimize therapy of cardiovascular patients during this pandemic.", "title": "Impaired cardiac function is associated with mortality in patients with acute COVID-19 infection", "pid": "07iqhhcl", "bm25_score": 216.67959594726562}, {"text": "There has been the need to make major modifications to the way cardiology is practised in light of the COVID-19 pandemic. There has also been the need to recognise the complex cardiovascular manifestations and complications of COVID-19. In this article we provide guidance on the management of cardiac patients without COVID-19 in the current pandemic as well as patients with cardiac disease and COVID-19 and patients with cardiac complications of COVID-19. There is also a focus on indications and interpretation of commonly performed cardiac investigations in the setting of COVID-19. References are included from a number of specialist societies and groups.", "title": "SARS-CoV-2 pandemic and the cardiovascular system: What the non-cardiologist needs to know", "pid": "2k1n07on", "bm25_score": 216.6728515625}, {"text": "Abstract Coronavirus Disease 2019 (COVID-19) is a rapidly progressing global pandemic that may present with a variety of cardiac manifestations including, but not limited to, myocardial injury, myocardial infarction, arrhythmias, heart failure, cardiomyopathy, shock, thromboembolism, and cardiac arrest. These cardiovascular effects are worse in patients who have pre-existing cardiac conditions such as coronary artery disease, hypertension, diabetes mellitus, and coagulation abnormalities. Other predisposing risk factors include advanced age, immunocompromised state, and underlying systemic inflammatory conditions. Here we review the cellular pathophysiology, clinical manifestations and treatment modalities of the cardiac manifestations seen in patients with COVID-19.", "title": "COVID-19 Cardiovascular Epidemiology, Cellular Pathogenesis, Clinical Manifestations and Management", "pid": "dl8vjwfn", "bm25_score": 216.6639862060547}, {"text": "Coronavirus disease 2019 (COVID-19) predominantly presents with symptoms of fever, fatigue, cough and respiratory failure. However, it appears to have a unique interplay with cardiovascular disease (CVD); patients with pre-existing CVD are at highest risk for mortality from COVID-19, along with the elderly. COVID-19 contributes to cardiovascular complications including arrhythmias, myocardial dysfunction and myocardial inflammation. Although the exact mechanism of myocardial inflammation in patients with COVID-19 is not known, several plausible mechanisms have been proposed based on early observational reports. In this article, the authors summarise the available literature on mechanisms of myocardial injury in COVID-19.", "title": "Mechanisms of Myocardial Injury in Coronavirus Disease 2019", "pid": "h2xmxwd1", "bm25_score": 216.64492797851562}, {"text": "BACKGROUND The global coronavirus disease 2019 pandemic has highlighted the importance of understanding the cardiovascular implications of coronavirus infections, with more severe disease in those with cardiovascular co-morbidities, and resulting cardiac manifestations such as myocardial injury, arrhythmias, and heart failure. DESIGN A systematic review of the current knowledge on the effects of coronavirus infection on the cardiovascular system in humans was performed and results were summarized. METHODS Databases such as MEDLINE, EMBASE, CENTRAL, Scopus, Web of Science, ClinicalTrials.gov, Chinese Knowledge Resource Integrated Database and Chinese Clinical Trial Registry were searched on 20 March 2020. RESULTS In total, 135 studies were included, involving severe acute respiratory syndrome, Middle East respiratory syndrome, coronavirus disease 2019 and other coronaviruses. Most were case reports, case series and cohort studies of poor to fair quality. In post-mortem examinations of subjects who died from infection, around half had virus identified in heart tissues in severe acute respiratory syndrome, but none in Middle East respiratory syndrome and coronavirus disease 2019. Cardiac manifestations reported include tachycardia, bradycardia, arrhythmias, and myocardial injury, secondary to both systemic infection and treatment. Cardiac injury and arrhythmias are more prevalent in coronavirus disease 2019, and elevated cardiac markers are associated with intensive care unit admission and death. In severe acute respiratory syndrome, Middle East respiratory syndrome, and coronavirus disease 2019, comorbidities such as hypertension, diabetes mellitus, and heart disease are associated with intensive care unit admission, mechanical ventilation, and mortality. There were cases of misdiagnosis due to overlapping presentations of cardiovascular diseases and coronavirus infections, leading to hospital spread and delayed management of life-threatening conditions. CONCLUSION This review highlighted the ways in which coronaviruses affect cardiovascular function and interacts with pre-existing cardiovascular diseases.", "title": "Effect of coronavirus infection on the human heart: A scoping review.", "pid": "ti7gcpf0", "bm25_score": 216.6439208984375}, {"text": "Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cardiovascular manifestations of COVID-19 are diverse and complex and include acute coronary syndrome, myocarditis masquerading as ST-segment elevation myocardial infarction, pericarditis and pericardial effusion. We present 2 cases of COVID-19 infection with myocardial involvement with distinct mechanistic pathways and outcomes. Important decision strategies such as the timing of cardiac catheterization (when indicated) and requirement of early hemodynamic support in critically ill patients are discussed.", "title": "COVID-19 (SARS-Cov-2) and the heart – An ominous association", "pid": "rsyiemgn", "bm25_score": 216.62855529785156}, {"text": "OBJECTIVE: The availability of public health information for optimised supportive care is critical during the COVID-19 pandemic. We describe the first case of COVID-19 complicated by Takotsubo cardiomyopathy. MATERIALS AND METHODS: We report the clinical, laboratory and radiological findings of a patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: The nasopharyngeal swab was positive for SARS-CoV-2 and x-ray images demonstrated pathognomonic pneumonia. The patient developed tachycardia and the echocardiogram confirmed the diagnosis of Takotsubo cardiomyopathy. CONCLUSIONS: Doctors should be aware of the need to thoroughly study this new infection in order to understand its underlying mechanisms and related complications. LEARNING POINTS: We report the first case of Takotsubo cardiomyopathy associated with COVID-19. We discuss a rare presentation in the current pandemic. COVID-19 can be associated with cardiac complications, even after the onset of pneumonia, and so strict monitoring of these patients is essential.", "title": "Takotsubo Syndrome Associated with COVID-19", "pid": "oa55l5cr", "bm25_score": 216.61929321289062}, {"text": "COVID-2019 disease mainly affects the respiratory tract and can progress in severe cases to pneumonia, acute respiratory distress syndrome and multi-organ failure. Patients with prior cardiovascular disease are at higher risk of developing an infection and progressing to a severe form of the disease. Also, due to the growing number of infected cases, it is clear that, in addition to the typical respiratory symptoms caused by the infection, some patients suffer from cardiovascular damage. This condition can, in fact, cause significant myocardial damage, which worsens the disease and affects the prognosis. Based on the results of currently published research, it seems important to discuss the manifestations and characteristics of myocardial damage induced by COVID-19 and its impact on patient prognosis.", "title": "COVID-19 et maladies cardiovasculaires./ [COVID-19 andcardiovascular diseases]", "pid": "f7ne994m", "bm25_score": 216.59881591796875}, {"text": "The recent outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has been declared a public health emergency of international concern. COVID-19 may present as acute respiratory distress syndrome in severe cases, and patients with pre-existing cardiovascular comorbidities are reported to be the most vulnerable. Notably, acute myocardial injury, determined by elevated high-sensitivity troponin levels, is commonly observed in severe cases, and is strongly associated with mortality. Therefore, understanding the effects of COVID-19 on the cardiovascular system is essential for providing comprehensive medical care for critically ill patients. In this review, we summarize the rapidly evolving data and highlight the cardiovascular considerations related to COVID-19.", "title": "Impact of COVID-19 on the Cardiovascular System: A Review", "pid": "cm7lvoxj", "bm25_score": 216.591064453125}, {"text": "Background. The pandemic of Novel Coronavirus Disease 2019 (COVID-19) is challenging, given the large number of hospitalized patients. Cardiovascular co-morbidities are linked to a higher mortality risk. Thus, patients with Congenital Heart Disease (CHD) might represent a high-risk population. Nevertheless, no data about them are available, yet. Hence, we conducted a nationwide survey to assess clinical characteristics and outcomes in patients with congenital heart disease affected by COVID-19. Methods and Results. This is a multi-centre, observational, nationwide survey, involving high-volume Italian CHD centres. COVID-19 diagnosis was defined as either “clinically suspected” or “confirmed”, where a severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) test had been performed and was positive. Cardiovascular comorbidities were observed among adult patients—atrial fibrillation (seven; 9%), hypertension (five; 7%), obesity (seven; 9%) and diabetes (one; 1%)—but were absent among children. Cardiovascular complications were mainly observed in the “confirmed” COVID-19+group, consisting of heart failure (9%), palpitations/arrhythmias (3%), stroke/TIA (3%) and pulmonary hypertension (3%). Cardiovascular symptoms such as chest pain (1%), myocardial injury (1%) and pericardial effusion (1%) were also recorded. On the contrary, CHD patients from the clinically suspected COVID-19 group presented no severe symptoms or complications. Conclusions. Despite previous reports pointing to a higher case-fatality rate among patients with cardiovascular co-morbidities, we observed a mild COVID-19 clinical course in our cohort of CHD patients. Although these results should be confirmed in larger cohorts to investigate the underlying mechanisms, the findings of low cardiovascular complications rates and no deaths are reassuring for CHD patients.", "title": "COVID-19 and congenital heart disease: Results from a nationwide survey", "pid": "wenp9sgs", "bm25_score": 216.58984375}, {"text": "AIMS: To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy. METHODS AND RESULTS: The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020. Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease. Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease. Mean age was 67 ± 12 years, and 80 (81%) patients were males. No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients. During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock. Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08-5.09). The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively). CONCLUSIONS: Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.", "title": "Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy", "pid": "haj8qla4", "bm25_score": 216.58570861816406}, {"text": "OBJECTIVES The coronavirus disease-2019 (COVID-19) pandemic has resulted in the worst global pandemic of our generation, affecting 215 countries with nearly 5.5 million cases. The association between COVID-19 and the cardiovascular system has been well described. We sought to systematically review the current published literature on the different cardiac manifestations and the use of cardiac-specific biomarkers in terms of their prognostic value in determining clinical outcomes and correlation to disease severity. METHODS A systematic literature review across PubMed, Cochrane database, Embase, Google Scholar, and Ovid was performed according to PRISMA guidelines to identify relevant articles that discussed risk factors for cardiovascular manifestations, cardiac manifestations in COVID-19 patients, and cardiac-specific biomarkers with their clinical implications on COVID-19. RESULTS Sixty-one relevant articles were identified which described risk factors for cardiovascular manifestations, cardiac manifestations (including heart failure, cardiogenic shock, arrhythmia, and myocarditis among others) and cardiac-specific biomarkers (including CK-MB, CK, myoglobin, troponin, and NT-proBNP). Cardiovascular risk factors can play a crucial role in identifying patients vulnerable to developing cardiovascular manifestations of COVID-19 and thus help to save lives. A wide array of cardiac manifestations is associated with the interaction between COVID-19 and the cardiovascular system. Cardiac-specific biomarkers provide a useful prognostic tool in helping identify patients with the severe disease early and allowing for escalation of treatment in a timely fashion. CONCLUSION COVID-19 is an evolving pandemic with predominate respiratory manifestations, however, due to the interaction with the cardiovascular system; cardiac manifestations/complications feature heavily in this disease, with cardiac biomarkers providing important prognostic information.", "title": "Cardiac manifestations in COVID-19 patients-A systematic review.", "pid": "8otl3781", "bm25_score": 216.57907104492188}, {"text": "", "title": "Cardiac considerations in patients with COVID-19", "pid": "emj1wdac", "bm25_score": 216.56463623046875}, {"text": "Abstract Background In this systematic review and meta-analysis, we aimed to explore the association between cardiac injury and mortality, the need for intensive care unit (ICU) care, acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19) in patients with COVID-19 pneumonia. Methods We performed a comprehensive literature search from several databases. Definition of cardiac injury follows that of the included studies, which includes highly sensitive cardiac troponin I (hs-cTnl) >99th percentile.The primary outcome was mortality, and the secondary outcomes were ARDS, the need for ICU care, and severe COVID-19. ARDS and severe COVID-19 were defined per the World Health Organization (WHO) interim guidance of severe acute respiratory infection (SARI) of COVID-19. Results There were a total of 2389 patients from 13 studies. This meta-analysis showed that cardiac injury was associated with higher mortality (RR 7.95 [5.12, 12.34], p < 0.001; I2: 65%). Cardiac injury was associated with higher need for ICU care (RR 7.94 [1.51, 41.78], p = 0.01; I2: 79%), and severe COVID-19 (RR 13.81 [5.52, 34.52], p < 0.001; I2: 0%). The cardiac injury was not significant for increased risk of ARDS (RR 2.57 [0.96, 6.85], p = 0.06; I2: 84%). The level of hs-cTnI was higher in patients with primary + secondary outcome (mean difference 10.38 pg/mL [4.44, 16.32], p = 0.002; I2: 0%). Conclusion Cardiac injury is associated with mortality, need for ICU care, and severity of disease in patients with COVID-19.", "title": "Cardiac injury is associated with mortality and critically ill pneumonia in COVID-19: A meta-analysis", "pid": "i7j15rxy", "bm25_score": 216.56158447265625}, {"text": "Abstract Objective To describe the clinical features of coronavirus disease 2019 (COVID-19). Methods We recruited 73 patients with COVID-19 [49 men and 24 women; average age: 58.36 years (SD: 14.31)] admitted to the intensive care unit of Wuhan Jinyintan Hospital from December 30, 2019 to February 16, 2020. Demographics, underlying diseases, and laboratory test results on admission were collected and analyzed. Data were compared between survivors and non-survivors. Results The non-survivors were older (65.46 [SD 9.74] vs 46.23 [12.01]) and were more likely to have chronic medical illnesses. Non-survivors tend to develop more severe lymphopenia, with higher C-reactive protein, interleukin-6, D-dimer, and hs-Troponin I(hs-TnI) levels. Patients with elevated hs-TnI levels on admission had shorter duration from symptom onset to death. Increased hs-TnI level was related to dismal prognosis. Death risk increased by 20.8% when the hs-TnI level increased by one unit. After adjusting for inflammatory or coagulation index, the independent predictive relationship between hs-TnI and death disappeared. Conclusions Cardiac injury may occur at the early stage of COVID-19, which is associated with high mortality. Inflammatory factor cascade and coagulation abnormality may be the potential mechanisms of COVID-19 combined with cardiac injury.", "title": "Cardiac injuries in patients with coronavirus disease 2019: Not to be ignored", "pid": "o8df8szx", "bm25_score": 216.55894470214844}, {"text": "It is clear that existing cardiovascular disease is a major risk factor for COVID-19 and related adverse outcomes. In addition to acute respiratory syndrome, a large cohort also develop myocardial and/or vascular dysfunction, in part from inflammation and renin angiotensin system activation with increased sympathetic outflow, cardiac arrhythmias, ischemia, heart failure, and thromboembolic complications that portend poor COVID-19 outcomes. We summarize here recent information for hospitalists/internists on the front-line of this pandemic regarding its cardiovascular impacts and management and need for cardiovascular consultation.", "title": "Cardiovascular Considerations for the Internist and Hospitalist in the COVID-19 Era", "pid": "fitz1vjs", "bm25_score": 216.55474853515625}, {"text": "OBJECTIVES: The coronavirus disease-2019 (COVID-19) pandemic has resulted in the worst global pandemic of our generation, affecting 215 countries with nearly 5.5 million cases. The association between COVID-19 and the cardiovascular system has been well described. We sought to systematically review the current published literature on the different cardiac manifestations and the use of cardiac-specific biomarkers in terms of their prognostic value in determining clinical outcomes and correlation to disease severity. METHODS: A systematic literature review across PubMed, Cochrane database, Embase, Google Scholar, and Ovid was performed according to PRISMA guidelines to identify relevant articles that discussed risk factors for cardiovascular manifestations, cardiac manifestations in COVID-19 patients, and cardiac-specific biomarkers with their clinical implications on COVID-19. RESULTS: Sixty-one relevant articles were identified which described risk factors for cardiovascular manifestations, cardiac manifestations (including heart failure, cardiogenic shock, arrhythmia, and myocarditis among others) and cardiac-specific biomarkers (including CK-MB, CK, myoglobin, troponin, and NT-proBNP). Cardiovascular risk factors can play a crucial role in identifying patients vulnerable to developing cardiovascular manifestations of COVID-19 and thus help to save lives. A wide array of cardiac manifestations is associated with the interaction between COVID-19 and the cardiovascular system. Cardiac-specific biomarkers provide a useful prognostic tool in helping identify patients with the severe disease early and allowing for escalation of treatment in a timely fashion. CONCLUSION: COVID-19 is an evolving pandemic with predominate respiratory manifestations, however, due to the interaction with the cardiovascular system; cardiac manifestations/complications feature heavily in this disease, with cardiac biomarkers providing important prognostic information.", "title": "Cardiac manifestations in COVID-19 patients-A systematic review", "pid": "qbby61wj", "bm25_score": 216.5547332763672}, {"text": "Due to the lack of prospective, randomized, controlled clinical studies on inflammation and cardiovascular involvement, the exact mechanism of cardiac injury among patients with Coronavirus Disease 2019 (COVID-19) still remains uncertain. It was demonstrated that there is a high and significantly positive linear correlation between troponin T and plasma high-sensitivity C-reactive protein levels, biomarkers of cardiac injury and systemic inflammation, respectively. Cardiac injury and inflammation is a relatively common association among patients hospitalized with COVID-19, and it is related to higher risk of in-hospital mortality. In our literature search, we identified several potential mechanisms of myocardial tissue damage, namely, coronavirus-associated acute myocarditis, angiotensin-converting enzyme 2 receptor binding affinity to the virus Spike protein, increased cytokine secretion, and hypoxia-induced cardiac myocyte apoptosis. Elucidation of the disease pathogenesis and prospective histopathological studies are crucial for future proper treatment in case of renewed outbreaks. Of interest is that with hundred of thousands of bodies available for autopsy studies, no prospective investigation has been reported so far. Strong efforts and continued research of the cardiovascular complications and identification of risk factors for poor prognosis in COVID-19 are steadily needed. The high morbidity and mortality of COVID-19, its monumental economic burden and social impact, the despair of a new pandemic outbreak, and the thread of potential utilization of novel severe acute respiratory syndrome coronavirus 2 as biologic weapons make it a preponderant necessity to better comprehend the therapeutic management of this lethal disease. Emerging as an acute infectious disease, COVID-19 may become a chronic epidemic because of genetic recombination. Therefore, we should be ready for the reemergence of COVID-19 or other coronaviruses.", "title": "Potential Mechanisms of Cardiac Injury and Common Pathways of Inflammation in Patients With COVID-19", "pid": "rhvv3l0l", "bm25_score": 216.54978942871094}, {"text": "Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Cardiovascular manifestations of COVID-19 are diverse and complex and include acute coronary syndrome, myocarditis masquerading as ST-segment elevation myocardial infarction, pericarditis and pericardial effusion. We present 2 cases of COVID-19 infection with myocardial involvement with distinct mechanistic pathways and outcomes. Important decision strategies such as the timing of cardiac catheterization (when indicated) and requirement of early hemodynamic support in critically ill patients are discussed.", "title": "COVID-19 (SARS-Cov-2) and the heart - An ominous association", "pid": "q0qjfoc0", "bm25_score": 216.54942321777344}, {"text": "OBJECTIVE: This retrospective study aimed to analysis the clinical characteristics and complications in death cases with novel coronavirus disease-19 (COVID-19). METHOD: We collected the medical records of 92 patients with COVID-19 in Renmin Hospital of Wuhan University who died during January 6th to February 25th, 2020, summarized the clinical characteristics of complications. RESULTS: There were 91 death cases who developed different complications including acute respiratory distress syndrome (ARDS) (73/91), myocardial injury (31/91), liver injury (15/91), renal insufficiency (14/91), multiple organ dysfunction syndrome (MODS) (14/91) and pneumothorax (1/91). Among these patients, 83 patients had at least one complication. While 1 patient who died of recurrent gastrointestinal bleeding was not directly linked to COVID-19. CONCLUSION: The main complications of deceased patients with COVID-19 were ARDS, myocardial injury, liver injury, renal insufficiency and MODS. This article is protected by copyright. All rights reserved.", "title": "Analysis of 92 deceased patients with COVID-19", "pid": "dumf55yg", "bm25_score": 216.5478973388672}, {"text": "BACKGROUND: During the current coronavirus disease 2019 (COVID-19) pandemic, a link between acute cardiac injury and COVID-19 infection has been observed. There is currently no consensus on the incidence of cardiac injury, its relationship to prognosis, or its possible cause. This article provides a comprehensive review and meta-analysis of the incidence, comorbidities, outcomes and possible mechanisms of acute cardiac injury in COVID-19 patients. METHODS: We searched PubMed and Embase for studies that evaluated cardiac injury in hospitalized COVID-19 patients. Demographic information, co-morbidities, and relevant laboratory values were extracted and a meta-analysis was performed. RESULTS: Sixteen studies from China, Italy and the US with 2224 patients were included in this meta-analysis. The incidence of cardiac injury was 24.4% (542/2224 patients) in hospitalized COVID-19 patients. The all-cause mortality in patients with cardiac injury was 72.6% (OR=17.32, 95% CI 9.21-32.57) compared to those without cardiac injury (14.5%). In subgroup analyses, factors associated with increased risk of developing cardiac injury were older age and history of hypertension (HTN), and chronic obstructive respiratory disease (COPD). CONCLUSION: Cardiac injury is common in hospitalized COVID-19 patients and is significantly associated with mortality. Patients who were older with HTN and COPD were prone to develop cardiac injury. Early screening, triage and cardiac monitoring are recommended for these patients.", "title": "Cardiac Injury and COVID-19: A Systematic Review and Meta-Analysis", "pid": "zr96k6p1", "bm25_score": 216.54559326171875}, {"text": "AIMS: To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy. METHODS AND RESULTS: The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020. Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease. Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease. Mean age was 67 ± 12 years, and 80 (81%) patients were males. No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients. During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock. Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08–5.09). The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively). CONCLUSIONS: Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.", "title": "Characteristics and outcomes of patients hospitalized for COVID-19 and cardiac disease in Northern Italy", "pid": "1xkl3mof", "bm25_score": 216.54286193847656}, {"text": "Coronavirus disease 2019 (COVID-19) has become a global pandemic. It is still uncontrolled in most countries and no therapies are currently available. Various drugs are under investigation for its treatment. The disease is known to have worse outcomes in patients who have underlying cardiovascular disease. Chloroquine/hydroxychloroquine, azithromycin, remdesivir and lopinavir/ritonavir are currently being studied in trials and show some promise. Conduction disorders, heart failure and mortality have been reported with the use of these drugs. It is important to have a knowledge of potential cardiotoxic effects of these drugs before using them for COVID-19 patients for better allocation of healthcare resources and improvement in clinical outcomes.", "title": "Cardiovascular Safety of Potential Drugs for the Treatment of Coronavirus Disease 2019", "pid": "01es0zv4", "bm25_score": 216.54124450683594}, {"text": "As the severe acute respiratory syndrome coronavirus 2 virus pandemic continues to grow globally, an association is apparent between patients with underlying cardiovascular disease comorbidities and the risk of developing severe COVID-19. Furthermore, there are potential cardiac manifestations of severe acute respiratory syndrome coronavirus 2 including myocyte injury, ventricular dysfunction, coagulopathy, and electrophysiologic abnormalities. Balancing management of the infection and treatment of underlying cardiovascular disease requires further study. Addressing the increasing reports of health care worker exposure and deaths remains paramount. This review summarizes the most contemporary literature on the relationship of the cardiovascular system and COVID-19 and society statements with relevance to protection of health care workers, and provides illustrative case reports in this context.", "title": "COVID-19 and the cardiovascular system: A review of current data, summary of best practices, outline of controversies, and illustrative case reports.", "pid": "u856vml7", "bm25_score": 216.5262451171875}, {"text": "Coronavirus disease 2019 (COVID-19) has become a global pandemic. It is still uncontrolled in most countries and no therapies are currently available. Various drugs are under investigation for its treatment. The disease is known to have worse outcomes in patients who have underlying cardiovascular disease. Chloroquine/hydroxychloroquine, azithromycin, remdesivir and lopinavir/ritonavir are currently being studied in trials and show some promise. Conduction disorders, heart failure, and mortality have been reported with the use of these drugs. It is important to have knowledge of potential cardiotoxic effects of these drugs before using them for COVID-19 patients for better allocation of healthcare resources and improvement in clinical outcomes.", "title": "Cardiovascular Safety of Potential Drugs for the Treatment of Coronavirus Disease 2019", "pid": "23bvmeym", "bm25_score": 216.51210021972656}, {"text": "Importance: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19) has reached a pandemic level. Coronaviruses are known to affect the cardiovascular system. We review the basics of coronaviruses, with a focus on COVID-19, along with their effects on the cardiovascular system. Observations: Coronavirus disease 2019 can cause a viral pneumonia with additional extrapulmonary manifestations and complications. A large proportion of patients have underlying cardiovascular disease and/or cardiac risk factors. Factors associated with mortality include male sex, advanced age, and presence of comorbidities including hypertension, diabetes mellitus, cardiovascular diseases, and cerebrovascular diseases. Acute cardiac injury determined by elevated high-sensitivity troponin levels is commonly observed in severe cases and is strongly associated with mortality. Acute respiratory distress syndrome is also strongly associated with mortality. Conclusions and Relevance: Coronavirus disease 2019 is associated with a high inflammatory burden that can induce vascular inflammation, myocarditis, and cardiac arrhythmias. Extensive efforts are underway to find specific vaccines and antivirals against SARS-CoV-2. Meanwhile, cardiovascular risk factors and conditions should be judiciously controlled per evidence-based guidelines.", "title": "Potential Effects of Coronaviruses on the Cardiovascular System: A Review", "pid": "l54hk7go", "bm25_score": 216.51065063476562}]}
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[{"text": "Hypertension is one of the most common comorbidities in patients with coronavirus disease 2019 (COVID-19). This study aimed to clarify the impact of hypertension on COVID-19 and investigate whether the prior use of renin-angiotensin-aldosterone system (RAAS) inhibitors affects the prognosis of COVID-19. A total of 996 patients with COVID-19 were enrolled, including 282 patients with hypertension and 714 patients without hypertension. Propensity score-matched analysis (1:1 matching) was used to adjust the imbalanced baseline variables between the 2 groups. Patients with hypertension were further divided into the RAAS inhibitor group (n=41) and non-RAAS inhibitor group (n=241) according to their medication history. The results showed that COVID-19 patients with hypertension had more severe secondary infections, cardiac and renal dysfunction, and depletion of CD8+ cells on admission. Patients with hypertension were more likely to have comorbidities and complications and were more likely to be classified as critically ill than those without hypertension. Cox regression analysis revealed that hypertension (hazard ratio, 95% CI, unmatched cohort [1.80, 1.20-2.70]; matched cohort [2.24, 1.36-3.70]) was independently associated with all-cause mortality in patients with COVID-19. In addition, hypertensive patients with a history of RAAS inhibitor treatment had lower levels of C-reactive protein and higher levels of CD4+ cells. The mortality of patients in the RAAS inhibitor group (9.8% versus 26.1%) was significantly lower than that of patients in the non-RAAS inhibitor group. In conclusion, hypertension may be an independent risk factor for all-cause mortality in patients with COVID-19. Patients who previously used RAAS inhibitors may have a better prognosis.", "title": "Clinical Features of COVID-19 in Patients With Essential Hypertension and the Impacts of Renin-angiotensin-aldosterone System Inhibitors on the Prognosis of COVID-19 Patients.", "pid": "95wclabe", "bm25_score": 219.21275329589844}, {"text": "Investigations reported that hypertension, diabetes, and cardiovascular diseases were the most prevalent comorbidities among the patients with coronavirus disease 2019 (COVID-19). Hypertension appeared consistently as the most prevalent risk factors in COVID-19 patients. Some investigations speculated about the association between renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and increased mortality in these patients. This raised concern about the potential association between hypertension (and its treatment) and propensity for COVID-19. There are only a few follow-up studies that investigated the impact of comorbidities on outcome in these patients with conflicting findings. Hypertension has been proven to be more prevalent in patients with an adverse outcome (admission in intensive care unit, use of mechanical ventilation, or death). So far, there is no study that demonstrated independent predictive value of hypertension on mortality in COVID-19 patients. There are many speculations about this coronavirus and its relation with different risk factors and underlying diseases. The aim of this review was to summarize the current knowledge about the relationship between hypertension and COVID-19 and the role of hypertension on outcome in these patients.", "title": "COVID-19 and arterial hypertension: Hypothesis or evidence?", "pid": "9nbj3ckb", "bm25_score": 218.55419921875}, {"text": "Considering the number of patients affected by SARS-CoV-2, the World Health Organization declared a pandemic on 11 March 2020. A number of publications regarding the course of COVID-19 infection and its relation to comorbidities have appeared since December 2019, when the first cases of atypical pneumonia were diagnosed in China. There is evidence of the higher susceptibility and higher risk of unfavourable outcomes in comorbid patients, including those with hypertension. We summarize the available data on the association with the COVID-19 infection and arterial hypertension, and discuss potential risks, e. g. the risks and benefits of antihypertensive therapy (in particular, related to the blockers of renin-angiotensin-aldosterone system) and the management approaches.", "title": "COVID-19: What are the risks in hypertensive patients?", "pid": "ta9g9ceh", "bm25_score": 218.50119018554688}, {"text": "INTRODUCTION As the coronavirus disease 2019 (COVID-19) outbreak, identification of clinical predictors of severe or fatal disease are necessary to enable risk stratification and optimize allocation of limited resources. Hypertension has been widely reported to be associated with increase disease severity, however, other studies have reported different findings. OBJECTIVES To evaluate the association of hypertension and severe and fatal COVID-19. PATIENTS AND METHODS Scopus, Medline, and Web of Science was performed to identify studies reporting the rate of hypertension in COVID-19 patients with severe or non-severe disease or among survivors and non-survivors. The obtained data was pooled into a meta-analysis to calculate odds ratio (OR) with 95% confidence intervals (95%CI). RESULTS Hypertension was associated with a nearly 2.5-fold significantly increased risk of severe COVID-19 disease (OR: 2.49 [95%CI: 1.98-3.12] I2=24%), as well as with a similarly significant higher risk of mortality (OR: 2.42 [95%CI: 1.51-3.90] I2=0%). In meta-regression, a significant correlation was observed with an increase in mean age of patients with severe COVID-19 associated with increased log odds of hypertension and severity (p=0.03). CONCLUSIONS The results of this pooled analysis of the current scientific literature would suggest that hypertension may be associated with an up to 2.5-fold higher risk of severe and fatal COVID-19, especially among older individuals.", "title": "Hypertension and its severity or mortality in Coronavirus Disease 2019 (COVID-19): a pooled analysis.", "pid": "komx6t5h", "bm25_score": 218.44256591796875}, {"text": "INTRODUCTION: As the outbreak of coronavirus disease 2019 (COVID­19) was recognized, the clinical predictors of severe or fatal course of the disease should be identified to enable risk stratification and to allocate limited resources optimally. Hypertension has been widely reported to be associated with increased disease severity; however, some studies reported different findings. OBJECTIVES: The study aimed to evaluate the association between hypertension and severe and fatal COVID­19. PATIENTS AND METHODS: The Scopus, Medline, and Web of Science databases were searched to identify studies reporting the rate of hypertensive patients in the population diagnosed with severe or nonsevere COVID­19 or in COVID-19 survivors and nonsurvivors. The obtained data were pooled into a meta­analysis to calculate odds ratios (ORs) with 95% CIs. RESULTS: Hypertension was associated with a nearly 2.5­fold increased risk of severe COVID­19 (OR, 2.49; 95% CI, 1.98-3.12; I2 = 24%), as well as with a similarly significant higher mortality risk (OR, 2.42; 95% CI, 1.51-3.90; I2 = 0%). In a meta­regression analysis, a correlation was observed between an increase in the mean age of patients with severe COVID­19 and an increased log OR of hypertension and COVID-19 severity (P = 0.03). CONCLUSIONS: This pooled analysis of the current literature would suggest that hypertension may be associated with an up to 2.5­fold higher risk of severe or fatal COVID­19, especially in older individuals.", "title": "Hypertension in patients with coronavirus disease 2019 (COVID-19): a pooled analysis", "pid": "g484ymy9", "bm25_score": 218.3199005126953}, {"text": "Investigations reported that hypertension, diabetes, and cardiovascular diseases were the most prevalent comorbidities among the patients with coronavirus disease 2019 (COVID‐19). Hypertension appeared consistently as the most prevalent risk factors in COVID‐19 patients. Some investigations speculated about the association between renin‐angiotensin‐aldosterone system (RAAS) and susceptibility to COVID‐19, as well as the relationship between RAAS inhibitors and increased mortality in these patients. This raised concern about the potential association between hypertension (and its treatment) and propensity for COVID‐19. There are only a few follow‐up studies that investigated the impact of comorbidities on outcome in these patients with conflicting findings. Hypertension has been proven to be more prevalent in patients with an adverse outcome (admission in intensive care unit, use of mechanical ventilation, or death). So far, there is no study that demonstrated independent predictive value of hypertension on mortality in COVID‐19 patients. There are many speculations about this coronavirus and its relation with different risk factors and underlying diseases. The aim of this review was to summarize the current knowledge about the relationship between hypertension and COVID‐19 and the role of hypertension on outcome in these patients.", "title": "COVID‐19 and arterial hypertension: Hypothesis or evidence?", "pid": "hzb2fkj5", "bm25_score": 218.04458618164062}, {"text": "The coronavirus disease (COVID-19) has spread all around the world in a very short period of time. Recent data are showing significant prevalence of arterial hypertension and cardiovascular diseases (CVD) among patients with COVID-19, which raised many questions about higher susceptibility of patients with these comorbidities to the novel coronavirus, as well as the role of hypertension and CVD in progression and the prognosis of COVID-19 patients. There is a very limited amount of data, usually obtained from a small population, regarding the effect of the underlying disease on the outcome in patients with COVID-19. The evaluation of the treatment of these comorbidities at baseline and during COVID-19 is scarce and the results are conflicting. Hypertension and CVD, after the adjustment for other clinical and demographic parameters, primarily age, did not remain independent predictors of the lethal outcome in COVID-19 patients. Some investigations speculated about the association between the renin-angiotensin-aldosterone system (RAAS) and susceptibility to COVID-19, as well as the relationship between RAAS inhibitors and the adverse outcome in these patients. Withdrawing or switching RAAS inhibitors would have uncertain benefits, but it would definitely have many disadvantages such as uncontrolled hypertension, cardiac function deterioration and renal function impairment, which could potentially induce more complications in patients with COVID-19 than the infection of coronavirus itself. The aim of this review article was to summarize the prevalence of hypertension and CVD in patients with COVID-19, their influence on the outcome and the effect of treatment of hypertension and CVD in COVID-19 patients.", "title": "COVID-19, hypertension and cardiovascular diseases: Should we change the therapy?", "pid": "bwkad2s0", "bm25_score": 218.0333251953125}, {"text": "This study aims to explore the effect of hypertension on disease progression and prognosis in patients with coronavirus disease 2019 (COVID-19). A total of 310 patients diagnosed with COVID-19 were studied. A comparison was made between two groups of patients, those with hypertension and those without hypertension. Their demographic data, clinical manifestations, laboratory indicators, and treatment methods were collected and analyzed. A total of 310 patients, including 113 patients with hypertension and 197 patients without hypertension, were included in the analysis. Compared with patients without hypertension, patients with hypertension were older, were more likely to have diabetes and cerebrovascular disease, and were more likely to be transferred to the intensive care unit. The neutrophil count and lactate dehydrogenase, fibrinogen, and D-dimer levels in hypertensive patients were significantly higher than those in nonhypertensive patients (P < 0.05). However, multivariate analysis (adjusted for age and sex) failed to show that hypertension was an independent risk factor for COVID-19 mortality or severity. COVID-19 patients with hypertension were more likely than patients without hypertension to have severe pneumonia, excessive inflammatory reactions, organ and tissue damage, and deterioration of the disease. Patients with hypertension should be given additional attention to prevent worsening of their condition.", "title": "COVID-19 patients with hypertension have more severe disease: a multicenter retrospective observational study", "pid": "es8ztvq5", "bm25_score": 218.01947021484375}, {"text": "Hypertension is a common comorbidity in COVID-19 patients. However, the association of hypertension with the severity and fatality of COVID-19 remain unclear. In the present meta-analysis, relevant studies reported the impacts of hypertension on SARS-CoV-2 infection were identified by searching PubMed, Elsevier Science Direct, Web of Science, Wiley Online Library, Embase and CNKI up to 20 March 2020. As the results shown, 12 publications with 2389 COVID-19 patients (674 severe cases) were included for the analysis of disease severity. The severity rate of COVID-19 in hypertensive patients was much higher than in non-hypertensive cases (37.58% vs 19.73%, pooled OR: 2.27, 95% CI: 1.80-2.86). Moreover, the pooled ORs of COVID-19 severity for hypertension vs. non-hypertension was 2.21 (95% CI: 1.58-3.10) and 2.32 (95% CI: 1.70-3.17) in age <50 years and ⩾50 years patients, respectively. Additionally, six studies with 151 deaths of 2116 COVID-19 cases were included for the analysis of disease fatality. The results showed that hypertensive patients carried a nearly 3.48-fold higher risk of dying from COVID-19 (95% CI: 1.72-7.08). Meanwhile, the pooled ORs of COVID-19 fatality for hypertension vs. non-hypertension was 6.43 (95% CI: 3.40-12.17) and 2.66 (95% CI: 1.27-5.57) in age <50 years and ⩾50 years patients, respectively. Neither considerable heterogeneity nor publication bias was observed in the present analysis. Therefore, our present results provided further evidence that hypertension could significantly increase the risks of severity and fatality of SARS-CoV-2 infection.", "title": "Association of hypertension with the severity and fatality of SARS-CoV-2 infection: A meta-analysis", "pid": "u7fqjti5", "bm25_score": 217.86119079589844}, {"text": "BACKGROUND: Previous studies have shown that Coronavirus Disease 2019 (COVID-19) patients with underlying comorbidities can have worse outcomes. However, the effect of hypertension on outcomes of COVID-19 patients remains unclear. RESEARCH QUESTION: The aim of this study was to explore the effect of hypertension on the outcomes of patients with COVID-19 by using propensity score–matching (PSM) analysis. STUDY DESIGN AND METHODS: Participants enrolled in this study were patients with COVID-19 who had been hospitalized at the Central Hospital of Wuhan, China. Chronic comorbidities and laboratory and radiological data were reviewed; patient outcomes and lengths of stay were obtained from discharge records. We used the Cox proportional-hazard model (CPHM) to analyze the effect of hypertension on these patients’ outcomes and PSM analysis to further validate the abovementioned effect. RESULTS: A total of 226 patients with COVID-19 were enrolled in this study, of whom 176 survived and 50 died. The proportion of patients with hypertension among non-survivors was higher than that among survivors (26.70% vs. 74.00%; P < 0.001). Results obtained via CPHM showed that hypertension could increase risk of mortality in COVID-19 patients (hazard ratio 3.317; 95% CI [1.709–6.440]; P < 0.001). Increased D-dimer levels and higher ratio of neutrophils to lymphocytes (N/L) were also found to increase these patients’ mortality risk. After matching on propensity score, we still came to similar conclusions. After we applied the same method in critically ill patients, we found that hypertension also increased risk of death in patients with severe COVID-19. CONCLUSION: Hypertension, increased D-dimer and the ratio of neutrophil to lymphocyte increased mortality in patients with COVID-19, with hypertension in particular.", "title": "Effect of hypertension on outcomes of adult inpatients with COVID-19 in Wuhan, China: a propensity score–matching analysis", "pid": "xj50b7zo", "bm25_score": 217.8225555419922}, {"text": "Comorbid hypertension correlates with poorer outcomes in patients with Covid-19.", "title": "Cardiovascular comorbidity and its impact on patients with Covid-19", "pid": "z28bws23", "bm25_score": 217.8138427734375}, {"text": "OBJECTIVE: To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. METHODS: We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19. Composite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest. RESULTS: A total of 6560 patients were pooled from 30 studies. Hypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), p < 0.001; I2, 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), p < 0.001; I2, 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), p < 0.001; I2 31%), ARDS (RR 1.64 (1.11, 2.43), p = 0.01; I2,0%, p = 0.35), ICU care (RR 2.11 (1.34, 3.33), p = 0.001; I2 18%, p = 0.30), and disease progression (RR 3.01 (1.51, 5.99), p = 0.002; I2 0%, p = 0.55). Meta-regression analysis showed that gender (p = 0.013) was a covariate that affects the association. The association was stronger in studies with a percentage of males < 55% compared to ⩾ 55% (RR 2.32 v. RR 1.79). CONCLUSION: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.", "title": "Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression", "pid": "z9u229yg", "bm25_score": 217.7973175048828}, {"text": "OBJECTIVE: To investigate the association between hypertension and outcome in patients with Coronavirus Disease 2019 (COVID-19) pneumonia. METHODS: We performed a systematic literature search from several databases on studies that assess hypertension and outcome in COVID-19. Composite of poor outcome, comprising of mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care and disease progression were the outcomes of interest. RESULTS: A total of 6560 patients were pooled from 30 studies. Hypertension was associated with increased composite poor outcome (risk ratio (RR) 2.11 (95% confidence interval (CI) 1.85, 2.40), p < 0.001; I(2), 44%) and its sub-group, including mortality (RR 2.21 (1.74, 2.81), p < 0.001; I(2), 66%), severe COVID-19 (RR 2.04 (1.69, 2.47), p < 0.001; I(2) 31%), ARDS (RR 1.64 (1.11, 2.43), p = 0.01; I(2),0%, p = 0.35), ICU care (RR 2.11 (1.34, 3.33), p = 0.001; I(2) 18%, p = 0.30), and disease progression (RR 3.01 (1.51, 5.99), p = 0.002; I(2) 0%, p = 0.55). Meta-regression analysis showed that gender (p = 0.013) was a covariate that affects the association. The association was stronger in studies with a percentage of males < 55% compared to ⩾ 55% (RR 2.32 v. RR 1.79). CONCLUSION: Hypertension was associated with increased composite poor outcome, including mortality, severe COVID-19, ARDS, need for ICU care and disease progression in patients with COVID-19.", "title": "Hypertension is associated with increased mortality and severity of disease in COVID-19 pneumonia: A systematic review, meta-analysis and meta-regression", "pid": "ucimsb8d", "bm25_score": 217.76522827148438}, {"text": "Objectives: It is unclear whether patients with hypertension are more likely to be infected with SARS-COV-2 than the general population and whether there is a difference in the severity of COVID-19 pneumonia in patients who have taken ACEI/ARB drugs to lower blood pressure compared to those who have not. Methods: This observational study included data from all patients with clinically confirmed COVID-19 who were admitted to the Hankou Hospital, Wuhan, China between January 5 and March 8, 2020. Data were extracted from clinical and laboratory records. Follow-up was cutoff on March 8, 2020. Results: A total of 274 patients, 75 with hypertension and 199 without hypertension, were included in the analysis. Patients with hypertension were older and were more likely to have pre-existing comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease than patients without hypertension. Moreover, patients with hypertension tended to have higher positive COVID-19 PCR detection rates. Patients with hypertension who had previously taken ACEI/ARB drugs for antihypertensive treatment have an increased tendency to develop severe pneumonia after infection with SARS-COV-2 (P = 0.064). Conclusions: COVID-19 patients with hypertension were significantly older and were more likely to have underlying comorbidities, including chronic renal insufficiency, cardiovascular disease, diabetes mellitus, and cerebrovascular disease. Patients with hypertension who had taken ACEI/ARB drugs for antihypertensive treatment have an increased tendency to develop severe pneumonia after infection with SARS-COV-2. In future studies, a larger sample size and multi-center clinical data will be needed to support our conclusions.", "title": "Hypertension in patients hospitalized with COVID-19 in Wuhan, China: A single-center retrospective observational study", "pid": "lujxql3a", "bm25_score": 217.73007202148438}, {"text": "Hypertension is a common comorbidity in COVID-19 patients. However, the association of hypertension with the severity and fatality of COVID-19 remain unclear. In the present meta-analysis, relevant studies reported the impacts of hypertension on SARS-CoV-2 infection were identified by searching PubMed, Elsevier Science Direct, Web of Science, Wiley Online Library, Embase and CNKI up to 20 March 2020. As the results shown, 12 publications with 2389 COVID-19 patients (674 severe cases) were included for the analysis of disease severity. The severity rate of COVID-19 in hypertensive patients was much higher than in non-hypertensive cases (37.58% vs 19.73%, pooled OR: 2.27, 95% CI: 1.80–2.86). Moreover, the pooled ORs of COVID-19 severity for hypertension vs. non-hypertension was 2.21 (95% CI: 1.58–3.10) and 2.32 (95% CI: 1.70–3.17) in age <50 years and ⩾50 years patients, respectively. Additionally, six studies with 151 deaths of 2116 COVID-19 cases were included for the analysis of disease fatality. The results showed that hypertensive patients carried a nearly 3.48-fold higher risk of dying from COVID-19 (95% CI: 1.72–7.08). Meanwhile, the pooled ORs of COVID-19 fatality for hypertension vs. non-hypertension was 6.43 (95% CI: 3.40–12.17) and 2.66 (95% CI: 1.27–5.57) in age <50 years and ⩾50 years patients, respectively. Neither considerable heterogeneity nor publication bias was observed in the present analysis. Therefore, our present results provided further evidence that hypertension could significantly increase the risks of severity and fatality of SARS-CoV-2 infection.", "title": "Association of hypertension with the severity and fatality of SARS-CoV-2 infection: A meta-analysis", "pid": "lnjlyaex", "bm25_score": 217.69969177246094}, {"text": "There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID-19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin-angiotensin system (RAS) inhibitors due to a key role of angiotensin-converting enzyme 2 receptors in the entry of the SARS-CoV-2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS-CoV-2 virus infection or worsens the course of COVID-19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID-19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N-terminal pro-B-type natriuretic peptide, D-dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID-19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well-being. For the ongoing management of patients with hypertension, telemedicine-based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID-19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.", "title": "COVID-19 and hypertension-evidence and practical management: Guidance from the HOPE Asia Network", "pid": "jhkc8of3", "bm25_score": 217.6162109375}, {"text": "The virus responsible for COVID-19 binds to the angiotensin converting enzyme-2 (ACE-2) receptor [1]. Several articles have noted that hypertension is a risk factor for COVID-19 [2-7]. It is currently difficult to distinguish between hypertension as an independent risk factor in COVID-19 from one that co-varies with other patient factors such as age and cardiovascular disease. It is difficult from individual reports to determine whether hypertension is a risk factor for development of symptomatic disease or hospitalisation or for more severe disease. Reviewing the literature that reports rates of hypertension amongst included patients indicates a consistent association with more severe disease and increased mortality.", "title": "The importance of hypertension as a risk factor for severe illness and mortality in COVID‐19", "pid": "4ko4lwjz", "bm25_score": 217.54759216308594}, {"text": "The association between hypertension, diabetes, cardio and cerebrovascular disease and severe and fatal COVID-19, described in different countries, is remarkable. Myocardial damage and myocardial dysfunction are postulated as a possible causal nexus. Frequent findings of elevated troponin levels and electrocardiographic anomalies support this concept. On the other hand, hypotheses in favour and against a deleterious effect of angiotensin converting enzyme inhibitors and angiotensin receptor blockers, a usual treatment for cardiovascular disease, have been raised. There is currently no solid evidence and thus properly designed studies on this subject are urgently needed. In this context, patients with cardiovascular disease should especially avoid being exposed to the virus, should not self-medicate and rapidly seek medical advice should they show symptoms of infection.", "title": "COVID-19, hipertensión y enfermedad cardiovascular./ [COVID-19 and its relationship with hypertension and cardiovascular disease]", "pid": "f8v51ouz", "bm25_score": 217.54434204101562}, {"text": "PURPOSE OF REVIEW: There is increasing evidence indicating an association between several risk factors and worse prognosis in patients with coronavirus disease 2019 (COVID-19), including older age, hypertension, heart failure, diabetes, and pulmonary disease. Hypertension is of particular interest because it is common in adults and there are concerns related to the use of renin-angiotensin system (RAS) inhibitors in patients with hypertension infected with COVID-19. Levels of angiotensin-converting enzyme 2 (ACE2), a protein that facilitates entry of coronavirus into cells, may increase in patients using RAS inhibitors. Thus, chronic use of RAS inhibition could potentially lead to a more severe and fatal form of COVID-19. In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? (2) Are the risks of complications in hypertension mediated by its treatment? (3) Is aging a major factor associated with worse prognosis in patients with COVID-19 and hypertension? RECENT FINDINGS: Despite the potential involvement of immune responses in the pathogenesis of hypertension, there is no evidence supporting that hypothesis that hypertension or RAS inhibitors contributes to unfavorable outcomes in viral infections. Future investigations adopting a strict protocol for confirming hypertension status as well as assessing associated comorbidities that may influence outcomes are necessary. From the therapeutic perspective, recombinant ACE2 may serve as a potential therapy, but relevant studies in humans are lacking. Definitive evidence regarding the use of RAS inhibitors in patients with COVID-19 is needed; 5 randomized trials examining this issue are currently underway. SUMMARY: There is no current scientific support for claiming that hypertension or its treatment with RAS inhibitors contribute to unfavorable outcomes in COVID-19.", "title": "Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic?", "pid": "n4dgqo73", "bm25_score": 217.51971435546875}, {"text": "PURPOSE OF REVIEW: There is increasing evidence indicating an association between several risk factors and worse prognosis in patients with coronavirus disease 2019 (COVID-19), including older age, hypertension, heart failure, diabetes, and pulmonary disease. Hypertension is of particular interest because it is common in adults and there are concerns related to the use of renin-angiotensin system (RAS) inhibitors in patients with hypertension infected with COVID-19. Levels of angiotensin-converting enzyme 2 (ACE2), a protein that facilitates entry of coronavirus into cells, may increase in patients using RAS inhibitors. Thus, chronic use of RAS inhibition could potentially lead to a more severe and fatal form of COVID-19. In this review, we provide a critical review to the following questions: (1) Does hypertension influence immunity or ACE2 expression favoring viral infections? (2) Are the risks of complications in hypertension mediated by its treatment? (3) Is aging a major factor associated with worse prognosis in patients with COVID-19 and hypertension? RECENT FINDINGS: Despite the potential involvement of immune responses in the pathogenesis of hypertension, there is no evidence supporting that hypothesis that hypertension or RAS inhibitors contributes to unfavorable outcomes in viral infections. Future investigations adopting a strict protocol for confirming hypertension status as well as assessing associated comorbidities that may influence outcomes are necessary. From the therapeutic perspective, recombinant ACE2 may serve as a potential therapy, but relevant studies in humans are lacking. Definitive evidence regarding the use of RAS inhibitors in patients with COVID-19 is needed; 5 randomized trials examining this issue are currently underway. There is no current scientific support for claiming that hypertension or its treatment with RAS inhibitors contribute to unfavorable outcomes in COVID-19.", "title": "Is Hypertension a Real Risk Factor for Poor Prognosis in the COVID-19 Pandemic?", "pid": "gwefujal", "bm25_score": 217.4986114501953}, {"text": "Systemic arterial hypertension (referred to as hypertension herein) is a major risk factor of mortality worldwide, and its importance is further emphasized in the context of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to as COVID-19. Patients with severe COVID-19 infections commonly are older and have a history of hypertension. Almost 75% of patients who have died in the pandemic in Italy had hypertension. This raised multiple questions regarding a more severe course of COVID-19 in relation to hypertension itself as well as its treatment with renin–angiotensin system (RAS) blockers, e.g. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We provide a critical review on the relationship of hypertension, RAS, and risk of lung injury. We demonstrate lack of sound evidence that hypertension per se is an independent risk factor for COVID-19. Interestingly, ACEIs and ARBs may be associated with lower incidence and/or improved outcome in patients with lower respiratory tract infections. We also review in detail the molecular mechanisms linking the RAS to lung damage and the potential clinical impact of treatment with RAS blockers in patients with COVID-19 and a high cardiovascular and renal risk. This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues. In summary, a critical review of available evidence does not support a deleterious effect of RAS blockers in COVID-19 infections. Therefore, there is currently no reason to discontinue RAS blockers in stable patients facing the COVID-19 pandemic.", "title": "Hypertension, the renin–angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19: European Society of Hypertension COVID-19 Task Force Review of Evidence", "pid": "y4h95kb4", "bm25_score": 217.4897918701172}, {"text": "", "title": "COVID-19 and hypertension", "pid": "6xntcvmb", "bm25_score": 217.4556427001953}, {"text": "The novel respiratory Syndrome Coronavirus-2 (SARS-CoV-2) caused a cluster of pneumonia cases in China at the end of 2019. After few months, it led to a pandemic that has spread throughout most countries of the world (https://coronavirus.jhu.edu/map.html).", "title": "Severity of COVID-19: The importance of being hypertensive.", "pid": "xm9k6fn2", "bm25_score": 217.4044647216797}, {"text": "The novel respiratory Syndrome Coronavirus-2 (SARS-CoV-2) caused a cluster of pneumonia cases in China at the end of 2019. After few months, it led to a pandemic that has spread throughout most countries of the world (https://coronavirus.jhu.edu/map.html).", "title": "Severity of COVID-19: The importance of being hypertensive", "pid": "5wpy9uzq", "bm25_score": 217.33807373046875}, {"text": "AIM: The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. METHODS: A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. RESULTS: Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2: 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2: 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2: 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2: 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2: 52.4%). CONCLUSIONS: Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.", "title": "Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis", "pid": "04s7w017", "bm25_score": 217.29425048828125}, {"text": "Abstract Aim The novel coronavirus infection (COVID-19), now a worldwide public health concern is associated with varied fatality. Patients with chronic underlying conditions like diabetes and hypertension have shown worst outcomes. The understanding of the association might be helpful in early vigilant monitoring and better management of COVID-19 patients at high risk. The aim of the meta-analysis was to assess the association of diabetes and hypertension with severity of disease. Methods A literature search was conducted using the databases PubMed and Cochrane until March 31, 2020. Seven studies were included in the meta- analysis, including 2018 CIVID-19 patients. Results Diabetes was lower in the survivors (OR: 0.56; 95%CI: 0.35-0.90; p=0.017; I2 : 0.0%) and non-severe (OR: 1.66; 95%CI: 1.20-2.30; p=0.002; I2 : 0.0%) patients. No association of diabetes was found with ICU care. Hypertension was positively associated with death (OR: 0.49; 95%CI: 0.34-0.73; p=0.000; I2 : 0.0%), ICU care (OR: 0.42; 95%CI: 0.22-0.81; p=0.009; I2 : 0.0%) and severity (OR: 2.69; 95%CI: 1.27-5.73; p=0.01; I2 : 52.4%). Conclusions Our findings suggest that diabetes and hypertension have a negative effect on health status of COVID-19 patients. However, large prevalence studies demonstrating the consequences of comorbid diabetes and hypertension are urgently needed to understand the magnitude of these vexatious comorbidities.", "title": "Association of diabetes and hypertension with disease severity in covid-19 patients: a systematic literature review and exploratory meta-analysis", "pid": "9qq049qb", "bm25_score": 217.29014587402344}, {"text": "We have read with great interest the recently published study from Guan et al. [1] entitled Comorbidity and its impact on 1590 patients with Covid-19 in China: A Nationwide Analysis. To the best of our knowledge this is the first large scale study that focuses on independent clinical risk factors associated with a composite outcome (death, use of ventilator or ICU requirement), using a Cox regression model.", "title": "Arterial hypertension and the risk of severity and mortality of COVID-19", "pid": "l2f6g7i6", "bm25_score": 217.267822265625}, {"text": "Background: COVID-19 patients with chronic diseases such as hypertension, diabetes and coronary heart diseases is more likely to worsen, but with mixed results for COVID-19 severity. This meta-analysis is to analyze the correlation between hypertension, diabetes, coronary heart disease and COVID-19 disease severity. Methods: Available data from PubMed, Web of Science, China National Knowledge Infrastructure Database, WanFang Database and VIP Database, were analyzed using a fixed effects model meta-analysis to derive overall odds ratios (OR) with 95% CIs. Funnel plots and Begg's were used to assess publication bias. Findings: Of 182 articles found following our initial search, we assessed 34 full-text articles, of which 9 articles with 1936 COVID-19 patients met all selection criteria for our meta-analysis. No significant heterogeneity between studies. There were significant correlations between COVID-19 severity and hypertension [OR=2.3 [95% CI (1.76, 3.00), P<0.01], diabetes [OR=2.67, 95% CI (1.91, 3.74), P<0.01], coronary heart disease [OR=2.85 [95% CI (1.68, 4.84), P<0.01]. Most of the studies in the funnel plot are on the upper part and few on the base part, and are roughly symmetrical left and right. Begg's test: hypertension (Z=-0.1, P=1.0), diabetes (Z=0.73, P=0.466), coronary heart disease (Z=0.38, P=0.707), all found no publication bias. Interpretation: Hypertension, diabetes, and coronary heart disease can affect the severity of COVID-19. It may be related to the imbalance of angiotensin-converting enzyme 2 (ACE2) and the cytokine storm induced by Glucolipid metabolic disorders (GLMD).", "title": "Effects of hypertension, diabetes and coronary heart disease on COVID-19 diseases severity: a systematic review and meta-analysis", "pid": "v6frcc5r", "bm25_score": 217.22225952148438}, {"text": "", "title": "Hypertension and COVID-19", "pid": "bzz8ydcs", "bm25_score": 217.2193603515625}, {"text": "", "title": "No adequate evidence indicating hypertension as an independent risk factor for COVID-19 severity", "pid": "49d3w525", "bm25_score": 217.19947814941406}, {"text": "", "title": "The importance of hypertension as a risk factor for severe illness and mortality in COVID-19", "pid": "tmrcgdal", "bm25_score": 217.16995239257812}, {"text": "COVID 19, caused by the SARS-CoV-2 virus, a newly discovered coronavirus, has caused the global pandemic of early 2020. The first case was described in December 2019 in Wuhan, China, and by March 2020, most countries around the world have put in place some of the strictest restrictions seen in decades in order to slow down the spread of the disease. Patients with pre-existing hypertension and cardiovascular comorbidities were reported to be at an increased risk of serious infections caused by SARS-CoV-2. Considering that those are among the most common chronic medical conditions in the Western world, the potential impact of it is huge. The proposed mechanism behind those associations is the expression of angiotensin converting enzyme II (ACE II) in those patients. Furthermore, the association between ACE inhibitors/AR blockers, which are among the most frequently prescribed medications, and serious cases of COVID 19 has been studied with the same mechanism in mind. The reports on the association between hypertension and COVID 19 morbidity and mortality are less clear, and the International Society of Hypertension even claims that there is none. The reports on the association between heart failure or coronary disease and COVID 19 are more uniform, and all seem to point to a greater risk from serious infections faced by patients with those comorbidities. A significant effort will need to be invested by the scientific community into finding strategies for protecting those patients from contracting the virus in the first place and then, once infected, into developing management plans aimed at preserving cardiac function as much as possible.", "title": "SARS-CoV-2 (COVID 19) Infection in Hypertensive Patients and in Patients With Cardiac Disease", "pid": "xw817l53", "bm25_score": 217.15963745117188}, {"text": "Systemic arterial hypertension (referred to as hypertension herein) is a major risk factor of mortality worldwide, and its importance is further emphasized in the context of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to as COVID-19. Patients with severe COVID-19 infections commonly are older and have a history of hypertension. Almost 75% of patients who have died in the pandemic in Italy had hypertension. This raised multiple questions regarding a more severe course of COVID-19 in relation to hypertension itself as well as its treatment with renin-angiotensin system (RAS) blockers, e.g. angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). We provide a critical review on the relationship of hypertension, RAS, and risk of lung injury. We demonstrate lack of sound evidence that hypertension per se is an independent risk factor for COVID-19. Interestingly, ACEIs and ARBs may be associated with lower incidence and/or improved outcome in patients with lower respiratory tract infections. We also review in detail the molecular mechanisms linking the RAS to lung damage and the potential clinical impact of treatment with RAS blockers in patients with COVID-19 and a high cardiovascular and renal risk. This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues. In summary, a critical review of available evidence does not support a deleterious effect of RAS blockers in COVID-19 infections. Therefore, there is currently no reason to discontinue RAS blockers in stable patients facing the COVID-19 pandemic.", "title": "Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19", "pid": "69qefbbo", "bm25_score": 217.06124877929688}, {"text": "BACKGROUND AND AIMS: To undertake a review and critical appraisal of published/preprint reports that offer methods of determining the effects of hypertension, diabetes, stroke, cancer, kidney issues, and high-cholesterol on COVID-19 disease severity. METHODS: A search was conducted by two authors independently on the freely available COVID-19 Open Research Dataset (CORD-19). We developed an automated search engine to screen a total of 59,000 articles in a few seconds. Filtering of the articles was then undertaken using keywords and questions, e.g. “Effects of diabetes on COVID/normal coronavirus/SARS-CoV-2/nCoV/COVID-19 disease severity, mortality?“. The search terms were repeated for all the comorbidities considered in this paper. Additional articles were retrieved by searching via Google Scholar and PubMed. FINDINGS: A total of 54 articles were considered for a full review. It was observed that diabetes, hypertension, and cholesterol levels possess an apparent relation to COVID-19 severity. Other comorbidities, such as cancer, kidney disease, and stroke, must be further evaluated to determine a strong relationship to the virus. CONCLUSION: Reports associating cancer, kidney disease, and stroke with COVID-19 should be carefully interpreted, not only because of the size of the samples, but also because patients could be old, have a history of smoking, or have any other clinical condition suggesting that these factors might be associated with the poor COVID-19 outcomes rather than the comorbidity itself. Further research regarding this relationship and its clinical management is warranted.", "title": "Association of hypertension, diabetes, stroke, cancer, kidney disease, and high-cholesterol with COVID-19 disease severity and fatality: A systematic review", "pid": "ab5tgbvm", "bm25_score": 217.0541229248047}, {"text": "ABSTRACT Hypertension emerged from early reports as a potential risk factor for worse outcomes for persons with coronavirus disease 2019 (COVID-19). Among the putative links between hypertension and COVID-19 is a key counter-regulatory component of the renin-angiotensin system (RAS): angiotensin-converting enzyme 2 (ACE2). ACE2 facilitates entry of SARS-CoV-2, the virus responsible for COVID-19, into host cells. Since RAS inhibitors have been suggested to increase ACE2 expression, healthcare providers and patients have grappled with the decision of whether to discontinue these medications during the COVID-19 pandemic. However, experimental models of analogous viral pneumonias suggest RAS inhibitors may exert protective effects against acute lung injury. We review how RAS and ACE2 biology may affect outcomes in COVID-19 through pulmonary and other systemic effects. In addition, we briefly detail the data for and against continuation of RAS inhibitors in persons with COVID-19 and summarize the current consensus recommendations from select specialty organizations.", "title": "COVID-19 and Hypertension: The Role of ACE2 and the Renin-Angiotensin System", "pid": "4ined9rx", "bm25_score": 217.04840087890625}, {"text": "There are several risk factors for worse outcomes in patients with coronavirus 2019 disease (COVID‐19). Patients with hypertension appear to have a poor prognosis, but there is no direct evidence that hypertension increases the risk of new infection or adverse outcomes independent of age and other risk factors. There is also concern about use of renin‐angiotensin system (RAS) inhibitors due to a key role of angiotensin‐converting enzyme 2 receptors in the entry of the SARS‐CoV‐2 virus into cells. However, there is little evidence that use of RAS inhibitors increases the risk of SARS‐CoV‐2 virus infection or worsens the course of COVID‐19. Therefore, antihypertensive therapy with these agents should be continued. In addition to acute respiratory distress syndrome, patients with severe COVID‐19 can develop myocardial injury and cytokine storm, resulting in heart failure, arteriovenous thrombosis, and kidney injury. Troponin, N‐terminal pro‐B‐type natriuretic peptide, D‐dimer, and serum creatinine are biomarkers for these complications and can be used to monitor patients with COVID‐19 and for risk stratification. Other factors that need to be incorporated into patient management strategies during the pandemic include regular exercise to maintain good health status and monitoring of psychological well‐being. For the ongoing management of patients with hypertension, telemedicine‐based home blood pressure monitoring strategies can facilitate maintenance of good blood pressure control while social distancing is maintained. Overall, multidisciplinary management of COVID‐19 based on a rapidly growing body of evidence will help ensure the best possible outcomes for patients, including those with risk factors such as hypertension.", "title": "COVID‐19 and hypertension—evidence and practical management: Guidance from the HOPE Asia Network", "pid": "254z62e4", "bm25_score": 217.03573608398438}, {"text": "Coronavirus disease 2019 (COVID-19) has caused a devastating global pandemic and continues to overwhelm the health-care facilities and shatter the economies of countries worldwide. Although it primarily affects the lungs, it shares a strong interplay with the cardiovascular system. The presence of underlying cardiovascular disease and its risk factors (diabetes, hypertension) predispose the patients to increased severity and mortality associated with COVID-19. On the other hand, COVID-19 itself leads to various cardiovascular complications, which increase its associated morbidity and mortality in affected patients. It is, therefore, prudent to review the rapidly evolving data in this field and understand the mechanisms behind the cardiovascular involvement of this lethal disease.", "title": "Cardiovascular comorbidities and complications associated with coronavirus disease 2019", "pid": "o6a30irm", "bm25_score": 217.02667236328125}, {"text": "Abstract Background and aims COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). Methods We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. Results From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. Conclusion Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider.", "title": "Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers", "pid": "7kw9lws0", "bm25_score": 216.97021484375}, {"text": "AIMS: It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17-3.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03-4.57, P = 0.041). The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28-2.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45-0.94, P = 0.20). CONCLUSION: While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.", "title": "Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study", "pid": "gjahdnay", "bm25_score": 216.95001220703125}, {"text": "In December 2019, COVID-19 outbroke in Wuhan, China. The current study aimed to explore the clinical characteristics of COVID-19 complicated by hypertension. In this retrospective, single-center study, we recruited 110 discharged patients with COVID-19 at Wuhan Fourth Hospital in Wuhan, China, from January 25 to February 20, 2020. All study cases were grouped according to whether they had a history of hypertension. Then, a subgroup analysis for all hypertensive patients was carried out based on whether to take ACEI or ARB drugs. The mean age of 110 patients was 57.7 years (range, 25–86 years), of which 60 (54.5%) were male patients. The main underlying diseases included hypertension [36 (32.7%)] and diabetes [11 (10.0%)]. Compared with the non-hypertensive group, the lymphocyte count was significantly lower in the hypertensive group (average value, 0.96 × 10(9)/L vs 1.26 × 10(9)/L), and analysis of clinical outcomes showed that the crude mortality rate was higher in the hypertensive group [7/36 (19.4%) vs 2/74 (2.7%)]. Patients treated with ACEI or ARB, compared with the control group, were younger (average age, 58.5 years vs 69.2 years), but there was no statistical difference in the crude cure rate [10/15 (66.7%) vs 15/21 (71.4%)] and the crude mortality rate [2/15 (13.3%) vs 5/21 (23.8%)]. In conclusions, the COVID-19 patients with a history of hypertension had a significantly lower lymphocyte count on admission. The elderly and comorbidities such as hypertension may together constitute risk factors for poor prognosis in patients with COVID-19. Taking ACEI or ARB drugs may not change the prognosis of COVID-19 patients with hypertension.", "title": "Clinical characteristics of coronavirus disease 2019 (COVID-19) patients with hypertension on renin–angiotensin system inhibitors", "pid": "d4mf43j9", "bm25_score": 216.90158081054688}, {"text": "Arterial hypertension is the most common comorbid disease in patients who died as a result of SARS-Cov-2 infection. Numerous observational studies indicate a relationship between arterial hypertension and its treatment and SARS-Cov-2 coronavirus infection. It is known from experimental studies that SARS-Cov-2 enters the cells by interacting with the ACE2 enzyme, while it is not known whether ACE2 is the only factor that allows the virus to enter the cell. There is no clear evidence of a link between the use of medications such as ACE and ARB and an increased risk of SARS-Cov-2 infection. It has been shown that the use of recombinant ACE2 can be potentially beneficial in COVID-19 therapy by limiting the entry of the virus into the cell. Blood glucose as well as lipid profile should be monitored during SARS-Cov-2 coronavirus infection. This article attempts to gather key information on arterial hypertension and COVID-19.", "title": "Coronavirus SARS-Cov-2 and arterial hypertension - facts and myths.", "pid": "r7vx32o2", "bm25_score": 216.89349365234375}, {"text": "", "title": "COVID-19 patients with hypertension have more severity condition, and ACEI/ARB treatment have no infulence on the clinical severity and outcome", "pid": "74qs8092", "bm25_score": 216.88299560546875}, {"text": "COVID-19 is a novel viral disease caused by SARS-CoV-2. The mid- and long-term outcomes have not yet been determined. COVID-19 infection is increasingly being associated with systemic and multi-organ involvement, encompassing cytokine release syndrome and thromboembolic, vascular and cardiac events. The patient described experienced unusually rapid development of pulmonary hypertension (PH) and right ventricular failure after recent severe COVID-19 pneumonia with cytokine release syndrome, which initially was successfully treated with methylprednisolone and tocilizumab. The development of pulmonary hypertension and right ventricular failure – in the absence of emboli on multiple CT angiograms – was most likely caused by progressive pulmonary parenchymal abnormalities combined with microvascular damage of the pulmonary arteries (group III and IV pulmonary hypertension, respectively). To the best of our knowledge, these complications have not previously been described and therefore awareness of PH as a complication of COVID-19 is warranted. LEARNING POINTS: COVID-19 increasingly presents with systemic and multi-organ involvement with vascular, thromboembolic and cardiac events. Patients with severe COVID-19 pneumonia and concomitant cytokine release syndrome may be particularly at risk for the development of secondary pulmonary hypertension and right ventricular failure. Pulmonary hypertension can develop unusually rapidly following COVID-19 pneumonia and probably results from progressive pulmonary interstitial and microvascular abnormalities due to COVID-19.", "title": "Unusually Rapid Development of Pulmonary Hypertension and Right Ventricular Failure after COVID-19 Pneumonia", "pid": "7xqmuoye", "bm25_score": 216.87440490722656}, {"text": "", "title": "Hypertension and coronavirus disease 2019: what do we really know?", "pid": "wh6pr6tn", "bm25_score": 216.87281799316406}, {"text": "In December 2019, COVID-19 outbroke in Wuhan, China. The current study aimed to explore the clinical characteristics of COVID-19 complicated by hypertension. In this retrospective, single-center study, we recruited 110 discharged patients with COVID-19 at Wuhan Fourth Hospital in Wuhan, China, from January 25 to February 20, 2020. All study cases were grouped according to whether they had a history of hypertension. Then, a subgroup analysis for all hypertensive patients was carried out based on whether to take ACEI or ARB drugs. The mean age of 110 patients was 57.7 years (range, 25-86 years), of which 60 (54.5%) were male patients. The main underlying diseases included hypertension [36 (32.7%)] and diabetes [11 (10.0%)]. Compared with the non-hypertensive group, the lymphocyte count was significantly lower in the hypertensive group (average value, 0.96 × 109/L vs 1.26 × 109/L), and analysis of clinical outcomes showed that the crude mortality rate was higher in the hypertensive group [7/36 (19.4%) vs 2/74 (2.7%)]. Patients treated with ACEI or ARB, compared with the control group, were younger (average age, 58.5 years vs 69.2 years), but there was no statistical difference in the crude cure rate [10/15 (66.7%) vs 15/21 (71.4%)] and the crude mortality rate [2/15 (13.3%) vs 5/21 (23.8%)]. In conclusions, the COVID-19 patients with a history of hypertension had a significantly lower lymphocyte count on admission. The elderly and comorbidities such as hypertension may together constitute risk factors for poor prognosis in patients with COVID-19. Taking ACEI or ARB drugs may not change the prognosis of COVID-19 patients with hypertension.", "title": "Clinical characteristics of coronavirus disease 2019 (COVID-19) patients with hypertension on renin-angiotensin system inhibitors", "pid": "faz8uw2d", "bm25_score": 216.8580322265625}, {"text": "", "title": "Are COVID-19 patients with hypertension at higher risk in China?", "pid": "2c0yen83", "bm25_score": 216.85182189941406}, {"text": "This article reports the diagnosis and treatment of two children with coronavirus disease 2019 (COVID-19) and hypertension. Case 1 was a boy aged 13 years and 3 months, with the main manifestations of fever and dry cough; chest CT showed ground-glass opacities, and the nucleic acid test of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) yielded a positive result. Case 2 was a boy aged 13 years and 8 months and had no clinical symptoms; chest CT showed no abnormality, while the nucleic acid test of SARS-CoV-2 yielded a positive result. Both cases were shown with family aggregation of SARS-CoV-2 infection. They had obesity and a family history of hypertension. Continuous blood pressure monitoring in the resting state during hospitalization showed that blood pressure was above the 95% reference interval of normal value for children of the same age, and the two boys were given calcium channel blockers or β-receptor blockers and were then recovered. It is concluded that comprehensive management of children with COVID-19 and underlying cardiovascular diseases, including hypertension, should be taken seriously during the epidemic.", "title": "[Coronavirus disease 2019 and hypertension in 2 children].", "pid": "hyzv8ofq", "bm25_score": 216.827392578125}, {"text": "BACKGROUND AND AIMS: COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). METHODS: We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. RESULTS: From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. CONCLUSION: Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider.", "title": "Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers", "pid": "1y78dfsl", "bm25_score": 216.79434204101562}, {"text": "", "title": "The association of hypertension with the severity and mortality of COVID-19 patients: Evidence based on adjusted effect estimates", "pid": "j12siti1", "bm25_score": 216.78343200683594}, {"text": "", "title": "The association of hypertension with the severity and mortality of COVID-19 patients: evidence based on adjusted effect estimates", "pid": "i7ng9gzw", "bm25_score": 216.78343200683594}, {"text": "In COVID-19 patients respiratory failure is associated with increase systemic blood pressure conceivably due to the modulation of renin-angiotensin-aldosterone system by SARS-CoV-2 infection.", "title": "The liaison between respiratory failure and high blood pressure: evidence from COVID-19 patients", "pid": "u36nf6jq", "bm25_score": 216.7742919921875}, {"text": "", "title": "Letter in response to the article: Comorbidities in COVID-19: outcomes in hypertensive cohort and controversies with renin angiotensin system blockers (Singh et al.)", "pid": "2rjt47j9", "bm25_score": 216.71121215820312}, {"text": "", "title": "Letter in response to the article: Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers (Singh et al.)", "pid": "e4q283yt", "bm25_score": 216.71121215820312}, {"text": "BACKGROUND: The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. OBJECTIVE: This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. DISCUSSION: The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. CONCLUSIONS: Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "title": "Cardiovascular complications in COVID-19", "pid": "hl225efn", "bm25_score": 216.7108154296875}, {"text": "AIMS: It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19). METHODS AND RESULTS: This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital. The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China. Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection. Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension. After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs. 1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17–3.82, P = 0.013]. Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs. 3.2%, adjusted HR 2.17, 95% CI 1.03–4.57, P = 0.041). The mortality rates were similar between the renin–angiotensin–aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs. 3.6%, adjusted HR 0.85, 95% CI 0.28–2.58, P = 0.774). However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45–0.94, P = 0.20). CONCLUSION: While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19. However, the results should be considered as exploratory and interpreted cautiously.", "title": "Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study", "pid": "2nftsv4f", "bm25_score": 216.70263671875}, {"text": "This article reports the diagnosis and treatment of two children with coronavirus disease 2019 (COVID-19) and hypertension. Case 1 was a boy aged 13 years and 3 months, with the main manifestations of fever and dry cough; chest CT showed ground-glass opacities, and the nucleic acid test of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) yielded a positive result. Case 2 was a boy aged 13 years and 8 months and had no clinical symptoms; chest CT showed no abnormality, while the nucleic acid test of SARS-CoV-2 yielded a positive result. Both cases were shown with family aggregation of SARS-CoV-2 infection. They had obesity and a family history of hypertension. Continuous blood pressure monitoring in the resting state during hospitalization showed that blood pressure was above the 95% reference interval of normal value for children of the same age, and the two boys were given calcium channel blockers or ß-receptor blockers and were then recovered. It is concluded that comprehensive management of children with COVID-19 and underlying cardiovascular diseases, including hypertension, should be taken seriously during the epidemic.", "title": "[Coronavirus disease 2019 and hypertension in 2 children]", "pid": "dhxux00x", "bm25_score": 216.6833953857422}, {"text": "Importance. Exploring the association of coronavirus-2019 disease (COVID-19) mortality with chronic pre-existing conditions may promote the importance of targeting these populations during this pandemic in order to optimize survival. Objective. To explore the association of pre-existing conditions with COVID-19 mortality. Data Sources. MEDLINE, the OVID databases, SCOPUS, and Cochrane Register of Controlled Trials were searched for the period October 1, 2019 to May 1, 2020. Snowballing was used to identify additional studies. Study Selection. Observational studies (n=19) reporting on 61,455 patients with relative risks (RR) or hazard ratios or odds ratios that reported the risk of mortality in patients with COVID-19 and comorbid conditions were included for the current study. Data Extraction and Synthesis. Two independent reviewers extracted data and assessed the risk of bias. All analyses were performed using random-effects models and heterogeneity was quantified. Main Outcomes and Measures The outcome of interest was the risk of COVID-19 mortality in patients with and without pre-existing conditions, reported as RR. Comorbidities explored were cardiovascular diseases (coronary artery disease, hypertension, cardiac arrhythmias, and congestive heart failure), chronic obstructive pulmonary disease, type 2 diabetes, cancer, chronic kidney disease, chronic liver disease, and stroke. Results. Ten chronic conditions from 19 studies were included in the meta-analysis (n=61,455 patients with COVID-19; mean age, 61 years; 57% male). Any cardiovascular disease, coronary heart disease, hypertension, congestive heart failure, and cancer significantly increased the risk of mortality from COVID-19. Cardiovascular disease was associated with a 135% higher risk of COVID-19 mortality (RR=2.35, 95%CI 1.44-3.84 n=9). The risk of mortality from COVID-19 in patients with coronary heart disease was 2.4 times as high as those without coronary heart disease (RR= 2.40, 95%CI=1.71-3.37, n=5) and twice as high in patients with hypertension as high as that compared to those without hypertension (RR=1.89, 95%CI= 1.58-2.27, n=9). Patients with cancer also were at twice the risk of mortality from COVID-19 compared to those without cancer (RR=1.93 95%CI 1.15-3.24, n=4), and those with congestive heart failure were at 2.5 times the risk of mortality compared to those without congestive heart failure (RR=2.66, 95%CI 1.58-4.48, n=3). Conclusions and Relevance COVID-19 patients with all any cardiovascular disease, coronary heart disease, hypertension, congestive heart failure, and cancer have an increased risk of mortality. Tailored infection prevention and treatment strategies targeting this high-risk population are warranted to optimize survival.", "title": "The association of cardiovascular disease and other pre-existing comorbidities with COVID-19 mortality: A systematic review and meta-analysis", "pid": "xn7kd6q8", "bm25_score": 216.6661376953125}, {"text": "OBJECTIVE: To explore the association between obesity, type 2 diabetes, hypertension, and severe COVID-19 on admission. METHODS: In the present study, a total of 23,593 patient samples were evaluated by a laboratory from the Mexican Institute of Epidemiological Diagnosis and Reference (InDRE, for its acronym in Spanish). Of these: 18,443 were negative for COVID-19, 3,844 were positive for COVID-19, and 1,306 were positive for other respiratory viruses. Severe types of respiratory disease were defined by the presence of pneumonia and other organ failure that requires intensive care. Multivariable logistic regression models were used to explore factors associated with severe COVID-19 on admission. RESULTS: Patients who tested positive for COVID-19 had a higher proportion of obesity (17.4%), diabetes (14.5%), and hypertension (18.9%), compared to those without a confirmed diagnosis. Compared to non-obese patients, those with obesity showed a 1.43-fold higher odds of developing severe COVID-19 on admission, while subjects with diabetes and hypertension showed a 1.87-fold and 1.77-fold higher odds of developing severe COVID-19 on admission, respectively. CONCLUSION: Obesity, diabetes, and hypertension were significantly associated with severe COVID-19 on admission and the association of obesity was stronger in patients < 50 y.", "title": "The association between obesity, type 2 diabetes, and hypertension with severe COVID-19 on admission among Mexicans", "pid": "xpn39pt8", "bm25_score": 216.66439819335938}, {"text": "The prevalence of hypertension is high in patients affected by coronavirus disease 2019 (COVID-2019) and it appears to be related to an increased risk of mortality, as shown in many epidemiological studies. The angiotensin-converting enzyme (ACE) system is not uniformly expressed in all of the human races, and current differences could explain some of the geographical discrepancies in infection around the world. Furthermore, animal studies have shown that the ACE2 receptor is a potential pathway for host infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. As two-thirds of hypertensive patients take ACE inhibitors/angiotensin receptor blockers, several concerns have been raised about the detrimental role of current antihypertensive drugs in COVID-19. This report summarizes the recent evidence for and against the administration of ACE blockade in the COVID-19 era.", "title": "Hypertension prevalence in human coronavirus disease: the role of ACE system in infection spread and severity", "pid": "ih8oxr40", "bm25_score": 216.6387176513672}, {"text": "Abstract Background The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. Objective This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. Discussion The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. Conclusions Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "title": "Cardiovascular complications in COVID-19", "pid": "mbbnk3la", "bm25_score": 216.62171936035156}, {"text": "Abstract A new coronavirus, called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was discovered in December 2019 in Wuhan, China; the virus escalated rapidly and on March 11, 2020, the World Health Organization declared it a pandemic.Emerging data suggests that older patients with COVID-19 associated with other comorbid conditions such as diabetes, hypertension, heart and lung diseases are particularly more susceptible, compared to general populations, and have higher mortality. It is not yet clear whether this increased association of high blood pressure with COVID-19 and the increased risk of mortality are directly related to high blood pressure or other associated comorbidities, or to antihypertensive treatment.Although the underlying pathogenic mechanism linking hypertension and severity of COVID-19 infection remains to be elucidated, it has been hypothesized that excessive activation of the renin-angiotensin system (RAS) could contribute to the progression of COVID-19 related lung injury.Concern about whether angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors may have deleterious effects on morbidity and mortality in patients with COVID-19 is based on speculation that these drugs would increase the regulation of angiotensin II converting enzyme (ACE2), a receptor for SARS-CoV-2, which would increase viral load and lung damage.Recent studies are consistent with the recommendations of scientific societies that propose avoiding the suspension or change of antihypertensive medication, as there is no evidence that shows that these can be taken as risk factors for severity or mortality from COVID-19.", "title": "Inhibidores de la enzima convertidora de angiotensina y antagonistas del receptor de angiotensina II: ¿Aumentan el riesgo de padecer COVID-19?", "pid": "ynias4ga", "bm25_score": 216.61215209960938}, {"text": "Abstract Aims To analyze the potential mechanism of cardiovascular dysfunctions induced by Coronavirus Disease 2019 (COVID-19) and to evaluate more effective therapeutic pathways for patients with cardiovascular diseases. Data Synthesis COVID-19 mainly invades the lungs, causing its serious damage. Studies found that COVID-19 induced the renin-angiotensin system imbalance, inflammatory storm, hypoxemia and stress response et al, all contributed to hypertension and serious myocardial damage in the process of virus pathogenesis, even increasing mortality in COVID-19 patients. Conclusions In the process of management of COVID-19 infections, close attention should be paid on both lung and cardiovascular damage, especially on those with only symptoms of cardiovascular diseases. Early identification, timely and effective treatments, maintenance of hemodynamics and electrophysiological stability are of great significance on effective treatment and long-term prognosis. The pandemic of COVID-19 has been taking lives worldwide. It caused by a novel coronavirus which human being are lack of defensive function in whole population. It targets human’s lung and causes serious damage of lungs. Based on early reports, for people with underlying heart issues, the concerns are serious. It appears people over 65 with coronary heart diseases or hypertension is more likely to be infected and to develop more severe symptoms. In addition, some of hospitalized COVID-19 patients had cardiovascular diseases in China. As characteristic analysis of COVID-19 patients, hypertension and severe myocardial damage contribute to severity [1] and mortality of COVID-19 patients [2]. Therefore, to better understand the development of COVID-19 and the impacts of cardiovascular diseases will add valuable measures to the management of COVID-19 patients.", "title": "A close-up on COVID-19 and cardiovascular diseases", "pid": "13akn7dm", "bm25_score": 216.56736755371094}, {"text": "BACKGROUND: Cardiovascular disease related mortality is the leading cause of death in the United States, with hypertension being the most prevalent and potent risk factor. For decades hypertension has disproportionately affected African Americans, who also have a higher burden of associated comorbidities including diabetes and heart failure. METHODS: Current literature including guideline reports and newer studies on hypertension in African Americans in PubMed were reviewed. We also reviewed newer publications on the relationship between COVID-19 and cardiovascular disease. FINDINGS: While APOL1 has been theorized in the epidemiology of hypertension, the increased prevalence and associated risks are primarily due to environmental and lifestyle factors. These factors include poor diet, adverse lifestyle, and social determinants. Hypertension control can be achieved by lifestyle modifications such as low sodium diet, weight loss, and adequate physical activity. When lifestyle modifications alone do not adequately control hypertension, a common occurrence among African Americans who suffer with greater prevalence of resistant hypertension, pharmacological intervention is indicated. The efficacy of renal denervation, and the use of sodium-glucose cotransporter 2 and aminopeptidase A inhibitors, have been studied for treatment of resistant hypertension. Furthermore, the recent COVID-19 crisis has been particularly devastating among African Americans who demonstrate increased incidence and poorer health outcomes related to the disease. CONCLUSION: The disparities in outcomes, which are largely attributable to a greater prevalence of comorbidities such as hypertension and obesity, in addition to adverse environmental and socioeconomic factors, highlight the necessity of specialized clinical approaches and programs for African Americans to address longstanding barriers to equitable care.", "title": "Contemporary and Future Concepts on Hypertension in African Americans: COVID-19 and Beyond", "pid": "cn2j9ih4", "bm25_score": 216.56578063964844}, {"text": "", "title": "Hypertension and coronavirus disease 2019 mortality", "pid": "r8n4heto", "bm25_score": 216.5553436279297}, {"text": "", "title": "Arterial hypertension and the risk of severity and mortality of COVID-19", "pid": "ba5zus8h", "bm25_score": 216.52110290527344}, {"text": "Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic. Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19. Furthermore, covid-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest. The cardiovascular interactions of covid-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza. Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.", "title": "Cardiovascular manifestations and treatment considerations in covid-19", "pid": "873txs85", "bm25_score": 216.50497436523438}, {"text": "Arterial hypertension is the most common comorbid disease in patients who died as a result of SARS-Cov-2 infection Numerous observational studies indicate a relationship between arterial hypertension and its treatment and SARS-Cov-2 coronavirus infection It is known from experimental studies that SARS-Cov-2 enters the cells by interacting with the ACE2 enzyme, while it is not known whether ACE2 is the only factor that allows the virus to enter the cell There is no clear evidence of a link between the use of medications such as ACE and ARB and an increased risk of SARS-Cov-2 infection It has been shown that the use of recombinant ACE2 can be potentially beneficial in COVID-19 therapy by limiting the entry of the virus into the cell Blood glucose as well as lipid profile should be monitored during SARS-Cov-2 coronavirus infection This article attempts to gather key information on arterial hypertension and COVID-19", "title": "Coronavirus SARS-Cov-2 and arterial hypertension - facts and myths", "pid": "yg1mma87", "bm25_score": 216.49754333496094}, {"text": "", "title": "Reply to the letter of Mahajan and Gaur in response to the article: Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers (Singh et al.)", "pid": "8gkkeekz", "bm25_score": 216.48992919921875}, {"text": "", "title": "Reply to the Letter of Mahajan and Gaur in response to the article: Comorbidities in COVID-19: outcomes in hypertensive cohort and controversies with renin angiotensin system blockers (Singh et al.)", "pid": "1iiwhmkm", "bm25_score": 216.48992919921875}, {"text": "INTRODUCTION: There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. METHODS: Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. RESULTS: 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 - 0.88). A similar albeit not significant trend was observed for ACEI. CONCLUSION: ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2.", "title": "Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors", "pid": "bwg3tzx8", "bm25_score": 216.44711303710938}, {"text": "Angiotensin converting enzyme 2 (ACE2) is the cellular entry point for severe acute respiratory syndrome coronavirus (SARS-CoV-2) - the cause of COVID-19 disease. It has been hypothesized that use of renin-angiotensin system (RAS) inhibiting medications in patients with hypertension, increases the expression of ACE2 and thereby increases the risk of COVID-19 infection and severe outcomes or death. However, the effect of RAS-inhibition on ACE2 expression in human tissues of key relevance to blood pressure regulation and COVID-19 infection has not previously been reported. We examined how hypertension, its major metabolic co-phenotypes and antihypertensive medications relate to ACE2 renal expression using information from up to 436 patients whose kidney transcriptomes were characterised by RNA-sequencing. We further validated some of the key observations in other human tissues and/or a controlled experimental model. Our data reveal increasing expression of ACE2 with age in both human lungs and the kidney. We show no association between renal expression of ACE2 and either hypertension or common types of RAS inhibiting drugs. We demonstrate that renal abundance of ACE2 is positively associated with a biochemical index of kidney function and show a strong enrichment for genes responsible for kidney health and disease in ACE2 co-expression analysis. Collectively, our data indicate that neither hypertension nor antihypertensive treatment are likely to alter individual risk of SARS-CoV-2 infection or influence clinical outcomes in COVID-19 through changes of ACE2 expression. Our data further suggest that in the absence of SARS-CoV-2 infection, kidney ACE2 is most likely nephro-protective but the age-related increase in its expression within lungs and kidneys may be relevant to the risk of SARS-CoV-2 infection.", "title": "Hypertension and renin-angiotensin system blockers are not associated with expression of Angiotensin Converting Enzyme 2 (ACE2) in the kidney", "pid": "uyyd1m1p", "bm25_score": 216.4259796142578}, {"text": "Mortality from coronavirus disease 2019 (COVID-19) is strongly associated with cardiovascular disease, diabetes, and hypertension. These disorders share underlying pathophysiology related to the renin-angiotensin system (RAS) that may be clinically insightful. In particular, activity of the angiotensin-converting enzyme 2 (ACE2) is dysregulated in cardiovascular disease, and this enzyme is used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to initiate the infection. Cardiovascular disease and pharmacologic RAS inhibition both increase ACE2 levels, which may increase the virulence of SARS-CoV-2 within the lung and heart. Conversely, mechanistic evidence from related coronaviruses suggests that SARS-CoV-2 infection may downregulate ACE2, leading to toxic overaccumulation of Angiotensin II that induces acute respiratory distress syndrome and fulminant myocarditis. RAS inhibition could mitigate this effect. With conflicting mechanistic evidence, we propose key clinical research priorities necessary to clarify the role of RAS inhibition in COVID-19 mortality that could be rapidly addressed by the international research community.", "title": "Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System-a Call for Epidemiologic Investigations", "pid": "eqeivvtx", "bm25_score": 216.40711975097656}, {"text": "Abstract Introduction There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. Methods Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. Results 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 – 0.88). A similar albeit not significant trend was observed for ACEI. Conclusion ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2.", "title": "Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors:", "pid": "wxpfg25n", "bm25_score": 216.40562438964844}, {"text": "Mortality from coronavirus disease 2019 (COVID-19) is strongly associated with cardiovascular disease, diabetes, and hypertension. These disorders share underlying pathophysiology related to the renin-angiotensin system (RAS) that may be clinically insightful. In particular, activity of the angiotensin-converting enzyme 2 (ACE2) is dysregulated in cardiovascular disease, and this enzyme is used by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to initiate the infection. Cardiovascular disease and pharmacologic RAS inhibition both increase ACE2 levels, which may increase the virulence of SARS-CoV-2 within the lung and heart. Conversely, mechanistic evidence from related coronaviruses suggests that SARS-CoV-2 infection may downregulate ACE2, leading to toxic overaccumulation of Angiotensin II that induces acute respiratory distress syndrome and fulminant myocarditis. RAS inhibition could mitigate this effect. With conflicting mechanistic evidence, we propose key clinical research priorities necessary to clarify the role of RAS inhibition in COVID-19 mortality that could be rapidly addressed by the international research community.", "title": "Is There an Association Between COVID-19 Mortality and the Renin-Angiotensin System—a Call for Epidemiologic Investigations", "pid": "f372jh4t", "bm25_score": 216.39723205566406}, {"text": "", "title": "COVID-19, hypertension and angiotensin receptor-blocking drugs", "pid": "f13fw7ye", "bm25_score": 216.34934997558594}, {"text": "", "title": "A Significance of High Prevalence of Diabetes and Hypertension in Severe COVID-19 Patients", "pid": "gmraihg6", "bm25_score": 216.33209228515625}, {"text": "Introduction: COVID-19 disproportionately affects those with comorbidities and the elderly. Hypertension is the most common pre-existing condition amongst COVID-19 patients. Upregulation of the renin-angiotensin-aldosterone system (RAAS) is common in hypertensive patients and may promote inflammation and ensuing cytokine storm in COVID-19. It is unknown whether RAAS inhibition with ACE1 inhibitors or angiotensin-receptor blockers (ARB) can be harmful or beneficial. Methods: Within Hackensack Meridian Health network, the largest healthcare provider in New Jersey, we performed a retrospective, multicenter, convenience sampling study of hospitalized COVID-19 patients. Demographics, clinical characteristics, treatments, and outcomes were manually abstracted. Fishers exact tests, and logistic regression were performed. Results: Among 3017 hospitalized COVID-19 patients, 1584 (52.5%) carried a diagnosis of hypertension. In the discharged or deceased cohort, the overall mortality was significantly increased at 35% vs 13% among COVID-19 patients with hypertension. However, when adjusted for age, the effect of hypertension on mortality was greatly diminished, with a reduction in odds-ratio by over half; and completely disappeared when adjusted for other major covariates. The mortality rates were lower for hypertensive patients prescribed ACE1 (27%, p=0.001) or ARBs (33%, p=0.12) compared to other anti-hypertensive agents (39%) in the unadjusted analyses. RAAS inhibitor therapy appeared protective compared to other anti-hypertensive agents (p=0.001). Conclusions: While our results are limited by the retrospective nature of our study and by potential confounders, our data argue against a harmful effect of RAAS inhibition and support the HFSA/AHA/ACC joint statement recommending continuing ACE1 and ARB therapy in hypertensive COVID-19 patients.", "title": "Hypertension and Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19", "pid": "61cwycg6", "bm25_score": 216.31100463867188}, {"text": "", "title": "INCREASED MORTALITY AMONG HYPERTENSIVE COVID-19 PATIENTS: PAY A CLOSER LOOK ON DIURETICS IN MECHANICALLY VENTILATED PATIENTS", "pid": "vtfwuojj", "bm25_score": 216.2947235107422}, {"text": "", "title": "Is aberrant CD8+ T cell activation by hypertension associated with cardiac injury in severe cases of COVID-19?", "pid": "9ve8bj4r", "bm25_score": 216.2918243408203}, {"text": "Type 2 diabetes mellitus and hypertension are the most common comorbidities in patients with coronavirus infections. Emerging evidence demonstrates an important direct metabolic and endocrine mechanistic link to the viral disease process. Clinicians need to ensure early and thorough metabolic control for all patients affected by COVID-19.", "title": "Endocrine and metabolic link to coronavirus infection", "pid": "puu8wib8", "bm25_score": 216.27969360351562}, {"text": "", "title": "Patients with arterial hypertension and COVID-19 are at higher risk of ICU admission", "pid": "ban5isc0", "bm25_score": 216.27638244628906}, {"text": "OBJECTIVE: To explore the association between obesity, type 2 diabetes, hypertension, and severe COVID‐19 on admission. METHODS: In the present study, a total of 23,593 patient samples were evaluated by a laboratory from the Mexican Institute of Epidemiological Diagnosis and Reference (InDRE, for its acronym in Spanish). Of these: 18,443 were negative for COVID‐19, 3,844 were positive for COVID‐19, and 1,306 were positive for other respiratory viruses. Severe types of respiratory disease were defined by the presence of pneumonia and other organ failure that requires intensive care. Multivariable logistic regression models were used to explore factors associated with severe COVID‐19 on admission. RESULTS: Patients who tested positive for COVID‐19 had a higher proportion of obesity (17.4%), diabetes (14.5%), and hypertension (18.9%), compared to those without a confirmed diagnosis. Compared to non‐obese patients, those with obesity showed a 1.43‐fold higher odds of developing severe COVID‐19 on admission, while subjects with diabetes and hypertension showed a 1.87‐fold and 1.77‐fold higher odds of developing severe COVID‐19 on admission, respectively. CONCLUSION: Obesity, diabetes, and hypertension were significantly associated with severe COVID‐19 on admission and the association of obesity was stronger in patients < 50 y.", "title": "The association between obesity, type 2 diabetes, and hypertension with severe COVID‐19 on admission among Mexicans", "pid": "170ec6zo", "bm25_score": 216.27415466308594}, {"text": "Several factors have been proposed to explain the high death rate of the coronavirus disease 2019 (COVID-19) outbreak, including hypertension and hypertension-related treatment with Renin Angiotensin System inhibitors. Also, age and multimorbidity might be confounders. No sufficient data are available to demonstrate their independent role. We designed a cross-sectional, observational, multicenter, nationwide survey in Italy to verify whether renin-angiotensin system inhibitors are related to COVID-19 severe outcomes. We analyzed information from Italian patients diagnosed with COVID-19, admitted in 26 hospitals. One thousand five hundred ninety-one charts (male, 64.1%; 66±0.4 years) were recorded. At least 1 preexisting condition was observed in 73.4% of patients, with hypertension being the most represented (54.9%). One hundred eighty-eight deaths were recorded (11.8%; mean age, 79.6±0.9 years). In nonsurvivors, older age, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, coronary artery diseases, and heart failure were more represented than in survivors. The Charlson Comorbidity Index was significantly higher in nonsurvivors compared with survivors (4.3±0.15 versus 2.6±0.05; P<0.001). ACE (angiotensin-converting enzyme) inhibitors, diuretics, and β-blockers were more frequently used in nonsurvivors than in survivors. After correction by multivariate analysis, only age (P=0.0001), diabetes mellitus (P=0.004), chronic obstructive pulmonary disease (P=0.011), and chronic kidney disease (P=0.004) but not hypertension predicted mortality. Charlson Comorbidity Index, which cumulates age and comorbidities, predicts mortality with an exponential increase in the odds ratio by each point of score. In the COVID-19 outbreak, mortality is predicted by age and the presence of comorbidities. Our data do not support a significant interference of hypertension and antihypertensive therapy on COVID-19 lethality. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT04331574.", "title": "Age and Multimorbidity Predict Death Among COVID-19 Patients: Results of the SARS-RAS Study of the Italian Society of Hypertension.", "pid": "l689noqi", "bm25_score": 216.2683868408203}, {"text": "", "title": "The liaison between respiratory failure and high blood pressure: evidence from COVID-19 patients", "pid": "nslos3rl", "bm25_score": 216.26449584960938}, {"text": "The current COVID-19 pandemic is associated with unprecedented morbidity and mortality. Early reports suggested an association between disease severity and hypertension but did not account for sources of confounding. However, the responsible virus — SARS-CoV-2 — gains entry to host cells via angiotensin-converting enzyme 2 (ACE2), highlighting the need to understand the relationship between the virus and the renin–angiotensin system (RAS) and how this might be affected by RAS inhibitors.", "title": "Controversies of renin–angiotensin system inhibition during the COVID-19 pandemic", "pid": "va34p27b", "bm25_score": 216.25445556640625}, {"text": "Several factors have been proposed to explain the high death rate of the coronavirus disease 2019 (COVID-19) outbreak, including hypertension and hypertension-related treatment with Renin Angiotensin System inhibitors. Also, age and multimorbidity might be confounders. No sufficient data are available to demonstrate their independent role. We designed a cross-sectional, observational, multicenter, nationwide survey in Italy to verify whether renin-angiotensin system inhibitors are related to COVID-19 severe outcomes. We analyzed information from Italian patients diagnosed with COVID-19, admitted in 26 hospitals. One thousand five hundred ninety-one charts (male, 64.1%; 66±0.4 years) were recorded. At least 1 preexisting condition was observed in 73.4% of patients, with hypertension being the most represented (54.9%). One hundred eighty-eight deaths were recorded (11.8%; mean age, 79.6±0.9 years). In nonsurvivors, older age, hypertension, diabetes mellitus, chronic obstructive pulmonary disease, chronic kidney disease, coronary artery diseases, and heart failure were more represented than in survivors. The Charlson Comorbidity Index was significantly higher in nonsurvivors compared with survivors (4.3±0.15 versus 2.6±0.05; P<0.001). ACE (angiotensin-converting enzyme) inhibitors, diuretics, and ß-blockers were more frequently used in nonsurvivors than in survivors. After correction by multivariate analysis, only age (P=0.0001), diabetes mellitus (P=0.004), chronic obstructive pulmonary disease (P=0.011), and chronic kidney disease (P=0.004) but not hypertension predicted mortality. Charlson Comorbidity Index, which cumulates age and comorbidities, predicts mortality with an exponential increase in the odds ratio by each point of score. In the COVID-19 outbreak, mortality is predicted by age and the presence of comorbidities. Our data do not support a significant interference of hypertension and antihypertensive therapy on COVID-19 lethality. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT04331574.", "title": "Age and Multimorbidity Predict Death Among COVID-19 Patients: Results of the SARS-RAS Study of the Italian Society of Hypertension", "pid": "pajy2vky", "bm25_score": 216.24380493164062}, {"text": "Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.", "title": "Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019", "pid": "kxtxzt9f", "bm25_score": 216.2427215576172}, {"text": "INTRODUCTION COVID-19, is a new corona virus of the Beta Coronavirus genus which originated in bats. The virus first emerged in China in December 2019 and has rapidly spread since to other areas worldwide. The World Health Organization (WHO) has therefore recently declared it as the source of a pandemic. The disease caused by the virus manifests in most cases as a lower respiratory tract infection leading to fever, cough and dyspnea, while more severe cases can led to respiratory failure and/or multi organ failure. COVID-19 enters the human cell using the ACE2, an enzyme abundant in renal tubular epithelial cells. Theoretically, this may be significant in several ways: acute kidney injury (AKI) as well as proteinuria and/or microhematuria could be associated with the penetration of COVID-19 into the cells. Moreover, medications based on RAAS inhibition, such and ACE inhibitors and ARBs, upregulate the enzyme ACE2 and could therefore hypothetically explain the high prevalence of hypertension and diabetes reported as previous diagnoses in severe cases. In the setting of chronic kidney disease, the risk of infection with COVID-19 is not clear at this time. However, hemodialysis patients represent a unique group of patients, mostly elderly and immunocompromised, for whom dialysis is a life-saving treatment which cannot be stopped. Hence, the COVID-19 pandemic has presented a complex medical and logistic challenge for the medical staff in hospital and community based dialysis units.", "title": "[COVID-19, THE KIDNEY AND HYPERTENSION].", "pid": "dx3jywv7", "bm25_score": 216.23043823242188}, {"text": "Abstract Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, is being defined as the worst pandemic disease of modern times. Several professional health organizations have published position papers stating that there is no evidence to change the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) in the management of elevated blood pressure in the context of avoiding or treating COVID-19 infection. In this article, we review the evidence on the relationship between the renin-angiotensin-aldosterone system and COVID-19 infection. In agreement with current guidelines, patients with hypertension should continue taking antihypertensive medications as prescribed without interruption. Because ACEIs and ARBs are also used to retard the progression of chronic kidney disease, we suggest that these recommendations also apply to the use of these agents in chronic kidney disease. No differences generally exist between ARBs and ACEIs in terms of efficacy in decreasing blood pressure and improving other outcomes, such as all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. The ACEIs are associated with cough secondary to accumulation of bradykinin and angioedema, and withdrawal rates due to adverse events are lower with ARBs. Given their equal efficacy but fewer adverse events, ARBs could potentially be a more favorable treatment option in patients with COVID-19 at higher risk for severe forms of disease.", "title": "Angiotensin-Converting Enzyme 2 and Antihypertensives (Angiotensin Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors) in Coronavirus Disease 2019", "pid": "7lonkj5p", "bm25_score": 216.21609497070312}, {"text": "INTRODUCTION: COVID-19, is a new corona virus of the Beta Coronavirus genus which originated in bats. The virus first emerged in China in December 2019 and has rapidly spread since to other areas worldwide. The World Health Organization (WHO) has therefore recently declared it as the source of a pandemic. The disease caused by the virus manifests in most cases as a lower respiratory tract infection leading to fever, cough and dyspnea, while more severe cases can led to respiratory failure and/or multi organ failure. COVID-19 enters the human cell using the ACE2, an enzyme abundant in renal tubular epithelial cells. Theoretically, this may be significant in several ways: acute kidney injury (AKI) as well as proteinuria and/or microhematuria could be associated with the penetration of COVID-19 into the cells. Moreover, medications based on RAAS inhibition, such and ACE inhibitors and ARBs, upregulate the enzyme ACE2 and could therefore hypothetically explain the high prevalence of hypertension and diabetes reported as previous diagnoses in severe cases. In the setting of chronic kidney disease, the risk of infection with COVID-19 is not clear at this time. However, hemodialysis patients represent a unique group of patients, mostly elderly and immunocompromised, for whom dialysis is a life-saving treatment which cannot be stopped. Hence, the COVID-19 pandemic has presented a complex medical and logistic challenge for the medical staff in hospital and community based dialysis units.", "title": "[covid-19, the Kidney and Hypertension]", "pid": "sr0umk33", "bm25_score": 216.20736694335938}, {"text": "The coronavirus disease-2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2. The link between cardiovascular disease and COVID-19 appears to be twofold. First, some reports of data indicate that certain groups of patients are more at risk of COVID-19. This includes patients with cardiovascular risk factors or pre-existing cardiovascular conditions and older patients. In addition, these patients incur disproportionately worse outcome. Second, SARS-CoV2 infection can be complicated by life-threatening cardiovascular acute diseases. Despite the rapid evolution of data on this pandemic, this review aims to highlight the cardiovascular considerations related to COVID-19 whether as comorbidities including concerns and uncertainty regarding the effect of renin-angiotensin-aldosterone system (RAAS) inhibitors on angiotensin conversion enzyme 2 or related to acute cardiovascular complications.", "title": "Pathologies cardiovasculaires et Covid-19 : particularités chez les personnes âgées./ COVID-19 and cardiovascular diseases: viewpoint for older patients", "pid": "pjtlk8ni", "bm25_score": 216.18374633789062}, {"text": "Background: Coronavirus disease 2019 (COVID-19), caused by a novel coronavirus (designated as SARS-CoV-2) has become a pandemic worldwide. Based on the current reports, hypertension may be associated with increased risk of sever condition in hospitalized COVID-19 patients. Angiotensin-converting enzyme 2 (ACE2) was recently identified to functional receptor of SARS-CoV-2. Previous experimental data revealed ACE2 level was increased following treatment with ACE inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Currently doctors concern whether these commonly used renin-angiotensin system (RAS) blockers-ACEIs/ARBs may increase the severity of COVID-19. Methods: We extracted data regarding 50 hospitalized hypertension patients with laboratory confirmed COVID-19 in the Renmin Hospital of Wuhan University from Feb 7 to Mar 03, 2020. These patients were grouped into RAS blockers group (Group A, n=20) and non-RAS blockers group (Group B, n=30) according to the basic blood pressure medications. All patients continued to use pre-admission antihypertensive drugs. Clinical severity (symptoms, laboratory and chest CT findings, etc.), clinical course, and short time outcome were analyzed after hospital admission. Results: Ten (50%) and seventeen (56.7%) of the Group A and Group B participants were males (P=0.643), and the average age was 52.65±13.12 and 67.77±12.84 years (P=0.000), respectively. The blood pressure of both groups was under effective control. There was no significant difference in clinical severity, clinical course and in-hospital mortality between Group A and Group B. Serum cardiac troponin I (cTnI) (P=0.03), and N-terminal (NT)-pro hormone BNP (NT-proBNP) (P=0.04) showed significant lower level in Group A than in Group B. But the patients with more than 0.04ng/mL or elevated NT-proBNP level had no statistical significance between the two groups. In patients over 65 years or under 65 years, cTnI or NT-proBNP level showed no difference between the two groups. Conclusions: We observed there was no obvious difference in clinical characteristics between RAS blockers and non-RAS blockers groups. These data suggest ACEIs/ARBs may have few effects on increasing the clinical severe conditions of COVID-19.", "title": "The effect of RAS blockers on the clinical characteristics of COVID-19 patients with hypertension", "pid": "gm9564re", "bm25_score": 216.1704559326172}, {"text": "We report the case of a young patient diagnosed with coronavirus disease 2019 with a history of hypertension. The patient improved after antiviral treatment but eventually developed severe respiratory distress syndrome and cardiac insufficiency. His respiratory secretions were tested for nucleic acids and turn negative twice. Computed tomography image of the patient showed evidence of viral pneumonia on the 11(th) day of onset and continued to worsen. The patient was finally intubated and transferred to a higher-level care center for further treatment. We were very focused on infectious disease protection throughout the treatment, however, suboptimal treatment was provided due to the switch in antihypertensive medication, lack of early nutritional support, and fluid restriction management.", "title": "COVID-19 in a young man with hypertension: A case study of missed opportunities in intensive progression", "pid": "wyxdodxd", "bm25_score": 216.15115356445312}, {"text": "", "title": "Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?", "pid": "t46yitdg", "bm25_score": 216.1474151611328}, {"text": "Based on some publications that associate SARS-CoV-2 infection with the use of anti-hypertensive drug groups such as angiotensin-converting-enzyme inhibitors (e.g. enalapril) or angiotensin II receptor blockers (e.g. losartan), many patients from South America, Central America or Spain, have stopped or intend to interrupt their treatments with these drugs. Hence, it may exist ominous consequences due to this drop out. For this reason, it is necessary to quickly warn about this situation and the risks associated with it.", "title": "Facts and reflections on COVID-19 and anti-hypertensives drugs.", "pid": "7zebj4bo", "bm25_score": 216.14324951171875}, {"text": "We report the case of a young patient diagnosed with coronavirus disease 2019 with a history of hypertension. The patient improved after antiviral treatment but eventually developed severe respiratory distress syndrome and cardiac insufficiency. His respiratory secretions were tested for nucleic acids and returned negative twice. Computed tomography imaging of the patient showed evidence of viral pneumonia on the 11th day of onset and continued to worsen. The patient was finally intubated and transferred to a higher-level care centre for further treatment. We were very focused on infectious disease protection throughout the treatment, however, suboptimal treatment was provided due to the switch in antihypertensive medication, lack of early nutritional support and fluid restriction management.", "title": "COVID-19 in a young man with hypertension: A case study of missed opportunities in intensive progression", "pid": "8u2g2e09", "bm25_score": 216.0904998779297}, {"text": "Based on some publications that associate SARS-CoV-2 infection with the use of anti-hypertensive drug groups such as angiotensin-converting-enzyme inhibitors (e.g. enalapril) or angiotensin II receptor blockers (e.g. losartan), many patients from South America, Central America or Spain, have stopped or intend to interrupt their treatments with these drugs. Hence, it may exist ominous consequences due to this drop out. For this reason, it is necessary to quickly warn about this situation and the risks associated with it.", "title": "Facts and reflections on COVID-19 and anti-hypertensives drugs", "pid": "wsleywry", "bm25_score": 216.08863830566406}, {"text": "The COVID-19 pandemic, caused by SARS-CoV-2, is an immense challenge for global healthcare. Diabetes mellitus, hypertension and obesity have been shown to portend poor prognosis in COVID-19 despite no greater susceptibility to the infection (1). Chronic hypertension is commonly associated with vasculopathy which can predispose to severe infection. In patients with diabetes, severity is attributable to impaired innate, adaptive immunity, upregulation of ACE2 (entry receptor for SARS-CoV2) by acute hyperglycemia and diabetic vasculopathy. The background of chronic low grade inflammation characterised by increased levels of IL-6 and CRP in diabetes and obesity can also lead to an enhanced 'cytokine storm' in COVID-19 (2). ACE2 expression on endothelial cells has been reported to cause viral mediated endothelitis and precipitate vascular dysfunction manifesting as acute respiratory distress syndrome as well as myocarditis, heart failure, arrhythmias, myocardial infarction and renal failure (3). In patients with pre-existing comorbidities like hypertension, diabetes, obesity and chronic kidney disease, this new-onset organ dysfunction can have deleterious additive effects.", "title": "SGLT2 inhibition and COVID-19: The road not taken.", "pid": "md9dbxb5", "bm25_score": 216.07833862304688}, {"text": "Importance: Data are lacking whether patients with hypertension who are taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have increased severity or risk of mortality during hospitalization for coronavirus disease 2019 (COVID-19). Objective: To investigate the association between ACEIs/ARBs and severity of illness and mortality in patients with hypertension hospitalized for COVID-19 infection. Design, Setting, and Participants: Retrospective, single-center case series of the 1178 hospitalized patients with COVID-19 infections at the Central Hospital of Wuhan, China, from January 15 to March 15, 2020. Main Outcomes and Measures: COVID-19 was confirmed by real-time reverse transcription-polymerase chain reaction and epidemiologic, clinical, radiologic, laboratory, and drug therapy data were analyzed in all patients. The percentage of patients with hypertension taking ACEIs/ARBs was compared between those with severe vs nonsevere illness and between survivors vs nonsurvivors. Results: Of the 1178 patients with COVID-19, the median age was 55.5 years (interquartile range, 38-67 years) and 545 (46.3%) were men. The overall in-hospital mortality was 11.0%. There were 362 patients with hypertension (30.7% of the total group; median age, 66.0 years [interquartile range, 59-73 years]; 189 [52.2%] were men), of whom 115 (31.8%) were taking ACEI/ARBs. The in-hospital mortality in the patients with hypertension was 21.3%. The percentage of patients with hypertension taking ACEIs/ARBs did not differ between those with severe and nonsevere infections (32.9% vs 30.7%; P = .65) nor did it differ between nonsurvivors and survivors (27.3% vs 33.0%; P = .34). Similar findings were observed when data were analyzed for patients taking ACEIs and those taking ARBs. Conclusions and Relevance: This study provides clinical data on the association between ACEIs/ARBs and outcomes in patients with hypertension hospitalized with COVID-19 infections, suggesting that ACEIs/ARBs are not associated with the severity or mortality of COVID-19 in such patients. These data support current guidelines and societal recommendations for treating hypertension during the COVID-19 pandemic.", "title": "Association of Renin-Angiotensin System Inhibitors With Severity or Risk of Death in Patients With Hypertension Hospitalized for Coronavirus Disease 2019 (COVID-19) Infection in Wuhan, China", "pid": "m6pth0tu", "bm25_score": 216.07342529296875}, {"text": "", "title": "Antihypertensive treatment with ACEI/ARB of patients with COVID-19 complicated by hypertension", "pid": "zum861la", "bm25_score": 216.06884765625}]}
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Diabetes is an established risk associated with poor clinical outcomes, but the association of diabetes with COVID-19 has not been reported yet. METHODS: In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital in Wuhan, China, recruited from January 29 to February 12, 2020. The clinical features, treatment strategies and prognosis data were collected and analyzed. Prognosis was followed up until March 12, 2020. RESULTS: Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease conditions with more complications, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR] = 3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR = 1.19; 95% CI: 1.08, 1.31) were associated with the fatality due to COVID-19, adjusting for potential confounders. CONCLUSIONS: Diabetes mellitus is associated with increased disease severity and a higher risk of mortality in patients with COVID-19.", "title": "Association of diabetes mellitus with disease severity and prognosis in COVID-19: A retrospective cohort study", "pid": "8ydwzl4z", "bm25_score": 218.90687561035156}, {"text": "Abstract The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, China, and was characterized as a pandemic by the World Health Organization. Diabetes is an established risk associated with poor clinical outcomes, but the association of diabetes with COVID-19 has not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital in Wuhan, China, recruited from January 29 to February 12, 2020. The clinical features, treatment strategies and prognosis data were collected and analyzed. Prognosis was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease conditions with more complications, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality due to COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with increased disease severity and a higher risk of mortality in patients with COVID-19.", "title": "Association of Diabetes Mellitus with Disease Severity and Prognosis in COVID-19: A Retrospective Cohort Study", "pid": "c2jm0g88", "bm25_score": 218.58609008789062}, {"text": "AIMS: To describe characteristics of COVID-19 patients with type 2 diabetes and to analyze risk factors for severity. METHODS: Demographics, comorbidities, symptoms, laboratory findings, treatments and outcomes of COVID-19 patients with diabetes were collected and analyzed. RESULTS: Seventy-four COVID-19 patients with diabetes were included. Twenty-seven patients (36.5%) were severe and 10 patients (13.5%) died. Higher levels of blood glucose, serum amyloid A (SAA), C reactive protein and interleukin 6 were associated with severe patients compared to non-severe ones (P < 0.05). Levels of albumin, cholesterol, high density lipoprotein, small and dense low density lipoprotein and CD4(+) T lymphocyte counts in severe patients were lower than those in non-severe patients (P < 0.05). Logistic regression analysis identified decreased CD4(+) T lymphocyte counts (odds ratio [OR] = 0.988, 95%Confidence interval [95%CI] 0.979–0.997) and increased SAA levels (OR = 1.029, 95%CI 1.002–1.058) as risk factors for severity of COVID-19 with diabetes (P < 0.05). CONCLUSIONS: Type 2 diabetic patients were more susceptible to COVID-19 than overall population, which might be associated with hyperglycemia and dyslipidemia. Aggressive treatment should be suggested, especially when these patients had low CD4(+) T lymphocyte counts and high SAA levels.", "title": "Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes()", "pid": "ulmm28d5", "bm25_score": 218.109375}, {"text": "BACKGROUND: Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial, and fungal infections. The coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries and claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19. SCOPE OF REVIEW: In this review, I summarize the clinical data on the risk for infectious diseases in individuals with diabetes while highlighting the mechanisms for altered immune regulation. The focus is on coronaviruses. Based on the new clinical data obtained from COVID-19 patients, a discussion of mechanisms, such as cytokine storm, pulmonary and endothelial dysfunction, and hypercoagulation, that may render individuals with diabetes more vulnerable to COVID-19 is provided. MAJOR CONCLUSIONS: Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and the pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to designing tailored treatments and clinical management of individuals affected by diabetes.", "title": "Diabetes, infection risk and COVID-19", "pid": "x9h81ij0", "bm25_score": 218.06228637695312}, {"text": "The pandemic of COVID-19, a disease caused by a novel coronavirus SARS-CoV-2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID-19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID-19 patients. There is only limited amount of data regarding follow-up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID-19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID-19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID-19 and its role in outcome in these patients.", "title": "COVID-19 and diabetes: Is there enough evidence?", "pid": "f0pwjxfv", "bm25_score": 218.02955627441406}, {"text": "Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favour of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.", "title": "COVID-19 in diabetic patients: Related risks and specifics of management", "pid": "lfdeowsl", "bm25_score": 218.00100708007812}, {"text": "AIMS: To describe characteristics of COVID-19 patients with type 2 diabetes and to analyze risk factors for severity. METHODS: Demographics, comorbidities, symptoms, laboratory findings, treatments and outcomes of COVID-19 patients with diabetes were collected and analyzed. RESULTS: Seventy-fourCOVID-19 patients with diabetes were included. Twenty-seven patients (36.5%) were severe and 10 patients (13.5%) died. Higher levels of blood glucose, serum amyloid A (SAA), C reactive protein and interleukin 6 were associated with severe patients compared to non-severe ones (P<0.05). Levels of albumin, cholesterol, high density lipoprotein, small and dense low density lipoprotein and CD4+T lymphocyte counts in severe patients were lower than those in non-severe patients (P<0.05). Logistic regression analysis identified decreased CD4+T lymphocyte counts (odds ratio [OR]=0.988, 95%Confidence interval [95%CI] 0.979-0.997) and increased SAA levels (OR=1.029, 95%CI 1.002-1.058) as risk factors for severity of COVID-19 with diabetes (P<0.05). CONCLUSIONS: Type 2 diabetic patients were more susceptible to COVID-19 than overall population, which might be associated with hyperglycemia and dyslipidemia. Aggressive treatment should be suggested, especially when these patients had low CD4+T lymphocyte counts and high SAA levels.", "title": "Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes", "pid": "rf6651nd", "bm25_score": 217.9345703125}, {"text": "Abstract Diabetes is among the most frequently reported comorbidities in patients infected with COVID-19. According to current data, diabetic patients do not appear to be at increased risk of contracting SARS-CoV-2 compared to the general population. On the other hand, diabetes is a risk factor for developing severe and critical forms of COVID-19, the latter requiring admission to an intensive care unit and/or use of invasive mechanical ventilation, with high mortality rates. The characteristics of diabetic patients at risk for developing severe and critical forms of COVID-19, as well as the prognostic impact of diabetes on the course of COVID-19, are under current investigation. Obesity, the main risk factor for incident type 2 diabetes, is more common in patients with critical forms of COVID-19 requiring invasive mechanical ventilation. On the other hand, COVID-19 is usually associated with poor glycemic control and a higher risk of ketoacidosis in diabetic patients. There are currently no recommendations in favor of discontinuing antihypertensive medications that interact with the renin-angiotensin-aldosterone system. Metformin and SGLT2 inhibitors should be discontinued in patients with severe forms of COVID-19 owing to the risks of lactic acidosis and ketoacidosis. Finally, we advise for systematic screening for (pre)diabetes in patients with proven COVID-19 infection.", "title": "COVID-19 in diabetic patients: related risks and specifics of management", "pid": "0tsefy6p", "bm25_score": 217.9114227294922}, {"text": "Abstract Background Individuals with diabetes are at a greater risk of hospitalization and mortality resulting from viral, bacterial and fungal infections. The Coronavirus Disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has spread quickly to more than 213 countries across the world and has claimed 395,779 lives as of June 7, 2020. Notably, in several studies, diabetes is one of the most reported comorbidities in patients with severe COVID-19. Scope of Review In this review, I will summarize the clinical data on the risk for infectious diseases in individuals with diabetes, highlighting the mechanisms for altered immune regulation. A special focus will be given to coronaviruses. In the light of the new clinical data obtained from COVID-19 patients, mechanisms such as cytokine storm, pulmonary and endothelial dysfunction, hypercoagulation that may render individuals with diabetes more vulnerable to COVID-19 will be discussed in the end. Major Conclusions Epidemiological studies show that poorly controlled diabetes is a risk factor for various infectious diseases. Given the global burden of diabetes and pandemic nature of coronaviruses, understanding how diabetes affects COVID-19 severity is critical to design tailored treatments and clinical management of individuals affected by diabetes.", "title": "Diabetes, Infection Risk And Covid-19", "pid": "12q9jjbb", "bm25_score": 217.90191650390625}, {"text": "AIM: To map COVID-19-specific worries and overall psychosocial health among people with diabetes in the initial phase of the COVID-19 pandemic in Denmark, and to explore characteristics of people with diabetes and high levels of worries related to the COVID-19 pandemic. METHODS: A cross-sectional survey was conducted by distributing online questionnaires to 2430 adult members (> 18 years) of two user panels consisting of people with diabetes who have volunteered to share information about their life with diabetes. The questionnaire included items on COVID-19-specific worries as well as such worries related to diabetes, sociodemographic and health status, social relations, diabetes-specific social support, diabetes distress and changes in diabetes-specific behaviours. Responses were analysed with descriptive statistics and logistic regressions. RESULTS: People with diabetes have COVID-19-specific worries related to their diabetes. More than half were worried about being overly affected due to diabetes if infected with COVID-19, about one-third about being characterized as a risk group due to diabetes and not being able to manage diabetes if infected. Logistic regressions showed that being female, having type 1 diabetes, diabetes complications and diabetes distress, feeling isolated and lonely, and having changed diabetes behaviours were associated with being more worried about COVID-19 and diabetes. CONCLUSION: People with diabetes have COVID-19-specific worries related to their diabetes which is associated with poorer psychosocial health. These worries should be addressed through support targeting specific questions and needs of individuals with diabetes as well as frequent updates on new knowledge regarding COVID-19 and diabetes.", "title": "Diabetes and COVID-19: psychosocial consequences of the COVID-19 pandemic in people with diabetes in Denmark-what characterizes people with high levels of COVID-19-related worries?", "pid": "hycd9zua", "bm25_score": 217.88885498046875}, {"text": "Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20-50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.", "title": "Practical recommendations for the management of diabetes in patients with COVID-19", "pid": "grz8hhal", "bm25_score": 217.88063049316406}, {"text": "AIM: To evaluate the influence of diabetes on the severity and fatality of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. MATERIALS AND METHODS: The medical records of 66 hospitalized coronavirus disease 2019 (COVID-19) patients were collected and classified into non-severe (mild/moderate cases) and severe (severe/critical cases) groups. Logistic regression analysis was used to estimate the risk of severe COVID-19 (severe/critical infection). In addition, a meta-analysis including published studies reported the impact of diabetes on the severity and fatality of COVID-19. The current study was conducted using fixed effects models. RESULTS: There were 22 diabetes and 44 non-diabetes cases among the 66 hospitalized COVID-19 patients. Seven patients with diabetes (31.82%) were diagnosed as severe COVID-19 cases, which was significantly higher than that in the non-diabetes group (4/44, 9.09%, P = .033). After adjustment for age and gender, diabetes was significantly associated with COVID-19 severity (OR: 5.29, 95% CI: 1.07-26.02). A meta-analysis further confirmed the positive association between diabetes and COVID-19 severity (pooled OR = 2.58, 95% CI: 1.93-3.45). Moreover, the patients with diabetes infected with SARS-CoV-2 had a 2.95-fold higher risk of fatality compared with those patients without diabetes (95% CI: 1.93-4.53). CONCLUSIONS: Our findings provide new evidence that diabetes is associated with a higher risk of severity and fatality of COVID-19. Therefore, intensive monitoring and antidiabetic therapy should be considered in patients with diabetes with SARS-CoV-2 infection.", "title": "Influence of diabetes mellitus on the severity and fatality of SARS-CoV-2 (COVID-19) infection", "pid": "i8uwia3a", "bm25_score": 217.81802368164062}, {"text": "Summary Diabetes is one of the most important comorbidities linked to the severity of all three known human pathogenic coronavirus infections, including severe acute respiratory syndrome coronavirus 2. Patients with diabetes have an increased risk of severe complications including Adult Respiratory Distress Syndrome and multi-organ failure. Depending on the global region, 20–50% of patients in the coronavirus disease 2019 (COVID-19) pandemic had diabetes. Given the importance of the link between COVID-19 and diabetes, we have formed an international panel of experts in the field of diabetes and endocrinology to provide some guidance and practical recommendations for the management of diabetes during the pandemic. We aim to briefly provide insight into potential mechanistic links between the novel coronavirus infection and diabetes, present practical management recommendations, and elaborate on the differential needs of several patient groups.", "title": "Practical recommendations for the management of diabetes in patients with COVID-19", "pid": "118x15od", "bm25_score": 217.8092803955078}, {"text": "AIMS: Nowadays, the ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Complications such as hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19. METHODS: No meta-analysis has explored if or not diabetes related to mortality of patients with COVID-19. Therefore, this meta-analysis first aims to explore the possible clinical mortality between diabetes and COVID-19, analyze if diabetes patients infected with SARS-CoV-2 are exposed to the worst clinical prognostic risk, and to evaluate the reliability of the evidence. RESULTS: Our results showed a close relationship between diabetes and mortality of COVID-19, with a pooled OR of 1.75 (95% CI 1.31-2.36; P = 0.0002). The pooled data were calculated with the fixed effects model (FEM) as no heterogeneity appeared in the studies. Sensitivity analysis showed that after omitting any single study or converting a random effect model to FEM, the main results still held. CONCLUSIONS: Our meta-analysis showed that diabetes increases the mortality of patients with COVID-19. These results indicated the disturbance of blood glucose in the COVID-19 patients. More importantly, this meta-analysis grades the reliability of evidence for further basic and clinical research into the diabetes dysfunction in COVID-19 patients.", "title": "Diabetes increases the mortality of patients with COVID-19: a meta-analysis", "pid": "ibpyqrq4", "bm25_score": 217.79159545898438}, {"text": "AIMS: Nowadays, the ongoing pandemic of COVID-19 caused by the novel coronavirus Syndrome-Coronavirus-2 (SARS-CoV-2) is an emerging, rapidly evolving situation. Complications such as hypertension, diabetes, COPD, cardiovascular disease, and cerebrovascular disease are major risk factors for patients with COVID-19. METHODS: No meta-analysis has explored if or not diabetes related to mortality of patients with COVID-19. Therefore, this meta-analysis first aims to explore the possible clinical mortality between diabetes and COVID-19, analyze if diabetes patients infected with SARS-CoV-2 are exposed to the worst clinical prognostic risk, and to evaluate the reliability of the evidence. RESULTS: Our results showed a close relationship between diabetes and mortality of COVID-19, with a pooled OR of 1.75 (95% CI 1.31–2.36; P = 0.0002). The pooled data were calculated with the fixed effects model (FEM) as no heterogeneity appeared in the studies. Sensitivity analysis showed that after omitting any single study or converting a random effect model to FEM, the main results still held. CONCLUSIONS: Our meta-analysis showed that diabetes increases the mortality of patients with COVID-19. These results indicated the disturbance of blood glucose in the COVID-19 patients. More importantly, this meta-analysis grades the reliability of evidence for further basic and clinical research into the diabetes dysfunction in COVID-19 patients.", "title": "Diabetes increases the mortality of patients with COVID-19: a meta-analysis", "pid": "f0lo04qq", "bm25_score": 217.76687622070312}, {"text": "Diabetes mellitus is a complex, multifactorial, chronic disease characterized by impaired metabolism of glucose, fats and proteins. Patients who suffer from it frequently have hyperglycemia and coronary artery disease is the leading cause of death. The comorbidities associated with diabetes are overweight and obesity, systemic arterial hypertension, atherogenic dyslipidemia and in some patients peripheral vascular disease, kidney damage, neuropathy and retinopathy. Chronic lack of control of the disease is associated with increased susceptibility to infections, which generally have few symptoms, but hyperglycemia is generally magnified, which worsens the course of infections. Since December 2019, when the disease caused by one of the coronaviruses (coronavirus 2 of severe acute respiratory syndrome, SARS-CoV-2) was identified and has been called coronavirus disease 2019 (COVID-19), there have been some reports that associate the presence of diabetes with an increased risk of mortality. In this review article we have focused on four specific points: 1) epidemiology of the prevalence and mortality of COVID 19 in the general population and in the population with type 2 diabetes mellitus; 2) pathophysiology related to the binding of SARS-CoV-2 to receptors in subjects with diabetes; 3) the immune response induced by SARS-CoV-2, and 4) the outpatient and hospital treatment recommended in patients with diabetes who become infected with SARS-CoV-2.", "title": "Coronavirus infection in patients with diabetes.", "pid": "ifmwfm43", "bm25_score": 217.76632690429688}, {"text": "Coronavirus disease 2019 (COVID-19) has become a global concern and public health issue due to its higher infection and mortality rate; particularly, the risk is very higher among the patients who have cardiovascular diseases (CVD) and/or diabetes mellitus (DM). In this review, we analyzed the recently published literature on CVD and DM associated with COVD-19 infections and highlight their association with potential mechanisms. The findings revealed that without any previous history of CVD, the COVID-19 patients have developed some CVD complications like myocardial injury, cardiomyopathy, and venous thromboembolism after being infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and required for those patients an emergency clinical support to be aware to manage those complications. Though the association between DM and COVID-19-induced severe complications is still unclear, the limited data predict that different markers like interleukin (IL)-1, IL-6, C-reactive protein, and D-dimer linked with the severity of COVID-19 infection in diabetic individuals. Further studies on a large scale are urgently needed to explore the underlying mechanisms between CVD, DM, and COVID-19 for better treatment.", "title": "The Association of Cardiovascular Diseases and Diabetes Mellitus with COVID-19 (SARS-CoV-2) and Their Possible Mechanisms", "pid": "9uymi395", "bm25_score": 217.75296020507812}, {"text": "Abstract Diabetes mellitus is challenging in the context of the COVID-19 pandemic. The prevalence of diabetes patients hospitalized in intensive care units for COVID-19 is two- to threefold higher, and the mortality rate at least double, than that of non-diabetes patients. As the population with diabetes is highly heterogeneous, it is of major interest to determine the risk factors of progression to a more serious life-threatening COVID-19 infection. This brief review discusses the main findings of CORONADO, a prospective observational study in France that specifically addressed this issue as well as related observations from other countries, mainly China and the US. Some prognostic factors beyond old age have been identified: for example, an increased body mass index is a major risk factor for requiring respiratory assistance. Indeed, obesity combines several risk factors, including impaired respiratory mechanics, the presence of other comorbidities and inappropriate inflammatory responses, partly due to ectopic fat deposits. While previous diabetic microvascular (renal) and macrovascular complications also increase risk of death, the quality of past glucose control had no independent influence on hospitalized diabetes patient outcomes, and whether the quality of glucose control might modulate risk of COVID-19 in non-hospitalized diabetes patients is still unknown. In addition, no negative signs regarding the use of RAAS blockers and DPP-4 inhibitors and outcomes of COVID-19 could be identified. Hyperglycaemia at the time of hospital admission is associated with poor outcomes, but it may simply be considered a marker of severity of the infection. Thus, the impact of glucose control during hospitalization on outcomes related to COVID-19, which was not investigated in the CORONADO study, is certainly deserving of specific investigation.", "title": "Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports", "pid": "bjq36px5", "bm25_score": 217.73858642578125}, {"text": "Background The 2019 novel coronavirus disease (COVID-19) emerged in Wuhan, Hubei province, China, and was characterized as pandemic by the World Health Organization. Diabetes mellitus is an established risk factor for poor clinical outcomes, but the association of diabetes with the prognosis of COVID-19 have not been reported yet. Methods In this cohort study, we retrospectively reviewed 258 consecutive hospitalized COVID-19 patients with or without diabetes at the West Court of Union Hospital of Huazhong University of Science and Technology in Wuhan, China, recruited from January 29 to February 12, 2020. The cases were confirmed by real-time PCR and the demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Prognosis was defined as hospitalization, discharged survivor and death, which was followed up until March 12, 2020. Results Of the 258 hospitalized patients (63 with diabetes) with COVID-19, the median age was 64 years (range 23-91), and 138 (53.5%) were male. No significant differences in age and sex were identified between patients with and without diabetes. Common symptoms included fever (82.2%), dry cough (67.1%), polypnea (48.1%), and fatigue (38%). Patients with diabetes had significantly higher leucocyte and neutrophil counts, and higher levels of fasting blood glucose, serum creatinine, urea nitrogen and creatine kinase isoenzyme MB at admission compared with those without diabetes. COVID-19 patients with diabetes were more likely to develop severe or critical disease condition with more complications at presentation, and had higher incidence rates of antibiotic therapy, non-invasive and invasive mechanical ventilation, and death (11.1% vs. 4.1%). Cox proportional hazard model showed that diabetes (adjusted hazard ratio [aHR]=3.64; 95% confidence interval [CI]: 1.09, 12.21) and fasting blood glucose (aHR=1.19; 95% CI: 1.08, 1.31) were associated with the fatality of COVID-19, adjusting for potential confounders. Conclusions Diabetes mellitus is associated with greater disease severity and a higher risk of mortality in patients with COVID-19. Primary and secondary prevention strategies are needed for COVID-19 patients with diabetes.", "title": "Comorbid Diabetes Mellitus was Associated with Poorer Prognosis in Patients with COVID-19: A Retrospective Cohort Study", "pid": "skknfc6h", "bm25_score": 217.66372680664062}, {"text": "Diabetes mellitus is challenging in the context of the COVID-19 pandemic. The prevalence of diabetes patients hospitalized in intensive care units for COVID-19 is two- to threefold higher, and the mortality rate at least double, than that of non-diabetes patients. As the population with diabetes is highly heterogeneous, it is of major interest to determine the risk factors of progression to a more serious life-threatening COVID-19 infection. This brief review discusses the main findings of CORONADO, a prospective observational study in France that specifically addressed this issue as well as related observations from other countries, mainly China and the US. Some prognostic factors beyond old age have been identified: for example, an increased body mass index is a major risk factor for requiring respiratory assistance. Indeed, obesity combines several risk factors, including impaired respiratory mechanics, the presence of other comorbidities and inappropriate inflammatory responses, partly due to ectopic fat deposits. While previous diabetic microvascular (renal) and macrovascular complications also increase risk of death, the quality of past glucose control had no independent influence on hospitalized diabetes patient outcomes, but whether the quality of glucose control might modulate risk of COVID-19 in non-hospitalized diabetes patients is still unknown. In addition, no negative signs regarding the use of RAAS blockers and DPP-4 inhibitors and outcomes of COVID-19 could be identified. Hyperglycaemia at the time of hospital admission is associated with poor outcomes, but it may simply be considered a marker of severity of the infection. Thus, the impact of glucose control during hospitalization on outcomes related to COVID-19, which was not investigated in the CORONADO study, is certainly deserving of specific investigation.", "title": "Prognostic factors in patients with diabetes hospitalized for COVID-19: Findings from the CORONADO study and other recent reports", "pid": "yjugtbg1", "bm25_score": 217.660400390625}, {"text": "The pandemic of COVID‐19, a disease caused by a novel coronavirus SARS‐CoV‐2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID‐19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID‐19 patients. There is only limited amount of data regarding follow‐up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID‐19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID‐19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID‐19 and its role in outcome in these patients.", "title": "COVID‐19 and diabetes: Is there enough evidence?", "pid": "sntawlnf", "bm25_score": 217.64816284179688}, {"text": "BACKGROUND: Many studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19. METHODS: We searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods. RESULTS: We included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37-2.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09-3.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74-2.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%-10.9%) (after adjusting for heterogeneity). CONCLUSIONS: Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.", "title": "Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis", "pid": "ufasdi1b", "bm25_score": 217.63487243652344}, {"text": "BACKGROUND: The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS: A search using keywords “COVID-19” and “Diabetes” was performed using different sources, including PubMed and World Health Organization. RESULTS: COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute β-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION: COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.", "title": "COVID-19 and diabetes: The why, the what and the how", "pid": "phf2sgw5", "bm25_score": 217.59780883789062}, {"text": "BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID-19). METHODS: A total of 174 consecutive patients confirmed with COVID-19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID-19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury-related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation-related biomarkers such as IL-6, C-reactive protein, serum ferritin and coagulation index, D-dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID-19. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID-19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.", "title": "Diabetes is a risk factor for the progression and prognosis of COVID-19", "pid": "ix2vjgph", "bm25_score": 217.59503173828125}, {"text": "BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, first appeared in Wuhan, China, and quickly spread throughout the world. We aimed to understand the relationship between diabetes mellitus and the prognosis of COVID-19. METHODS: Demographic, clinical, laboratory, radiologic, treatments, complications, and clinical outcomes data were extracted from electronic medical records and compared between diabetes (n=84) and non-diabetes (n=500) groups. Kaplan-Meier method and multivariate Cox analysis were applied to determine the risk factors for the prognosis of COVID-19. RESULTS: Compared to non-diabetic patients, diabetic patients had higher levels of neutrophils (p = 0.014), c-reactive protein (p = 0.008), procalcitonin (p < 0.01), and D-dimer (p = 0.033), and lower levels of lymphocytes (p = 0.032) and albumin (p = 0.035). Furthermore, diabetic patients had a significant higher incidence of bilateral pneumonia (86.9%, p = 0.020). In terms of complications and clinical outcomes, the incidence of respiratory failure (36.9% vs. 24.2%, p = 0.022), acute cardiac injury (47.4% vs. 21.2%, p < 0.01) and death (20.2% vs. 8.0%, p = 0.001) in the diabetes group was significantly higher than that in non-diabetes group. Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time. Multivariate Cox analysis indicated that diabetes (HR 2.180, p = 0.031) was an independent risk factor for COVID-19 prognosis. In subgroup analysis, we divided diabetic patients into insulin required and non-insulin required groups according to whether they needed insulin, and found that diabetic patients requiring insulin may have a higher risk of disease progression and worse prognosis after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSIONS: Diabetes is an independent risk factor for the prognosis of COVID-19. More attention should be paid to the prevention and treatment for diabetic patients, especially those who require insulin therapy.", "title": "The Relationship between Diabetes Mellitus and COVID-19 Prognosis: A Retrospective Cohort Study in Wuhan, China", "pid": "zcdkohu6", "bm25_score": 217.58563232421875}, {"text": "BACKGROUND: The novel coronavirus SARS-CoV-2 has taken the world by storm. Alongside COVID-19, diabetes is a long-standing global epidemic. The diabetes population has been reported to suffer adverse outcomes if infected by COVID-19. The aim was to summarise information and resources available on diabetes and COVID-19, highlighting special measures that individuals with diabetes need to follow. METHODS: A search using keywords \"COVID-19\" and \"Diabetes\" was performed using different sources, including PubMed and World Health Organization. RESULTS: COVID-19 may enhance complications in individuals with diabetes through an imbalance in angiotension-converting enzyme 2 (ACE2) activation pathways leading to an inflammatory response. ACE2 imbalance in the pancreas causes acute ß-cell dysfunction and a resultant hyperglycemic state. These individuals may be prone to worsened COVID-19 complications including vasculopathy, coagulopathy as well as psychological stress. Apart from general preventive measures, remaining hydrated, monitoring blood glucose regularly and monitoring ketone bodies in urine if on insulin is essential. All this while concurrently maintaining physical activity and a healthy diet. Different supporting entities are being set up to help this population. CONCLUSION: COVID-19 is a top priority. It is important to remember that a substantial proportion of the world's population is affected by other co-morbidities such as diabetes. These require special attention during this pandemic to avoid adding on to the burden of countries' healthcare systems.", "title": "COVID-19 and diabetes: The why, the what and the how", "pid": "wl1uihn3", "bm25_score": 217.57798767089844}, {"text": "A possible association could exist between type 2 diabetes mellitus (T2DM) and Coronavirus-19 (Covid-19) infection. Indeed, patients with T2DM show high prevalence, severity of disease and mortality during Covid-19 infection. However, the rates of severe disease are significantly higher in patients with diabetes compared with non-diabetes (34.6% vs. 14.2%; p < 0.001). Similarly, T2DM patients have higher rates of need for Intensive Care Unit (ICU, 37.0% vs. 26.7%; p = 0.028). Thus, about the pneumonia of Covid-19, we might speculate that the complicated alveolar-capillary network of lungs could be targeted by T2DM micro-vascular damage. Therefore, T2DM patients frequently report respiratory symptoms and are at increased risk of several pulmonary diseases. In addition, pro-inflammatory pathways as that involving interleukin 6 (IL-6), could be a severity predictor of lung diseases. Therefore, it looks intuitive to speculate that this condition could explain the growing trend of cases, hospitalization and mortality for patients with T2DM during Covid-19 infection. To date, an ongoing experimental therapy with monoclonal antibody against the IL-6 receptor in Italy seems to have beneficial effects on severe lung disease and prognosis in patients with Covid-19 infection. Therefore, should patients with T2DM be treated with more attention to glycemic control and monoclonal antibody against the IL-6 receptor during the Covid-19 infection?", "title": "Impact of diabetes mellitus on clinical outcomes in patients affected by Covid-19", "pid": "5759p02f", "bm25_score": 217.55377197265625}, {"text": "BACKGROUND: Coronavirus disease 2019 (COVID-19) is an emerging infectious disease, first appeared in Wuhan, China, and quickly spread throughout the world. We aimed to understand the relationship between diabetes mellitus and the prognosis of COVID-19. METHODS: Demographic, clinical, laboratory, radiologic, treatments, complications, and clinical outcomes data were extracted from electronic medical records and compared between diabetes (n=84) and non-diabetes (n=500) groups. Kaplan-Meier method and multivariate Cox analysis were applied to determine the risk factors for the prognosis of COVID-19. RESULTS: Compared to non-diabetic patients, diabetic patients had higher levels of neutrophils (p = 0.014), c-reactive protein (p = 0.008), procalcitonin (p < 0.01), and D-dimer (p = 0.033), and lower levels of lymphocytes (p = 0.032) and albumin (p = 0.035). Furthermore, diabetic patients had a significant higher incidence of bilateral pneumonia (86.9%, p = 0.020). In terms of complications and clinical outcomes, the incidence of respiratory failure (36.9% vs. 24.2%, p = 0.022), acute cardiac injury (47.4% vs. 21.2%, p < 0.01) and death (20.2% vs. 8.0%, p = 0.001) in the diabetes group was significantly higher than that in non-diabetes group. Kaplan-Meier survival curve showed that COVID-19 patients with diabetes had a shorter overall survival time. Multivariate Cox analysis indicated that diabetes (HR 2.180, p = 0.031) was an independent risk factor for COVID-19 prognosis. In subgroup analysis, we divided diabetic patients into insulin required and non-insulin required groups according to whether they needed insulin, and found that diabetic patients requiring insulin may have a higher risk of disease progression and worse prognosis after the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CONCLUSIONS: Diabetes is an independent risk factor for the prognosis of COVID-19. More attention should be paid to the prevention and treatment for diabetic patients, especially those who require insulin therapy.", "title": "The Relationship between Diabetes Mellitus and COVID-19 Prognosis: A Retrospective Cohort Study in Wuhan, China", "pid": "f4qljghz", "bm25_score": 217.5459442138672}, {"text": "A major infectious disease associated with severe acute respiratory syndrome coronavirus 2 (2019-nCoV)has emerged in Wuhan, China. Current clinical studies have shown that diabetes is commonly complicated with this disorder. Hyperglycemia is a risk factor for severe infection, and also an independent risk factor for the progression of mild infection to severe infection. This may be related to the immune deficiency of diabetics. Besides, virus may cause direct damage to the islets and induce acute stress hyperglycemia. Special attention should be payed to diabetics with 2019-nCoV infection. Systemic steroid hormones should be used with particular caution in patients with 2019-nCoV infection, especially those with diabetes.", "title": "Paying close attention to diabetic patients with novel coronavirus infection/ 中华内分泌代谢杂志", "pid": "sc8q1rox", "bm25_score": 217.47508239746094}, {"text": "Abstract Background Many studies on COVID-19 have reported diabetes to be associated with severe disease and mortality, however, the data is conflicting. The objectives of this meta-analysis were to explore the relationship between diabetes and COVID-19 mortality and severity, and to determine the prevalence of diabetes in patients with COVID-19. Methods We searched the PubMed for case-control studies in English, published between Jan 1 and Apr 22, 2020, that had data on diabetes in patients with COVID-19. The frequency of diabetes was compared between patients with and without the composite endpoint of mortality or severity. Random effects model was used with odds ratio as the effect size. We also determined the pooled prevalence of diabetes in patients with COVID-19. Heterogeneity and publication bias were taken care by meta-regression, sub-group analyses, and trim and fill methods. Results We included 33 studies (16,003 patients) and found diabetes to be significantly associated with mortality of COVID-19 with a pooled odds ratio of 1.90 (95% CI: 1.37–2.64; p < 0.01). Diabetes was also associated with severe COVID-19 with a pooled odds ratio of 2.75 (95% CI: 2.09–3.62; p < 0.01). The combined corrected pooled odds ratio of mortality or severity was 2.16 (95% CI: 1.74–2.68; p < 0.01). The pooled prevalence of diabetes in patients with COVID-19 was 9.8% (95% CI: 8.7%–10.9%) (after adjusting for heterogeneity). Conclusions Diabetes in patients with COVID-19 is associated with a two-fold increase in mortality as well as severity of COVID-19, as compared to non-diabetics. Further studies on the pathogenic mechanisms and therapeutic implications need to be done.", "title": "Is diabetes mellitus associated with mortality and severity of COVID-19? A meta-analysis", "pid": "ja9qu3p8", "bm25_score": 217.4671630859375}, {"text": "BACKGROUND AND AIMS: Diabetes mellitus is associated with poor prognosis in patients with COVID-19. On the other hand, COVID-19 contributes to worsening of dysglycemia in people with diabetes mellitus over and above that contributed by stress hyperglycemia. Herein, we have reviewed the two-way interactions between COVID-19 and diabetes mellitus. METHODS: We have performed an extensive literature search for articles in PubMed, EMBASE and Google Scholar databases till April 25, 2020, with the following keywords: \"COVID-19\", \"SARS-CoV-2\", \"diabetes\", \"diabetes mellitus\", \"SARS\", \"infection\" and \"management of diabetes mellitus\" with interposition of the Boolean operator \"AND\". RESULTS: Compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists in people with diabetes mellitus contribute to poor prognosis in COVID-19. On the contrary, direct ß-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir) can contribute to worsening of glucose control in people with diabetes mellitus. CONCLUSIONS: The two-way interaction between COVID-19 and diabetes mellitus sets up a vicious cycle wherein COVID-19 leads to worsening of dysglycemia and diabetes mellitus, in turn, exacerbates the severity of COVID-19. Thus, it is imperative that people with diabetes mellitus take all necessary precautions and ensure good glycemic control amid the ongoing pandemic.", "title": "COVID-19 and diabetes mellitus: An unholy interaction of two pandemics", "pid": "dgl7qapx", "bm25_score": 217.46556091308594}, {"text": "Based on the epidemiological data currently available, diabetes does not seem to be a risk factor for infection with SARS-CoV-2 but may be associated with a more severe course. Diabetes is extremely common in older patients with co-morbidities who are at risk of unfavorable outcomes. As with any other infection, poorly controlled pre-existing diabetes can promote secondary infections and lead to acute complications related to hyperglycemia, worsened itself by the infection. It is important to advise patients to have enough diabetic equipment and supplies at home, to make regular blood glucose self-tests, and to contact a caregiver immediately in case of glycemic imbalance or signs of infection. Antidiabetic therapy may need adjustments following usual sick day rules. Insulin therapy should be considered to treat any persistent hyperglycemia in patients hospitalized for an acute infection.", "title": "[Diabetes and COVID-19 infection].", "pid": "nih2cnnz", "bm25_score": 217.46536254882812}, {"text": "AIMS: Rising prevalence of non-communicable diseases world-wide has made diabetes an important comorbidity in patients with coronavirus disease-19 (COVID-19). We sought to review the risk, severity and mortality in COVID-19 and its relation to the glycemic control, and role of anti-diabetic agents in patients with diabetes. METHODS: A Boolean search was made in PubMed, MedRxiv and Google Scholar database until May 10, 2020 and full articles with supplementary appendix were retrieved using the specific key words related to the topic. RESULTS: There is a high prevalence of diabetes in patients with COVID-19. Patients with diabetes had a significantly more severe variety of COVID-19 and increased mortality, compared to the groups without diabetes. Moreover, poor glycemic control is associated with a significantly higher severe COVID-19 and increased mortality, compared to the well-controlled glycemic groups. No data currently available for or against any anti-diabetic agents in COVID-19. CONCLUSIONS: Diabetes, in particular poorly-controlled group is associated with a significantly higher risk of severe COVID-19 and mortality. This calls for an optimal glycemic control and an increased emphasis on future preventative therapies including the vaccination programs for these groups in addition to the traditional risk prevention such as social distancing and self-isolation.", "title": "Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A narrative review", "pid": "dlv0kyb2", "bm25_score": 217.44203186035156}, {"text": "Diabetes and its related metabolic disorders have been reported as the leading comorbidities in patients with coronavirus disease 2019 (COVID-19). This clinical study aims to investigate the clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes in COVID-19 patients with or without diabetes. This retrospective study included 208 hospitalized patients (≥ 45 years old) with laboratory-confirmed COVID-19 during the period between 12 January and 25 March 2020. Information from the medical record, including clinical features, radiographic and laboratory tests, complications, treatments, and clinical outcomes, were extracted for the analysis. 96 (46.2%) patients had comorbidity with type 2 diabetes. In COVID-19 patients with type 2 diabetes, the coexistence of hypertension (58.3% vs. 31.2%), coronary heart disease (17.1% vs. 8.0%), and chronic kidney diseases (6.2% vs. 0%) was significantly higher than in COVID-19 patients without type 2 diabetes. The frequency and degree of abnormalities in computed tomography (CT) chest scans in COVID-19 patients with type 2 diabetes were markedly increased, including ground-glass opacity (85.6% vs. 64.9%, P < 0.001) and bilateral patchy shadowing (76.7% vs. 37.8%, P < 0.001). In addition, the levels of blood glucose (7.23 mmol·L(-1) (interquartile range (IQR): 5.80–9.29) vs. 5.46 mmol·L(-1) (IQR: 5.00–6.46)), blood low-density lipoprotein cholesterol (LDL-C) (2.21 mmol·L(-1) (IQR: 1.67–2.76) vs. 1.75 mmol·L(-1) (IQR: 1.27–2.01)), and systolic pressure (130 mmHg (IQR: 120–142) vs. 122 mmHg (IQR: 110–137), P = 0.001) in COVID-19 patients with diabetes were significantly higher than in patients without diabetes (P < 0.001). The coexistence of type 2 diabetes and other metabolic disorders is common in patients with COVID-19, which may potentiate the morbidity and aggravate COVID-19 progression. Optimal management of the metabolic hemostasis of glucose and lipids is the key to ensuring better clinical outcomes. Increased clinical vigilance is warranted for COVID-19 patients with diabetes and other metabolic diseases that are fundamental and chronic conditions.", "title": "Clinical Characteristics and Outcomes of Type 2 Diabetes Patients Infected with COVID-19: A Retrospective Study", "pid": "fhpvshr2", "bm25_score": 217.4316864013672}, {"text": "AIM: To map COVID‐19‐specific worries and overall psychosocial health among people with diabetes in the initial phase of the COVID‐19 pandemic in Denmark, and to explore characteristics of people with diabetes and high levels of worries related to the COVID‐19 pandemic. METHODS: A cross‐sectional survey was conducted by distributing online questionnaires to 2430 adult members (> 18 years) of two user panels consisting of people with diabetes who have volunteered to share information about their life with diabetes. The questionnaire included items on COVID‐19‐specific worries as well as such worries related to diabetes, sociodemographic and health status, social relations, diabetes‐specific social support, diabetes distress and changes in diabetes‐specific behaviours. Responses were analysed with descriptive statistics and logistic regressions. RESULTS: People with diabetes have COVID‐19‐specific worries related to their diabetes. More than half were worried about being overly affected due to diabetes if infected with COVID‐19, about one‐third about being characterized as a risk group due to diabetes and not being able to manage diabetes if infected. Logistic regressions showed that being female, having type 1 diabetes, diabetes complications and diabetes distress, feeling isolated and lonely, and having changed diabetes behaviours were associated with being more worried about COVID‐19 and diabetes. CONCLUSION: People with diabetes have COVID‐19‐specific worries related to their diabetes which is associated with poorer psychosocial health. These worries should be addressed through support targeting specific questions and needs of individuals with diabetes as well as frequent updates on new knowledge regarding COVID‐19 and diabetes.", "title": "Diabetes and COVID‐19: psychosocial consequences of the COVID‐19 pandemic in people with diabetes in Denmark—what characterizes people with high levels of COVID‐19‐related worries?", "pid": "3jolt83r", "bm25_score": 217.41357421875}, {"text": "Abstract Background and aims High prevalence of diabetes makes it an important comorbidity in patients with COVID-19. We sought to review and analyze the data regarding the association between diabetes and COVID-19, pathophysiology of the disease in diabetes and management of patients with diabetes who develop COVID-19 infection. Methods PubMed database and Google Scholar were searched using the key terms ‘COVID-19’, ‘SARS-CoV-2’, ‘diabetes’, ‘antidiabetic therapy’ up to April 2, 2020. Full texts of the retrieved articles were accessed. Results There is evidence of increased incidence and severity of COVID-19 in patients with diabetes. COVID-19 could have effect on the pathophysiology of diabetes. Blood glucose control is important not only for patients who are infected with COVID-19, but also for those without the disease. Innovations like telemedicine are useful to treat patients with diabetes in today’s times.", "title": "Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations", "pid": "bqxyb61p", "bm25_score": 217.39927673339844}, {"text": "Diabetes and Obesity are major risk factors which confer vulnerability to Covid 19 . Diabetes has immune defects which makes the individual susceptible to infections and covid 19 is no exception . Also covid 19 can cause pancreatic damage as well as stress hyperglycaemia in hospitals which may need Insulin . Among diabetes male gender,elderly,hypertension ,heart disease and chronic renal disease are more vulbwdvale to covid 19 and need strict supervision . Diabetes management in hospitalised situation merits early diabetes specific nutrition with Insulin. Adherence to lifestyle with self monitoring of blood glucose and adequate supply of Insulin and Oral antidiabetic agents is encouraged.", "title": "COVID 19: Diabetes and Obesity API-ICP Recommendations.", "pid": "25v7qies", "bm25_score": 217.35537719726562}, {"text": "• It is currently uncertain whether people with diabetes are at higher risk of severe illness from coronavirus disease 2019 (COVID-19). • We found that diabetes was associated with an approximately 4-fold increased risk of having severe/critical COVID-19 illness. • This association was independent of age, sex, obesity, hypertension and smoking. • These findings highlight the urgent need for a multidisciplinary team-based approach to management of this patient population.", "title": "Patients with diabetes are at higher risk for severe illness from COVID-19", "pid": "z0t43pmx", "bm25_score": 217.32598876953125}, {"text": "The current pandemic of SARS-CoV­2 coronavirus disease 2019 (COVID-19) is a particular challenge for diabetes patients. Diabetes mellitus predisposes to a particularly severe course of the disease and doubles the COVID-19 mortality risk due to pulmonary and cardiac involvement. In addition, diabetes patients often suffer from comorbidities which further worsen clinical outcomes. Glycemic control during infectious diseases is often suboptimal, and antidiabetic drugs and insulin therapy have to be adapted accordingly. On the other hand, access of diabetes patients to outpatient clinics are limited during the ongoing season urging alternative treatment options, particularly the implementation of novel telemedicine strategies. Hence, the opportunity of the COVID 19 crisis should be taken to make a significant step forward in the care for diabetes patients.", "title": "Diabetes and COVID-19 : Disease-Management-People", "pid": "7ptxz652", "bm25_score": 217.3187255859375}, {"text": "AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10-31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th-75th percentile: 25.0-32.7) kg/m2; with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin-angiotensin-aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA1c, diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736.", "title": "Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study", "pid": "hlnjp7v6", "bm25_score": 217.3136749267578}, {"text": "Abstract Aims Rising prevalence of non-communicable diseases world-wide has made diabetes an important comorbidity in patients with coronavirus disease-19 (COVID-19). We sought to review the risk, severity and mortality in COVID-19 and its relation to glycemic control and role of anti-diabetic agents in patients with diabetes. Methods A Boolean search was made in PubMed, MedRxiv and Google Scholar database until May 10, 2020 and full articles with supplementary appendix were retrieved using the specific key words related to the topic. Results There is a high prevalence of diabetes in patients with COVID-19. Patients with diabetes had a significantly more severe variety of COVID-19 and increased mortality, compared to the groups without diabetes. Moreover, poor glycemic control is associated with a significantly higher severe variety of COVID-19 and increased mortality, compared to the well-controlled glycemic groups. No data currently available for or against any anti-diabetic agents in COVID-19. Conclusions Diabetes, in particular poorly-controlled group is associated with a significantly higher risk of severe COVID-19 and mortality. This calls for an optimal glycemic control and an increased emphasis on future preventative therapies including the vaccination programs for these groups in addition to the traditional risk prevention such as social distancing and self-isolation.", "title": "Assessment of risk, severity, mortality, glycemic control and antidiabetic agents in patients with diabetes and COVID-19: A Narrative Review", "pid": "k5ro0edf", "bm25_score": 217.3072052001953}, {"text": "The coronavirus disease-2019 (COVID-19) has been designated as a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) since December 2019, when an outbreak of pneumonia cases emerged in Wuhan, China. The COVID-19 pandemic has led to a global health crisis, devastating the social, economic and political aspects of life. Many clinicians, health professionals, scientists, organizations, and governments have actively defeated COVID-19 and shared their experiences of the SARS-CoV2. Diabetes is one of the major risk factors for fatal outcomes from COVID-19. Patients with diabetes are vulnerable to infection because of hyperglycemia; impaired immune function; vascular complications; and comorbidities such as hypertension, dyslipidemia, and cardiovascular disease. In addition, angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 in the human body. Hence, the use of angiotensin-directed medications in patients with diabetes requires attention. The severity and mortality from COVID-19 was significantly higher in patients with diabetes than in those without. Thus, the patients with diabetes should take precautions during the COVID-19 pandemic. Therefore, we review the current knowledge of COVID-19 including the global and regional epidemiology, virology, impact of diabetes on COVID-19, treatment of COVID-19, and standard of care in the management of diabetes during this critical period.", "title": "Diabetes and COVID-19: Global and Regional Perspectives", "pid": "t8wg07ew", "bm25_score": 217.29541015625}, {"text": "The novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) outbreak originating in December 2019 has resulted in a worldwide pandemic affecting millions across almost 200 countries. People with diabetes appear to develop more severe forms of the disease and to require intensive care unit support and/or mechanical ventilation more frequently than those with other underlying medical conditions. The mortality rate among people with diabetes is also significantly higher than that among people without diabetes. A diagnosis of diabetes is often an indicator of poor underlying metabolic health, and frequently people with diabetes have multiple risk factors for severe coronavirus disease 2019 (COVID-19), including cardiovascular and renal disease. In this review, we discuss the potential biological mechanisms by which SARS-CoV-2 may interact with disease processes implicated in diabetes and discuss how treatments commonly used for people with diabetes may affect COVID-19 severity and progression. There is currently a lack of evidence from human studies, and further trials in this area will prove useful to further expand our understanding of this rapidly developing disease process to improve outcomes for this high-risk group of patients. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s13300-020-00858-2) contains supplementary material, which is available to authorized users.", "title": "Diabetes and Novel Coronavirus Infection: Implications for Treatment", "pid": "8t7rrgmp", "bm25_score": 217.27149963378906}, {"text": "BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01-01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of a dysregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention.", "title": "Diabetes and metabolic syndrome as risk factors for COVID-19", "pid": "i4t1jq29", "bm25_score": 217.2447509765625}, {"text": "AIMS: To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. METHODS: From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of &#8804;11mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. RESULTS: Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of &#8805;1.5 µg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of &#8805;10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. CONCLUSIONS: In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) may be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.", "title": "Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study", "pid": "nmolo7rt", "bm25_score": 217.24429321289062}, {"text": "Diabetes and Obesity are major risk factors which confer vulnerability to Covid 19 . Diabetes has immune defects which makes the individual susceptible to infections and covid 19 is no exception . Also covid 19 can cause pancreatic damage as well as stress hyperglycaemia in hospitals which may need Insulin . Among diabetes male gender,elderly,hypertension ,heart disease and chronic renal disease are more vulbwdvale to covid 19 and need strict supervision . Diabetes management in hospitalised situation merits early diabetes specific nutrition with Insulin. Adherence to lifestyle with self monitoring of blood glucose and adequate supply of Insulin and Oral antidiabetic agents is encouraged.", "title": "COVID 19: Diabetes and Obesity API-ICP Recommendations", "pid": "e582ueut", "bm25_score": 217.23709106445312}, {"text": "BACKGOUND: To figure out whether diabetes is a risk factor influencing the progression and prognosis of 2019 novel coronavirus disease (COVID‐19). METHODS: A total of 174 consecutive patients confirmed with COVID‐19 were studied. Demographic data, medical history, symptoms and signs, laboratory findings, chest computed tomography (CT) as well the treatment measures were collected and analysed. RESULTS: We found that COVID‐19 patients without other comorbidities but with diabetes (n = 24) were at higher risk of severe pneumonia, release of tissue injury‐related enzymes, excessive uncontrolled inflammation responses and hypercoagulable state associated with dysregulation of glucose metabolism. Furthermore, serum levels of inflammation‐related biomarkers such as IL‐6, C‐reactive protein, serum ferritin and coagulation index, D‐dimer, were significantly higher (P < .01) in diabetic patients compared with those without, suggesting that patients with diabetes are more susceptible to an inflammatory storm eventually leading to rapid deterioration of COVID‐19. CONCLUSIONS: Our data support the notion that diabetes should be considered as a risk factor for a rapid progression and bad prognosis of COVID‐19. More intensive attention should be paid to patients with diabetes, in case of rapid deterioration.", "title": "Diabetes is a risk factor for the progression and prognosis of COVID‐19", "pid": "wizlpkrk", "bm25_score": 217.2349395751953}, {"text": "BACKGROUND AND AIMS: Clinical evidence exists that patients with diabetes are at higher risk for Coronavirus disease 2019 (COVID-19). We investigated the physiological origins of this clinical observation linking diabetes with severity and adverse outcome of COVID-19. METHODS: Publication mining was applied to reveal common physiological contexts in which diabetes and COVID-19 have been investigated simultaneously. Overall, we have acquired 1,121,078 publications from PubMed in the time span between 01 and 01-2000 and 17-04-2020, and extracted knowledge graphs interconnecting the topics related to diabetes and COVID-19. RESULTS: The Data Mining revealed three pathophysiological pathways linking diabetes and COVID-19. The first pathway indicates a higher risk for COVID-19 because of an upregulation of Angiotensin-converting enzyme 2. The other two important physiological links between diabetes and COVID-19 are liver dysfunction and chronic systemic inflammation. A deep network analysis has suggested clinical biomarkers predicting the higher risk: Hypertension, elevated serum Alanine aminotransferase, high Interleukin-6, and low Lymphocytes count. CONCLUSIONS: The revealed biomarkers can be applied directly in clinical practice. For newly infected patients, the medical history needs to be checked for evidence of a long-term, chronic dysregulation of these biomarkers. In particular, patients with diabetes, but also those with prediabetic state, deserve special attention.", "title": "Diabetes and metabolic syndrome as risk factors for COVID-19", "pid": "qzev2reb", "bm25_score": 217.2331085205078}, {"text": "The current pandemic of SARS-CoV‑2 coronavirus disease 2019 (COVID-19) is a particular challenge for diabetes patients. Diabetes mellitus predisposes to a particularly severe course of the disease and doubles the COVID-19 mortality risk due to pulmonary and cardiac involvement. In addition, diabetes patients often suffer from comorbidities which further worsen clinical outcomes. Glycemic control during infectious diseases is often suboptimal, and antidiabetic drugs and insulin therapy have to be adapted accordingly. On the other hand, access of diabetes patients to outpatient clinics are limited during the ongoing season urging alternative treatment options, particularly the implementation of novel telemedicine strategies. Hence, the opportunity of the COVID 19 crisis should be taken to make a significant step forward in the care for diabetes patients.", "title": "Diabetes and COVID-19: Disease—Management—People", "pid": "mx9nyd2q", "bm25_score": 217.21694946289062}, {"text": "Abstract Background and aims Diabetes mellitus is associated with poor prognosis in patients with COVID-19. On the other hand, COVID-19 contributes to worsening of dysglycemia in people with diabetes mellitus over and above that contributed by stress hyperglycemia. Herein, we have reviewed the two-way interactions between COVID-19 and diabetes mellitus. Methods We have performed an extensive literature search for articles in PubMed, EMBASE and Google Scholar databases till April 25, 2020, with the following keywords: “COVID-19”, “SARS-CoV-2”, “diabetes”, “diabetes mellitus”, “SARS”, “infection” and “management of diabetes mellitus” with interposition of the Boolean operator “AND”. Results Compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists in people with DM contribute to poor prognosis in COVID-19. On the contrary, direct β-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir) can contribute to worsening of glucose control in people with diabetes mellitus. Conclusions The two-way interaction between COVID-19 and diabetes mellitus sets up a vicious cycle wherein COVID-19 leads to worsening of dysglycemia and diabetes mellitus, in turn, exacerbates the severity of COVID-19. Thus, it is imperative that people with DM take all necessary precautions and ensure good glycemic control amid the ongoing pandemic.", "title": "COVID-19 and diabetes mellitus: An unholy interaction of two pandemics", "pid": "fe8f7tk1", "bm25_score": 217.20455932617188}, {"text": "Diabetes has been associated with more severe outcomes and higher mortality in coronavirus disease 2019 (COVID-19) patients compare to morbidity and mortality in patients without diabetes. Several mechanisms may play a role in this greater morbidity and mortality, especially uncontrolled hyperglycemia, an impaired immune system, pre-existing proinflammatory states, multiple comorbidities, and dysregulated angiotensin-converting enzyme 2 signaling. Thus, the diabetes medical community emergently needs to know about COVID-19 and its effects on patients with diabetes, as they must take precautions to carefully manage these patients during the COVID-19 pandemic. The Korean Diabetes Association provides some guidance and practical recommendations for the management of diabetes during the pandemic. This report provides insight into the association between diabetes and COVID-19, proper management of diabetes in patients with COVID-19 and an official suggestion by the Korean Diabetes Association for managing the COVID-19 outbreak.", "title": "Coronavirus Disease 2019 and Diabetes: The Epidemic and the Korean Diabetes Association Perspective", "pid": "u1c9pusk", "bm25_score": 217.18165588378906}, {"text": "In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID-19.", "title": "Diabetes and severity of COVID-19: what is the link?", "pid": "lp89v4ak", "bm25_score": 217.17784118652344}, {"text": "In Diabetes Mellitus the loss of capacity to regulate immunity, the reduction of pulmonary functions and the pro-thrombotic state determine the severity of COVID-19.", "title": "Diabetes and severity of COVID-19: What is the link?", "pid": "un6u1suu", "bm25_score": 217.17784118652344}, {"text": "Abstract The coronavirus disease-2019 (COVID-19) has been designated as a highly contagious infectious disease caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) since December 2019, when an outbreak of pneumonia cases emerged in Wuhan, China. The COVID-19 pandemic has led to a global health crisis, devastating the social, economic and political aspects of life. Many clinicians, health professionals, scientists, organizations, and governments have actively defeated COVID-19 and shared their experiences of the SARS-CoV2. Diabetes is one of the major risk factors for fatal outcomes from COVID-19. Patients with diabetes are vulnerable to infection because of hyperglycemia; impaired immune function; vascular complications; and comorbidities such as hypertension, dyslipidemia, and cardiovascular disease. In addition, angiotensin-converting enzyme 2 (ACE2) is a receptor for SARS-CoV-2 in the human body. Hence, the use of angiotensin-directed medications in patients with diabetes requires attention. The severity and mortality from COVID-19 was significantly higher in patients with diabetes than in those without. Thus, the patients with diabetes should take precautions during the COVID-19 pandemic. Therefore, we review the current knowledge of COVID-19 including the global and regional epidemiology, virology, impact of diabetes on COVID-19, treatment of COVID-19, and standard of care in the management of diabetes during this critical period.", "title": "Diabetes and COVID-19: Global and Regional Perspectives", "pid": "cvltwjbz", "bm25_score": 217.16201782226562}, {"text": "The pandemic of coronavirus disease (COVID-19), a disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on SARS-CoV-2, Middle East respiratory syndrome (MERS-CoV), and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.", "title": "COVID-19 pandemic, coronaviruses, and diabetes mellitus", "pid": "lntg6yb8", "bm25_score": 217.12887573242188}, {"text": "Based on the epidemiological data currently available, diabetes does not seem to be a risk factor for infection with SARS-CoV-2 but may be associated with a more severe course Diabetes is extremely common in older patients with co-morbidities who are at risk of unfavorable outcomes As with any other infection, poorly controlled pre-existing diabetes can promote secondary infections and lead to acute complications related to hyperglycemia, worsened itself by the infection It is important to advise patients to have enough diabetic equipment and supplies at home, to make regular blood glucose self-tests, and to contact a caregiver immediately in case of glycemic imbalance or signs of infection Antidiabetic therapy may need adjustments following usual sick day rules Insulin therapy should be considered to treat any persistent hyperglycemia in patients hospitalized for an acute infection", "title": "[Diabetes and COVID-19 infection]", "pid": "m9d88do0", "bm25_score": 217.1272735595703}, {"text": "Diabetes mellitus is a complex, multifactorial, chronic disease characterized by impaired metabolism of glucose, fats and proteins Patients who suffer from it frequently have hyperglycemia and coronary artery disease is the leading cause of death The comorbidities associated with diabetes are overweight and obesity, systemic arterial hypertension, atherogenic dyslipidemia and in some patients peripheral vascular disease, kidney damage, neuropathy and retinopathy Chronic lack of control of the disease is associated with increased susceptibility to infections, which generally have few symptoms, but hyperglycemia is generally magnified, which worsens the course of infections Since December 2019, when the disease caused by one of the coronaviruses (coronavirus 2 of severe acute respiratory syndrome, SARS-CoV-2) was identified and has been called coronavirus disease 2019 (COVID-19), there have been some reports that associate the presence of diabetes with an increased risk of mortality In this review article we have focused on four specific points: 1) epidemiology of the prevalence and mortality of COVID 19 in the general population and in the population with type 2 diabetes mellitus;2) pathophysiology related to the binding of SARS-CoV-2 to receptors in subjects with diabetes;3) the immune response induced by SARS-CoV-2, and 4) the outpatient and hospital treatment recommended in patients with diabetes who become infected with SARS-CoV-2", "title": "Infección por coronavirus en pacientes con diabetes", "pid": "5ps6pw6c", "bm25_score": 217.1042022705078}, {"text": "Abstract Aims To estimate the prevalence of established diabetes and its association with the clinical severity and in-hospital mortality associated with COVID-19. Data synthesis We systematically searched PubMed, Scopus and Web of Science, from 1st January 2020 to 15th May 2020, for observational studies of patients admitted to hospital with COVID-19. Meta-analysis was performed using random-effects modeling. A total of 83 eligible studies with 78,874 hospitalized patients with laboratory-confirmed COVID-19 were included. The pooled prevalence of established diabetes was 14.34% (95% CI 12.62-16.06%). However, the prevalence of diabetes was higher in non-Asian vs. Asian countries (23.34% [95% CI 16.40-30.28] vs. 11.06% [95% CI 9.73-12.39]), and in patients aged ≥60 years vs. those aged <60 years (23.30% [95% CI 19.65-26.94] vs. 8.79% [95% CI 7.56-10.02]). Pre-existing diabetes was associated with an approximate twofold higher risk of having severe/critical COVID-19 illness (n=22 studies; random-effects odds ratio 2.10, 95% CI 1.71-2.57; I 2 =41.5%) and ∼threefold increased risk of in-hospital mortality (n=15 studies; random-effects odds ratio 2.68, 95% CI 2.09-3.44; I 2 =46.7%). Funnel plots and Egger’s tests did not reveal any significant publication bias. Conclusions Pre-existing diabetes is significantly associated with greater risk of severe/critical illness and in-hospital mortality in patients admitted to hospital with COVID-19.", "title": "Diabetes as a risk factor for greater COVID-19 severity and in-hospital death: a meta-analysis of observational studies", "pid": "rhojc8hx", "bm25_score": 217.0753936767578}, {"text": "The coronavirus disease 2019 (covid-19) pandemic has caused a public health emergency worldwide. Risk, severity and mortality of the disease have been associated with non-communicable chronic diseases, such as diabetes mellitus. Accumulated evidence has caused great concern in countries with high prevalence of this morbidity, such as Brazil. This text shows the picture of diabetes in Brazil, followed by epidemiological data and explanatory hypothesis for the association between diabetes and covid-19. We emphasized how the burden of these two morbidities in a middle-income country has aggravated this pandemic scenario. The comprehension of this association and biological plausibility may help face this pandemic and future challenges.", "title": "Diabetes and covid-19: more than the sum of two morbidities", "pid": "lxjgysp9", "bm25_score": 217.0658721923828}, {"text": "Background: Identification of risk factors of severe Covid-19 is critical for improving therapies and understanding SARS-CoV-2 pathogenesis. Methods: We analyzed 184 patients hospitalized for Covid-19 in Livingston, New Jersey for clinical characteristics associated with severe disease. Results: The majority of Covid-19 patients had diabetes mellitus (DM) (62.0%), Pre-DM (23.9%) with elevated FBG, or a BMI > 30 with normal HbA1C (4.3%). SARS-CoV-2 infection was associated with new and persistent hyperglycemia in 29 patients, including several with normal HbA1C levels. Forty-four patients required intubation, which occurred significantly more often in patients with DM as compared to non-diabetics. Conclusions: Severe Covid-19 occurs in the presence of impaired glucose metabolism in patients with SARS-CoV-2 infection. The association of dysregulated glucose metabolism and severe Covid-19 suggests a previously unrecognized manifestation of primary SARS-CoV-2 infection. Exploration of pathways by which SARS-CoV-2 impacts glucose metabolism is critical for understanding disease pathogenesis and developing therapies.", "title": "Impaired glucose metabolism in patients with diabetes, prediabetes and obesity is associated with severe Covid-19", "pid": "hf9cyr16", "bm25_score": 217.0521697998047}, {"text": "Abstract Aims To investigate the clinical characteristics, laboratory findings and high- resolution CT (HRCT) features and to explore the risk factors for in-hospital death and complications of coronavirus disease 2019 (COVID-19) patients with diabetes. Methods From Dec 31, 2019, to Apr 5, 2020, a total of 132 laboratory-confirmed COVID-19 patients with diabetes from two hospitals were retrospectively included in our study. Clinical, laboratory and chest CT data were analyzed and compared between the two groups with an admission glucose level of ≤11mmol/L (group 1) and >11mmol/L (group 2). Logistic regression analyses were used to identify the risk factors associated with in-hospital death and complications. Results Of 132 patients, 15 died in hospital and 113 were discharged. Patients in group 2 were more likely to require intensive care unit care (21.4% vs. 9.2%), to develop acute respiratory distress syndrome (ARDS) (23.2% vs. 9.25%) and acute cardiac injury (12.5% vs. 1.3%), and had a higher death rate (19.6% vs. 5.3%) than group 1. In the multivariable analysis, patients with admission glucose of >11 mmol/l had an increased risk of death (OR: 7.629, 95%CI: 1.391-37.984) and in-hospital complications (OR: 3.232, 95%CI: 1.393-7.498). Admission d-dimer of ≥1.5 μg/mL (OR: 6.645, 95%CI: 1.212-36.444) and HRCT score of ≥10 (OR: 7.792, 95%CI: 2.195-28.958) were associated with increased odds of in-hospital death and complications, respectively. Conclusions In COVID-19 patients with diabetes, poorly-controlled blood glucose (>11mmol/L) may be associated with poor outcomes. Admission hyperglycemia, elevated d-dimer and high HRCT score are potential risk factors for adverse outcomes and death.", "title": "Baseline characteristics and risk factors for short-term outcomes in 132 COVID-19 patients with diabetes in Wuhan China: a retrospective study", "pid": "5m4ybd1v", "bm25_score": 217.0492706298828}, {"text": "An altered immune response to pathogens has been suggested to explain increased susceptibility to infectious diseases in patients with diabetes. Recent evidence has documented several immunometabolic pathways in patients with diabetes directly related to the COVID-19 infection. This also seems to be the case for prediabetic subjects with proinflammatory insulin resistance syndrome accompanied with prothrombotic hyperinsulinemic and dysglycemic states. Patients with frank hyperglycemia, dysglycemia and/or hyperinsulinemia develop systemic immunometabolic inflammation with higher levels of circulating cytokines. This deleterious scenario has been proposed as the underlying mechanism enhancing a cytokine storm-like hyperinflammatory state in diabetics infected with severe COVID-19 triggering multi-organ failure. Compared with moderately affected COVID-19 patients, diabetes was found to be highly prevalent among severely affected patients suggesting that this non-communicable disease should be considered as a risk factor for adverse outcomes. The COVID-19 pandemic mirrors with the diabetes pandemic in many pathobiological aspects. Our interest is to emphasize the ties between the immunoinflammatory mechanisms that underlie the morbidity and lethality when COVID-19 meets diabetes. This review brings attention to two pathologies of highly complex, multifactorial, developmental and environmentally dependent manifestations of critical importance to human survival. Extreme caution should be taken with diabetics with suspected symptoms of COVID-19 infection.", "title": "The COVID-19 Pandemic during the Time of the Diabetes Pandemic: Likely Fraternal Twins?", "pid": "pruvl2l4", "bm25_score": 217.0375518798828}, {"text": "Diabetes has been identified as an important risk factor for mortality and rates of progression to acute respiratory distress syndrome (ARDS) in hospitalized patients with coronavirus disease 2019 (COVID-19). However, many recent reports on this topic reflect hurried approaches and have lacked careful epidemiologic design, conduct, and analysis. Features of prior studies have posed problems for our understanding of the true contribution of diabetes and other underlying comorbidities to prognosis in COVID-19. In this Perspective, we discuss some of the challenges of interpreting the current literature on diabetes and COVID-19 and discuss opportunities for future epidemiologic studies. We contend that the COVID-19 pandemic is a defining moment for the field of epidemiology and that diabetes epidemiology should play a significant role.", "title": "Diabetes Epidemiology in the COVID-19 Pandemic.", "pid": "ina400b0", "bm25_score": 217.03343200683594}, {"text": "AIMS: To estimate the prevalence of established diabetes and its association with the clinical severity and in-hospital mortality associated with COVID-19. DATA SYNTHESIS: We systematically searched PubMed, Scopus and Web of Science, from 1st January 2020 to 15th May 2020, for observational studies of patients admitted to hospital with COVID-19. Meta-analysis was performed using random-effects modeling. A total of 83 eligible studies with 78,874 hospitalized patients with laboratory-confirmed COVID-19 were included. The pooled prevalence of established diabetes was 14.34% (95% CI 12.62-16.06%). However, the prevalence of diabetes was higher in non-Asian vs. Asian countries (23.34% [95% CI 16.40-30.28] vs. 11.06% [95% CI 9.73-12.39]), and in patients aged &#8805;60 years vs. those aged <60 years (23.30% [95% CI 19.65-26.94] vs. 8.79% [95% CI 7.56-10.02]). Pre-existing diabetes was associated with an approximate twofold higher risk of having severe/critical COVID-19 illness (n = 22 studies; random-effects odds ratio 2.10, 95% CI 1.71-2.57; I2 = 41.5%) and ~threefold increased risk of in-hospital mortality (n = 15 studies; random-effects odds ratio 2.68, 95% CI 2.09-3.44; I2 = 46.7%). Funnel plots and Egger's tests did not reveal any significant publication bias. CONCLUSIONS: Pre-existing diabetes is significantly associated with greater risk of severe/critical illness and in-hospital mortality in patients admitted to hospital with COVID-19.", "title": "Diabetes as a risk factor for greater COVID-19 severity and in-hospital death: A meta-analysis of observational studies", "pid": "x22nems9", "bm25_score": 217.02955627441406}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic has emerged as one of the greatest challenges faced by humankind in the recent past. People with diabetes and related comorbidities are at increased risk of its complications and of COVID-19-related death. Older age, multi-morbidity, hyperglycaemia, cardiac injury and severe inflammatory response are predictors of poor outcome. The complex interplay between COVID-19, diabetes and the effects of related therapies is being explored. Most patients experience a mild illness with COVID-19, while people with diabetes are at increased risk of severe disease. Optimising glycaemic control and adopting measures to prevent disease spread are critical aspects. The management of mild disease is supportive, while very many immunomodulatory and antiviral therapies are being investigated for the treatment of severe disease. Several of these agents have specific considerations for use in people with diabetes. Since mass population lockdowns are considered a key step in controlling disease spread, it follows that, in addition to the direct vulnerability to severe COVID-19, people with diabetes can be affected by limited access to healthcare, insulin, other medications and blood glucose monitoring equipment. Measures to prevent disease spread at the individual and community level are the key to mitigating the rapidly escalating pandemic, while agents for chemoprophylaxis and vaccines are being explored. People with diabetes should be recognised as a vulnerable group for complicated disease and are at risk during times of disturbed social systems. Strategies are needed to safeguard the health of patients with diabetes during the pandemic. This review summarises the current knowledge and perceived challenges for prevention and management of COVID-19 in people with diabetes.", "title": "Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature", "pid": "e5mf6qdo", "bm25_score": 217.02212524414062}, {"text": "OBJECTIVE: Diabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 was confirmed or clinically diagnosed (with typical features on lung imaging and symptoms) and their association with glucose-lowering or blood pressure-lowering medications. RESEARCH DESIGN AND METHODS: In this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used to explore risk factors associated with mortality or poor prognosis. RESULTS: The proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P = 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P = 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among COVID-19 patients with diabetes and hypertension. CONCLUSIONS: C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death related to COVID-19. Attention needs to be paid to patients with diabetes and COVID-19 who use insulin. ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have COVID-19.", "title": "Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication", "pid": "p3qsn8di", "bm25_score": 217.01295471191406}, {"text": "The outbreak of the coronavirus disease 2019 (Covid-19) has become an evolving worldwide health crisis. With the rising prevalence of obesity and diabetes has come an increasing awareness of their impacts on infectious diseases, including increased risk for various infections, post-infection complications and mortality from critical infections. Although epidemiological and clinical characteristics of Covid-19 have been constantly reported, no article has systematically illustrated the role of obesity and diabetes in Covid-19, or how Covid-19 affects obesity and diabetes, or special treatment in these at-risk populations. Here, we present a synthesis of the recent advances in our understanding of the relationships between obesity, diabetes and Covid-19 along with the underlying mechanisms, and provide special treatment guidance for these at-risk populations.", "title": "Obesity and diabetes as high-risk factors for severe coronavirus disease 2019 (COVID-19)", "pid": "hs0wu3zu", "bm25_score": 216.99557495117188}, {"text": "Background: Infectious diseases are more frequent and can be associated with worse outcomes in patients with diabetes. Our aim was to systematically review and synthesize with a meta-analysis the available observational studies reporting the effect of diabetes in mortality among hospitalized patients with COVID-19. Methods: Medline, Embase, Google Scholar, and medRxiv databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. In-hospital mortality was defined as the endpoint. Sensitivity, subgroup, and meta-regression analyses were performed. Results: 18,506 patients were included in this meta-analysis (3,713 diabetics and 14,793 non-diabetics). Patients with diabetes were associated with a higher risk of death compared to patients without diabetes (OR: 1.65; 95% CI: 1.35, 1.96; I2 77.4%). The heterogeneity was high. A study level meta-regression analysis was performed for all the important covariates and no significant interactions were found between the covariates and the outcome of mortality. Conclusion: This meta-analysis shows that that the likelihood of death is 65% higher in diabetic hospitalized patients with COVID-19 compared to non-diabetics. Further studies are needed to assess whether this association is independent or not, as well as to investigate to role of glucose control prior or during the disease.", "title": "Diabetes is associated with increased risk for in-hospital mortality in patients with COVID-19: a systematic review and meta-analysis comprising 18,506 patients", "pid": "ok8wgvil", "bm25_score": 216.9925537109375}, {"text": "BACKGROUND: Identification of risk factors of severe Covid-19 is critical for improving therapies and understanding SARS-CoV-2 pathogenesis. METHODS: We analyzed 184 patients hospitalized for Covid-19 in Livingston, New Jersey for clinical characteristics associated with severe disease. RESULTS: The majority of Covid-19 patients had diabetes mellitus (DM) (62.0%), Pre-DM (23.9%) with elevated FBG, or a BMI > 30 with normal HbA1C (4.3%). SARS-CoV-2 infection was associated with new and persistent hyperglycemia in 29 patients, including several with normal HbA1C levels. Forty-four patients required intubation, which occurred significantly more often in patients with DM as compared to non-diabetics. CONCLUSIONS: Severe Covid-19 occurs in the presence of impaired glucose metabolism in patients, including those with DM, PreDM and obesity. Covid-19 is asociated with elevated FBG and several patients presented with new onset DM or in DKA. The association of dysregulated glucose metabolism and severe Covid-19 suggests that SARS-CoV-2 pathogenesis involves a novel interplay with glucose metabolism. Exploration of pathways by which SARS-CoV-2 interacts glucose metabolism is critical for understanding disease pathogenesis and developing therapies. This article is protected by copyright. All rights reserved.", "title": "Impaired glucose metabolism in patients with diabetes, prediabetes and obesity is associated with severe Covid-19", "pid": "x5843yao", "bm25_score": 216.97610473632812}, {"text": "Aim: To describe the clinical characteristics and outcomes of hospitalised Coronavirus Disease 2019 (COVID-19) patients with diabetes. Methods: A cross-sectional observational study was conducted in patients with diabetes admitted with COVID-19 to Mediclinic Parkview Hospital in Dubai, United Arab Emirates (UAE) from 30th March to 7th June 2020. They had laboratory and/or radiologically confirmed severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), known as COVID-19. Variation in characteristics, length of stay in hospital, diabetes status, comorbidities and outcomes were examined. Results: A total of 103 patients with confirmed COVID-19 presentations had diabetes. During the same timeframe, 410 patients overall were admitted with COVID-19 infection. This gives a total proportion of persons admitted with COVID-19 infection and coexistent diabetes/prediabetes of 25%. 67% (n=69) of the COVID-19 diabetes cohort were male. Patients admitted with COVID-19 and diabetes represented 17 different ethnicities. Of these, 59.2% (n=61) were Asians and 35% (n=36) were from Arab countries. Mean age (SD) was 54 (12.5) years. 85.4% (n=88) were known to have diabetes prior to admission, while 14.6% (n=15) were newly diagnosed with either diabetes or prediabetes during admission. Most patients in the study cohort had type 2 diabetes or prediabetes, with only 3% overall having type 1 diabetes (n=3). 46.9% of patients had evidence of good glycaemic control of their diabetes during the preceding 4-12 weeks prior to admission as defined arbitrarily by admission HbA1c <7.5%. 73.8% (n=76) had other comorbidities including hypertension, ischaemic heart disease, and dyslipidaemia. Laboratory data Mean(SD) on admission for those who needed ward-based care versus those needing intensive care unit (ICU) care: Fibrinogen 462.75 (125.16) mg/dl vs 660 (187.58) mg/dl ; D-dimer 0.66 (0.55) mcg/ml vs 2.3 (3.48) mcg/ml; Ferritin 358.08 (442.05) mg/dl vs 1762.38 (2586.38) mg/dl; and CRP 33.9 (38.62) mg/L vs 137 (111.72) mg/L were all statistically significantly higher for the ICU cohort (p<0.05). Average length of stay in hospital was 14.55 days. 28.2% of patients needed ICU admission. 4.9% (n=5) overall died during hospitalisation (all in ICU). Conclusions: In this single-centre study in Dubai, 25% of patients admitted with COVID-19 also had diabetes/prediabetes. Most diabetes patients admitted to hospital with COVID-19 disease were males of Asian origin. 14.6% had new diagnosis of diabetes/prediabetes on admission. The majority of patients with diabetes/prediabetes and COVID-19 infection had other important comorbidities (n=76; 73.8%). Only 4 patients had negative COVID-19 RT-PCR but had pathognomonic changes of COVID-19 radiologically. Our comprehensive laboratory analysis revealed distinct abnormal patterns of biomarkers that are associated with poor prognosis: Fibrinogen, D-dimer, Ferritin and CRP levels were all statistically significantly higher (p<0.05) at presentation in patients who subsequently needed ICU care compared with those patients who remained ward-based. 28.2% overall needed ICU admission, out of which 5 patients died. More studies with larger sample sizes are needed to compare data of COVID-19 patients admitted with and without diabetes within the UAE region.", "title": "Clinical characteristics and outcomes in diabetes patients admitted with COVID-19 in Dubai: a cross-sectional single centre study.", "pid": "nohilcmu", "bm25_score": 216.96975708007812}, {"text": "Summary According to previous reports, diabetes seems to be a risk factor which worsens the serious clinical events caused by COVID-19. But is diabetes per se a risk factor that increases the probability of getting the virus? This paper will discuss this point. There are not many research data on antidiabetic drugs in this context. The potential influence of glucose-lowering agents on the severity of COVID-19 has not been described yet. Dipeptidylpeptidase-4 (DPP-4) is a cell surface protein ubiquitously expressed in many tissues and it is also a soluble molecule found in serum/plasma fluids. DPP-4 is involved in infection of cells by some viruses. This paper reviews data about the use of DPP-4 inhibitors and others diabetes drugs on COVID-19 patients. As such, no available evidence has yet suggested that glucose-lowering drugs – including those targeting DPP4-related pathways – produce any significant harm or benefit in the context of human infections. However, insulin must remain the first-choice agent in the management of critically ill-hospitalized patients, while it is recommended to suspend other agents in unstable patients. This paper provides related French and international recommendations for people with diabetes who got infected by COVID-19 and upholds that infections may alter glucose control and may require additional vigilance.", "title": "Diabetes and COVID-19", "pid": "o99mtt0v", "bm25_score": 216.9656982421875}, {"text": "Diabetes has been identified as an important risk factor for mortality and rates of progression to acute respiratory distress syndrome (ARDS) in hospitalized patients with coronavirus disease 2019 (COVID-19). However, many recent reports on this topic reflect hurried approaches and have lacked careful epidemiologic design, conduct, and analysis. Features of prior studies have posed problems for our understanding of the true contribution of diabetes and other underlying comorbidities to prognosis in COVID-19. In this Perspective, we discuss some of the challenges of interpreting the current literature on diabetes and COVID-19 and discuss opportunities for future epidemiologic studies. We contend that the COVID-19 pandemic is a defining moment for the field of epidemiology and that diabetes epidemiology should play a significant role.", "title": "Diabetes Epidemiology in the COVID-19 Pandemic", "pid": "vhmga8rh", "bm25_score": 216.96554565429688}, {"text": "The pandemic of COVID-19, a disease caused by a novel coronavirus (CoV), SARS-CoV-2, is causing substantial morbidity and mortality. Older age and presence of diabetes mellitus, hypertension, and obesity significantly increases the risk for hospitalization and death in COVID-19 patients. In this Perspective, informed by the studies on severe acute respiratory syndrome, SARS-CoV, and Middle East respiratory syndrome, MERS-CoV, and the current literature on SARS-CoV-2, we discuss potential mechanisms by which diabetes modulates the host-viral interactions and host-immune responses. We hope to highlight gaps in knowledge that require further studies pertinent to COVID-19 in patients with diabetes.", "title": "COVID-19 Pandemic, Corona Viruses, and Diabetes Mellitus.", "pid": "22vz79nz", "bm25_score": 216.9653778076172}, {"text": "BACKGROUND AND AIMS: Diabetes Mellitus (DM) is chronic conditions with devastating multi-systemic complication and may be associated with severe form of Coronavirus Disease 2019 (COVID-19). We conducted a systematic review and meta-analysis in order to investigate the association between DM and poor outcome in patients with COVID-19 pneumonia. METHODS: Systematic literature search was performed from several electronic databases on subjects that assess DM and outcome in COVID-19 pneumonia. The outcome of interest was composite poor outcome, including mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care, and disease progression. RESULTS: There were a total of 6452 patients from 30 studies. Meta-analysis showed that DM was associated with composite poor outcome (RR 2.38 [1.88, 3.03], p < 0.001; I2: 62%) and its subgroup which comprised of mortality (RR 2.12 [1.44, 3.11], p < 0.001; I2: 72%), severe COVID-19 (RR 2.45 [1.79, 3.35], p < 0.001; I2: 45%), ARDS (RR 4.64 [1.86, 11.58], p = 0.001; I2: 9%), and disease progression (RR 3.31 [1.08, 10.14], p = 0.04; I2: 0%). Meta-regression showed that the association with composite poor outcome was influenced by age (p = 0.003) and hypertension (p < 0.001). Subgroup analysis showed that the association was weaker in studies with median age &#8805;55 years-old (RR 1.92) compared to <55 years-old (RR 3.48), and in prevalence of hypertension &#8805;25% (RR 1.93) compared to <25% (RR 3.06). Subgroup analysis on median age <55 years-old and prevalence of hypertension <25% showed strong association (RR 3.33) CONCLUSION: DM was associated with mortality, severe COVID-19, ARDS, and disease progression in patients with COVID-19.", "title": "Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia - A systematic review, meta-analysis, and meta-regression", "pid": "hj5zcw2v", "bm25_score": 216.9619903564453}, {"text": "Diabetes is one of the main comorbidities in patients infected with the SARS-CoV-2 virus, the causative agent of the new coronavirus disease 2019 (COVID-19). Because the presence of diabetes and COVID-19 in the same patient is related to a poor clinical prognosis and a high probability of death, it is necessary to determine what findings allow us to predict a good or bad resolution of the disease in order to opt for a traditional treatment or a more incisive one. In this way, in the present work we analyze which laboratory parameters showed differences in patients with COVID-19 and diabetes who recovered and in those who had complications or died.", "title": "Laboratory findings that predict a poor prognosis in COVID-19 patients with diabetes: A meta-analysis", "pid": "tsd6sjcx", "bm25_score": 216.90560913085938}, {"text": "OBJECTIVE Diabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 has been confirmed or clinically diagnosed (with typical features on lung imaging and symptoms), and their association with glucose-lowering or blood pressure-lowering medications. RESEARCH DESIGN AND METHODS In this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used in order to explore risk factors associated with mortality or poor prognosis. RESULTS The proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P = 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P = 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among patients with diabetes and hypertension who have COVID-19. CONCLUSIONS C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death related to COVID-19. Attention needs to be paid to patients with diabetes and COVID-19 who use insulin. ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have COVID-19.", "title": "Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication.", "pid": "p536yuvi", "bm25_score": 216.89852905273438}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus responsible for the current coronavirus disease 2019 (COVID-19) pandemic, has infected over 3.5 million people all over the world since the first case was reported from Wuhan, China 5 months ago. As more epidemiological data regarding COVID-19 patients is acquired, factors that increase the severity of the infection are being identified and reported. One of the most consistent co-morbidities associated with worse outcome in COVID-19 patients is diabetes, along with age and cardiovascular disease. Studies on the association of diabetes with other acute respiratory infections, namely SARS, MERS, and Influenza, outline what seems to be an underlying factor in diabetic patients that makes them more susceptible to complications. In this review we summarize what we think may be the factors driving this pattern between diabetes, aging and poor outcomes in respiratory infections. We also review therapeutic considerations and strategies for treatment of COVID-19 in diabetic patients, and how the additional challenge of this co-morbidity requires attention to glucose homeostasis so as to achieve the best outcomes possible for patients.", "title": "SARS-CoV-2 disease severity and diabetes: why the connection and what is to be done?", "pid": "5zb96j4a", "bm25_score": 216.872802734375}, {"text": "Patients with diabetes who get coronavirus disease 2019 (COVID-19) are at risk of a severe disease course and mortality. Several factors especially the impaired immune response, heightened inflammatory response and hypercoagulable state contribute to the increased disease severity. However, there are many contentious issues about which the evidence is rather limited. There are some theoretical concerns about the effects of different anti-hyperglycaemic drugs. Similarly, despite the recognition of angiotensin converting enzyme 2 (ACE2) as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), and the role of ACE2 in lung injury; there are conflicting results with the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) in these patients. Management of patients with diabetes in times of restrictions on mobility poses some challenges and novel approaches like telemedicine can be useful. There is a need to further study the natural course of COVID-19 in patients with diabetes and to understand the individual, regional and ethnic variations in disease prevalence and course.", "title": "Diabetes and COVID-19: evidence, current status and unanswered research questions.", "pid": "4ti8l2ea", "bm25_score": 216.8559112548828}, {"text": "", "title": "Letter to the Editor: COVID-19 in patients with diabetes: Risk factors that increase morbidity", "pid": "6yb3mf4c", "bm25_score": 216.85357666015625}, {"text": "OBJECTIVE: This study explores the clinical characteristics of patients with diabetes with severe covid-19, and the association of diabetes with survival duration in patients with severe covid-19. RESEARCH DESIGN AND METHODS: In this single-center, retrospective, observational study, the clinical and laboratory characteristics of 193 patients with severe covid-19 were collected. 48 patients with severe covid-19 had diabetes, and 145 patients (ie, the controls) did not have diabetes. A severe case was defined as including at least one of the following criteria: (1) Respiratory rate >30/min. (2) Oxygen saturation ≤93%. (3) PaO(2)/FiO(2)≤300 mm Hg. (4) Patients, either with shock or respiratory failure, requiring mechanical ventilation, or combined with other organ failure, requiring admission to intensive care unit (ICU). RESULTS: Of 193 patients with severe covid-19, 48 (24.9%) had diabetes. Compared with patients with severe covid-19 without diabetes, patients with diabetes were older, susceptible to receiving mechanical ventilation and admission to ICU, and had higher mortality. In addition, patients with severe covid-19 with diabetes had higher levels of leukocyte count, neutrophil count, high-sensitivity C reaction protein, procalcitonin, ferritin, interleukin (IL) 2 receptor, IL-6, IL-8, tumor necrosis factor α, D-dimer, fibrinogen, lactic dehydrogenase and N-terminal pro-brain natriuretic peptide. Among patients with severe covid-19 with diabetes, more non-survivors were men (30 (76.9%) vs 9 (23.1%)). Non-survivors had severe inflammatory response, and cardiac, hepatic, renal and coagulation impairment. Finally, the Kaplan-Meier survival curve showed a trend towards poorer survival in patients with severe covid-19 with diabetes than patients without diabetes. The HR was 1.53 (95% CI 1.02 to 2.30; p=0.041) after adjustment for age, sex, hypertension, cardiovascular disease and cerebrovascular disease by Cox regression. The median survival durations from hospital admission in patients with severe covid-19 with and without diabetes were 10 days and 18 days, respectively. CONCLUSION: The mortality rate in patients with severe covid-19 with diabetes is considerable. Diabetes may lead to an increase in the risk of death.", "title": "Clinical characteristics and outcomes of patients with severe covid-19 with diabetes", "pid": "wtov0a4f", "bm25_score": 216.8467254638672}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic has emerged as one of the greatest challenges faced by humankind in the recent past. People with diabetes and related comorbidities are at increased risk of its complications and of COVID-19-related death. Older age, multi-morbidity, hyperglycaemia, cardiac injury and severe inflammatory response are predictors of poor outcome. The complex interplay between COVID-19, diabetes and the effects of related therapies is being explored. Most patients experience a mild illness with COVID-19, while people with diabetes are at increased risk of severe disease. Optimising glycaemic control and adopting measures to prevent disease spread are critical aspects. The management of mild disease is supportive, while very many immunomodulatory and antiviral therapies are being investigated for the treatment of severe disease. Several of these agents have specific considerations for use in people with diabetes. Since mass population lockdowns are considered a key step in controlling disease spread, it follows that, in addition to the direct vulnerability to severe COVID-19, people with diabetes can be affected by limited access to healthcare, insulin, other medications and blood glucose monitoring equipment. Measures to prevent disease spread at the individual and community level are the key to mitigating the rapidly escalating pandemic, while agents for chemoprophylaxis and vaccines are being explored. People with diabetes should be recognised as a vulnerable group for complicated disease and are at risk during times of disturbed social systems. Strategies are needed to safeguard the health of patients with diabetes during the pandemic. This review summarises the current knowledge and perceived challenges for prevention and management of COVID-19 in people with diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05164-x) contains peer-reviewed but unedited supplementary material including a slideset of the figures for download, which is available to authorised users.", "title": "Prevention and management of COVID-19 among patients with diabetes: an appraisal of the literature", "pid": "15hqzcig", "bm25_score": 216.8458251953125}, {"text": "AIMS/HYPOTHESIS: Coronavirus disease-2019 (COVID-19) is a life-threatening infection caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus. Diabetes has rapidly emerged as a major comorbidity for COVID-19 severity. However, the phenotypic characteristics of diabetes in COVID-19 patients are unknown. METHODS: We conducted a nationwide multicentre observational study in people with diabetes hospitalised for COVID-19 in 53 French centres in the period 10–31 March 2020. The primary outcome combined tracheal intubation for mechanical ventilation and/or death within 7 days of admission. Age- and sex-adjusted multivariable logistic regressions were performed to assess the prognostic value of clinical and biological features with the endpoint. ORs are reported for a 1 SD increase after standardisation. RESULTS: The current analysis focused on 1317 participants: 64.9% men, mean age 69.8 ± 13.0 years, median BMI 28.4 (25th–75th percentile: 25.0–32.7) kg/m(2); with a predominance of type 2 diabetes (88.5%). Microvascular and macrovascular diabetic complications were found in 46.8% and 40.8% of cases, respectively. The primary outcome was encountered in 29.0% (95% CI 26.6, 31.5) of participants, while 10.6% (9.0, 12.4) died and 18.0% (16.0, 20.2) were discharged on day 7. In univariate analysis, characteristics prior to admission significantly associated with the primary outcome were sex, BMI and previous treatment with renin–angiotensin–aldosterone system (RAAS) blockers, but not age, type of diabetes, HbA(1c), diabetic complications or glucose-lowering therapies. In multivariable analyses with covariates prior to admission, only BMI remained positively associated with the primary outcome (OR 1.28 [1.10, 1.47]). On admission, dyspnoea (OR 2.10 [1.31, 3.35]), as well as lymphocyte count (OR 0.67 [0.50, 0.88]), C-reactive protein (OR 1.93 [1.43, 2.59]) and AST (OR 2.23 [1.70, 2.93]) levels were independent predictors of the primary outcome. Finally, age (OR 2.48 [1.74, 3.53]), treated obstructive sleep apnoea (OR 2.80 [1.46, 5.38]), and microvascular (OR 2.14 [1.16, 3.94]) and macrovascular complications (OR 2.54 [1.44, 4.50]) were independently associated with the risk of death on day 7. CONCLUSIONS/INTERPRETATIONS: In people with diabetes hospitalised for COVID-19, BMI, but not long-term glucose control, was positively and independently associated with tracheal intubation and/or death within 7 days. TRIAL REGISTRATION: clinicaltrials.gov NCT04324736. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00125-020-05180-x) contains peer-reviewed but unedited supplementary material, which is available to authorised users.", "title": "Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study", "pid": "97j1gt5k", "bm25_score": 216.8256072998047}, {"text": "OBJECTIVE: This study explores the clinical characteristics of patients with diabetes with severe covid-19, and the association of diabetes with survival duration in patients with severe covid-19. RESEARCH DESIGN AND METHODS: In this single-center, retrospective, observational study, the clinical and laboratory characteristics of 193 patients with severe covid-19 were collected. 48 patients with severe covid-19 had diabetes, and 145 patients (ie, the controls) did not have diabetes. A severe case was defined as including at least one of the following criteria: (1) Respiratory rate >30/min. (2) Oxygen saturation &#8804;93%. (3) PaO2/FiO2&#8804;300 mm Hg. (4) Patients, either with shock or respiratory failure, requiring mechanical ventilation, or combined with other organ failure, requiring admission to intensive care unit (ICU). RESULTS: Of 193 patients with severe covid-19, 48 (24.9%) had diabetes. Compared with patients with severe covid-19 without diabetes, patients with diabetes were older, susceptible to receiving mechanical ventilation and admission to ICU, and had higher mortality. In addition, patients with severe covid-19 with diabetes had higher levels of leukocyte count, neutrophil count, high-sensitivity C reaction protein, procalcitonin, ferritin, interleukin (IL) 2 receptor, IL-6, IL-8, tumor necrosis factor &#945;, D-dimer, fibrinogen, lactic dehydrogenase and N-terminal pro-brain natriuretic peptide. Among patients with severe covid-19 with diabetes, more non-survivors were men (30 (76.9%) vs 9 (23.1%)). Non-survivors had severe inflammatory response, and cardiac, hepatic, renal and coagulation impairment. Finally, the Kaplan-Meier survival curve showed a trend towards poorer survival in patients with severe covid-19 with diabetes than patients without diabetes. The HR was 1.53 (95% CI 1.02 to 2.30; p=0.041) after adjustment for age, sex, hypertension, cardiovascular disease and cerebrovascular disease by Cox regression. The median survival durations from hospital admission in patients with severe covid-19 with and without diabetes were 10 days and 18 days, respectively. CONCLUSION: The mortality rate in patients with severe covid-19 with diabetes is considerable. Diabetes may lead to an increase in the risk of death.", "title": "Clinical characteristics and outcomes of patients with severe covid-19 with diabetes", "pid": "lf88bwh2", "bm25_score": 216.82366943359375}, {"text": "According to previous reports, diabetes seems to be a risk factor which worsens the serious clinical events caused by COVID-19. But is diabetes per se a risk factor that increases the probability of getting the virus? This paper will discuss this point. There are not many research data on antidiabetic drugs in this context. The potential influence of glucose-lowering agents on the severity of COVID-19 has not been described yet. Dipeptidylpeptidase-4 (DPP-4) is a cell surface protein ubiquitously expressed in many tissues and it is also a soluble molecule found in serum/plasma fluids. DPP-4 is involved in infection of cells by some viruses. This paper reviews data about the use of DPP-4 inhibitors and others diabetes drugs on COVID-19 patients. As such, no available evidence has yet suggested that glucose-lowering drugs - including those targeting DPP4-related pathways - produce any significant harm or benefit in the context of human infections. However, insulin must remain the first-choice agent in the management of critically ill-hospitalized patients, while it is recommended to suspend other agents in unstable patients. This paper provides related French and international recommendations for people with diabetes who got infected by COVID-19 and upholds that infections may alter glucose control and may require additional vigilance.", "title": "Diabetes and COVID-19", "pid": "1gswvgya", "bm25_score": 216.8231201171875}, {"text": "Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events.", "title": "Diabetes and COVID-19: Risks, Management, and Learnings From Other National Disasters.", "pid": "8qao0tmx", "bm25_score": 216.81809997558594}, {"text": "Abstract Background and aims Diabetes Mellitus (DM) is chronic conditions with devastating multi-systemic complication and may be associated with severe form of Coronavirus Disease 2019 (COVID-19). We conducted a systematic review and meta-analysis in order to investigate the association between DM and poor outcome in patients with COVID-19 pneumonia. Methods Systematic literature search was performed from several electronic databases on subjects that assess DM and outcome in COVID-19 pneumonia. The outcome of interest was composite poor outcome, including mortality, severe COVID-19, acute respiratory distress syndrome (ARDS), need for intensive care unit (ICU) care, and disease progression. Results There were a total of 6452 patients from 30 studies. Meta-analysis showed that DM was associated with composite poor outcome (RR 2.38 [1.88, 3.03], p < 0.001; I2: 62%) and its subgroup which comprised of mortality (RR 2.12 [1.44, 3.11], p < 0.001; I2: 72%), severe COVID-19 (RR 2.45 [1.79, 3.35], p < 0.001; I2: 45%), ARDS (RR 4.64 [1.86, 11.58], p = 0.001; I2: 9%), and disease progression (RR 3.31 [1.08, 10.14], p = 0.04; I2: 0%). Meta-regression showed that the association with composite poor outcome was influenced by age (p = 0.003) and hypertension (p < 0.001). Subgroup analysis showed that the association was weaker in studies with median age ≥55 years-old (RR 1.92) compared to <55 years-old (RR 3.48), and in prevalence of hypertension ≥25% (RR 1.93) compared to <25% (RR 3.06). Subgroup analysis on median age <55 years-old and prevalence of hypertension <25% showed strong association (RR 3.33) Conclusion DM was associated with mortality, severe COVID-19, ARDS, and disease progression in patients with COVID-19.", "title": "Diabetes mellitus is associated with increased mortality and severity of disease in COVID-19 pneumonia – A systematic review, meta-analysis, and meta-regression", "pid": "u6uqroi0", "bm25_score": 216.8158416748047}, {"text": "Coronavirus disease 2019 (COVID-19) is a global pandemic that is caused by a novel coronavirus, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Data from several countries have demonstrated higher morbidity and mortality among individuals with chronic metabolic diseases such as diabetes mellitus (DM). In this review, we explore the contributing factors for poorer prognosis in these individuals. As a significant proportion of patients with COVID-19 also have DM, this adds another layer of complexity to their management. We explore potential interactions between anti-diabetic medications and renin-angiotensin-aldosterone-system inhibitors with COVID-19. Suggested recommendations for the use of anti-diabetic medications in COVID-19 patients with DM are provided. We also review pertinent clinical considerations in the management of diabetic ketoacidosis in the COVID-19 patient. In addition, we aim to increase the awareness of clinicians to the metabolic effects of promising drug therapies for COVID-19. Finally, we highlight the importance of timely vaccinations for patients with DM.", "title": "Dissecting the Interaction between Coronavirus Disease 2019 and Diabetes Mellitus", "pid": "09qp0sts", "bm25_score": 216.81021118164062}, {"text": "With the accumulation of observational data showing association of metabolic comorbidities with adverse outcomes from COVID-19, there is a need to disentangle the contributions of pre-existing macro- and microvascular disease, obesity and glycaemia. This article outlines the complex mechanistic and clinical interplay between diabetes and COVID-19, the clinical and research questions that arise from these; and the types of studies needed to answer them. The authors are clinicians and academics working in diabetes and obesity medicine, but the article is pitched to an audience of generalists with clinical experience or interest in management of COVID-19. This article is protected by copyright. All rights reserved.", "title": "Diabetes, Obesity and COVID-19: A Complex Interplay", "pid": "msr78qwy", "bm25_score": 216.80186462402344}, {"text": "Diabetes has been identified as a pre-existing health condition linked with worse outcomes following coronavirus disease 2019 infection. Here we explore the association between hyperglycaemia and more severe illness, the impact of the pandemic on diabetes service delivery, and the resultant opportunities for innovation.", "title": "COVID-19: Impact of and on Diabetes", "pid": "3mm3xe1g", "bm25_score": 216.79766845703125}, {"text": "", "title": "COVID-19 in patients with diabetes: risk factors that increase morbidity", "pid": "b9fxrt0z", "bm25_score": 216.77662658691406}, {"text": "AIM: To evaluate the association between different degrees of hyperglycaemia and the risk of all-cause mortality among hospitalized patients with COVID-19. MATERIALS AND METHODS: In a retrospective study conducted from 22 January to 17 March 2020, 453 patients were admitted to Union Hospital in Wuhan, China, with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Patients were classified into four categories: normal glucose, hyperglycaemia (fasting glucose 5.6-6.9 mmol/L and/or HbA1c 5.7%-6.4%), newly diagnosed diabetes (fasting glucose &#8805;7 mmol/L and/or HbA1c &#8805;6.5%) and known diabetes. The major outcomes included in-hospital mortality, intensive care unit (ICU) admission and invasive mechanical ventilation (IMV). RESULTS: Patients with newly diagnosed diabetes constituted the highest percentage to be admitted to the ICU (11.7%) and require IMV (11.7%), followed by patients with known diabetes (4.1%; 9.2%) and patients with hyperglycaemia (6.2%; 4.7%), compared with patients with normal glucose (1.5%; 2.3%), respectively. The multivariable-adjusted hazard ratios of mortality among COVID-19 patients with normal glucose, hyperglycaemia, newly diagnosed diabetes and known diabetes were 1.00, 3.29 (95% confidence interval [CI] 0.65-16.6), 9.42 (95% CI 2.18-40.7) and 4.63 (95% CI 1.02-21.0), respectively. CONCLUSION: We showed that COVID-19 patients with newly diagnosed diabetes had the highest risk of all-cause mortality compared with COVID-19 patients with known diabetes, hyperglycaemia and normal glucose. Patients with COVID-19 need to be kept under surveillance for blood glucose screening.", "title": "Newly diagnosed diabetes is associated with a higher risk of mortality than known diabetes in hospitalized patients with COVID-19", "pid": "k9p82pt5", "bm25_score": 216.7202911376953}, {"text": "AIMS: We aimed to briefly review the general characteristics of the novel coronavirus (SARS-CoV-2) and provide a better understanding of the coronavirus disease (COVID-19) in people with diabetes, and its management. METHODS: We searched for articles in PubMed and Google Scholar databases till 02 April 2020, with the following keywords: \"SARS-CoV-2\", \"COVID-19\", \"infection\", \"pathogenesis\", \"incubation period\", \"transmission\", \"clinical features\", \"diagnosis\", \"treatment\", \"diabetes\", with interposition of the Boolean operator \"AND\". RESULTS: The clinical spectrum of COVID-19 is heterogeneous, ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Older age, diabetes and other comorbidities are reported as significant predictors of morbidity and mortality. Chronic inflammation, increased coagulation activity, immune response impairment, and potential direct pancreatic damage by SARS-CoV-2 might be among the underlying mechanisms of the association between diabetes and COVID-19. No conclusive evidence exists to support the discontinuation of angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers or thiazolidinediones because of COVID-19 in people with diabetes. Caution should be taken to potential hypoglycemic events with the use of chloroquine in these subjects. Patient tailored therapeutic strategies, rigorous glucose monitoring and careful consideration of drug interactions might reduce adverse outcomes. CONCLUSIONS: Suggestions are made on the possible pathophysiological mechanisms of the relationship between diabetes and COVID-19, and its management. No definite conclusions can be made based on current limited evidence. Further research regarding this relationship and its clinical management is warranted.", "title": "COVID-19 and diabetes: Knowledge in progress", "pid": "0tdt0wej", "bm25_score": 216.67359924316406}, {"text": "Background: The Coronavirus disease 2019 (COVID19) pandemic is straining the healthcare system, particularly for patients with severe outcomes who require admittance to the intensive care unit (ICU). This study aimed to investigate the potential associations of obesity and diabetes with COVID19 severe outcomes, assessed as ICU admittance. Subjects: Demographic and patient characteristics from a retrospective cohort of 1158 patients hospitalized with COVID19 in a single center in Kuwait, along with their medical history, were analyzed. Univariate and multivariate analyses were performed to explore the associations between different variables and ICU admittance. Results: From the 1158 hospitalized patients, 271 (23.4%) had diabetes, 236 (20.4%) had hypertension and 104 (9%) required admittance into the ICU. From patients with available measurements, 157 (21.6%) had body mass index (BMI)[≥]25 kg/m2. Univariate analysis showed that overweight (BMI=25.0~29.9 kg/m2), obesity class I (BMI=30~34.9 kg/m2) and morbid obesity (BMI[≥]40 kg/m2) associated with ICU admittance (odds ratio (OR) [95% confidence intervals (CI)]: 2.45 [1.26~4.74] p value=0.008; OR [95% CI]: 3.51 [1.60~7.69] p value=0.002; and OR [95% CI]: 5.18 [1.50~17.85] p value=0.009], respectively). Patients with diabetes were more likely to be admitted to ICU (OR [95% CI]: 9.38 [5.49~16.02]). Two models for multivariate regression analysis were used, assessing either BMI or diabetes on ICU outcomes. In the BMI model, class I obesity and morbid obesity were associated with ICU admittance (adjusted OR (AOR) [95% CI]: 2.7 [1.17~6.20] p value=0.019 and AOR [95% CI]: 3.95 [1.00~15.20] p value=0.046, respectively). In the diabetes model, diabetes was associated with higher ICU admittance (AOR [95% CI]: 5.49 [3.13~9.65] p value<0.001) whereas hypertension had a protective effect on ICU admittance (AOR [95% CI]: 0.51 (0.28-0.91). Conclusions: In our cohort, overweight, obesity and diabetes in patients with COVID19 were associated with ICU admittance, putting these patients at higher risk of poor outcomes.", "title": "COVID-19: Impact of Obesity and Diabetes in Disease Severity", "pid": "u8ngna9d", "bm25_score": 216.67164611816406}, {"text": "Abstract Aims We aimed to briefly review the general characteristics of the novel coronavirus (SARS-CoV-2) and provide a better understanding of the coronavirus disease (COVID-19) in people with diabetes, and its management. Methods We searched for articles in PubMed and Google Scholar databases till 02 April 2020, with the following keywords: “SARS-CoV-2”, “COVID-19”, “infection”, “pathogenesis”, “incubation period”, “transmission”, “clinical features”, “diagnosis”, “treatment”, “diabetes”, with interposition of the Boolean operator “AND”. Results The clinical spectrum of COVID-19 is heterogeneous, ranging from mild flu-like symptoms to acute respiratory distress syndrome, multiple organ failure and death. Older age, diabetes and other comorbidities are reported as significant predictors of morbidity and mortality. Chronic inflammation, increased coagulation activity, immune response impairment, and potential direct pancreatic damage by SARS-CoV-2 might be among the underlying mechanisms of the association between diabetes and COVID-19. No conclusive evidence exists to support the discontinuation of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers because of COVID-19 in people with diabetes. Caution should be taken to potential hypoglycemic events with the use of chloroquine in these subjects. Patient tailored therapeutic strategies, rigorous glucose monitoring and careful consideration of drug interactions might reduce adverse outcomes. Conclusions Suggestions are made on the possible pathological mechanisms of the relationship between diabetes and COVID-19, and its management. No definite conclusions can be made based on current limited evidence. Further research regarding this relationship and its clinical management is warranted.", "title": "COVID-19 and Diabetes: Knowledge in Progress", "pid": "4cx6fe5v", "bm25_score": 216.66343688964844}, {"text": "Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events.", "title": "Diabetes and COVID-19: Risks, Management, and Learnings From Other National Disasters", "pid": "a7npp99p", "bm25_score": 216.65570068359375}, {"text": "", "title": "Severity of COVID-19 and diabetes mellitus: there is still a lot to be learned", "pid": "7i6lhnfr", "bm25_score": 216.6497802734375}, {"text": "Patients with diabetes who get coronavirus disease 2019 (COVID-19) are at risk of a severe disease course and mortality. Several factors especially the impaired immune response, heightened inflammatory response and hypercoagulable state contribute to the increased disease severity. However, there are many contentious issues about which the evidence is rather limited. There are some theoretical concerns about the effects of different anti-hyperglycaemic drugs. Similarly, despite the recognition of angiotensin converting enzyme 2 (ACE2) as the receptor for severe acute respiratory syndrome coronavirus 2 (SARS CoV-2), and the role of ACE2 in lung injury; there are conflicting results with the use of angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB) in these patients. Management of patients with diabetes in times of restrictions on mobility poses some challenges and novel approaches like telemedicine can be useful. There is a need to further study the natural course of COVID-19 in patients with diabetes and to understand the individual, regional and ethnic variations in disease prevalence and course.", "title": "Diabetes and COVID-19: evidence, current status and unanswered research questions", "pid": "sjcadz5j", "bm25_score": 216.64654541015625}, {"text": "OBJECTIVE Recent publications on Coronavirus Disease-2019 (COVID-19) report that diabetic people with or without co-morbidities are at higher risk of developing severe and/or fatal illnesses. METHOD AND RESULT We report the first case of a 60-year-old man with a 27-year history of type 1 diabetes mellitus, infected by SARS-CoV-2 presenting with an euglycaemic ketoacidosis and an acute respiratory distress syndrome. CONCLUSION This case report reminds us of the importance of adjusting more recent glucose-lowering drugs, including sodium-glucose cotransporter 2 inhibitors, in the overall management of type 1 diabetic individuals during the ongoing COVID-19 outbreak. ABBREVIATIONS COVID-19: Coronavirus disease 2019 (SARS-CoV-2) virus, T1DM: Type 1 diabetes mellitus, T2DM: Type 2 diabetes mellitus, SGLT2i: Sodium-glucose cotransporter 2 inhibitor, DKA: diabetic ketoacidosis, euDKA: euglycaemic diabetic ketoacidosis.", "title": "Euglycemic diabetic ketoacidosis in a patient with type 1 diabetes and SARS-CoV-2 pneumonia: case report and review of the literature.", "pid": "kbo8bc8m", "bm25_score": 216.63412475585938}, {"text": "AIMS: Diabetes mellitus is one of the most common comorbidities in Coronavirus disease 2019 (COVID‐19) patients. The objective of this study was to evaluate the influences of diabetes mellitus on the severity and fatality of SARS‐CoV‐2 infection. MATERIALS AND METHODS: Medical records of 66 hospitalized COVID‐19 patients were collected and classified into non‐severe (mild/moderate cases) and severe (severe/critical cases) groups, respectively. Logistic regression analysis was used to estimate the risk of severe COVID‐19 (severe/critical infection). In addition, a meta‐analysis including published studies reported the impacts of diabetes mellitus on severity and fatality of COVID‐19, and our current study was conducted using fixed‐effects models. RESULTS: There were 22 diabetic and 44 non‐diabetic cases among the 66 hospitalized COVID‐19 patients. As the results shown, seven cases (31.82%) were diagnosed as severe COVID‐19 in diabetic patients, which was significantly higher than that in non‐diabetic group (4/44, 9.09%, P = 0.033). After adjustment for age and gender, the results showed that diabetes mellitus was significantly associated with COVID‐19 severity (OR: 5.29, 95% CI: 1.07–26.02). A meta‐analysis further confirmed the positive association between diabetes mellitus and COVID‐19 severity (pooled OR = 2.58, 95% CI: 1.93–3.45). Moreover, the diabetic patients infected with SARS‐CoV‐2 showed to have 2.95‐fold higher risk of fatality compared to those patients without diabetes mellitus (95% CI: 1.93–4.53). CONCLUSIONS: Our findings provide new evidences that diabetes mellitus is associated with a higher risk of severity and fatality of COVID‐19. Therefore, intensive monitoring and antidiabetic therapy should be considered in diabetic patients with SARS‐CoV‐2 infection. This article is protected by copyright. All rights reserved.", "title": "Influence of diabetes mellitus on the severity and fatality of SARS‐CoV‐2 infection", "pid": "bq7460ca", "bm25_score": 216.62754821777344}, {"text": "The COVID-19 outbreak was declared a pandemic on March 2020. Many patients with SARS-CoV-2 infection have underlying chronic medical conditions such as diabetes, cardiovascular disease (CVD), and hypertension. Patient-related outcomes are worse if there are associated comorbidities. We do not have enough evidence regarding the most appropriate management of patients with diabetes during COVID-19 infection. Insulin resistance and CVD together increase the inflammatory state of the body, which can contribute to and perhaps mediate the increase of COVID-19 severity. Hence, in addition to management of dysglycemia, other CVD risk factors should be targeted. We explore the possible pathophysiologic links between diabetes and COVID-19 and discuss various options to treat dysglycemia, hypertension, and dyslipidemia in the era of COVID-19.", "title": "Challenging Issues in the Management of Cardiovascular Risk Factors in Diabetes During the COVID-19 Pandemic: A Review of Current Literature", "pid": "ntv2g7ne", "bm25_score": 216.5972137451172}]}
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"xyd3iao9": 0, "xykob69g": 0, "98a96t12": 0, "y0l943xg": 0, "y0s2winq": 0, "71jjbyds": 2, "y4r9nfu9": 2, "tnorzarg": 0, "y5lgk0m6": 0, "y5t5wuha": 0, "y5ut2w8r": 2, "y6hu31aa": 1, "y6rfq2mx": 1, "y7lrp0gc": 0, "y99ylw6q": 0, "y9lxxar7": 2, "yb54i1ne": 0, "yci0a6bt": 0, "iur5dc2l": 0, "x8y6njm4": 2, "yd7tu7u4": 0, "ydssboge": 0, "ye0ry61s": 0, "yf5g53a9": 0, "yflng8m3": 2, "xdn3alp9": 0, "yi25yh8f": 0, "yk8f9jtn": 0, "ym44s4oc": 0, "ymljoxge": 2, "roong0oi": 0, "ymw9avlm": 0, "yn3raqd0": 0, "yo0szyon": 0, "yok3icrn": 2, "ys51rshu": 0, "yt1ytasw": 1, "ytlb8p6w": 0, "yvjrcgxu": 0, "yw7w65xw": 0, "ywu0k22x": 0, "yx1fc3xx": 0, "yx3j6373": 1, "yx8b2moc": 1, "rcxctwhv": 0, "yydc7ksy": 1, "yzffm05r": 1, "yzloau0d": 0, "z0476b47": 2, "z0qzgu5m": 0, "z0vup2lr": 2, "z16d3rnm": 0, "z2uj589q": 0, "z3mxqslb": 0, "z3pknjbl": 2, "z3rpoqao": 1, "z3x0c37y": 0, "z4l3pk23": 0, "z5i8hyja": 0, "z73q22v3": 0, "z9dolxky": 0, "za3qypgg": 0, "zavmp85i": 2, "zayzw78f": 0, "zblitbo0": 2, "zcjsvwso": 2, "zeaqi1uc": 1, "zeed3hzz": 0, "zel9a3u6": 0, "zeoaq4jr": 2, "zf60po1s": 0, "zghlogmr": 2, "zgqbfmzl": 0, "zgta5ah8": 0, "zhidc837": 0, "zhw8vh3e": 0, "zimj5bh1": 0, "zir02q69": 0, "68qqc64r": 0, "zp4uy1v7": 0, "zppc6p20": 0, "zqpz15og": 0, "zrylju4f": 0, "v0v0ahjh": 1, "zu1ojh4e": 0, "zuchss0s": 2, "zueoyesj": 0, "zurd5d64": 0, "zv0ysi8m": 0, "lg2a8gz8": 0, "zxqefqge": 0, "zzljrkbf": 0}, "bm25_results": [{"text": "The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.", "title": "Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury", "pid": "9k8r18x7", "bm25_score": 218.83238220214844}, {"text": "The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1643-8 and is accessible for authorized users.", "title": "Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury", "pid": "t996fbad", "bm25_score": 218.8052215576172}, {"text": "Background: Severe ill patients with 2019 novel coronavirus (2019-nCoV) infection progressed rapidly to acute respiratory failure. We aimed to select the most useful prognostic factor for severe illness incidence. Methods: The study prospectively included 61 patients with 2019-nCoV infection treated at Beijing Ditan Hospital from January 13, 2020 to January 31, 2020. Prognostic factor of severe illness was selected by the LASSO COX regression analyses, to predict the severe illness probability of 2019-CoV pneumonia. The predictive accuracy was evaluated by concordance index, calibration curve, decision curve and clinical impact curve. Results: The neutrophil-to-lymphocyte ratio (NLR) was identified as the independent risk factor for severe illness in patients with 2019-nCoV infection. The NLR had a c-index of 0.807 (95% confidence interval, 0.676-0.38), the calibration curves fitted well, and the decision curve and clinical impact curve showed that the NLR had superior standardized net benefit. In addition, the incidence of severe illness was 9.1% in age ≥ 50 and NLR < 3.13 patients, and half of patients with age ≥ 50 and NLR ≥ 3.13 would develop severe illness. Based on the risk stratification of NLR with age, the study developed a 2019-nCoV pneumonia management process. Conclusions: The NLR was the early identification of risk factors for 2019-nCoV severe illness. Patients with age ≥ 50 and NLR ≥ 3.13 facilitated severe illness, and they should rapidly access to intensive care unit if necessary.", "title": "Neutrophil-to-Lymphocyte Ratio Predicts Severe Illness Patients with 2019 Novel Coronavirus in the Early Stage", "pid": "pd70i3d8", "bm25_score": 218.332275390625}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil-lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.", "title": "Biomarkers associated with COVID-19 disease progression", "pid": "vcpo3qob", "bm25_score": 217.90232849121094}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic is a scientific, medical, and social challenge. The complexity of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is centered on the unpredictable clinical course of the disease that can rapidly develop, causing severe and deadly complications. The identification of effective laboratory biomarkers able to classify patients based on their risk is imperative in being able to guarantee prompt treatment. The analysis of recently published studies highlights the role of systemic vasculitis and cytokine mediated coagulation disorders as the principal actors of multi organ failure in patients with severe COVID-19 complications. The following biomarkers have been identified: hematological (lymphocyte count, neutrophil count, neutrophil–lymphocyte ratio (NLR)), inflammatory (C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), procalcitonin (PCT)), immunological (interleukin (IL)-6 and biochemical (D-dimer, troponin, creatine kinase (CK), aspartate aminotransferase (AST)), especially those related to coagulation cascades in disseminated intravascular coagulation (DIC) and acute respiratory distress syndrome (ARDS). New laboratory biomarkers could be identified through the accurate analysis of multicentric case series; in particular, homocysteine and angiotensin II could play a significant role.", "title": "Biomarkers associated with COVID-19 disease progression", "pid": "3l2t9w9l", "bm25_score": 217.8525848388672}, {"text": "Infection of novel Coronavirus has been declared pandemic by the WHO and now is a world public health crisis. Laboratory activity becames essential for the timely diagnosis. Few parameters, such Lymphocytes count, SaO2 and CRP serum level can be used to assess the severity of COVID-19 in emergency room.", "title": "Laboratory Biomarkers Predicting COVID-19 Severity in the Emergency Room", "pid": "x7pd537e", "bm25_score": 217.82388305664062}, {"text": "", "title": "ACE2, COVID19 and serum ACE as a possible biomarker to predict severity of disease", "pid": "lwazc221", "bm25_score": 217.77597045898438}, {"text": "", "title": "Biomarkers of biological age as predictors of COVID-19 disease severity", "pid": "qwiyqkxb", "bm25_score": 217.74957275390625}, {"text": "OBJECTIVE: Most cases of coronavirus disease 2019 (COVID-19) are identified as moderate, which is defined as having a fever or dry cough and lung imaging with ground-glass opacities. The risk factors and predictors of prognosis in such cohorts remain uncertain. METHODS: All adults with COVID-19 of moderate severity diagnosed using quantitative RT-PCR and hospitalized at the Central Hospital of Wuhan, China, from 1 January to 20 March 2020 were enrolled in this retrospective study. The main outcomes were progression from moderate to severe or critical condition or death. RESULTS: Among the 456 enrolled patients with moderate COVID-19, 251/456 (55.0%) had poor prognosis. Multivariate logistic regression analysis identified higher neutrophil count: lymphocyte count ratio (NLR) on admission (OR 1.032, 95% CI 1.042-1.230, p 0.004) and higher C-reactive protein (CRP) on admission (OR 3.017, 95% CI 1.941-4.690, p < 0.001) were associated with increased OR of poor prognosis. The area under the receiver operating characteristic curve (AUC) for NLR and CRP in predicting progression to critical condition was 0.77 (95% CI 0.694-0.846, p < 0.001) and 0.84 (95% CI 0.780-0.905, p < 0.001), with a cut-off value of 2.79 and 25.95 mg/L, respectively. The AUC of NLR and CRP in predicting death was 0.81 (95% CI 0.732-0.878, p < 0.001) and 0.89 (95% CI 0.825-0.946, p < 0.001), with a cut-off value of 3.19 and 33.4 mg/L, respectively. CONCLUSIONS: Higher levels of NLR and CRP at admission were associated with poor prognosis of individuals with moderate COVID-19. NLR and CRP were good predictors of progression to critical condition and death.", "title": "Predictors of progression from moderate to severe coronavirus disease 2019: a retrospective cohort", "pid": "52ewsgwk", "bm25_score": 217.72366333007812}, {"text": "COVID-19 is characterised by dysregulated immune responses, metabolic dysfunction and adverse effects on the function of multiple organs. To understand how host responses contribute to COVID-19 pathophysiology, we used a multi-omics approach to identify molecular markers in peripheral blood and plasma samples that distinguish COVID-19 patients experiencing a range of disease severities. A large number of expressed genes, proteins, metabolites and extracellular RNAs (exRNAs) were identified that exhibited strong associations with various clinical parameters. Multiple sets of tissue-specific proteins and exRNAs varied significantly in both mild and severe patients, indicative of multi-organ damage. The continuous activation of IFN-I signalling and neutrophils, as well as a high level of inflammatory cytokines, were observed in severe disease patients. In contrast, COVID-19 in mild patients was characterised by robust T cell responses. Finally, we show that some of expressed genes, proteins and exRNAs can be used as biomarkers to predict the clinical outcomes of SARS-CoV-2 infection. These data refine our understanding of the pathophysiology and clinical progress of COVID-19 and will help guide future studies in this area.", "title": "COVID-19 severity is associated with immunopathology and multi-organ damage", "pid": "o2k8pquk", "bm25_score": 217.7222900390625}, {"text": "BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. OBJECTIVE: We sought to identify biomarkers for disease severity and progression of COVID-19. METHODS: Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe, and 14 moderate patients were measured and analyzed in combination with clinical data. RESULTS: Levels of 14 cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IFN-γ-induced protein 10, monocyte chemotactic protein-3, hepatocyte growth factor, monokine-induced gamma IFN, and macrophage inflammatory protein 1 alpha, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the 5 cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IFN-γ-induced protein 10 and monocyte chemotactic protein-3 were excellent predictors for the progression of COVID-19, and the combination of the 2 cytokines showed the biggest area under the curve of the receiver-operating characteristics calculations with a value of 0.99. CONCLUSIONS: In this study, we report biomarkers that are highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of severe acute respiratory syndrome coronavirus 2 infection, and provide potential therapeutic targets and strategies.", "title": "Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19", "pid": "7rjzontt", "bm25_score": 217.71578979492188}, {"text": "Abstract Background The inflammatory response plays a critical role in coronavirus disease 2019 (COVID-19), and inflammatory cytokine storm increases the severity of COVID-19. Objective To investigate the ability of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) to predict mild and severe cases of COVID-19. Study design This retrospective cohort study included 140 patients diagnosed with COVID-19 from January 18, 2020, to March 12, 2020. The study population was divided into two groups according to disease severity: a mild group (MG) (n = 107) and a severe group (SG) (n = 33). Data on demographic characteristics, baseline clinical characteristics, and the levels of IL-6, CRP, and PCT on admission were collected. Results Among the 140 patients, the levels of IL-6, CRP, and PCT increased in 95 (67.9 %), 91 (65.0 %), and 8 (5.7 %) patients on admission, respectively. The proportion of patients with increased IL-6, CRP, and PCT levels was significantly higher in the SG than in the MG. Cox proportional hazard model showed that IL-6 and CRP could be used as independent factors to predict the severity of COVID-19. Furthermore, patients with IL-6 > 32.1 pg/mL or CRP > 41.8 mg/L were more likely to have severe complications. Conclusion The serum levels of IL-6 and CRP can effectively assess disease severity and predict outcome in patients with COVID-19.", "title": "Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19", "pid": "4cr6z7tc", "bm25_score": 217.621337890625}, {"text": "BACKGROUND: The inflammatory response plays a critical role in coronavirus disease 2019 (COVID-19), and inflammatory cytokine storm increases the severity of COVID-19. OBJECTIVE: To investigate the ability of interleukin-6 (IL-6), C-reactive protein (CRP), and procalcitonin (PCT) to predict mild and severe cases of COVID-19. STUDY DESIGN: This retrospective cohort study included 140 patients diagnosed with COVID-19 from January 18, 2020, to March 12, 2020. The study population was divided into two groups according to disease severity: a mild group (MG) (n = 107) and a severe group (SG) (n = 33). Data on demographic characteristics, baseline clinical characteristics, and the levels of IL-6, CRP, and PCT on admission were collected. RESULTS: Among the 140 patients, the levels of IL-6, CRP, and PCT increased in 95 (67.9 %), 91 (65.0 %), and 8 (5.7 %) patients on admission, respectively. The proportion of patients with increased IL-6, CRP, and PCT levels was significantly higher in the SG than in the MG. Cox proportional hazard model showed that IL-6 and CRP could be used as independent factors to predict the severity of COVID-19. Furthermore, patients with IL-6 > 32.1 pg/mL or CRP > 41.8 mg/L were more likely to have severe complications. CONCLUSION: The serum levels of IL-6 and CRP can effectively assess disease severity and predict outcome in patients with COVID-19.", "title": "Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19", "pid": "zgrr2hdi", "bm25_score": 217.58383178710938}, {"text": "There is a high mortality and long hospitalization period for severe cases with 2019 novel coronavirus disease (COVID-19) pneumonia. Therefore, it makes sense to search for a potential biomarker that could rapidly and effectively identify severe cases early. Clinical samples from 28 cases of COVID-19 (8 severe cases, 20 mild cases) in Zunyi District from January 29, 2020 to February 21, 2020 were collected and otherwise statistically analysed for biochemical markers. Serum urea, creatinine (CREA) and cystatin C (CysC) concentrations in severe COVID-19 patients were significantly higher than those in mild COVID-19 patients (P<0.001), and there were also significant differences in serum direct bilirubin (DBIL), cholinesterase (CHE) and lactate dehydrogenase (LDH) concentrations between severe and mild COVID-19 patients (P<0.05). Serum urea, CREA, CysC, DBIL, CHE and LDH could be used to distinguish severe COVID-19 cases from mild COVID-19 cases. In particular, serum biomarkers, including urea, CREA, CysC, which reflect glomerular filtration function, may have some significance as potential indicators for the early diagnosis of severe COVID-19 and to distinguish it from mild COVID-19. Glomerular filtration function injury in severe COVID-19 patients should also be considered by clinicians.", "title": "Potential biochemical markers to identify severe cases among COVID-19 patients", "pid": "6rs86u5v", "bm25_score": 217.55970764160156}, {"text": "", "title": "Presepsin as a predictive biomarker of severity in COVID-19: A case series", "pid": "gygw29fj", "bm25_score": 217.53724670410156}, {"text": "Guidelines for the diagnosis and treatment of the novel coronavirus disease 2019 (COVID‐19) present clear criteria, including respiratory rate, hemoglobin oxygen saturation (SaO(2)), and oxygenation indicator (PaO(2)/FiO(2))(1). This article is protected by copyright. All rights reserved.", "title": "Presepsin as a predictive biomarker of severity in COVID‐19: a case series", "pid": "gv9q7sf1", "bm25_score": 217.50027465820312}, {"text": "Abstract Background The outbreak of Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, December 2019, and continuously poses a serious threat to public health, highlighting the urgent need of identifying biomarkers for disease severity and progression. Objective To identify biomarkers for disease severity and progression of COVID-19. Methods Forty-eight cytokines in the plasma samples from 50 COVID-19 cases including 11 critically ill, 25 severe and 14 moderate patients were measured and analyzed in combination with clinical data. Results Fourteen cytokines were found to be significantly elevated in COVID-19 cases and showed different expression profiles in patients with different disease severity. Moreover, expression levels of IP-10, MCP-3, HGF, MIG and MIP-1α, which were shown to be highly associated with disease severity during disease progression, were remarkably higher in critically ill patients, followed by severe and then the moderate patients. Serial detection of the five cytokines in 16 cases showed that continuously high levels were associated with deteriorated progression of disease and fatal outcome. Furthermore, IP-10 and MCP-3 were excellent predictors for the progression of COVID-19, and the combination of the two cytokines showed the biggest area under the curve (AUC) of the receiver-operating characteristics (ROC) calculations with a value of 0.99. Conclusion In this study, we report biomarkers that highly associated with disease severity and progression of COVID-19. These findings add to our understanding of the immunopathologic mechanisms of SARS-CoV-2 infection, and provide potential therapeutic targets and strategies.", "title": "Plasma IP-10 and MCP-3 levels are highly associated with disease severity and predict the progression of COVID-19", "pid": "8ceabd6e", "bm25_score": 217.4735107421875}, {"text": "We read the article by D'Alessandro Miriana et al. with great interest and appreciate their efforts to evaluate the role of serum Krebs von den Lungen-6 (KL-6) as a prognostic biomarker of severe coronavirus disease 2019 (COVID-19).1 This article is protected by copyright. All rights reserved.", "title": "Serum KL-6 can distinguish between different phenotypes of severe COVID-19", "pid": "1tyo148f", "bm25_score": 217.47256469726562}, {"text": "Background: The global pandemic caused by COVID-19 remains poorly understood by clinicians. Identifying biologic markers associated with prognosis can help clinicians recognize disease severity. Objective: To describe the association between D-dimer, CRP, IL-6, ferritin, LDH, and clinical outcomes in a cohort of COVID-19 patients treated on the inpatient medical service at a university hospital in Washington, DC. Design: In this retrospective study, we included all adults admitted to the inpatient medicine service at George Washington University Hospital between March 12, 2020 and May 9, 2020 with laboratory confirmed COVID-19. Clinical and laboratory data were extracted from electronic medical records and compared between survivors not requiring ICU transfer, survivors requiring ICU transfer, survivors requiring intubation, and non-survivors. Key Results: 299 patients were included in our study, of whom 69 required transfer to the ICU, 39 required intubation, and 71 died. Threshold values for IL-6 (>50 pg/mL), D-dimer (>3 mcg/mL), ferritin (>450 ng/mL), CRP (>100 mg/L), and LDH (1,200 u/L) were found to be statistically significant and independently associated with higher odd of clinical deterioration and death. Hypertension, CVA and heart disease independently had an increased risk of all three outcomes, while CKD had only an increased risk of death. Patient co-morbidities had no effect on the different biomarkers' significant association with poor patient clinical outcomes, except cancer. Conclusion: Laboratory markers of inflammation and coagulopathy can help clinicians identify patients who are at high risk for clinical deterioration, independent of clinically significant medical comorbidities", "title": "The Association Between Biomarkers and Clinical Outcomes in Novel Coronavirus (COVID-19) Pneumonia in a U.S. Cohort", "pid": "93a34bnd", "bm25_score": 217.42112731933594}, {"text": "", "title": "Tumor biomarkers predict clinical outcome of COVID-19 patients", "pid": "86jwep6f", "bm25_score": 217.36590576171875}, {"text": "BACKGROUND: The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. OBJECTIVE: The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of patients with noncritical COVID-19. METHODS: A total of 208 patients with noncritical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained on admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. RESULTS: Clinical worsening occurred in 63 patients (16 = died; 39 = transferred to intensive care unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (P = .005), C-reactive protein (CRP) (P = .003), and SaO2/FiO2 (P = .014) were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an area under the curve = 0.88 (95% confidence interval: 0.83-0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14- or 21-day worsening and in predicting death occurring during all the follow-up. CONCLUSIONS: Combining IL-6, CRP, and SaO2/FiO2 in a score may help clinicians to identify on admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.", "title": "Prompt Predicting of Early Clinical Deterioration of Moderate-to-Severe COVID-19 Patients: Usefulness of a Combined Score Using IL-6 in a Preliminary Study", "pid": "hf9q39m7", "bm25_score": 217.34420776367188}, {"text": "OBJECTIVE To identify the biomarkers as early warning signals for severe COVID-19. METHODS We retrospectively analyzed the clinical data of 63 patients with COVID- 19 from Hubei Provincial Hospital of Integrated Chinese and Western Medicine, including 32 moderate cases and 31 severe cases. The demographic data, underlying diseases, clinical manifestations and laboratory test results were compared between the two groups. Logistic regression analysis was performed to identify the factors that predicted the severity of COVID-19. The receiver- operating characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) was calculated, and the area under the curve (AUC) was determined to estimate the optimal threshold of NLR for predicting severe cases of COVID-19. RESULTS The patients with moderate and server COVID-19 showed significant differences in the rate of diabetes, NLR, serum amyloid A (SSA), C-reactive protein (CRP) and serum albumin (ALB) levels (P < 0.05). The co- morbidity of diabetes, NLR, SSA and CRP were found to positively correlate and ALB to inversely correlate with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for severe COVID-19 (OR=1.264, 95% CI: 1.046-1.526, P=0.015) with an AUC of 0.831 (95% CI: 0.730-0.932), an optimal diagnostic threshold of 4.795, a sensitivity of 0.839, and a specificity of 0.750. CONCLUSIONS An increased NLR can serve as an early warning signal of severe COVID-19.", "title": "[An increased neutrophil/lymphocyte ratio is an early warning signal of severe COVID-19].", "pid": "japmze1b", "bm25_score": 217.3265380859375}, {"text": "Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.", "title": "Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis", "pid": "apgh3j3r", "bm25_score": 217.32504272460938}, {"text": "This study aims to investigate blood and biochemical laboratory findings in patients with severe Corona Virus Disease 2019 (COVID-19) and to develop a joint predictor for predicting the likelihood of severe COVID-19 and its adverse clinical outcomes, to provide more information for treatment. We collected the data of 88 patients with laboratory-confirmed COVID-19. Then patients were divided into a non-severe group and a critical group (including critically ill cases). Univariate analysis showed that the absolute lymphocyte count, albumin level, albumin/globulin (A/G) ratio, lactate dehydrogenase (LDH) level, interleukin-6 (IL-6) level, erythrocyte count, globulin level, blood glucose level, and age were significantly correlated with the severity of COVID-19. The multivariate binary logistic regression model revealed that Age, absolute lymphocyte count, and IL-6 level were independent risk factors in patients with COVID-19. The receiver operating characteristic (ROC) curve revealed that the combination of IL-6 level, absolute lymphocyte count and age is superior to a single factor as predictors for predicting severe COVID-19, regardless of whether it is the area under curve (AUC) or the prediction sensitivity and specificity. Early application is beneficial to early identification of critically ill patients and timing individual treatments to reduce mortality.", "title": "Prediction of the severity of Corona Virus Disease 2019 and its adverse clinical outcomes.", "pid": "dmbc8kb4", "bm25_score": 217.32351684570312}, {"text": "OBJECTIVE: To identify the biomarkers as early warning signals for severe COVID-19. METHODS: We retrospectively analyzed the clinical data of 63 patients with COVID- 19 from Hubei Provincial Hospital of Integrated Chinese and Western Medicine, including 32 moderate cases and 31 severe cases. The demographic data, underlying diseases, clinical manifestations and laboratory test results were compared between the two groups. Logistic regression analysis was performed to identify the factors that predicted the severity of COVID-19. The receiver- operating characteristic curve (ROC) of neutrophil/lymphocyte ratio (NLR) was calculated, and the area under the curve (AUC) was determined to estimate the optimal threshold of NLR for predicting severe cases of COVID-19. RESULTS: The patients with moderate and server COVID-19 showed significant differences in the rate of diabetes, NLR, serum amyloid A (SSA), C-reactive protein (CRP) and serum albumin (ALB) levels (P < 0.05). The co- morbidity of diabetes, NLR, SSA and CRP were found to positively correlate and ALB to inversely correlate with the severity of COVID-19 (P < 0.05). Multivariate logistic regression analysis showed that NLR was an independent risk factor for severe COVID-19 (OR=1.264, 95% CI: 1.046-1.526, P=0.015) with an AUC of 0.831 (95% CI: 0.730-0.932), an optimal diagnostic threshold of 4.795, a sensitivity of 0.839, and a specificity of 0.750. CONCLUSIONS: An increased NLR can serve as an early warning signal of severe COVID-19.", "title": "[An increased neutrophil/lymphocyte ratio is an early warning signal of severe COVID-19]", "pid": "u1v2p9wp", "bm25_score": 217.31610107421875}, {"text": "Background As coronavirus disease 2019 (COVID-19) pandemic rages on, there is urgent need for identification of clinical and laboratory predictors for progression towards severe and fatal forms of this illness. In this study we aimed to evaluate the discriminative ability of hematologic, biochemical and immunologic biomarkers in patients with and without the severe or fatal forms of COVID-19. Methods An electronic search in Medline (PubMed interface), Scopus, Web of Science and China National Knowledge Infrastructure (CNKI) was performed, to identify studies reporting on laboratory abnormalities in patients with COVID-19. Studies were divided into two separate cohorts for analysis: severity (severe vs. non-severe and mortality, i.e. non-survivors vs. survivors). Data was pooled into a meta-analysis to estimate weighted mean difference (WMD) with 95% confidence interval (95% CI) for each laboratory parameter. Results A total number of 21 studies was included, totaling 3377 patients and 33 laboratory parameters. While 18 studies (n = 2984) compared laboratory findings between patients with severe and non-severe COVID-19, the other three (n = 393) compared survivors and non-survivors of the disease and were thus analyzed separately. Patients with severe and fatal disease had significantly increased white blood cell (WBC) count, and decreased lymphocyte and platelet counts compared to non-severe disease and survivors. Biomarkers of inflammation, cardiac and muscle injury, liver and kidney function and coagulation measures were also significantly elevated in patients with both severe and fatal COVID-19. Interleukins 6 (IL-6) and 10 (IL-10) and serum ferritin were strong discriminators for severe disease. Conclusions Several biomarkers which may potentially aid in risk stratification models for predicting severe and fatal COVID-19 were identified. In hospitalized patients with respiratory distress, we recommend clinicians closely monitor WBC count, lymphocyte count, platelet count, IL-6 and serum ferritin as markers for potential progression to critical illness.", "title": "Hematologic, biochemical and immune biomarker abnormalities associated with severe illness and mortality in coronavirus disease 2019 (COVID-19): a meta-analysis.", "pid": "fg69m7o0", "bm25_score": 217.2835235595703}, {"text": "TRIAL REGISTRATION: ChiCTR, ChiCTR2000029758. Registered 12 February 2020 - Retrospectively registered.", "title": "Neutrophil-to-lymphocyte ratio as a predictive biomarker for moderate-severe ARDS in severe COVID-19 patients", "pid": "lfqa4maq", "bm25_score": 217.26510620117188}, {"text": "This study aims to investigate blood and biochemical laboratory findings in patients with severe Corona Virus Disease 2019 (COVID-19) and to develop a joint predictor for predicting the likelihood of severe COVID-19 and its adverse clinical outcomes, to provide more information for treatment. We collected the data of 88 patients with laboratory-confirmed COVID-19. Then patients were divided into a non-severe group and a critical group (including critically ill cases). Univariate analysis showed that the absolute lymphocyte count, albumin level, albumin/globulin (A/G) ratio, lactate dehydrogenase (LDH) level, interleukin-6 (IL-6) level, erythrocyte count, globulin level, blood glucose level, and age were significantly correlated with the severity of COVID-19. The multivariate binary logistic regression model revealed that Age, absolute lymphocyte count, and IL-6 level were independent risk factors in patients with COVID-19. The receiver operating characteristic (ROC) curve revealed that the combination of IL-6 level, absolute lymphocyte count and age is superior to a single factor as predictors for predicting severe COVID-19, regardless of whether it is the area under curve (AUC) or the prediction sensitivity and specificity. Early application is beneficial to early identification of critically ill patients and timing individual treatments to reduce mortality.", "title": "Prediction of the severity of Corona Virus Disease 2019 and its adverse clinical outcomes", "pid": "2bjn0fmr", "bm25_score": 217.2352752685547}, {"text": "The novel coronavirus infection has spread worldwide, causing a wide spectrum of clinical manifestations. Most patients develop moderate clinical illness, but a substantial number will experience severe pneumonia, which may rapidly progress to acute respiratory distress syndrome and multiple organ failure. In this population, soluble urokinase plasminogen activator receptor (suPAR) could serve as a quick triage test and independent marker of clinical severity, hospital and intensive care unit admission, complications, and mortality.", "title": "Soluble Urokinase Plasminogen Activator Receptor: A Biomarker for Predicting Complications and Critical Care Admission of COVID-19 Patients", "pid": "3sy3jc5c", "bm25_score": 217.23153686523438}, {"text": "To study the relationship between clinical indexes and the severity of coronavirus disease 2019 (COVID‐19), and to explore its role in predicting the severity of COVID‐19. Clinical data of 443 patients with COVID‐19 admitted to our hospital were retrospectively analyzed, which were divided into nonsevere group (n = 304) and severe group (n = 139) according to their condition. Clinical indicators were compared between different groups. The differences in sex, age, the proportion of patients with combined heart disease, leukocyte, neutrophil‐to‐lymphocyte ratio (NLR), neutrophil, lymphocyte, platelet, D‐dimer, C‐reactive protein (CRP), procalcitonin, lactate dehydrogenase, and albumin on admission between the two groups were statistically significant (P < .05). Multivariate logistic regression analysis showed NLR and CRP were independent risk factors for severe COVID‐19. Platelets were independent protective factors for severe COVID‐19. The receiver operating characteristic (ROC) curve analysis demonstrated area under the curve of NLR, platelet, CRP, and combination was 0.737, 0.634, 0.734, and 0.774, respectively. NLR, CRP, and platelets can effectively assess the severity of COVID‐19, among which NLR is the best predictor of severe COVID‐19, and the combination of three clinical indicators can further predict severe COVID‐19.", "title": "The value of clinical parameters in predicting the severity of COVID‐19", "pid": "926yxpbf", "bm25_score": 217.17861938476562}, {"text": "We read the article by D'Alessandro Miriana et al. with great interest and appreciate their efforts to evaluate the role of serum Krebs von den Lungen‐6 (KL‐6) as a prognostic biomarker of severe coronavirus disease 2019 (COVID‐19).(1) This article is protected by copyright. All rights reserved.", "title": "Serum KL‐6 can distinguish between different phenotypes of severe COVID‐19", "pid": "a0s74x4m", "bm25_score": 217.17510986328125}, {"text": "To study the relationship between clinical indexes and the severity of coronavirus disease 2019 (COVID-19), and to explore its role in predicting the severity of COVID-19. Clinical data of 443 patients with COVID-19 admitted to our hospital were retrospectively analyzed, which were divided into nonsevere group (n = 304) and severe group (n = 139) according to their condition. Clinical indicators were compared between different groups. The differences in sex, age, the proportion of patients with combined heart disease, leukocyte, neutrophil-to-lymphocyte ratio (NLR), neutrophil, lymphocyte, platelet, D-dimer, C-reactive protein (CRP), procalcitonin, lactate dehydrogenase, and albumin on admission between the two groups were statistically significant (P < .05). Multivariate logistic regression analysis showed NLR and CRP were independent risk factors for severe COVID-19. Platelets were independent protective factors for severe COVID-19. The receiver operating characteristic (ROC) curve analysis demonstrated area under the curve of NLR, platelet, CRP, and combination was 0.737, 0.634, 0.734, and 0.774, respectively. NLR, CRP, and platelets can effectively assess the severity of COVID-19, among which NLR is the best predictor of severe COVID-19, and the combination of three clinical indicators can further predict severe COVID-19.", "title": "The value of clinical parameters in predicting the severity of COVID-19", "pid": "a049fnva", "bm25_score": 217.1673583984375}, {"text": "The sudden increase of COVID-19 cases is putting a high pressure on healthcare services worldwide. At the current stage, fast, accurate and early clinical assessment of the disease severity is vital. To support decision making and logistical planning in healthcare systems, this study leverages a database of blood samples from 404 infected patients in the region of Wuhan, China to identify crucial predictive biomarkers of disease severity. For this purpose, machine learning tools selected three biomarkers that predict the survival of individual patients with more than 90% accuracy: lactic dehydrogenase (LDH), lymphocyte and high-sensitivity C-reactive protein (hs-CRP). In particular, relatively high levels of LDH alone seem to play a crucial role in distinguishing the vast majority of cases that require immediate medical attention. This finding is consistent with current medical knowledge that high LDH levels are associated with tissue breakdown occurring in various diseases, including pulmonary disorders such as pneumonia. Overall, this paper suggests a simple and operable formula to quickly predict patients at the highest risk, allowing them to be prioritised and potentially reducing the mortality rate.", "title": "A machine learning-based model for survival prediction in patients with severe COVID-19 infection", "pid": "s9j21zsy", "bm25_score": 217.1251220703125}, {"text": "Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease-2019 (COVID-19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID-19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C-reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)-2R, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-&#945;] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL-2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL-2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL-2R/lymphocytes were superior compared with other markers for the identification of COVID-19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL-2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease-deteriorated patients, which might be correlated with the outcome of COVID-19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL-2R/lymphocyte was a prominent biomarker for early identification of severe COVID-19 and predicting the clinical progression of the disease.", "title": "Using IL-2R/lymphocytes for predicting the clinical progression of patients with COVID-19", "pid": "wesk2dhi", "bm25_score": 217.12278747558594}, {"text": "OBJECTIVE: Most coronavirus disease 2019 (COVID-19) cases were identified as moderate, which is defined as having a fever or dry cough and lung imaging with ground-glass opacities. The risk factors and predictors of prognosis in such cohorts remain uncertain. METHODS: All adult patients with COVID-19 of moderate severity diagnosed using qRT-PCR and hospitalized at the Central Hospital of Wuhan, China, from Jan 1 to Mar 20, 2020 were enrolled in this retrospective study. The main outcomes were progression from moderate to severe or critical condition or death. RESULTS: Among the 456 enrolled patients with moderate COVID-19, 251/456 (55.0%) had poor prognosis. Multivariate logistic regression analysis identified higher NLR on admission (OR =1.032, 95%CI 1.042-1.230, P = 0.004) and higher CRP on admission (OR =3.017, 95%CI 1.941-4.690, P < 0.001) were associated with increased odds ratios of poor prognosis. The area under the receiver operating characteristic (ROC) curve (AUC) for NLR and CRP in predicting progression to critical condition was 0.77 (95% CI 0.694-0.846, P < 0.001) and 0.84 (95% CI 0.780-0.905, P < 0.001), with a cut-off value of 2.79 and 25.95 mg/l, respectively. The AUC of NLR and CRP in predicting death was 0.81 (95% CI, 0.732-0.878, P < 0.001) and 0.89 (95% CI 0.825-0.946, P < 0.001), with a cut-off value of 3.19 and 33.4 mg/l, respectively. CONCLUSIONS: Higher levels of NLR and CRP at admission were associated with poor prognosis of moderate COVID-19 patients. NLR and CRP were good predictors of progression to critical condition and death.", "title": "Predictors of progression from moderate to severe COVID-19: a retrospective cohort", "pid": "ipmcqz8n", "bm25_score": 217.08950805664062}, {"text": "Abstract Background The early identification of patients at risk of clinical deterioration is of interest considering the timeline of COVID-19 after the onset of symptoms. Objective The aim of our study was to evaluate the usefulness of testing serum IL-6 and other serological and clinical biomarkers, to predict a short-term negative clinical course of non critical COVID-19 patients. Methods 208 patients with non critical COVID-19 pneumonia at admission were consecutively enrolled. Clinical and laboratory findings obtained upon admission were analyzed by using survival analysis and stepwise logistic regression for variable selection. Three-day worsening as outcome in a logistic model to generate a prognostic score was used. Results Clinical worsening occurred in 63 patients (16=died; 39=transferred to Intensive Care Unit; 8 worsening of respiratory failure). Forty-five of them worsened within 3 days after admission. The risk of clinical worsening was progressively enhanced along with increasing quartiles of IL-6 levels. Multivariate analysis showed that IL-6 (p=0.005), CRP (p=0.003) and SaO2/FiO2 (p=0.014) and were the best predictors for clinical deterioration in the first 3 days after admission. The combined score yielded an AUC=0.88 (95% CI 0.83–0.93). A nomogram predicting the probability of 3-day worsening was generated. The score also showed good performance for 7-day and 14-day or 21-day worsening and in predicting death occurring during all the follow-up. Conclusions Combining IL-6, CRP and SaO2/FiO2 in a score, may help clinicians to identify upon admission those patients with COVID-19 who are at high risk for a further 3-day clinical deterioration.", "title": "Prompt predicting of early clinical deterioration of moderate-to-severe COVID-19 patients: usefulness of a combined score using IL-6 in a preliminary study", "pid": "zghlogmr", "bm25_score": 217.07754516601562}, {"text": "Context: A relevant portion of COVID-19 patients develop severe disease with negative outcomes. Several biomarkers have been proposed to predict COVID-19 severity, but no definite interpretative criteria have been established to date for stratifying risk. Objective: To evaluate six serum biomarkers (C-reactive protein, lactate dehydrogenase, D-dimer, albumin, ferritin and cardiac troponin T) for predicting COVID-19 severity and to define related cut-offs able to aid clinicians in risk stratification of hospitalized patients. Design: A retrospective study of 427 COVID-19 patients was performed. Patients were divided into groups based on their clinical outcome: non-survivors vs. survivors and patients admitted to intensive care unit vs. others. ROC curves and likelihood ratios were employed to define predictive cut-offs for evaluated markers. Results: Marker concentrations at peak were significantly different between groups for both selected outcomes. At univariate logistic regression analysis, all parameters were significantly associated with higher odds of death and intensive care. At the multivariate analysis, high concentrations of lactate dehydrogenase and low concentrations of albumin in serum remained significantly associated with higher odds of death, while only low lactate dehydrogenase activities remained associated with lower odds of intensive care admission. The best cut-offs for death prediction were >731 U/L for lactate dehydrogenase and &#8804;18 g/L for albumin, while a lactate dehydrogenase activity <425 U/L was associated with a negative likelihood ratio of 0.10 for intensive treatment. Conclusions: Our study identifies which biochemistry tests represent major predictors of COVID-19 severity and defines the best cut-offs for their use.", "title": "A comprehensive appraisal of laboratory biochemistry tests as major predictors of COVID-19 severity", "pid": "ss6nskfk", "bm25_score": 217.0668182373047}, {"text": "The novel coronavirus (2019-nCoV) infection caused pneumonia. we retrospectively analyzed the virus presence in the pharyngeal swab, blood, and the anal swab detected by real-time PCR in the clinical lab. Unexpectedly, the 2109-nCoV RNA was readily detected in the blood (6 of 57 patients) and the anal swabs (11 of 28 patients). Importantly, all of the 6 patients with detectable viral RNA in the blood cohort progressed to severe symptom stage, indicating a strong correlation of serum viral RNA with the disease severity (p-value = 0.0001). Meanwhile, 8 of the 11 patients with annal swab virus-positive was in severe clinical stage. However, the concentration of viral RNA in the anal swab (Ct value = 24 + 39) was higher than in the blood (Ct value = 34 + 39) from patient 2, suggesting that the virus might replicate in the digestive tract. Altogether, our results confirmed the presence of virus RNA in extra-pulmonary sites.", "title": "Detectable 2019-nCoV viral RNA in blood is a strong indicator for the further clinical severity", "pid": "eiofivki", "bm25_score": 217.06634521484375}, {"text": "Background: The coronavirus disease 2019 (COVID-19) is spreading worldwide with 16,558 deaths till date. Serum albumin, high-density lipoprotein (HDL-C), and C-reactive protein have been known to be associated with the severity and mortality of community-acquired pneumonia. However, the characteristics and role of metabolic and inflammatory indicators in COVID-19 is unclear. Methods: We included 97 hospitalized patients with laboratory-confirmed COVID-19. Epidemiological, clinical, and laboratory indices; radiological features; and treatment were analysed. The differences in the clinical and laboratory parameters between mild and severe COVID-19 patients and the role of these indicators in severity prediction of COVID-19 were investigated. Results: All were Wuhan residents with contact with confirmed COVID-19 cases. The median age was 39 years (IQR: 30-59). The most common presenting symptoms were fever (58.8%), cough (55.7%), and fatigue (33%). Other features were lymphopenia, impaired fasting glucose, hypoproteinaemia, hypoalbuminemia, low high-density lipoproteinemia. Decrease in lymphocyte count, serum total protein, serum albumin, high-density lipoprotein cholesterol (HDL-C), ApoA1, CD3+T%, and CD8+T% were found to be valuable in predicting the transition of COVID-19 from mild to severe illness. Chest computed tomography (CT) images showed that the absorption of bilateral lung lesions synchronized with the recovery of metabolic and inflammatory indicators. Conclusions: Hypoproteinaemia, hypoalbuminemia, low high-density lipoproteinemia, and decreased ApoA1, CD3+T%, and CD8+T% could predict severity of COVID-19. Lymphocyte count, total serum protein, and HDL-C may be potentially useful for the evaluation of COVID-19.", "title": "Metabolic disturbances and inflammatory dysfunction predict severity of coronavirus disease 2019 (COVID-19): a retrospective study", "pid": "asivq33u", "bm25_score": 217.05702209472656}, {"text": "Context: A relevant portion of COVID-19 patients develop severe disease with negative outcomes. Several biomarkers have been proposed to predict COVID-19 severity, but no definite interpretative criteria have been established to date for stratifying risk. Objective: To evaluate six serum biomarkers (C-reactive protein, lactate dehydrogenase, D-dimer, albumin, ferritin and cardiac troponin T) for predicting COVID-19 severity and to define related cut-offs able to aid clinicians in risk stratification of hospitalized patients. Design: A retrospective study of 427 COVID-19 patients was performed. Patients were divided into groups based on their clinical outcome: non-survivors vs. survivors and patients admitted to intensive care unit vs. others. ROC curves and likelihood ratios were employed to define predictive cut-offs for evaluated markers. Results: Marker concentrations at peak were significantly different between groups for both selected outcomes. At univariate logistic regression analysis, all parameters were significantly associated with higher odds of death and intensive care. At the multivariate analysis, high concentrations of lactate dehydrogenase and low concentrations of albumin in serum remained significantly associated with higher odds of death, while only low lactate dehydrogenase activities remained associated with lower odds of intensive care admission. The best cut-offs for death prediction were >731 U/L for lactate dehydrogenase and ≤18 g/L for albumin, while a lactate dehydrogenase activity <425 U/L was associated with a negative likelihood ratio of 0.10 for intensive treatment. Conclusions: Our study identifies which biochemistry tests represent major predictors of COVID-19 severity and defines the best cut-offs for their use.", "title": "A comprehensive appraisal of laboratory biochemistry tests as major predictors of COVID-19 severity.", "pid": "dakuwflh", "bm25_score": 217.0535430908203}, {"text": "Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.", "title": "[Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia].", "pid": "iprkszdn", "bm25_score": 217.02090454101562}, {"text": "Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients, serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased (15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mild group. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-α), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.", "title": "[Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia].", "pid": "0deyspy2", "bm25_score": 217.02090454101562}, {"text": "ChiCTR, ChiCTR2000029758. Registered 12 February 2020 - Retrospectively registered", "title": "Neutrophil-to-lymphocyte ratio as a predictive biomarker for moderate-severe ARDS in severe COVID-19 patients", "pid": "gctt3gpm", "bm25_score": 216.99069213867188}, {"text": "Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory disease, which can evolve into multi-organ failure (MOF), leading to death. Several biochemical alterations have been described in COVID-19 patients. To date, many biomarkers reflecting the main pathophysiological characteristics of the disease have been identified and associated with the risk of developing severe disease. Lymphopenia represents the hallmark of the disease, and it can be detected since the early stage of infection. Increased levels of several inflammatory biomarkers, including c-reactive protein, have been found in COVID-19 patients and associated with an increased risk of severe disease, which is characterised by the so-called \"cytokine storm\". Also, the increase of cardiac and liver dysfunction biomarkers has been associated with poor outcome. In this review, we provide an overview of the main biochemical characteristics of COVID-19 and the associated biomarkers alterations.", "title": "Biochemical biomarkers alterations in Coronavirus Disease 2019 (COVID-19).", "pid": "tljjkvu5", "bm25_score": 216.9808349609375}, {"text": "Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory disease, which can evolve into multi-organ failure (MOF), leading to death. Several biochemical alterations have been described in COVID-19 patients. To date, many biomarkers reflecting the main pathophysiological characteristics of the disease have been identified and associated with the risk of developing severe disease. Lymphopenia represents the hallmark of the disease, and it can be detected since the early stage of infection. Increased levels of several inflammatory biomarkers, including c-reactive protein, have been found in COVID-19 patients and associated with an increased risk of severe disease, which is characterised by the so-called \"cytokine storm\". Also, the increase of cardiac and liver dysfunction biomarkers has been associated with poor outcome. In this review, we provide an overview of the main biochemical characteristics of COVID-19 and the associated biomarkers alterations.", "title": "Biochemical biomarkers alterations in Coronavirus Disease 2019 (COVID-19)", "pid": "qrhrv31x", "bm25_score": 216.96624755859375}, {"text": "The novel avian origin influenza A (H7N9) virus has caused severe diseases in humans in eastern China since the spring of 2013. Fatal outcomes of H7N9 infections are often attributed to the severe pneumonia and acute respiratory distress syndrome (ARDS). There is urgent need to discover biomarkers predicting the progression of disease and fatal outcome of potentially lethal flu infections, based on sound statistical analysis. We discovered that 34 of the 48 cytokines and chemokines examined in this study were significantly elevated in the plasma samples from patients infected with H7N9. We report for the first time that the levels of MIF, SCF, MCP-1, HGF, and SCGF-β are highly positively linked to disease severity and the profile of mediators MIF, SCF, MCP-1, HGF, SCGF-β, IP-10, IL-18, and IFN-γ is an independent outcome predictor.", "title": "The Serum Profile of Hypercytokinemia Factors Identified in H7N9-Infected Patients can Predict Fatal Outcomes", "pid": "v6ufrk1g", "bm25_score": 216.95492553710938}, {"text": "", "title": "Elevated interleukin-6, interleukin-10 and neutrophil : lymphocyte ratio as identifiers of severe coronavirus disease 2019", "pid": "ae1i0pzv", "bm25_score": 216.94796752929688}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a worldwide health threat. Here, we report that low plasma interleukin-3 (IL-3) levels were associated with increased severity and mortality during SARS-CoV-2 infections. IL-3 promoted the recruitment of antiviral circulating plasmacytoid dendritic cells (pDCs) into the airways by stimulating CXCL12 secretion from pulmonary CD123+ epithelial cells. This study identifies IL-3 as a predictive disease marker and potential therapeutic target for SARS-CoV-2 infections.", "title": "Interleukin-3 is a predictive marker for severity and outcome during SARS-CoV-2 infections", "pid": "7ety2r9y", "bm25_score": 216.9475555419922}, {"text": "Effective laboratory markers for the estimation of disease severity and predicting the clinical progression of coronavirus disease‐2019 (COVID‐19) is urgently needed. Laboratory tests, including blood routine, cytokine profiles and infection markers, were collected from 389 confirmed COVID‐19 patients. The included patients were classified into mild (n = 168), severe (n = 169) and critical groups (n = 52). The leukocytes, neutrophils, infection biomarkers [such as C‐reactive protein (CRP), procalcitonin (PCT) and ferritin] and the concentrations of cytokines [interleukin (IL)‐2R, IL‐6, IL‐8, IL‐10 and tumor necrosis factor (TNF)‐α] were significantly increased, while lymphocytes were significantly decreased with increased severity of illness. The amount of IL‐2R was positively correlated with the other cytokines and negatively correlated with lymphocyte number. The ratio of IL‐2R to lymphocytes was found to be remarkably increased in severe and critical patients. IL‐2R/lymphocytes were superior compared with other markers for the identification of COVID‐19 with critical illness, not only from mild but also from severe illness. Moreover, the cytokine profiles and IL‐2R/lymphocytes were significantly decreased in recovered patients, but further increased in disease‐deteriorated patients, which might be correlated with the outcome of COVID‐19. Lymphopenia and increased levels of cytokines were closely associated with disease severity. The IL‐2R/lymphocyte was a prominent biomarker for early identification of severe COVID‐19 and predicting the clinical progression of the disease.", "title": "Using IL‐2R/lymphocytes for predicting the clinical progression of patients with COVID‐19", "pid": "7dy95eta", "bm25_score": 216.93946838378906}, {"text": "Abstract Objective To explore the clinical value of immune-inflammatory markers to assess the severity of coronavirus disease 2019 (COVID-19). Methods 127 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study, and classified into non-severe and severe groups. Demographics, symptoms, underlying diseases and laboratory data were collected and assessed for predictive value. Results Of 127 COVID-19 patients, 16 cases (12.60%) were classified into the severe group. High level of interleukin-6 (IL-6), C-reaction protein (CRP) and hypertension were independent risk factors for the severity of COVID-19. The risk model based on IL-6, CRP and hypertension had the highest area under the receiver operator characteristic curve (AUROC). Additionally, the baseline IL-6 was positively correlated with other immune-inflammatory parameters and the dynamic change of IL-6 in the severe cases were parallel to the amelioration of the disease. Conclusion Our study showed that high level of IL-6, CRP and hypertension were independent risk factors for assessing the severity of COVID-19. The risk model established upon IL-6, CRP and hypertension had the highest predictability in this study. Besides, IL-6 played a pivotal role in the severity of COVID-19 and had a potential value for monitoring the process of severe cases.", "title": "Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019", "pid": "8ek694p3", "bm25_score": 216.9203643798828}, {"text": "Background: Identification of healthy people at high risk for severe COVID-19 is a global health priority. We investigated whether blood biomarkers measured by high-throughput metabolomics could be predictive of severe pneumonia and COVID-19 hospitalisation years after the blood sampling. Methods: Nuclear magnetic resonance metabolomics was used to quantify a comprehensive biomarker profile in 105,146 plasma samples collected in the UK Biobank during 2007-2010 (age range 39-70). The biomarkers were tested for association with severe pneumonia (2507 cases, defined as diagnosis in hospital or death record occurring during a median of 8.1-year follow-up) and with severe COVID-19 (195 cases, defined as diagnosis in hospital between mid-March to mid-June 2020). A multi-biomarker score was derived for prediction of severe pneumonia based on half of the study population and validated in the other half. We explored how this biomarker score relates to the risk of severe COVID-19. Findings: The biomarker associations with risk of severe COVID-19 followed an overall pattern similar to associations with risk of severe pneumonia (correlation 0.83). The multi-biomarker score, comprised of 25 blood biomarkers including inflammatory proteins, fatty acids, amino acids and advanced lipid measures, was strongly associated with risk of severe pneumonia (odds ratio 1.67 per standard deviation [95% confidence interval 1.59-1.76]; 3.8-fold risk increase for individuals in upper vs lower quintile). The multi-biomarker score was also associated with risk of severe COVID-19 (odds ratio 1.33 [1.17-1.53]; 2.5-fold risk for upper vs lower quintile) and remained significant when adjusting for body mass index, smoking, and existing respiratory and cardiometabolic diseases. Mimicking the decade lag from blood sampling to COVID-19, severe pneumonia events occurring after 7-11 years associated with the multi-biomarker score to a similar magnitude (odds ratio 1.43 [1.29-1.59]; 2.6-fold risk for upper vs lower quintile) as for severe COVID-19. However, the short-term risk of severe pneumonia events associated to the multi-biomarker score at even 3 times higher magnitude (odds ratio 2.21 [1.95-2.50]; 8.0-fold risk for upper vs lower quintile in analysis of the first 2 years after blood sampling). Interpretation: In decade-old blood samples from the UK Biobank, a biomarker score measured by high-throughput metabolomics is indicative of the risk for severe COVID-19. The molecular signature of biomarker changes reflective of risk for severe COVID-19 is similar to that for severe pneumonia, in particular when accounting for the time lag to the COVID-19 pandemic. The even stronger association of the biomarker score with 2-year risk for severe pneumonia lends support to promising screening possibilities for identifying people at high risk for severe COVID-19.", "title": "Blood biomarker score identifies individuals at high risk for severe COVID-19 a decade prior to diagnosis: metabolic profiling of 105,000 adults in the UK Biobank", "pid": "0hxwkzvy", "bm25_score": 216.9132843017578}, {"text": "OBJECTIVE: To explore the clinical value of immune-inflammatory markers to assess the severity of coronavirus disease 2019 (COVID-19). METHODS: 127 consecutive hospitalized patients with confirmed COVID-19 were enrolled in this study, and classified into non-severe and severe groups. Demographics, symptoms, underlying diseases and laboratory data were collected and assessed for predictive value. RESULTS: Of 127 COVID-19 patients, 16 cases (12.60%) were classified into the severe group. High level of interleukin-6 (IL-6), C-reaction protein (CRP) and hypertension were independent risk factors for the severity of COVID-19. The risk model based on IL-6, CRP and hypertension had the highest area under the receiver operator characteristic curve (AUROC). Additionally, the baseline IL-6 was positively correlated with other immune-inflammatory parameters and the dynamic change of IL-6 in the severe cases were parallel to the amelioration of the disease. CONCLUSION: Our study showed that high level of IL-6, CRP and hypertension were independent risk factors for assessing the severity of COVID-19. The risk model established upon IL-6, CRP and hypertension had the highest predictability in this study. Besides, IL-6 played a pivotal role in the severity of COVID-19 and had a potential value for monitoring the process of severe cases.", "title": "Clinical value of immune-inflammatory parameters to assess the severity of coronavirus disease 2019", "pid": "n75u9qk2", "bm25_score": 216.8878631591797}, {"text": "Abstract Background The severity and outcome of COVID-19 cases has been associated with percentage of circulating lymphocytes (LYM%), levels of C-reactive protein (CRP), interleukin 6 (IL-6), procalcitonin (PCT), lactic acid (LA) and viral load (ORF1ab Ct). However, the predictive power of each of these indicators in disease classification and prognosis remains largely unclear. Methods we retrospectively collected information on the above parameters in 142 patients with COVID-19, stratifying them by survival or disease severity. Findings CRP, PCT, IL-6, LYM% and ORF1ab Ct were significantly altered between survivors and non-survivors. LYM%, CRP and IL-6 were the most sensitive and reliable factors in distinguishing between survivors and non-survivors. These indicators were significantly different between critically ill and severe/moderate patients. Only LYM% levels were significantly different between severe and moderate types. Among all the investigated indicators, LYM% was the most sensitive and reliable in discriminating between critically ill, severe and moderate types, and between survivors and non-survivors. Conclusions CRP, PCT, IL-6, LYM% and ORF1ab Ct, but not LA, could predict prognosis and guide classification of COVID-19 patients. LYM% was the most sensitive and reliable predictor for disease typing and prognosis. We recommend that LYM% be further investigated in the management of COVID-19.", "title": "Validation of predictors of disease severity and outcomes in COVID-19 patients: a descriptive and retrospective study", "pid": "5i9b5q0d", "bm25_score": 216.8863983154297}, {"text": "The COVID-19 pandemic caused by infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has led to more than 100,000 deaths in the United States. Several studies have revealed that the hyper-inflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. However, predictive biomarkers of pathogenic inflammation to help guide targetable immune pathways are critically lacking. We implemented a rapid multiplex cytokine assay to measure serum IL-6, IL-8, TNF-, and IL-1{beta} in hospitalized COVID-19 patients upon admission to the Mount Sinai Health System in New York. Patients (n=1484) were followed up to 41 days (median 8 days) and clinical information, laboratory test results and patient outcomes were collected. In 244 patients, cytokine measurements were repeated over time, and effect of drugs could be assessed. Kaplan-Meier methods were used to compare survival by cytokine strata, followed by Cox regression models to evaluate the independent predictive value of baseline cytokines. We found that high serum IL-6, IL-8, and TNF- levels at the time of hospitalization were strong and independent predictors of patient survival. Importantly, when adjusting for disease severity score, common laboratory inflammation markers, hypoxia and other vitals, demographics, and a range of comorbidities, IL-6 and TNF- serum levels remained independent and significant predictors of disease severity and death. We propose that serum IL-6 and TNF- levels should be considered in the management and treatment of COVID-19 patients to stratify prospective clinical trials, guide resource allocation and inform therapeutic options. We also propose that patients with high IL-6 and TNF- levels should be assessed for combinatorial blockade of pathogenic inflammation in this disease.", "title": "An inflammatory cytokine signature helps predict COVID-19 severity and death", "pid": "9rgv88qf", "bm25_score": 216.88125610351562}, {"text": "Objective: To analyze the clinical characteristics of 2019 novel coronavirus (2019-nCoV) pneumonia and to investigate the correlation between serum inflammatory cytokines and severity of the disease. Methods: 29 patients with 2019-ncov admitted to the isolation ward of Tongji hospital affiliated to Tongji medical college of Huazhong University of Science and Technology in January 2020 were selected as the study subjects. Clinical data were collected and the general information, clinical symptoms, blood test and CT imaging characteristics were analyzed. According to the relevant diagnostic criteria, the patients were divided into three groups: mild (15 cases), severe (9 cases) and critical (5 cases). The expression levels of inflammatory cytokines and other markers in the serum of each group were detected, and the changes of these indicators of the three groups were compared and analyzed, as well as their relationship with the clinical classification of the disease. Results: (1) The main symptoms of 2019-nCoV pneumonia was fever (28/29) with or without respiratory and other systemic symptoms. Two patients died with underlying disease and co-bacterial infection, respectively. (2) The blood test of the patients showed normal or decreased white blood cell count (23/29), decreased lymphocyte count (20/29), increased hypersensitive C reactive protein (hs-CRP) (27/29), and normal procalcitonin. In most patients,serum lactate dehydrogenase (LDH) was significantly increased (20/29), while albumin was decreased(15/29). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (Tbil), serum creatinine (Scr) and other items showed no significant changes. (3) CT findings of typical cases were single or multiple patchy ground glass shadows accompanied by septal thickening. When the disease progresses, the lesion increases and the scope expands, and the ground glass shadow coexists with the solid shadow or the stripe shadow. (4) There were statistically significant differences in the expression levels of interleukin-2 receptor (IL-2R) and IL-6 in the serum of the three groups (P<0.05), among which the critical group was higher than the severe group and the severe group was higher than the mildgroup. However, there were no statistically significant differences in serum levels of tumor necrosis factor-alpha (TNF-&#945;), IL-1, IL-8, IL-10, hs-CRP, lymphocyte count and LDH among the three groups (P>0.05). Conclusion: The clinical characteristics of 2019-nCoV pneumonia are similar to those of common viral pneumonia. High resolution CT is of great value in the differential diagnosis of this disease. The increased expression of IL-2R and IL-6 in serum is expected to predict the severity of the 2019-nCoV pneumonia and the prognosis of patients.", "title": "[Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]", "pid": "wmlme0f4", "bm25_score": 216.8778533935547}, {"text": "", "title": "Urinalysis parameters for predicting severity in coronavirus disease 2019 (COVID-19).", "pid": "3e4mt1fl", "bm25_score": 216.86553955078125}, {"text": "Coronavirus disease 2019 (COVID19) is a life-threatening infection with uncertain progression and outcome. Assessing the severity of the disease for worsening patients is of importance in making decisions related to supportive mechanical ventilation and aggressive treatments. This was a prospective, non-randomized study that included hospitalized patients diagnosed with COVID19. Pro-inflammatory cytokines were assessed during hospitalization, and we calculated a prediction paradigm for 30-day mortality based on the serum levels of interleukin1β (IL1β), interleukin6 (IL6), interleukin8 (IL8), and tumor necrosis factor alpha (TNFα) measured by next-generation ELISA. Data of 71 COVID19 patients, mean age 62 years, SD13.8, 50 males, 21 females, were analyzed. Twelve (16.9%) patients died within 7–39 days of their first COVID19 positive nasopharyngeal test. Levels of IL6 and TNFα were significantly higher in patients that did not survive. IL6 predicted mortality at the cut-off value of 163.4 pg/ml, with a sensitivity of 91.7% and specificity of 57.6%. Our findings demonstrate that IL6 expression is significant for the prediction of 30-day mortality in hospitalized COVID19 patients and, therefore, may assist in treatment decisions.", "title": "Cytokine prediction of mortality in COVID19 patients", "pid": "3mv8pkwu", "bm25_score": 216.84738159179688}, {"text": "AIMS: As of the 28th April 2020, the COVID-19 pandemic has infiltrated over 200 countries and affected over three million confirmed people. We review different biomarkers to evaluate if they are able to predict clinical outcomes and correlate with the severity of COVID-19 disease. METHODS: A systematic review of the literature was carried out to identify relevant articles using six different databases. Keywords to refine the search included 'COVID-19', 'SARS-CoV2', 'Biomarkers', among others. Only studies which reported data on pre-defined outcomes were included. KEY FINDINGS: Thirty-four relevant articles were identified which reviewed the following biomarkers: C-reactive protein, serum amyloid A, interleukin-6, lactate dehydrogenase, neutrophil-to-lymphocyte ratio, D-dimer, cardiac troponin, renal biomarkers, lymphocytes and platelet count. Of these, all but two, showed significantly higher levels in patients with severe complications of COVID-19 infection compared to their non-severe counterparts. Lymphocytes and platelet count showed significantly lower levels in severe patients compared to non-severe patients. SIGNIFICANCE: Although research is still in its early stages, the discovery of how different biomarkers behave during the course of the disease could help clinicians in identifying severe disease earlier and subsequently improve prognosis. Nevertheless, we urge for more research across the globe to corroborate these findings.", "title": "The role of biomarkers in diagnosis of COVID-19 - A systematic review", "pid": "aph6yf7n", "bm25_score": 216.84698486328125}, {"text": "OBJECTIVES: The study was aimed at investigating the characteristics of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus (2019-nCoV) pneumonia. METHODS: Children with 2019-nCoV pneumonia or with respiratory syncytial virus (RSV) pneumonia were included. Data including lymphocyte subsets and serum cytokines were collected and analyzed. RESULTS: 56 patients were included in the study, 40 children with 2019-nCoV pneumonia and 16 children with RSV pneumonia. Compared with children with RSV pneumonia, patients with 2019-nCoV pneumonia had higher count of CD3+8+ lymphocyte, higher percentages of CD3+, CD3+8+ lymphocytes and a lower percentage of CD19+ lymphocyte. The serum IL-10 level was significantly higher in children with RSV pneumonia. One 2019-nCoV pneumonia child who was with an obvious increase of IL-10 developed severe pneumonia. CONCLUSIONS: Immune response played a very important role in the development of 2019-nCoV pneumonia. The effective CD8+ T cell response might influence the severity of 2019-nCoV pneumonia. The adaptable change in IL-10 level might contribute to the relatively mild pneumonia symptoms in children with 2019-nCoV pneumonia and bacterial co-infection might be a risk factor of severe 2019-nCoV pneumonia.", "title": "The profile of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus pneumonia", "pid": "97q9e8u7", "bm25_score": 216.84449768066406}, {"text": "BACKGROUND: Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investigate the association between several biomarkers, including serum C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and serum ferritin, and COVID-19 severity. METHODS: We performed a comprehensive systematic literature search through electronic databases. The outcome of interest for this study was the composite poor outcome, which comprises mortality, acute respiratory distress syndrome, need for care in an intensive care unit, and severe COVID-19. RESULTS: A total of 5350 patients were pooled from 25 studies. Elevated CRP was associated with an increased composite poor outcome [risk ratio (RR) 1.84 (1.45, 2.33), p < 0.001; I2: 96%] and its severe COVID-19 (RR 1.41; I2: 93%) subgroup. A CRP ⩾10 mg/L has a 51% sensitivity, 88% specificity, likelihood ratio (LR) + of 4.1, LR- of 0.5, and an area under curve (AUC) of 0.84. An elevated PCT was associated with an increased composite poor outcome [RR 3.92 (2.42, 6.35), p < 0.001; I2: 85%] and its mortality (RR 6.26; I2: 96%) and severe COVID-19 (RR 3.93; I2: 63%) subgroups. A PCT ⩾0.5 ng/ml has an 88% sensitivity, 68% specificity, LR+ of 2.7, LR- of 0.2, and an AUC of 0.88. An elevated D-dimer was associated with an increased composite poor outcome [RR 2.93 (2.14, 4.01), p < 0.001; I2: 77%], including its mortality (RR 4.15; I2: 83%) and severe COVID-19 (RR 2.42; I2: 58%) subgroups. A D-dimer >0.5 mg/L has a 58% sensitivity, 69% specificity, LR+ of 1.8, LR- of 0.6, and an AUC of 0.69. Patients with a composite poor outcome had a higher serum ferritin with a standardized mean difference of 0.90 (0.64, 1.15), p < 0.0001; I2: 76%. CONCLUSION: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19. The reviews of this paper are available via the supplemental material section.", "title": "C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis", "pid": "s92chxzv", "bm25_score": 216.81802368164062}, {"text": "In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID-19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 ± 38.3 vs 46.5 ± 14.7 pmol/L; P < .001), cytokeratin-19 fragment (CYFRA21-1) (2.2 ± 0.9 vs 1.9 ± 0.8 µg/L; P < .001), carcinoembryonic antigen (CEA) (3.4 ± 2.2 vs 2.1 ± 1.2 µg/L; P < .001), carbohydrate antigens (CA) 125 (18.1 ± 13.5 vs 10.5 ± 4.6 µg/L; P < .001), and 153 (14.4 ± 8.9 vs 10.1 ± 4.4 µg/L; P < .001) in COVID-19 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21-1, and CA125: P < .001; CEA and CA153: P < .01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID-19 as compared with mild and severe cases and normal controls (P < .01). There were positive associations between levels of C-reactive protein and levels of HE4 (R = .631; P < .001), CYFRA21-1 (R = .431; P < .001), CEA (R = .316; P < .001), SCC (R = .351; P < .001), CA153 (R = .359; P < .001) and CA125 (R = .223; P = .031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID-19, demonstrating diffuse and acute pathophysiological injuries in COVID-19.", "title": "Elevations of serum cancer biomarkers correlate with severity of COVID-19", "pid": "y5ut2w8r", "bm25_score": 216.8084259033203}, {"text": "Severe acute respiratory syndrome coronavirus 2-induced direct cytopathic effects against type I and II pneumocytes mediate lung damage. Krebs von den Lungen-6 (KL-6) is mainly produced by damaged or regenerating alveolar type II pneumocytes. This preliminary study analyzed serum concentrations of KL-6 in patients with coronavirus disease (COVID-19) to verify its potential as a prognostic biomarker of severity. Twenty-two patients (median age [interquartile range] 63 [59-68] years, 16 males) with COVID-19 were enrolled prospectively. Patients were divided into mild-moderate and severe groups, according to respiratory impairment and clinical management. KL-6 serum concentrations and lymphocyte subset were obtained. Peripheral natural killer (NK) cells/µL were significantly higher in nonsevere patients than in the severe group (P = .0449) and the best cut-off value was 119 cells/µL. KL-6 serum concentrations were significantly higher in severe patients than the nonsevere group (P = .0118). Receiver operating characteristic analysis distinguished severe and nonsevere patients according to KL-6 serum levels and the best cut-off value was 406.5 U/mL. NK cell analysis and assay of KL-6 in serum can help identify severe COVID-19 patients. Increased KL-6 serum concentrations were observed in patients with severe pulmonary involvement, revealing a prognostic value and supporting the potential usefulness of KL-6 measurement to evaluate COVID-19 patients' prognosis.", "title": "Serum KL-6 concentrations as a novel biomarker of severe COVID-19", "pid": "snxsa622", "bm25_score": 216.79425048828125}, {"text": "OBJECTIVE: To explore the indicators for severity in young COVID-19 patients age between 18 to 40. METHODS: This retrospective cohort study includes 65 consecutively admitted COVID-19 patients age between 18 to 40 in Zhongnan Hospital of Wuhan University. Among them, 53 were moderate cases, 12 were severe or critical cases. Epidemiological, clinical and laboratory characteristics and treatment data were collected. A multivariate logistic regression analysis was implemented to explore risk factors. RESULTS: The severe/critical cases have obviously higher BMI (average 29.23 vs. 22.79kg/m2 ) and lower liver CT value (average 50.00 vs. 65.00mU) than moderate cases group. The severe/critical cases have higher fasting glucose, alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , and creatinine (Cr) compared with moderate cases (All P<0.01) . More severe/critical cases (58.33% vs. 1.92%) have positive urine protein. The severe/critical cases will experience a significant process of serum albumin decline. Logistic regression analysis showed that male, high body mass index (especially obesity), elevated fasting blood glucose and urinary protein positive are all risk factors for severe young COVID-19 patients. CONCLUSION: Obesity is an important predictor of severity in young COVID-19 patients. The main mechanism is related to the damage of liver and kidney.", "title": "Obesity as a Potential Predictor of Disease Severity in Young COVID-19 Patients: A Retrospective Study", "pid": "aiwjfx7r", "bm25_score": 216.787353515625}, {"text": "BACKGROUND: Patients critically ill with coronavirus disease-2019 (COVID-19) feature hyperinflammation, and the associated biomarkers may be beneficial for risk stratification. We aimed to investigate the association between several biomarkers, including serum C-reactive protein (CRP), procalcitonin (PCT), D-dimer, and serum ferritin, and COVID-19 severity. METHODS: We performed a comprehensive systematic literature search through electronic databases. The outcome of interest for this study was the composite poor outcome, which comprises mortality, acute respiratory distress syndrome, need for care in an intensive care unit, and severe COVID-19. RESULTS: A total of 5350 patients were pooled from 25 studies. Elevated CRP was associated with an increased composite poor outcome [risk ratio (RR) 1.84 (1.45, 2.33), p < 0.001; I(2): 96%] and its severe COVID-19 (RR 1.41; I(2): 93%) subgroup. A CRP ⩾10 mg/L has a 51% sensitivity, 88% specificity, likelihood ratio (LR) + of 4.1, LR- of 0.5, and an area under curve (AUC) of 0.84. An elevated PCT was associated with an increased composite poor outcome [RR 3.92 (2.42, 6.35), p < 0.001; I(2): 85%] and its mortality (RR 6.26; I(2): 96%) and severe COVID-19 (RR 3.93; I(2): 63%) subgroups. A PCT ⩾0.5 ng/ml has an 88% sensitivity, 68% specificity, LR+ of 2.7, LR- of 0.2, and an AUC of 0.88. An elevated D-dimer was associated with an increased composite poor outcome [RR 2.93 (2.14, 4.01), p < 0.001; I(2): 77%], including its mortality (RR 4.15; I(2): 83%) and severe COVID-19 (RR 2.42; I(2): 58%) subgroups. A D-dimer >0.5 mg/L has a 58% sensitivity, 69% specificity, LR+ of 1.8, LR- of 0.6, and an AUC of 0.69. Patients with a composite poor outcome had a higher serum ferritin with a standardized mean difference of 0.90 (0.64, 1.15), p < 0.0001; I(2): 76%. CONCLUSION: This meta-analysis showed that an elevated serum CRP, PCT, D-dimer, and ferritin were associated with a poor outcome in COVID-19. The reviews of this paper are available via the supplemental material section.", "title": "C-reactive protein, procalcitonin, D-dimer, and ferritin in severe coronavirus disease-2019: a meta-analysis", "pid": "izzavogm", "bm25_score": 216.7840576171875}, {"text": "", "title": "Urinalysis parameters for predicting severity in coronavirus disease 2019 (COVID-19)", "pid": "pf5leb4c", "bm25_score": 216.78033447265625}, {"text": "Aim: We aimed to explore the biomarkers for disease progression or the risk of nonsurvivors. Materials & methods: This study included 134 hospitalized patients with confirmed COVID-19 infection. The outcome of moderate versus severe versus critically ill patients and survivors versus nonsurvivors were compared. Results: An increase in the severity of COVID-19 pneumonia was positively associated with lower levels of platelets and albumin (all p < 0.05). In the critical group, the plasma levels of albumin continued to have a significant association for the risk of nonsurvivors (p < 0.05), even after adjusting for confounding factors. Conclusion: Albumin levels could be used as an independent predictor of the risk of nonsurvivors in critically ill patients with COVID-19.", "title": "Plasma albumin levels predict risk for nonsurvivors in critically ill patients with COVID-19", "pid": "kbp47abd", "bm25_score": 216.77403259277344}, {"text": "In this retrospective study, we evaluated the levels of a series of serum biomarkers in coronavirus disease 2019 (COVID‐19) patients (mild: 131; severe: 98; critical: 23). We found that there were significant increases in levels of human epididymis protein 4 (HE4) (73.6 ± 38.3 versus 46.5 ± 14.7, p<0.001), cytokeratin‐19 fragment (CYFRA21‐1) (2.2 ± 0.9 versus 1.9 ± 0.8, p<0.001), carcinoembryonic antigen (CEA) (3.4 ± 2.2 versus 2.1 ± 1.2, p<0.001), carbohydrate antigens (CA) 125 (18.1 ± 13.5 versus 10.5 ± 4.6, p<0.001) and 153 (14.4 ± 8.9 versus 10.1 ± 4.4, p<0.001) in COVID‐19 mild cases as compared to normal control subjects; their levels showed continuous and significant increases in severe and critical cases (HE4, CYFRA21‐1 and CA125: p<0.001; CEA and CA153: p<0.01). Squamous cell carcinoma antigen (SCC) and CA199 increased significantly only in critical cases of COVID‐19 as compared with mild and severe cases and normal controls (p<0.01). There were positive associations between levels of C‐reactive protein and levels of HE4 (R= 0.631, p<0.001), CYFRA21‐1(R= 0.431, p<0.001), CEA (R= 0.316, p<0.001), SCC (R= 0.351, p<0.001), CA153 (R= 0.359, p<0.001) and CA125 (R= 0.223, p=0.031). We concluded that elevations of serum cancer biomarkers positively correlated with the pathological progressions of COVID‐19, demonstrating diffuse and acute lung injuries. This article is protected by copyright. All rights reserved.", "title": "Elevations of serum cancer biomarkers correlate with severity of COVID‐19", "pid": "i1nehm61", "bm25_score": 216.76991271972656}, {"text": "COVID-19 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID-19 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID-19 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID-19, the lymphocytes in the severe COVID-19 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C-reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P < .01), erythrocyte sedimentation rate (R = .55; P < .01) and granulocyte/lymphocyte ratio (R = .49; P < .01) were positively associated with the CT severity scores. In contrast, the number of lymphocytes (R = -.37; P < .01) was negatively correlated with the CT severity scores. The receiver-operating characteristic analysis demonstrated that area under the curve of CRP on the first visit for predicting severe COVID-19 was 0.87 (95% CI 0.10-1.00) at 20.42 mg/L cut-off, with sensitivity and specificity 83% and 91%, respectively. CRP in severe COVID-19 patients increased significantly at the initial stage, before CT findings. Importantly, CRP, which was associated with disease development, predicted early severe COVID-19.", "title": "C-reactive protein correlates with computed tomographic findings and predicts severe COVID-19 early", "pid": "q37fwcgt", "bm25_score": 216.7692108154297}, {"text": "Abstract: Objective: Coronavirus disease 2019 (COVID-19) is an escalating global epidemic caused by SARS-CoV-2, with a high mortality in critical patients. Effective indicators for predicting disease severity in SARS-CoV-2 infected patients are urgently needed. Methods: In this study, 43 COVID-19 patients admitted in Chongqing Public Health Medical Center were involved. Demographic data, clinical features, and laboratory examinations were obtained through electronic medical records. Peripheral blood specimens were collected from COVID-19 patients and examined for lymphocyte subsets and cytokine profiles by flow cytometry. Potential contributing factors for prediction of disease severity were further analyzed. Results: A total of 43 COVID-19 patients were included in this study, including 29 mild patients and 14 sever patients. Severe patients were significantly older (61.9+/-9.4 vs 44.4+/-15.9) and had higher incidence in co-infection with bacteria compared to mild group (85.7%vs27.6%). Significantly more severe patients had the clinical symptoms of anhelation (78.6%) and asthma (71.4%). For laboratory examination, 57.1% severe cases showed significant reduction in lymphocyte count. The levels of Interluekin-6 (IL6), IL10, erythrocyte sedimentation rate (ESR) and D-Dimer (D-D) were significantly higher in severe patients than mild patients, while the level of albumin (ALB) was remarkably lower in severe patients. Further analysis demonstrated that ESR, D-D, age, ALB and IL6 were the major contributing factors for distinguishing severe patients from mild patients. Moreover, ESR was identified as the most powerful factor to predict disease progression of COVID-19 patients. Conclusion: Age and the levels of ESR, D-D, ALB and IL6 are closely related to the disease severity of COVID-19 patients. ESR can be used as a valuable indicator for distinguishing severe COVID-19 patients in early stage, so as to increase the survival of severe patients. Keyword: COVID-19, erythrocyte sedimentation rate, cytokines, lymphocytes", "title": "Potential Factors for Prediction of Disease Severity of COVID-19 Patients", "pid": "tv9xsned", "bm25_score": 216.76834106445312}, {"text": "BACKGROUND AND AIMS: Cardiac biomarkers like cardiac troponins and natriuretic peptides are elevated in a substantial proportion of patients with coronavirus disease 2019 (COVID-19). We propose an algorithmic approach using cardiac biomarkers to triage, risk-stratify and prognosticate patients with severe COVID-19. METHODS: We systematically searched the PubMed and Google Scholar databases until May 31st, 2020, and accessed the available data on the role of cardiac biomarkers in patients with COVID-19. RESULTS: COVID-19 is associated with acute cardiac injury in around 7–28% of patients, significantly increasing its associated complications and mortality. Patients with underlying cardiovascular disease are more prone to develop acute cardiac injury as a result of COVID-19. The use of cardiac biomarkers may aid in differentiating the cardiac cause of dyspnea in patients with severe COVID-19. Cardiac biomarkers may also aid in triaging, risk-stratification, clinical decision-making, and prognostication of patients with COVID-19. However, there are concerns that routine testing in all patients with COVID-19 irrespective of severity, may result in unnecessary downstream investigations which may be misleading. In this brief review, using an algorithmic approach, we have tried to rationalize the use of cardiac biomarkers among patients with severe COVID-19. This approach is also likely to lessen the infection exposure risk to the cardiovascular team attending patients with severe COVID-19. CONCLUSION: It appears beneficial to triage, risk-stratify, and prognosticate patients with COVID-19 based on the evidence of myocardial injury and the presence of underlying cardiovascular disease. Future research studies are, however, needed to validate these proposed benefits.", "title": "Cardiac biomarker-based risk stratification algorithm in patients with severe COVID-19", "pid": "1hvihwkz", "bm25_score": 216.76185607910156}, {"text": "Background Approximately 15-20% of COVID-19 patients will develop severe pneumonia, about 10 % of which will die if not properly managed. Methods 125 COVID-19 patients enrolled in this study were classified into mild (93 cases) and severe (32 cases) groups, basing on their 3 to 7-days clinical outcomes. Patients' gender, age, comorbid with underlying diseases, epidemiological history, clinical manifestations, and laboratory tests on admission were collected and subsequently analyzed with single-factor and multivariate logistic regression methods. Finally, we evaluate their prognostic values with the receiver operating characteristic curve (ROC) analysis. Results Seventeen factors on admission differed significantly between mild and severe groups. Next, only four factors, including the comorbid with underlying diseases, increased respiratory rate (>24/min), elevated C-reactive protein (CRP >10mg/liter), and lactate dehydrogenase (LDH >250U/liter), were found to be independently associated with the later disease development. Prognostic value analysis by ROC indicated that individual factors could not confidently predict the occurrence of severe pneumonia, but that the combination of fast respiratory rate and elevated LDH significantly increase the predictive confidence (AUC= 0.944, sensitivity= 0.941, and specificity= 0.902). Three- or four-factors combinations, including elevated LDH and fast respiratory rate, further increased the prognostic value. Additionally, measurable serum viral RNA post-admission could independently predict the severe illness occurrence. Conclusions General clinical characteristics and laboratory tests, such as combinations consisting of elevated LDH and fast respiratory rate, and detectable viral RNA in serum post-admission could provide high confident prognostic value for identifying potential severe COVID-19 pneumonia patients.", "title": "Prognostic factors for COVID-19 pneumonia progression to severe symptom based on the earlier clinical features: a retrospective analysis", "pid": "uizdigo0", "bm25_score": 216.75953674316406}, {"text": "Abstract Background: A new virus broke out in Wuhan, Hubei, China, and was later named 2019 novel coronavirus (2019-nCoV). The clinical characteristics of severe pneumonia caused by 2019-nCoV are still not clear. Objectives: The aim of this study was to explore the clinical characteristics and risk factors of the severe pneumonia caused by the 2019-nCoV in Wuhan, China. Method: The study included patients hospitalized at the central hospital of Wuhan who had been diagnosed with a pneumonia caused by the novel coronavirus. Clinical features, chronic co-morbidities, demographic data, laboratory examinations, and chest computed tomography (CT) scans were reviewed through electronic medical records. SPSS was used for data analysis to explore the clinical characteristics and risk factors of the patients with the severe pneumonia. Results: A total of 110 patients diagnosed with 2019 novel coronavirus pneumonia were included in the study, including 38 with severe pneumonia and 72 with non-severe pneumonia. Statistical analysis showed that advanced age, an increase of D-dimer, and a decrease of lymphocytes were characteristics of the patients with severe pneumonia. Moreover, in the early stage of the disease, chest CT scans of patients with the severe pneumonia showed the illness can progress rapidly. Conclusions: Advanced age, lymphocyte decline, and D-dimer elevation are important characteristics of patients with severe pneumonia. Clinicians should focus on these characteristics to identify high-risk patients at an early stage.", "title": "Clinical Characteristics of Patients with Severe Pneumonia Caused by the 2019 Novel Coronavirus in Wuhan, China", "pid": "qlkt5fzp", "bm25_score": 216.7573699951172}, {"text": "AIMS: As of the 28th April 2020, the COVID-19 pandemic has infiltrated over 200 countries and affected over three million confirmed people. We review different biomarkers to evaluate if they are able to predict clinical outcomes and correlate with the severity of COVID-19 disease. METHODS: A systematic review of the literature was carried out to identify relevant articles using six different databases. Keywords to refine the search included ‘COVID-19’, ‘SARS-CoV2’, ‘Biomarkers’, among others. Only studies which reported data on pre-defined outcomes were included. KEY FINDINGS: Thirty-four relevant articles were identified which reviewed the following biomarkers: C-reactive protein, serum amyloid A, interleukin-6, lactate dehydrogenase, neutrophil-to-lymphocyte ratio, D-dimer, cardiac troponin, renal biomarkers, lymphocytes and platelet count. Of these, all but two, showed significantly higher levels in patients with severe complications of COVID-19 infection compared to their non-severe counterparts. Lymphocytes and platelet count showed significantly lower levels in severe patients compared to non-severe patients. SIGNIFICANCE: Although research is still in its early stages, the discovery of how different biomarkers behave during the course of the disease could help clinicians in identifying severe disease earlier and subsequently improve prognosis. Nevertheless, we urge for more research across the globe to corroborate these findings.", "title": "The role of biomarkers in diagnosis of COVID-19 – A systematic review", "pid": "r8mn4lzv", "bm25_score": 216.75723266601562}, {"text": "BACKGROUND AND AIMS: Cardiac biomarkers like cardiac troponins and natriuretic peptides are elevated in a substantial proportion of patients with coronavirus disease 2019 (COVID-19). We propose an algorithmic approach using cardiac biomarkers to triage, risk-stratify and prognosticate patients with severe COVID-19. METHODS: We systematically searched the PubMed and Google Scholar databases until May 31st, 2020, and accessed the available data on the role of cardiac biomarkers in patients with COVID-19. RESULTS: COVID-19 is associated with acute cardiac injury in around 7-28% of patients, significantly increasing its associated complications and mortality. Patients with underlying cardiovascular disease are more prone to develop acute cardiac injury as a result of COVID-19. The use of cardiac biomarkers may aid in differentiating the cardiac cause of dyspnea in patients with severe COVID-19. Cardiac biomarkers may also aid in triaging, risk-stratification, clinical decision-making, and prognostication of patients with COVID-19. However, there are concerns that routine testing in all patients with COVID-19 irrespective of severity, may result in unnecessary downstream investigations which may be misleading. In this brief review, using an algorithmic approach, we have tried to rationalize the use of cardiac biomarkers among patients with severe COVID-19. This approach is also likely to lessen the infection exposure risk to the cardiovascular team attending patients with severe COVID-19. CONCLUSION: It appears beneficial to triage, risk-stratify, and prognosticate patients with COVID-19 based on the evidence of myocardial injury and the presence of underlying cardiovascular disease. Future research studies are, however, needed to validate these proposed benefits.", "title": "Cardiac biomarker-based risk stratification algorithm in patients with severe COVID-19", "pid": "p3fi4yej", "bm25_score": 216.75624084472656}, {"text": "Among 417 COVID-19 patients in Shenzhen, demographic characteristics, clinical manifestations and baseline laboratory tests showed significant differences between mild-moderate cohort and severe-critical cohort.Based on these differences, a convenient mathematical model was established to predict the illness severity of COVID-19. The model includes four parameters: age, BMI, CD4(+) lymphocytes and IL-6 levels. The AUC of the model is 0.911.The high risk factors for developing to severe COVID-19 are: age ≥ 55 years, BMI > 27 kg / m(2), IL-6 ≥ 20 pg / ml, CD4(+) T cell ≤ 400 count / μ L.Among 249 discharged COVID-19 patients, those who recovered after 20 days had a lower count of platelet, a higher level of estimated glomerular filtration rate, and higher level of interleukin-6 and myoglobin than those who recovered within 20 days.", "title": "Predicting Illness Severity and Short-Term Outcomes of COVID-19: A Retrospective Cohort Study in China", "pid": "jkmtpin4", "bm25_score": 216.7425994873047}, {"text": "BACKGROUND: The emerging infection of the 2019 novel coronavirus (2019-nCoV) in late December, 2019 in Wuhan, China, has caused an extreme health concern, with many patients having progressed to acute respiratory disease or other complications in a short period. Meanwhile, the risk factors associated with the disease progression still remain elusive. METHODS: A cohort of 17 patients with laboratory-confirmed 2019-nCoV infections who were admitted to the Ninth Hospital of Nanchang between January 28 and February 6, 2020, were enrolled in this study. All the patients received standardized treatment. The disease progression was evaluated every 7 days after admission. The clinical, radiologic, and laboratory characteristics were retrospectively analyzed, and the factors associated with the disease progression were screened by binary logistic regression analysis. RESULTS: The cohort comprised 11 women (64.7%) and 6 men (35.3%) between the ages of 18 to 70 years old. All patients had a reported history of contact with infection-confirmed patients. Fever (11/64.7%) and cough (8/47.1%) were the most common symptoms, whereas dyspnea (2/11.8%) and fatigue (3/17.6%) were rare, and there was no patient with diarrhea symptoms. There were 5 patients with aggravated disease at the first disease progression evaluation, and no patient received mechanical ventilation, transferred to the intensive care unit (ICU), or progressed to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, coagulation dysfunction, or death. Based on the disease progression, patients were divided into the non-aggravation group (12 cases) and the aggravation group (5 cases). There were no significant differences between the 2 groups with respect to their clinical characteristics. Chest computed tomography (CT) on admission revealed there were 8 patients (47.1%) with invasive lesions found bilaterally on the lungs on multiple lobes, 4 patients (23.5%) with invasive lesions on 1 lobe, and 5 patients (29.4%) with normal chest CT. The aggravation group had1 patient (20.0%) with invasive lesions on one lobe, 3 (60.0%) with invasive lesions on multiple lobes, bilaterally, and 1 (20.0%) with normal chest CT; meanwhile, the nonaggravation group had 3 patients (25.0%) with invasive lesions on one lobe, 5 (41.7%) with invasive lesions on multiple lobes, bilaterally, and 4 (33.3%) with normal chest CT. No significant difference was found between the 2 groups. In the aggravation group, the total lymphocyte counts significantly decreased in comparison to that in the non-aggravation group. Further analysis showed that the CD4+ T cell count but not the CD8+ T cell count of the aggravation group was significantly lower than that of the non-aggravation group. Correlation analysis indicated total lymphocyte count was positively correlated with CD4+ T cell count, and no significant differences were found between the 2 groups in other laboratory measurements, including those of white blood cell (WBC) count, C-reactive protein (CRP), albumin, lactate dehydrogenase (LDH), and D-dimer. Finally, a binary logistic regression model was used to identify the factors associated with the disease progression. It was found that total lymphocyte count was a risk factor associated with disease progression in patients infected with 2019-nCoV. CONCLUSIONS: A higher cell count of total lymphocytes may indicate a better outcome of the disease, and immune response may be a vital factor for directing disease progression in the early stage of 2019-nCoV infection.", "title": "Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus", "pid": "ijtz50ut", "bm25_score": 216.73760986328125}, {"text": "OBJECTIVE: To explore the indicators for severity in young COVID‐19 patients age between 18 to 40. METHODS: This retrospective cohort study includes 65 consecutively admitted COVID‐19 patients age between 18 to 40 in Zhongnan Hospital of Wuhan University. Among them, 53 were moderate cases, 12 were severe or critical cases. Epidemiological, clinical and laboratory characteristics and treatment data were collected. A multivariate logistic regression analysis was implemented to explore risk factors. RESULTS: The severe/critical cases have obviously higher BMI (average 29.23 vs. 22.79kg/m(2)) and lower liver CT value (average 50.00 vs. 65.00mU) than moderate cases group. The severe/critical cases have higher fasting glucose, alanine aminotransferase (ALT) , aspartate aminotransferase (AST) , and creatinine (Cr) compared with moderate cases (All P<0.01) . More severe/critical cases (58.33% vs. 1.92%) have positive urine protein. The severe/critical cases will experience a significant process of serum albumin decline. Logistic regression analysis showed that male, high body mass index (especially obesity), elevated fasting blood glucose and urinary protein positive are all risk factors for severe young COVID‐19 patients. CONCLUSION: Obesity is an important predictor of severity in young COVID‐19 patients. The main mechanism is related to the damage of liver and kidney.", "title": "Obesity as a Potential Predictor of Disease Severity in Young COVID‐19 Patients: A Retrospective Study", "pid": "vuuxthx2", "bm25_score": 216.7345733642578}, {"text": "Since March 11, 2020, the World Health Organization (WHO) defined Coronavirus disease 2019 (COVID-19) as a pandemic, with a series of confirmed cases that currently exceeded 300,000 people worldwide and with approximately 14,500 deaths. Accumulated evidence suggests that a subgroup of patients with severe COVID-19 could have a dysregulation of the immune response that allows the development of viral hyperinflammation. Thus, all patients with severe COVID-19 should be screened for hyperinflammation using laboratory parameters in order to improve mortality. Neutrophil-to-Lymphocyte ratio (NLR) and Lymphocyte-to-C-reactive protein ratio (LCR) are established inflammation markers that reflect systemic inflammatory response, and both are available in almost all laboratories. In this study, a meta-analysis was performed to investigate whether NLR and LCR values can help predict clinical severity in patients with COVID-19. This article is protected by copyright. All rights reserved.", "title": "Neutrophil‐to‐lymphocyte ratio and lymphocyte‐to‐C‐reactive protein ratio in patients with severe coronavirus disease 2019 (COVID‐19): A meta‐analysis", "pid": "u1npw7tw", "bm25_score": 216.71176147460938}, {"text": "Current pandemic caused by SARS-CoV-2 inducing viral COVID-19 pneumonia, is categorized in 3 stages. Some biomarkers could be assigned to one of these stages, showing a correlation to mortality in COVID-19 patients. Laboratory findings in COVID-19, especially when serially evaluated, may represent individual disease severity and prognosis. These may help planning and controlling therapeutic interventions. Biomarkers for myocardial injury (high sensitive cardiac troponin, hsTn) or hemodynamic stress (NTproBNP) may occur in COVID-19 pneumonia such as in other pneumonias, correlating with severity and prognosis of the underlying disease. In hospitalized COVID-19 patients' mild increases of hsTn or NTproBNP may be explained by cardiovascular comorbidities and direct or indirect cardiac damage or stress caused by or during COVID-19 pneumonia. In case of suspected NSTE-ACS and COVID-19, indications for echocardiography or reperfusion strategy should be carefully considered against the risk of contamination.", "title": "[Cardiac biomarkers and COVID-19 - Phenotypes and Interpretation].", "pid": "1nczw70h", "bm25_score": 216.6839599609375}, {"text": "COVID‐19 has developed into a worldwide pandemic; early identification of severe illness is critical for controlling it and improving the prognosis of patients with limited medical resources. The present study aimed to analyze the characteristics of severe COVID‐19 and identify biomarkers for differential diagnosis and prognosis prediction. In total, 27 consecutive patients with COVID‐19 and 75 patients with flu were retrospectively enrolled. Clinical parameters were collected from electronic medical records. The disease course was divided into four stages: initial, progression, peak, and recovery stages, according to computed tomography (CT) progress. to mild COVID‐19, the lymphocytes in the severe COVID‐19 progressively decreased at the progression and the peak stages, but rebound in the recovery stage. The levels of C‐reactive protein (CRP) in the severe group at the initial and progression stages were higher than those in the mild group. Correlation analysis showed that CRP (R = .62; P < .01), erythrocyte sedimentation rate (R = .55; P < .01) and granulocyte/lymphocyte ratio (R = .49; P < .01) were positively associated with the CT severity scores. In contrast, the number of lymphocytes (R = −.37; P < .01) was negatively correlated with the CT severity scores. The receiver‐operating characteristic analysis demonstrated that area under the curve of CRP on the first visit for predicting severe COVID‐19 was 0.87 (95% CI 0.10–1.00) at 20.42 mg/L cut‐off, with sensitivity and specificity 83% and 91%, respectively. CRP in severe COVID‐19 patients increased significantly at the initial stage, before CT findings. Importantly, CRP, which was associated with disease development, predicted early severe COVID‐19.", "title": "C‐reactive protein correlates with computed tomographic findings and predicts severe COVID‐19 early", "pid": "xfptlkuc", "bm25_score": 216.6815948486328}, {"text": "Abstract Objectives The study was aimed at investigating the characteristics of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus (2019-nCoV) pneumonia. Methods Children with 2019-nCoV pneumonia or with respiratory syncytial virus (RSV) pneumonia were included. Data including lymphocyte subsets and serum cytokines were collected and analyzed. Results : 56 patients were included in the study, 40 children with 2019-nCoV pneumonia and 16 children with RSV pneumonia. Compared with children with RSV pneumonia, patients with 2019-nCoV pneumonia had higher count of CD3+8+ lymphocyte, higher percentages of CD3+, CD3+8+ lymphocytes and a lower percentage of CD19+ lymphocyte. The serum IL-10 level was significantly higher in children with RSV pneumonia. One 2019-nCoV pneumonia child who was with an obvious increase of IL-10 developed severe pneumonia. Conclusions Immune response played a very important role in the development of 2019-nCoV pneumonia. The effective CD8+ T cell response might influence the severity of 2019-nCoV pneumonia. The adaptable change in IL-10 level might contribute to the relatively mild pneumonia symptoms in children with 2019-nCoV pneumonia and bacterial co-infection might be a risk factor of severe 2019-nCoV pneumonia.", "title": "The profile of peripheral blood lymphocyte subsets and serum cytokines in children with 2019 novel coronavirus pneumonia", "pid": "i0mnxqa0", "bm25_score": 216.66827392578125}, {"text": "Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p<0.001), in which SpO2≤89%, lymphocyte≤0.64×10(9)/L, CRP>77.35mg/L, PCT>0.20μg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p<0.04). In the course, persistently lower lymphocyte with higher levels of CRP, PCT, IL-6, neutrophil, LDH, D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and increased CD4+/CD8+ T-lymphocyte ratio and were observed in death events group, while these parameters stayed stable or improved in discharge group. Conclusions: On admission, the levels of SpO2, lymphocyte, CRP, PCT, and LDH could predict the prognosis of severe COVID-19 patients. Systematic inflammation with induced cardiac dysfunction was likely a primary reason for death events in severe COVID-19 except for acute respiratory distress syndrome.", "title": "Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study", "pid": "6i5zbmm1", "bm25_score": 216.62301635742188}, {"text": "OBJECTIVE To examine if baseline soluble urokinase plasminogen activator receptor (suPAR) can predict whether patients with COVID-19 symptoms will need mechanical ventilation during a 14-day follow-up. Furthermore, to examine differences in demographics, clinical signs, and biomarkers in patients tested either positive or negative for SARS-CoV-2. DESIGN Prospective cohort study including patients presenting with symptoms of COVID-19. SETTING Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark. PARTICIPANTS 407 patients presenting with symptoms of COVID-19 were included from the Emergency Department (ED). Patients were included from March 19 to April 3 and follow-up data was collected until April 17, 2020. MAIN OUTCOME MEASURES Primary outcomes were respiratory failure in patients presenting with symptoms of COVID-19 and in those with a positive SARS-CoV-2 RT-PCR test, respectively. Furthermore, we analysed differences between patients testing positive and negative for SARS-CoV-2, and disease severity outcomes in SARS-CoV-2 positive patients according to baseline suPAR. BACKGROUND Patients admitted to ED with clinical signs or symptoms of COVID-19 infection need a safe and quick triage, in order to determine if an in-hospital stay is necessary or if the patient can safely be isolated in their own home with relevant precautions. suPAR is a biomarker previously shown to be associated with adverse outcomes in acute medical patients. We aimed to examine if suPAR at baseline presentation is predictive of respiratory failure in patients presenting with symptoms of COVID-19. Furthermore, we examined demographic, clinical, and biochemical differences between SARS-CoV-2-positive and negative patients. RESULTS Among the 407 symptomatic patients, the median (interquartile range) age was 64 years (47-77), 58% were women, and median suPAR was 4.2 ng/ml (2.7-6.4). suPAR level below 4.75 ng/ml at admission ruled out respiratory failure during follow-up with an area under the curve (95% CI) of 0.89 (0.85-0.94) and a negative predictive value of 99.5%. Of the 407 symptomatic patients, 117 (28.8%) had a positive RT-PCR test for SARS-CoV-2 and presented with significant differences in vital signs, cell counts, and biomarkers compared to SARS-CoV-2 negative patients. In SARS-CoV-2 positive patients eligible for mechanical ventilation (N=87), 26 (30%) developed respiratory failure. Best baseline predictors of respiratory failure were suPAR with an area under the curve (95% CI) of 0.88 (0.80-0.95), EWS 0.84 (0.75-0.93), lactate dehydrogenase 0.82 (0.71-0.93), and C-reactive protein 0.80 (0.70-0.89). CONCLUSION SARS-CoV-2 affects several patient parameters underpinning the severe impact of the infection. A low suPAR level (<4.75 ng/ml) at baseline is a useful biomarker for aiding clinical decisions including discharge of patients presenting with symptoms of COVID-19.", "title": "Low levels of the prognostic biomarker suPAR are predictive of mild outcome in patients with symptoms of COVID-19 - a prospective cohort study", "pid": "mu72ht3u", "bm25_score": 216.60389709472656}, {"text": "INTRODUCTION Since December 2019, an outbreak of coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome - Coronavirus 2 (SARS-CoV-2) emerged in China and has become a global threat. Comparison of hematological parameters between mild and severe cases of SARS-CoV 2 is so far limited, but significant differences in parameters such as interleukin-6, d-dimers, glucose, fibrinogen and C-reactive protein have been already reported. PURPOSE In this study we analyzed the changes observed in easily measured blood biomarkers in the patients and provided evidence of how these markers can be used as prognostic factors of the disease. METHODS Demographic characteristics, detailed medical history, and laboratory findings of all enrolled SARS-CoV 2 infection positive patients who were referred to Patras University Hospital from the period of March 4th 2020 (when first confirmed case in Greece appeared in our hospital) until April 4th 2020 were extracted from electronic medical records and analyzed. RESULTS We provided evidence that some very common laboratory values can be used as independent predictive factors in SARS-CoV 2 infection. Despite the retrospective nature of this study and the small number of subjects analyzed, we showed that NLR, LDH, d-dimers, CRP, fibrinogen and ferritin can be used early at the patient's first visit for SARS-CoV 2 infection symptoms and can predict the severity of infection. CONCLUSION More studies are warranted to further objectively confirm the clinical value of prognostic factors related to SARS-CoV 2 and establish an easy-to-get panel of laboratory findings for evaluating the disease severity.", "title": "Prognosis of COVID-19: Changes in laboratory parameters.", "pid": "ljc7ojzt", "bm25_score": 216.5979461669922}, {"text": "Mortality is high among severe patients with 2019 novel coronavirus-infected disease (COVID-19). Early prediction of progression to severe cases is needed. We retrospectively collected patients with COVID-19 in two hospital of Chongqing from 1st January to 29th February 2020. At admission, we collected the demographics and laboratory tests to predict whether the patient would progress to severe cases in hospitalization. Severe case was confirmed when one of the following criteria occurred: (a) dyspnea, respiratory rate &#8805;30 breaths/min, (b) blood oxygen saturation &#8804;93%, and (c) PaO2 /FiO2 &#8804; 300 mm Hg. At admission, 348 mild cases were enrolled in this study. Of them, 20 (5.7%) patients progressed to severe cases after median 4.0 days (interquartile range: 2.3-6.0). Pulmonary inflammation index, platelet counts, sodium, C-reactive protein, prealbumin, and PaCO2 showed good distinguishing power to predict progression to severe cases (each area under the curve of receiver operating characteristics [AUC] &#8805; 0.8). Age, heart rate, chlorine, alanine aminotransferase, aspartate aminotransferase, procalcitonin, creatine kinase, pH, CD3 counts, and CD4 counts showed moderate distinguishing power (each AUC between 0.7-0.8). And potassium, creatinine, temperature, and D-dimer showed mild distinguishing power (each AUC between 0.6-0.7). In addition, higher C-reactive protein was associated with shorter time to progress to severe cases (r = -0.62). Several easily obtained variables at admission are associated with progression to severe cases during hospitalization. These variables provide a reference for the medical staffs when they manage the patients with COVID-19.", "title": "Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID-19 in Chongqing", "pid": "yzgac737", "bm25_score": 216.58441162109375}, {"text": "BACKGROUND The emerging infection of the 2019 novel coronavirus (2019-nCoV) in late December, 2019 in Wuhan, China, has caused an extreme health concern, with many patients having progressed to acute respiratory disease or other complications in a short period. Meanwhile, the risk factors associated with the disease progression still remain elusive. METHODS A cohort of 17 patients with laboratory-confirmed 2019-nCoV infections who were admitted to the Ninth Hospital of Nanchang between January 28 and February 6, 2020, were enrolled in this study. All the patients received standardized treatment. The disease progression was evaluated every 7 days after admission. The clinical, radiologic, and laboratory characteristics were retrospectively analyzed, and the factors associated with the disease progression were screened by binary logistic regression analysis. RESULTS The cohort comprised 11 women (64.7%) and 6 men (35.3%) between the ages of 18 to 70 years old. All patients had a reported history of contact with infection-confirmed patients. Fever (11/64.7%) and cough (8/47.1%) were the most common symptoms, whereas dyspnea (2/11.8%) and fatigue (3/17.6%) were rare, and there was no patient with diarrhea symptoms. There were 5 patients with aggravated disease at the first disease progression evaluation, and no patient received mechanical ventilation, transferred to the intensive care unit (ICU), or progressed to acute respiratory distress syndrome, septic shock, refractory metabolic acidosis, coagulation dysfunction, or death. Based on the disease progression, patients were divided into the non-aggravation group (12 cases) and the aggravation group (5 cases). There were no significant differences between the 2 groups with respect to their clinical characteristics. Chest computed tomography (CT) on admission revealed there were 8 patients (47.1%) with invasive lesions found bilaterally on the lungs on multiple lobes, 4 patients (23.5%) with invasive lesions on 1 lobe, and 5 patients (29.4%) with normal chest CT. The aggravation group had1 patient (20.0%) with invasive lesions on one lobe, 3 (60.0%) with invasive lesions on multiple lobes, bilaterally, and 1 (20.0%) with normal chest CT; meanwhile, the nonaggravation group had 3 patients (25.0%) with invasive lesions on one lobe, 5 (41.7%) with invasive lesions on multiple lobes, bilaterally, and 4 (33.3%) with normal chest CT. No significant difference was found between the 2 groups. In the aggravation group, the total lymphocyte counts significantly decreased in comparison to that in the non-aggravation group. Further analysis showed that the CD4+ T cell count but not the CD8+ T cell count of the aggravation group was significantly lower than that of the non-aggravation group. Correlation analysis indicated total lymphocyte count was positively correlated with CD4+ T cell count, and no significant differences were found between the 2 groups in other laboratory measurements, including those of white blood cell (WBC) count, C-reactive protein (CRP), albumin, lactate dehydrogenase (LDH), and D-dimer. Finally, a binary logistic regression model was used to identify the factors associated with the disease progression. It was found that total lymphocyte count was a risk factor associated with disease progression in patients infected with 2019-nCoV. CONCLUSIONS A higher cell count of total lymphocytes may indicate a better outcome of the disease, and immune response may be a vital factor for directing disease progression in the early stage of 2019-nCoV infection.", "title": "Risk factors associated with disease progression in a cohort of patients infected with the 2019 novel coronavirus.", "pid": "z3rpoqao", "bm25_score": 216.57423400878906}, {"text": "BACKGROUND Severe acute respiratory coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) has become a pandemic. This study addressed the clinical and immunopathological characteristics of severe COVID-19. METHODS Sixty-nine COVID-19 patients were classified into as severe and non-severe groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from two deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations. RESULTS Circulating cytokines, including IL8, IL6, TNFα, IP10, MCP1, and RANTES, were significantly elevated in severe COVID-19 patients. Dynamic IL6 and IL8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II, type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4+ and CD8+ T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues. CONCLUSIONS A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both SARS-CoV-2 caused cytopathy and immunopathologic damage. Strategies that encourage pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of severe COVID-19 patients.", "title": "Clinical and pathological investigation of severe COVID-19 patients.", "pid": "2ik1rbto", "bm25_score": 216.5737762451172}, {"text": "Coronavirus disease 2019 (COVID-19) has spread rapidly around the world since its emergence in humans last December. Previous studies suggested that numerous markers of inflammation were elevated in patients in with severe disease relative to patients with milder conditions, and an elevated level of interleukin-6 (IL-6) was associated with a high case fatality of COVID-19 infection. This article is protected by copyright. All rights reserved.", "title": "Elevated interleukin-6 is associated with severity of COVID-19: a meta-analysis", "pid": "ejj82q46", "bm25_score": 216.57330322265625}, {"text": "Mortality is high among severe patients with 2019 novel coronavirus‐infected disease (COVID‐19). Early prediction of progression to severe cases is needed. We retrospectively collected patients with COVID‐19 in two hospital of Chongqing from 1st January to 29th February 2020. At admission, we collected the demographics and laboratory tests to predict whether the patient would progress to severe cases in hospitalization. Severe case was confirmed when one of the following criteria occurred: (a) dyspnea, respiratory rate ≥30 breaths/min, (b) blood oxygen saturation ≤93%, and (c) PaO(2)/FiO(2) ≤ 300 mm Hg. At admission, 348 mild cases were enrolled in this study. Of them, 20 (5.7%) patients progressed to severe cases after median 4.0 days (interquartile range: 2.3‐6.0). Pulmonary inflammation index, platelet counts, sodium, C‐reactive protein, prealbumin, and PaCO(2) showed good distinguishing power to predict progression to severe cases (each area under the curve of receiver operating characteristics [AUC] ≥ 0.8). Age, heart rate, chlorine, alanine aminotransferase, aspartate aminotransferase, procalcitonin, creatine kinase, pH, CD3 counts, and CD4 counts showed moderate distinguishing power (each AUC between 0.7‐0.8). And potassium, creatinine, temperature, and D‐dimer showed mild distinguishing power (each AUC between 0.6‐0.7). In addition, higher C‐reactive protein was associated with shorter time to progress to severe cases (r = −0.62). Several easily obtained variables at admission are associated with progression to severe cases during hospitalization. These variables provide a reference for the medical staffs when they manage the patients with COVID‐19.", "title": "Correlation between the variables collected at admission and progression to severe cases during hospitalization among patients with COVID‐19 in Chongqing", "pid": "m3hwkbqx", "bm25_score": 216.56533813476562}, {"text": "", "title": "Elevated interleukin‐6, interleukin‐10 and neutrophil : lymphocyte ratio as identifiers of severe coronavirus disease 2019", "pid": "7ex3z3el", "bm25_score": 216.56410217285156}, {"text": "Objectives In December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19. Methods In this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy. Results The data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954-10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097-0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111-0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746-0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients. Conclusions We designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.", "title": "The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study", "pid": "rkm6c8z6", "bm25_score": 216.56039428710938}, {"text": "BACKGROUND: Several previously healthy young adults have developed Coronavirus Disease 2019 (COVID-19), and a few of them progressed to the severe stage. However, the factors are not yet determined. METHOD: We retrospectively analyzed 123 previously healthy young adults diagnosed with COVID-19 from January to March 2020 in a tertiary hospital in Wuhan. Patients were classified as having mild or severe COVID-19 based on their respiratory rate, SpO(2), and PaO(2)/FiO(2) levels. Patients’ symptoms, computer tomography (CT) images, preadmission drugs received, and the serum biochemical examination on admission were compared between the mild and severe groups. Significant variables were enrolled into logistic regression model to predict the factors affecting disease severity. A receiver operating characteristic (ROC) curve was applied to validate the predictive value of predictors. RESULT: Age; temperature; anorexia; and white blood cell count, neutrophil percentage, platelet count, lymphocyte count, C-reactive protein, aspartate transaminase, creatine kinase, albumin, and fibrinogen values were significantly different between patients with mild and severe COVID-19 (P < 0.05). Logistic regression analysis confirmed that lymphopenia (P = 0.010) indicated severe prognosis in previously healthy young adults with COVID-19, with the area under the curve (AUC) was 0.791(95% Confidence Interval (CI) 0.704–0.877)(P < 0.001). CONCLUSION: For previously healthy young adults with COVID-19, lymphopenia on admission can predict severe prognosis.", "title": "Predictive factors of severe coronavirus disease 2019 in previously healthy young adults: a single-center, retrospective study", "pid": "d4m8ro3n", "bm25_score": 216.55670166015625}, {"text": "Objectives In December 2019, there was an outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China, and since then, the disease has been increasingly spread throughout the world. Unfortunately, the information about early prediction factors for disease progression is relatively limited. Therefore, there is an urgent need to investigate the risk factors of developing severe disease. The objective of the study was to reveal the risk factors of developing severe disease by comparing the differences in the hemocyte count and dynamic profiles in patients with severe and non-severe COVID-19. Methods In this retrospectively analyzed cohort, 141 confirmed COVID-19 patients were enrolled in Taizhou Public Health Medical Center, Taizhou Hospital, Zhejiang Province, China, from January 17, 2020 to February 26, 2020. Clinical characteristics and hemocyte counts of severe and non-severe COVID patients were collected. The differences in the hemocyte counts and dynamic profiles in patients with severe and non-severe COVID-19 were compared. Multivariate Cox regression analysis was performed to identify potential biomarkers for predicting disease progression. A concordance index (C-index), calibration curve, decision curve and the clinical impact curve were calculated to assess the predictive accuracy. Results The data showed that the white blood cell count, neutrophil count and platelet count were normal on the day of hospital admission in most COVID-19 patients (87.9%, 85.1% and 88.7%, respectively). A total of 82.8% of severe patients had lymphopenia after the onset of symptoms, and as the disease progressed, there was marked lymphopenia. Multivariate Cox analysis showed that the neutrophil count (hazard ratio [HR] = 4.441, 95% CI = 1.954-10.090, p = 0.000), lymphocyte count (HR = 0.255, 95% CI = 0.097-0.669, p = 0.006) and platelet count (HR = 0.244, 95% CI = 0.111-0.537, p = 0.000) were independent risk factors for disease progression. The C-index (0.821 [95% CI, 0.746-0.896]), calibration curve, decision curve and the clinical impact curve showed that the nomogram can be used to predict the disease progression in COVID-19 patients accurately. In addition, the data involving the neutrophil count, lymphocyte count and platelet count (NLP score) have something to do with improving risk stratification and management of COVID-19 patients. Conclusions We designed a clinically predictive tool which is easy to use for assessing the progression risk of COVID-19, and the NLP score could be used to facilitate patient stratification management.", "title": "The hemocyte counts as a potential biomarker for predicting disease progression in COVID-19: a retrospective study.", "pid": "nqee1shq", "bm25_score": 216.55564880371094}, {"text": "• Fibrosis indicators were early warning markers for critical COVID-19 patients. • Dynamic changes of lymphocyte count and CRP levels were related to the prognosis. • Rapid pulmonary consolidation was the major feature for died COVID-19 patients. • Pathological changes included inflammatory exudation and formation of granulomatous nodule.", "title": "Correlation analysis of the severity and clinical prognosis of 32 cases of patients with COVID-19", "pid": "urk4ro0g", "bm25_score": 216.54644775390625}, {"text": "Abstract Background COVID-19 can manifest as a viral induced hyperinflammation with multi-organ involvement. Such patients often experience rapid deterioration and need for mechanical ventilation. Currently, no prospectively validated biomarker of impending respiratory failure is available. Objective We aimed to identify and prospectively validate biomarkers that allow the identification of patients in need of impending mechanical ventilation. Methods Patients with COVID-19 hospitalized from February 29th to April 09th, 2020 were analyzed for baseline clinical and laboratory findings at admission and during the disease. Data from 89 evaluable patients were available for the purpose of analysis comprising an initial evaluation cohort (n=40) followed by a temporally separated validation cohort (n=49). Results We identified markers of inflammation, LDH and creatinine as most predictive variables of respiratory failure in the evaluation cohort. Maximal interleukin-6 (IL-6) levels before intubation showed the strongest association with the need of mechanical ventilation followed by maximal CRP. Respective AUC values for IL-6 and CRP in the evaluation cohort were 0.97 and 0.86 and similar in the validation cohort 0.90 and 0.83. The calculated optimal cutoff values in the course of disease from the evaluation cohort (IL-6> 80 pg/ml and CRP> 97 mg/l) both correctly classified 80% of patients in the validation cohort regarding their risk of respiratory failure. Conclusion Maximal levels of IL-6 followed by CRP were highly predictive of the need for mechanical ventilation. This suggests the possibility of using IL-6 or CRP levels to guide escalation of treatment in patients with COVID-19 related hyperinflammatory syndrome.", "title": "Elevated levels of interleukin-6 and CRP predict the need for mechanical ventilation in COVID-19", "pid": "rnuf8pum", "bm25_score": 216.54469299316406}, {"text": "Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) broke out in Wuhan, Hubei, China. This study sought to elucidate a novel predictor of disease severity in patients with coronavirus disease-19 (COVID-19) cased by SARS-CoV-2. Methods: Patients enrolled in this study were all hospitalized with COVID-19 in the Central Hospital of Wuhan, China. Clinical features, chronic comorbidities, demographic data, and laboratory and radiological data were reviewed. The outcomes of patients with severe pneumonia and those with non-severe pneumonia were compared using the Statistical Package for the Social Sciences (IBM Corp., Armonk, NY, USA) to explore clinical characteristics and risk factors. The receiver operating characteristic curve was used to screen optimal predictors from the risk factors and the predictive power was verified by internal validation. Results: A total of 377 patients diagnosed with COVID-19 were enrolled in this study, including 117 with severe pneumonia and 260 with non-severe pneumonia. The independent risk factors for severe pneumonia were age [odds ratio (OR): 1.059, 95% confidence interval (CI): 1.036-1.082; p < 0.001], N/L (OR: 1.322, 95% CI: 1.180-1.481; p < 0.001), CRP (OR: 1.231, 95% CI: 1.129-1.341; p = 0.002), and D-dimer (OR: 1.059, 95% CI: 1.013-1.107; p = 0.011). We identified a product of N/L*CRP*D-dimer as having an important predictive value for the severity of COVID-19. The cutoff value was 5.32. The negative predictive value of less than 5.32 for the N/L*CRP*D-dimer was 93.75%, while the positive predictive value was 46.03% in the test sets. The sensitivity and specificity were 89.47% and 67.42%. In the training sets, the negative and positive predictive values were 93.80% and 41.32%, respectively, with a specificity of 70.76% and a sensitivity of 89.87%. Conclusions: A product of N/L*CRP*D-dimer may be an important predictor of disease severity in patients with COVID-19.", "title": "A New Predictor of Disease Severity in Patients with COVID-19 in Wuhan, China", "pid": "s9vv7rw4", "bm25_score": 216.52423095703125}, {"text": "A subgroup of COVID-19 patients develop very severe disease with requirement for ICU treatment, ventilation, and ECMO therapy. Laboratory tests indicate that the immune and clotting system show marked alterations with hyper-activation, hyper-inflammation, cytokine storm development. Furthermore, organ-specific biomarkers demonstrate the involvement of cardiac muscle, kidney, and liver dysfunction in many patients. In this article the use of laboratory biomarkers is discussed with regard to their use for diagnosis, disease progression, and risk assessment.", "title": "Laboratory characteristics of patients infected with the novel SARS-CoV-2 virus", "pid": "j79dfjfh", "bm25_score": 216.52023315429688}, {"text": "Rationale: Up to date, the exploration of clinical features in severe COVID-19 patients were mostly from the same center in Wuhan, China. The clinical data in other centers is limited. This study aims to explore the feasible parameters which could be used in clinical practice to predict the prognosis in hospitalized patients with severe coronavirus disease-19 (COVID-19). Methods: In this case-control study, patients with severe COVID-19 in this newly established isolation center on admission between 27 January 2020 to 19 March 2020 were divided to discharge group and death event group. Clinical information was collected and analyzed for the following objectives: 1. Comparisons of basic characteristics between two groups; 2. Risk factors for death on admission using logistic regression; 3. Dynamic changes of radiographic and laboratory parameters between two groups in the course. Results: 124 patients with severe COVID-19 on admission were included and divided into discharge group (n=35) and death event group (n=89). Sex, SpO2, breath rate, diastolic pressure, neutrophil, lymphocyte, C-reactive protein (CRP), procalcitonin (PCT), lactate dehydrogenase (LDH), and D-dimer were significantly correlated with death events identified using bivariate logistic regression. Further multivariate logistic regression demonstrated a significant model fitting with C-index of 0.845 (p<0.001), in which SpO2&#8804;89%, lymphocyte&#8804;0.64×109/L, CRP>77.35mg/L, PCT>0.20µg/L, and LDH>481U/L were the independent risk factors with the ORs of 2.959, 4.015, 2.852, 3.554, and 3.185, respectively (p<0.04). In the course, persistently lower lymphocyte with higher levels of CRP, PCT, IL-6, neutrophil, LDH, D-dimer, cardiac troponin I (cTnI), brain natriuretic peptide (BNP), and increased CD4+/CD8+ T-lymphocyte ratio and were observed in death events group, while these parameters stayed stable or improved in discharge group. Conclusions: On admission, the levels of SpO2, lymphocyte, CRP, PCT, and LDH could predict the prognosis of severe COVID-19 patients. Systematic inflammation with induced cardiac dysfunction was likely a primary reason for death events in severe COVID-19 except for acute respiratory distress syndrome.", "title": "Factors associated with death outcome in patients with severe coronavirus disease-19 (COVID-19): a case-control study", "pid": "fa63dmwr", "bm25_score": 216.51611328125}, {"text": "Objective: To determine the predictive value of CT and clinical characteristics for short-term disease progression in patients with 2019 novel coronavirus pneumonia (NCP). Materials and Methods: 224 patients with confirmed 2019 novel coronavirus (COVID-19) infection outside Wuhan who had chest CT examinations were retrospectively screened. Clinical data were obtained from electronic medical records. CT images were reviewed and scored for lesion distribution, lobe and segment involvement, ground-glass opacities, consolidation, and interstitial thickening. All included patients with moderate NCP were observed for at least 14 days from admission to determine whether they exacerbated to severe NCP (progressive group) or not (stable group). CT and clinical characteristics between the two groups were compared, and multivariate logistic regression and sensitivity analyses were performed to identify the risk factors for developing severe NCP. Results: A total of 141 patients with moderate NCP were included, of which 15 (10.6%) patients developed severe NCP during hospitalization and assigned to the progressive group. Multivariate logistic regression analysis showed that higher neutrophil-to-lymphocyte ratio (NLR) (odds ratio [OR] and 95% confidence interval [CI], 1.26 [1.04-1.53]; P = 0.018) and CT severity score (OR and 95% CI, 1.25 [1.08-1.46]; P = 0.004) on admission were independent predictors for progression to severe NCP, and sensitivity analysis confirmed the consistent results in nonimported patients but not in imported patients. However, no significant difference in lung involvement was found on CT between imported and nonimported patients (all P > 0.05). Patients who were admitted more than 4 days from symptom onset tended to have more severe lung involvement. Spearman correlation analysis showed the close association between CT severity score and inflammatory indexes (r = 0.17~0.47, all P < 0.05). Conclusion: CT severity score was associated with inflammatory levels and higher NLR and CT severity score on admission were independent risk factors for short-term progression in patients with NCP outside Wuhan. Furthermore, early admission and surveillance by CT should be recommended to improve clinical outcomes.", "title": "Early Prediction of Disease Progression in 2019 Novel Coronavirus Pneumonia Patients Outside Wuhan with CT and Clinical Characteristics", "pid": "j0ufth5d", "bm25_score": 216.45599365234375}, {"text": "BACKGROUND: Coronavirus disease‐2019 (COVID‐19) has a deleterious effect on several systems, including the cardiovascular system. We aim to systematically explore the association of COVID‐19 severity and mortality rate with the history of cardiovascular diseases and/or other comorbidities and cardiac injury laboratory markers. METHODS: The standardized mean difference (SMD) or odds ratio (OR) and 95% confidence intervals (CI) were applied to estimate pooled results from the 56 studies. The prognostic performance of cardiac markers for predicting adverse outcomes and to select the best cutoff threshold was estimated by ROC curve analysis. Decision tree analysis by combining cardiac markers with demographic and clinical features was applied to predict mortality and severity in COVID‐19 patients. RESULTS: A meta‐analysis of 17,794 patients showed patients with high cardiac troponin I (OR=5.22, 95%CI=3.73‐7.31, p<0.001) and AST levels (OR=3.64, 95%CI=2.84‐4.66, p<0.001) were more likely to develop adverse outcomes. High troponin I >13.75 ng/L combined with either advanced age >60 years or elevated AST level >27.72 U/L was the best model to predict poor outcomes. CONCLUSIONS: COVID‐19 severity and mortality are complicated by myocardial injury. Assessment of cardiac injury biomarkers may improve the identification of those patients at the highest risk and potentially lead to improved therapeutic approaches. This article is protected by copyright. All rights reserved.", "title": "Association of cardiac biomarkers and comorbidities with increased mortality, severity, and cardiac injury in COVID‐19 patients: A meta‐regression and Decision tree analysis", "pid": "g9qlo3xh", "bm25_score": 216.44351196289062}]}
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"zpb9jicw": 2, "zph6r4il": 2, "zr19c351": 0, "zrr958yx": 0, "zrx8l9d7": 0, "j48ajsfx": 0, "ztcij4wb": 0, "v0v0ahjh": 2, "zv45usvu": 2, "zwqycuw4": 2, "zz4cczuj": 0, "zz6ur1tn": 2, "zzfjnhgo": 0}, "bm25_results": [{"text": "Information about the clinical presentation and course of COVID-19 is rapidly evolving. Data are emerging from retrospective clinical studies conducted in Wuhan, China, showing the symptoms and characteristics of COVID-19 caused by severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infection, including fever, cough, and shortness of breath. Radiographic data on COVID-19 cases reveal bilateral opacities on chest radiography and ground-glass opacities on computed tomography. Data on laboratory markers and mortality and morbidity are also emerging.", "title": "Clinical presentation and course of COVID-19.", "pid": "g4luqtjv", "bm25_score": 214.54635620117188}, {"text": "Recently, some global cases of 2019 novel coronavirus (COVID-19) pneumonia have been caused by second- or third-generation transmission of the viral infection, resulting in no traceable epidemiological history. Owing to the complications of COVID-19 pneumonia, the first symptom and imaging features of patients can be very atypical and early diagnosis of COVID-19 infections remains a challenge. It would aid radiologists and clinicians to be aware of the early atypical symptom and imaging features of the disease and contribute to the prevention of infected patients being missed.", "title": "2019 Novel Coronavirus (COVID-19) Pneumonia with Hemoptysis as the Initial Symptom: CT and Clinical Features", "pid": "i34j6mzv", "bm25_score": 214.47714233398438}, {"text": "We report here the case of a 27-year-old man who consulted by telemedicine during the Coronavirus disease 2019 (COVID-19) pandemic, due to foreign body sensation and left eye redness. Examination revealed unilateral eyelid edema and moderate conjunctival hyperemia. A few hours later, the patient experienced intense headache and developed fever, cough and severe dyspnea. A nasopharyngeal swab proved positive for SARS-CoV-2. This case demonstrates that conjunctivitis can be the inaugural manifestation of the COVID-19 infection. It illustrates the interest of telemedicine in ophthalmology during the COVID-19 pandemic, since moderate conjunctival hyperemia can be the first sign of a severe respiratory distress.", "title": "Ocular manifestation as first sign of Coronavirus Disease 2019 (COVID-19): Interest of telemedicine during the pandemic context", "pid": "bfeq9i1m", "bm25_score": 214.28375244140625}, {"text": "Abstract We report here the case of a 27-year-old man who consulted by telemedicine during the Coronavirus Disease 2019 (COVID-19) pandemic, due to foreign body sensation and left eye redness. Examination revealed unilateral eyelid edema and moderate conjunctival hyperemia. A few hours later the patient experienced intense headache and developed fever, cough and severe dyspnea. A nasopharyngeal swab proved positive for SARS-CoV-2. This case demonstrates that conjunctivitis can be the inaugural manifestation of the COVID-19 infection. It illustrates the interest of telemedicine in ophthalmology during the COVID-19 pandemic, since moderate conjunctival hyperemia can be the first sign of a severe respiratory distress.", "title": "Ocular manifestation as first sign of Coronavirus Disease 2019 (COVID-19): interest of telemedicine during the pandemic context", "pid": "urrroc3k", "bm25_score": 214.22705078125}, {"text": "According to WHO recommendations, everyone must protect themselves against Coronavirus disease 2019 (COVID-19), which will also protect others. Due to the lack of current effective treatment and vaccine for COVID-19, screening, rapid diagnosis and isolation of the patients are essential (1, 2). Therefore, identifying the early symptoms of COVID-19 is of particular importance and is a health system priority. Early studies from COVID-19 outbreak in China have illustrated several non-specific signs and symptoms in infected patients, including fever, dry cough, dyspnea, myalgia, fatigue, lymphopenia, and radiographic evidence of pneumonia (3, 4). Recently, a probability of association between COVID-19 and altered olfactory function has been reported in South Korea, Iran, Italy, France, UK and the United States (5-8). However, to our knowledge, the definite association between COVID-19 and anosmia has not been published.", "title": "Anosmia as a prominent symptom of COVID-19 infection.", "pid": "k23iyivp", "bm25_score": 214.2207489013672}, {"text": "According to WHO recommendations, everyone must protect themselves against Coronavirus disease 2019 (COVID-19), which will also protect others. Due to the lack of current effective treatment and vaccine for COVID-19, screening, rapid diagnosis and isolation of the patients are essential (1, 2). Therefore, identifying the early symptoms of COVID-19 is of particular importance and is a health system priority. Early studies from COVID-19 outbreak in China have illustrated several non-specific signs and symptoms in infected patients, including fever, dry cough, dyspnea, myalgia, fatigue, lymphopenia, and radiographic evidence of pneumonia (3, 4). Recently, a probability of association between COVID-19 and altered olfactory function has been reported in South Korea, Iran, Italy, France, UK and the United States (5-8). However, to our knowledge, the definite association between COVID-19 and anosmia has not been published.", "title": "Anosmia as a prominent symptom of COVID-19 infection", "pid": "ils991dx", "bm25_score": 214.18475341796875}, {"text": "", "title": "Clinical features of covid-19.", "pid": "4mvsbl1b", "bm25_score": 214.10598754882812}, {"text": "COVID-19 is the disease caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first arose in Wuhan, China, in December 2019 and has since been declared a pandemic. The clinical sequelae vary from mild, self-limiting upper respiratory infection symptoms to severe respiratory distress, acute cardiopulmonary arrest and death. Otolaryngologists around the globe have reported a significant number of mild or otherwise asymptomatic patients with COVID-19 presenting with olfactory dysfunction. We present a case of COVID-19 resulting in intensive care unit (ICU) admission, presenting with the initial symptom of disrupted taste and flavour perception prior to respiratory involvement. After 4 days in the ICU and 6 days on the general medicine floor, our patient regained a majority of her sense of smell and was discharged with only lingering dysgeusia. In this paper, we review existing literature and the clinical course of SARS-CoV-2 in relation to the reported symptoms of hyposmia, hypogeusia and dysgeusia.", "title": "Hypogeusia as the initial presenting symptom of COVID-19", "pid": "z5u32l0w", "bm25_score": 214.10484313964844}, {"text": "Since the coronavirus disease 2019 (COVID 19) outbreak was first reported in the Chinese city of Wuhan on December 31, 2019, it has stricken more than 1,000,000 persons worldwide, of whom over 50,000 have died (1). Having been infected by severe acute respiratory syndrome coronavirus 2 (SARS-COV-2), patients with COVID-19 mainly present with fever and respiratory symptoms (2). Isolated sudden onset anosmia has also frequently been reported (3). Less frequently, rhinorrhea, diarrhoea and dysgeusia may be associated. While only a few reports have evoked cutaneous manifestations (4), we read with interest an initial study on the topic entitled \"Cutaneous manifestations in COVID-19: a first perspective \" by Recalcati S. (5).", "title": "Comment on \"Cutaneous manifestations in COVID-19: a first perspective \" by Recalcati S", "pid": "5c3t4znm", "bm25_score": 214.0946502685547}, {"text": "Information about the clinical presentation and course of COVID-19 is evolving rapidly. On presentation, cough and fever predominate, but extrapulmonary symptoms are also common; in some patients, loss of sense of smell may be an early but favorable sign. The mortality rate varies widely in different reports but should become clearer as more data are collected. Risk factors for severe disease and death include comorbid conditions such as hypertension, cardiovascular disease, diabetes mellitus, and chronic obstructive pulmonary disease. Other implicated factors include older age, obesity, end-stage renal disease, and a higher neutrophil-lymphocyte ratio.", "title": "Clinical presentation and course of COVID-19", "pid": "1gp58zxg", "bm25_score": 214.0827178955078}, {"text": "COVID‐19 (Coronavirus Disease 2019) is a fatal disease that could lead to a serious respiratory illness. It is caused by SARS‐CoV‐2 virus. In December 2019, the first of human cases were identified in China and the infection spread quickly around the world. The World Health Organisation (WHO) declared the disease, a global pandemic on 11 March 2020, even as COVID‐19 rapidly spread across the world. According to clinical reports, fever, headache, cough and myalgia are common clinical symptoms. Many symptoms also occur, such as sputum formation, haemoptysis and diarrhea.", "title": "New emerging dermatological symptoms in coronavirus pandemic", "pid": "46njnlct", "bm25_score": 214.07289123535156}, {"text": "", "title": "Gastrointestinal symptoms as the first, atypical indication of SARS-CoV-2 infection.", "pid": "17ugnbd0", "bm25_score": 214.03448486328125}, {"text": "Since December 2019, multiple cases of 2019 coronavirus disease (COVID-19) have been reported in Wuhan in China's Hubei Province, a disease which has subsequently spread rapidly across the entire country. Highly infectious, COVID-19 has numerous transmission channels and humans are highly susceptible to infection. The main clinical symptoms of COVID-19 are fever, fatigue, and a dry cough. Laboratory examination in the early stage of the disease shows a normal or decreased white blood cell count, and a decreased lymphocyte count. While CT examination serves as the screening and diagnostic basis for COVID-19, its accuracy is limited. The nucleic acid testing is the gold standard for the diagnosis of COVID-19, but has a low sensitivity is low. There is clearly a divide between the two means of examination. This paper reviews the published literature, guidelines and consensus, and summarizes the clinical and imaging characteristics of COVID-19, in order to provide a reliable basis for early diagnosis and treatment.", "title": "Clinical and imaging features of COVID-19", "pid": "9k0741ct", "bm25_score": 214.02684020996094}, {"text": "A woman with acute abdominal pain was admitted to hospital with suspected cholecystitis. In addition to abdominal pain, she had vomiting, loss of appetite, diarrhoea and symptoms of pyrexia. She had no symptoms from the respiratory tract, but was later found to have COVID-19. A number of patients have presented with similar symptoms at our hospital. This has led to temporary changes in our procedures for handling and investigating patients with acute abdominal pain.", "title": "Acute abdomen as an early symptom of COVID-19.", "pid": "y7iwmw3c", "bm25_score": 214.01197814941406}, {"text": "Coronavirus 19 (COVID-19) was declared as a pandemic viral infection by the World Health organization on March 11th 2020. Usual clinical manifestations of COVID-19 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). Skin symptoms of COVID-19 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2-7). Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for COVID-19.", "title": "Vascular skin symptoms in COVID-19: a french observational study", "pid": "vp5xj8m5", "bm25_score": 214.00465393066406}, {"text": "The novel coronavirus (SARS-CoV2) has led to an outbreak of multiple cases of pneumonia in Wuhan city in December 2019. The disease caused by this virus was named coronavirus disease 2019 or \"COVID-19\", which was declared by the World Health Organization as a global pandemic in March 2020. It typically presents with respiratory symptoms and febrile illness. However, there are few reported extrapulmonary and atypical presentations, such as hemoptysis, cardiac, neurological, gastrointestinal, ocular, and cutaneous manifestations, as well as venous and arterial thrombosis. Lack of awareness of these presentations might lead to misdiagnosis, delayed diagnosis, and isolation of suspected patients which increases the risk of transmission of infection between patients and doctors. All these issues will be discussed in this review.", "title": "Extrapulmonary and atypical clinical presentations of COVID-19", "pid": "1cwdgwgw", "bm25_score": 213.9685516357422}, {"text": "Abstract Since December 2019, multiple cases of 2019 coronavirus disease (COVID-19) have been reported in Wuhan in China's Hubei Province, a disease which has subsequently spread rapidly across the entire country. Highly infectious, COVID-19 has numerous transmission channels and humans are highly susceptible to infection. The main clinical symptoms of COVID-19 are fever, fatigue, and a dry cough. Laboratory examination in the early stage of the disease shows a normal or decreased white blood cell count, and a decreased lymphocyte count. While CT examination serves as the screening and diagnostic basis for COVID-19, its accuracy is limited. The nucleic acid testing is the gold standard for the diagnosis of COVID-19, but has a low sensitivity is low. There is clearly a divide between the two means of examination. This paper reviews the published literature, guidelines and consensus, and summarizes the clinical and imaging characteristics of COVID-19, in order to provide a reliable basis for early diagnosis and treatment.", "title": "Clinical and imaging features of COVID-19", "pid": "wap7lo05", "bm25_score": 213.95294189453125}, {"text": "", "title": "Gastrointestinal symptoms as the first, atypical indication of severe acute respiratory syndrome coronavirus 2 infection", "pid": "1ihqelui", "bm25_score": 213.93858337402344}, {"text": "COVID-2019 emerged from China in late December. It follows two other coronavirus outbreaks, the SARS-CoV and the MERS-CoV. Coronaviruses usually circulate among animals but sometimes can jump to humans. These three strains have caused severe disease in humans and global transmission concerns. Symptoms of COVID-2019 include cough, fever, and shortness of breath. Related illnesses can range from mild to severe to fatal. Primary care providers must be alert to respiratory symptoms they encounter that are associated with pertinent travel history, be prepared to safely screen, examine and possibly test and/or report suspicions to the health department for further evaluation.", "title": "Coronavirus 101", "pid": "9zetheol", "bm25_score": 213.93765258789062}, {"text": "Since Dec 2019, a cluster of pneumonia outbreak in Wuhan, Hubei province, China, and soon spread to all province of China. The pathogen was proved to be a novel betacoronavirus called 2019 novel coronavirus (officially named by the World Health Organization as COVID-19). The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Less common symptoms included headache, diarrhea, nausea and vomiting. However diarrhea as the first symptom is rarely reported. Here we reported a case of 2019 novel coronavirus-infected patient (NCIP) with diarrhea as the initial symptom. Image of CT scan and laboratory examination and careful collected as well as detection of viral RNA in pharynx. The case demonstrate that gastrointestinal symptoms ware not rare in NCIP, and diarrhea could be the initial symptom.", "title": "A case of COVID-19 patient with the diarrhea as initial symptom and literature review", "pid": "0ylislv9", "bm25_score": 213.9312286376953}, {"text": "Recently, COVID-19 has spread in more than 100 countries and regions around the world, raising grave global concerns. COVID-19 transmits mainly through respiratory droplets and close contacts, causing cluster infections. The symptoms are dominantly fever, fatigue, and dry cough, and can be complicated with tiredness, sore throat, and headache. A few patients have symptoms such as stuffy nose, runny nose, and diarrhea. The severe disease can progress rapidly into the acute respiratory distress syndrome (ARDS). Reverse transcription polymerase chain reaction (RT-PCR) and Next-generation sequencing (NGS) are the gold standard for diagnosing COVID-19. Chest imaging is used for cross validation. Chest CT is highly recommended as the preferred imaging diagnosis method for COVID-19 due to its high density and high spatial resolution. The common CT manifestation of COVID-19 includes multiple segmental ground glass opacities (GGOs) distributed dominantly in extrapulmonary/subpleural zones and along bronchovascular bundles with crazy paving sign and interlobular septal thickening and consolidation. Pleural effusion or mediastinal lymphadenopathy is rarely seen. In CT imaging, COVID-19 manifests differently in its various stages including the early stage, the progression (consolidation) stage, and the absorption stage. In its early stage, it manifests as scattered flaky GGOs in various sizes, dominated by peripheral pulmonary zone/subpleural distributions. In the progression state, GGOs increase in number and/or size, and lung consolidations may become visible. The main manifestation in the absorption stage is interstitial change of both lungs, such as fibrous cords and reticular opacities. Differentiation between COVID-19 pneumonia and other viral pneumonias are also analyzed. Thus, CT examination can help reduce false negatives of nucleic acid tests.", "title": "Clinical and radiological features of novel coronavirus pneumonia", "pid": "8nnc5qkq", "bm25_score": 213.89637756347656}, {"text": "BACKGROUND: The corona pandemic is currently the greatest challenge for health systems of all countries worldwide. The timely detection of the disease and the immediate separation and isolation of suspected cases make a significant contribution to breaking the chain of infection. METHODS: Based on the first 35 patients admitted to the hospital with COVID-19, we evaluated the various symptoms with which patients presented. RESULTS: The majority of patients have respiratory symptoms (e.g., cough and reduced peripheral oxygen saturation) and fever. In individual patients, however, there may only be other symptoms, e.g., gastrointestinal, neurological, or nonspecific symptoms.", "title": "COVID-19 in der zentralen Notaufnahme: Übersicht über die klinische Präsentation der ersten 35 Patienten in der Frühphase der Pandemie", "pid": "pe7as1qp", "bm25_score": 213.89454650878906}, {"text": "The novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19). The pandemic condition was declared by the WHO on March 11, 2020. The main clinical symptoms are fever, dry cough and dyspnea, although new symptoms are emerging, such as diarrhea, anosmia and ageusia. The virus enters cells, likely including those lining blood vessels, by binding to angiotensin converting enzyme 2 (ACE2) receptors on the cell surface. Infection can also promote blood clots, heart attacks and cardiac inflammation.", "title": "The red half‐moon nail sign: a novel manifestation of coronavirus infection", "pid": "1trid65d", "bm25_score": 213.89212036132812}, {"text": "Summary Since Dec 2019, a cluster of pneumonia outbreak in Wuhan, Hubei province, China, and soon spread to all province of China. The pathogen was proved to be a novel betacoronavirus called 2019 novel coronavirus (officially named by the World Health Organization as COVID-19). The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Less common symptoms included headache, diarrhea, nausea and vomiting. However diarrhea as the first symptom is rarely reported. Here we reported a case of 2019 novel coronavirus-infected patient (NCIP) with diarrhea as the initial symptom. Image of CT scan and laboratory examination and careful collected as well as detection of viral RNA in pharynx. The case demonstrate that gastrointestinal symptoms ware not rare in NCIP, and diarrhea could be the initial symptom.", "title": "A case of COVID-19 patient with the diarrhea as initial symptom and literature review", "pid": "1aqtqaod", "bm25_score": 213.8536376953125}, {"text": "COVID-2019 emerged from China in late December of 2019. It follows 2 other coronavirus outbreaks, the SARS-CoV and the MERS-CoV. Coronaviruses usually circulate among animals but sometimes can jump to humans. These 3 strains have caused severe disease in humans and global transmission concerns. Symptoms of COVID-2019 include cough, fever, and shortness of breath. Related illnesses can range from mild to severe to fatal. Primary care providers must be alert to respiratory symptoms they encounter that are associated with pertinent travel history, be prepared to safely screen, examine, and possibly test and/or report suspicions to the health department for further evaluation.", "title": "Corona Virus 101", "pid": "4nho5wa0", "bm25_score": 213.8422393798828}, {"text": "Recently, COVID-19 has spread in more than 100 countries and regions around the world, raising grave global concerns. COVID-19 transmits mainly through respiratory droplets and close contacts, causing cluster infections. The symptoms are dominantly fever, fatigue, and dry cough, and can be complicated with tiredness, sore throat, and headache. A few of patients have symptoms such as stuffy nose, runny nose, and diarrhea. The severe disease can progress rapidly into the acute respiratory distress syndrome (ARDS). Reverse transcription polymerase chain reaction (RT-PCR) and Next-generation sequencing (NGS) are the gold standard for diagnosing COVID-19. Chest imaging is used for cross validation. Chest CT is highly recommended as the preferred imaging diagnosis method for COVID-19 due to its high density and high spatial resolution. The common CT manifestation of COVID-19 includes multiple segmental ground glass opacities (GGOs) distributed dominantly in extrapulmonary/subpleural zones and along bronchovascular bundles with crazy paving sign and interlobular septal thickening and consolidation. Pleural effusion or mediastinal lymphadenopathy is rarely seen. In CT imaging, COVID-19 manifests differently in its various stages including the early stage, the progression (consolidation), and the absorption. In its early stage, it manifests as scattered flaky GGOs in various sizes, dominated by peripheral pulmonary zone/subpleural distributions. In the progression state, GGOs increase in number and/or size, and lung consolidations may become visible. The main manifestation in the absorption stage is interstitial change of both lungs, such as fibrous cords and reticular opacities. Differentiation between COVID-19 pneumonia and other viral pneumonias are also analyzed. Thus, CT examination can help reduce false negatives of nucleic acid tests.", "title": "Clinical and radiological features of novel coronavirus pneumonia.", "pid": "jlyy9z4t", "bm25_score": 213.8340301513672}, {"text": "In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, \"crazy-paving\" pattern and the \"reverse halo\" sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).", "title": "Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection", "pid": "85z0eeic", "bm25_score": 213.8328857421875}, {"text": "OBJECTIVES: To systematically analyze CT findings during the early and progressive stages of natural course of coronavirus disease 2019 and also to explore possible changes in pulmonary parenchymal abnormalities during these two stages. METHODS: We retrospectively reviewed the initial chest CT data of 62 confirmed coronavirus disease 2019 patients (34 men, 28 women; age range 20–91 years old) who did not receive any antiviral treatment between January 21 and February 4, 2020, in Chongqing, China. Patients were assigned to the early-stage group (onset of symptoms within 4 days) or progressive-stage group (onset of symptoms within 4–7 days) for analysis. CT characteristics and the distribution, size, and CT score of pulmonary parenchymal abnormalities were assessed. RESULTS: In our study, the major characteristic of coronavirus disease 2019 was ground-glass opacity (61.3%), followed by ground-glass opacity with consolidation (35.5%), rounded opacities (25.8%), a crazy-paving pattern (25.8%), and an air bronchogram (22.6%). No patient presented cavitation, a reticular pattern, or bronchial wall thickening. The CT scores of the progressive-stage group were significantly greater than those of the early-stage group (p = 0.004). CONCLUSIONS: Multiple ground-glass opacities with consolidations in the periphery of the lungs were the primary CT characteristic of coronavirus disease 2019. CT score can be used to evaluate the severity of the disease. If these typical alterations are found, then the differential diagnosis of coronavirus disease 2019 must be considered. KEY POINTS: • Multiple GGOs with consolidations in the periphery of the lungs were the primary CT characteristic of COVID-19. • The halo sign may be a special CT feature in the early-stage COVID-19 patients. • Significantly increased CT score may indicate the aggravation of COVID-19 in the progressive stage.", "title": "Coronavirus disease 2019: initial chest CT findings", "pid": "zlzuoeh2", "bm25_score": 213.8261260986328}, {"text": "Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2), is an ongoing pandemic that has already affected millions of patients worldwide, and is associated with significant morbidity and mortality burden. Although the clinical and laboratory characteristics of this illness have been reported in patients from China and Europe, data are scant in the United States. Methods We extracted data regarding all patients hospitalized at our hospital with COVID-19 infection between March 1 and April 4, 2020. Presenting signs and symptoms, laboratory and imaging findings, treatment, and complications were recorded from electronic medical records (EMRs). The primary composite endpoint was admission to intensive care unit (ICU), shock, or death. Results We had a total of 43 patients tested for COVID-19 at the emergency room (ER) or during hospitalization, 16 (37%) of whom were admitted with COVID-19 infection. The mean age was 65.5 years and 75% were males. The most common presenting symptoms were fever (94%), cough (88%), and dyspnea (81%). A loss of smell and taste sensations were reported by three (19%) patients. Low oxygen saturation was present in 38% of patients, whilst 31% were hypotensive on admission. Hyponatremia (50%), elevated C-reactive protein (CRP; 100%), and lactate dehydrogenase (LDH; 80%) were common. Acute renal failure, myocardial injury, and elevation in aminotransferases occurred in 69%, 19%, and 38% patients, respectively. The primary composite endpoint occurred in 50% of patients. A total of three patients died; all were aged 70 years or older. Conclusions Laboratory abnormalities and acute renal failure were common in hospitalized patients with SARS-CoV2 infection in our center. Admission to ICU and mechanical ventilation were common.", "title": "Clinical features, laboratory characteristics, and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19): Early report from the United States", "pid": "byq9xghc", "bm25_score": 213.8141632080078}, {"text": "", "title": "Coronavirus disease 2019 presenting with conjunctivitis as the first symptom", "pid": "9c38uqr9", "bm25_score": 213.81304931640625}, {"text": "The Centers for Disease Control and Prevention (CDC) suggest several possible symptoms associated with coronavirus disease 2019 (COVID-19), including cough, shortness of breath (SOB), fever, chills, muscle pain, sore throats, new loss of taste or smell, nausea, vomiting, or diarrhea. (\"Centers for Disease Control and Prevention. Symptoms of Coronavirus.,\") The clinical characteristics from the study by Yu et al. published in Transboundary and Emerging Diseases and other Chinese studies were different from those we observe in the United States.", "title": "Differences in Clinical Characteristics of Covid-19 in Hispanic/Latino Population.", "pid": "03z3wk6i", "bm25_score": 213.80038452148438}, {"text": "BACKGROUND: In December 2019 the coronavirus disease of 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, was identified in Wuhan, China. In the ensuing months, the COVID-19 pandemic has spread globally and case load is exponentially increasing across the United States. Emergency departments have adopted screening and triage procedures to identify potential cases and isolate them during evaluation. CASE PRESENTATION: We describe a case of COVID-19 pneumonia requiring hospitalization that presented with fever and extensive rash as the primary presenting symptoms. Rash has only been rarely reported in COVID-19 patients, and has not been previously described.", "title": "A Case of COVID-19 Pneumonia in a Young Male with Full Body Rash as a Presenting Symptom", "pid": "h6qukrak", "bm25_score": 213.78671264648438}, {"text": "Coronavirus infection is a transmissible disease. It was first described in China in December, 2019. It has been said to have a person-to-person transmission after prolonged and unprotected exposure. Patients with a potential SARS-CoV-2 exposure present with symptoms of low-grade pyrexia, dry cough, or shortness of breath. People with these symptoms should contact health-care providers before seeking medical intervention so that appropriate preventive actions may be implemented. Health-care facilities should rapidly isolate suspected individuals and notify local health departments for support involved in performing laboratory tests and efforts in containment. The present article describes the nature of virus, method of detection, and its mode of transmission.", "title": "Coronavirus: An emergency for healthcare professionals", "pid": "yxmkaqo8", "bm25_score": 213.7803192138672}, {"text": "", "title": "Hemoptysis as an Initial Presentation of COVID-19 - An Observation.", "pid": "csvqmwvq", "bm25_score": 213.77708435058594}, {"text": "Background Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV2), is an ongoing pandemic that has already affected millions of patients worldwide, and is associated with significant morbidity and mortality burden. Although the clinical and laboratory characteristics of this illness have been reported in patients from China and Europe, data are scant in the United States. Methods We extracted data regarding all patients hospitalized at our hospital with COVID-19 infection between March 1 and April 4, 2020. Presenting signs and symptoms, laboratory and imaging findings, treatment, and complications were recorded from electronic medical records (EMRs). The primary composite endpoint was admission to intensive care unit (ICU), shock, or death. Results We had a total of 43 patients tested for COVID-19 at the emergency room (ER) or during hospitalization, 16 (37%) of whom were admitted with COVID-19 infection. The mean age was 65.5 years and 75% were males. The most common presenting symptoms were fever (94%), cough (88%), and dyspnea (81%). A loss of smell and taste sensations were reported by three (19%) patients. Low oxygen saturation was present in 38% of patients, whilst 31% were hypotensive on admission. Hyponatremia (50%), elevated C-reactive protein (CRP; 100%), and lactate dehydrogenase (LDH; 80%) were common. Acute renal failure, myocardial injury, and elevation in aminotransferases occurred in 69%, 19%, and 38% patients, respectively. The primary composite endpoint occurred in 50% of patients. A total of three patients died; all were aged 70 years or older. Conclusions Laboratory abnormalities and acute renal failure were common in hospitalized patients with SARS-CoV2 infection in our center. Admission to ICU and mechanical ventilation were common.", "title": "Clinical features, laboratory characteristics, and outcomes of patients hospitalized with coronavirus disease 2019 (COVID-19): Early report from the United States.", "pid": "ifamg1ix", "bm25_score": 213.76953125}, {"text": "In this retrospective study, chest CTs of 121 symptomatic patients infected with coronavirus disease-19 (COVID-19) from four centers in China from January 18, 2020 to February 2, 2020 were reviewed for common CT findings in relationship to the time between symptom onset and the initial CT scan (i.e. early, 0-2 days (36 patients), intermediate 3-5 days (33 patients), late 6-12 days (25 patients)). The hallmarks of COVID-19 infection on imaging were bilateral and peripheral ground-glass and consolidative pulmonary opacities. Notably, 20/36 (56%) of early patients had a normal CT. With a longer time after the onset of symptoms, CT findings were more frequent, including consolidation, bilateral and peripheral disease, greater total lung involvement, linear opacities, “crazy-paving” pattern and the “reverse halo” sign. Bilateral lung involvement was observed in 10/36 early patients (28%), 25/33 intermediate patients (76%), and 22/25 late patients (88%).", "title": "Chest CT Findings in Coronavirus Disease-19 (COVID-19): Relationship to Duration of Infection", "pid": "497z31h6", "bm25_score": 213.7577362060547}, {"text": "Abstract During novel coronavirus 2019 (COVID-19) pandemic, patients usually present with several reports showing symptoms of severe systemic or respiratory illness and, although rare, some genital complaints such as scrotal discomfort can be seen. In the majority of patients, however, genital complaints seem not to be the initial or sole symptoms. In this article, we report an unusual presentation of a male case with severe external genital pain which was suspected to be the first clinical sign of COVID-19.", "title": "Atypical presentation of SARS-CoV-2 infection in male genitalia", "pid": "2n4uqomp", "bm25_score": 213.75733947753906}, {"text": "In late 2019, cases of atypical pneumonia caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were first reported in Wuhan, China. The disease was officially called coronavirus disease 2019 (COVID-19) and has been declared a pandemic disease by the World Health Organization (WHO). The clinical symptoms may include fever, cough, fatigue, headache, and diarrhea. The radiographic features comprise various presentations, including ground-glass opacities, tiny nodules, and consolidation. However, some atypical pathogens related to community-acquired pneumonia (CAP) may share similar presentations. They may be difficult to distinguish according to the clinical presentation and radiographic findings. Recently, there have been several reports reminding physicians to heed the possibility of co-infection with other pathogens in patients diagnosed with COVID-19. We report a COVID-19 patient co-infected with Mycoplasma pneumoniae who recovered well after combination therapy. We propose that all COVID-19 patients should undergo a meticulous screening routine to ensure that they receive adequate treatments.", "title": "Concomitant Infection with COVID-19 and Mycoplasma Pneumoniae", "pid": "rs0y48ob", "bm25_score": 213.74696350097656}, {"text": "A new pathogenic virus, COVID-19, appeared in 2019, in Wuhan, China, typically causing fever, cough, diarrhea and fatigue and significant mortality (Mao, 2020). From mid-January to mid-February in 2020, 214 patients with both non-severe and severe COVID-19 infections confirmed by nucleic acid tests, were examined by a panel of neurologists. Seventy-eight patients (36.4%) displayed neurological symptoms, including central nervous system symptoms of dizziness, headache, impaired consciousness, acute cerebrovascular disease with either ischemic stroke or cerebral hemorrhage, ataxia, seizures; peripheral nervous system symptoms of taste impairment, smell impairment, vision impairment, and nerve pain; and skeletal muscle injury (Mao, 2020).", "title": "Explanation for COVID‐19 infection neurological damage and reactivations", "pid": "s3wo3ten", "bm25_score": 213.7220916748047}, {"text": "", "title": "SARS-CoV-2-Induced Vomiting as Onset Symptom in a Patient with COVID-19", "pid": "dycq2m3b", "bm25_score": 213.71902465820312}, {"text": "Background: Preventing communicable diseases requires understanding the spread, epidemiology, clinical features, progression, and prognosis of the disease. Early identification of risk factors and clinical outcomes might help to identify critically ill patients, provide proper treatment and prevent mortality. Methods: We conducted a prospective study in patients with flu-like symptoms referred to the imaging department of a tertiary hospital in IRAN between 3 March 2020 and 8 April 2020. Patients with COVID-19 were followed up to check their health condition after two months. The categorical data between groups were analyzed by Fisher exact test and continuous data by Wilcoxon Rank-Sum Test. Findings: 319 patients (mean age 45.48 years, 177 women) were enrolled. Fever, dyspnea, weakness, shivering, C-reactive protein (CRP), fatigue, dry cough, anorexia, anosmia, ageusia, dizziness, sweating and age were the most important symptoms of COVID-19 infection. Traveling in past three months, asthma, taking corticosteroids, liver disease, rheumatological disease, cough with sputum, eczema, conjunctivitis, tobacco use, and chest pain did not have any relationship with COVID-19. Interpretation: Finding clinical symptoms for early diagnosis of COVID-19 is a critical part of prevention. These symptoms can help in the assessment of disease progression. To the best of our knowledge, some of the effective features on the mortality due to COVID-19 are investigated for the first time in this research. Funding: None", "title": "Risk Factors Prediction, Clinical Outcomes, and Mortality of COVID-19 Patients", "pid": "fntwg3g8", "bm25_score": 213.71702575683594}, {"text": "Abstract Purpose To analyse the high-resolution computed tomography (HRCT) early imaging features and the changing trend of coronavirus disease 2019 (COVID-19) pneumonia. Materials and Methods Forty-six patients with COVID-19 pneumonia who had an isolated lesion on the first positive CT were enrolled in this study. The following parameters were recorded for each lesion: sites, sizes, location (peripheral or central), attenuation (ground-glass opacity or consolidation), and other abnormalities (supply pulmonary artery dilation, air bronchogram, interstitial thickening, etc.). The follow-up CT images were compared with the previous CT scans, and the development of the lesions was evaluated. Results The lesions tended to be peripheral and subpleural. All the lesions exhibited ground-glass opacity with or without consolidation. A higher proportion of supply pulmonary artery dilation (89.13% [41/46]) and air bronchogram (69.57% [32/46]) were found. Other findings included thickening of the intralobular interstitium and a halo sign of ground glass around a solid nodule. Cavitation, calcification or lymphadelopathy were not observed. The reticular patterns were noted from the 14 days after symptoms onset in 7 of 20 patients (45%). At 22-31 days, the lesions were completely absorbed only in 2 of 7 patients(28.57%). Conclusion The typical early CT features of COVID-19 pneumonia are ground-glass opacity, and located peripheral or subpleural location, and with supply pulmonary artery dilation. Reticulation was evident after the 2nd week and persisted in half of patients evaluated in 4 weeks after the onset. Long-term follow-up is required to determine whether the reticulation represents irreversible fibrosis.", "title": "Early CT features and temporal lung changes in COVID-19 pneumonia in Wuhan, China", "pid": "0soyxeoy", "bm25_score": 213.71441650390625}, {"text": "We report a case series of 6 patients with confirmed coronavirus disease 2019 (COVID-19) in Wakayama prefecture, Japan. All 6 of the patients tested positive via pharyngeal swab polymerase chain reaction (PCR) tests, and 2 of the 6 were still positive at 3 weeks after onset. All of the patients exhibited bilateral ground glass opacities on computed tomography (CT). This article also reports narrative information on the spectrum of symptoms collected directly from the patients. It would be difficult to triage patients with COVID-19 based on the typical symptoms of fever and/or cough, although PCR and CT are definitive in diagnosis.", "title": "Clinical Characteristics of Patients With Coronavirus Disease 2019 in Japan: A Single-Center Case Series", "pid": "m5eple6p", "bm25_score": 213.69642639160156}, {"text": "", "title": "Alteration of Consciousness as Initial Presentation in COVID-19: Observation", "pid": "2g2n4s8c", "bm25_score": 213.6959228515625}, {"text": "Covid-19 is a novel virus with high affinity to spread in the community In December 2019, it was first identified in Wuhan, China The symptoms are non-specific, so fever, cough, dyspnea, are prominent features Respiratory failure and mortality have also been reported The most common lung CT scan findings are bilateral ground glass opacities", "title": "COVID-19: A New Virus as a Potential Rapidly Spreading in the Worldwide", "pid": "0em5sf3g", "bm25_score": 213.69558715820312}, {"text": "Clinical characteristics of COVID-19 disease were identified in a cohort study involving 1099 patients from China. COVID-19 most commonly present with fever, cough, fatigue, and congestion. Two out of 1099 patients were reported to have skin rash, but time of onset and clinical description of rash were missing (Reference B). Another study focused primarily on cutaneous manifestations associated with COVID-19 evaluated 88 patients from Italy. 18 out of the 88 patients developed cutaneous manifestations, but only 8 patients developed skin lesions at onset of disease.", "title": "Two cases of COVID‐19 presenting with a clinical picture resembling chilblains: first report from the Middle East", "pid": "y1ba8ffw", "bm25_score": 213.69224548339844}, {"text": "2019 novel coronavirus disease (COVED-19, previously known as novel coronavirus pneumonia) was first discovered in December 2019 and spread widely in China and all over the world in 2020 The initial symptoms of most patients include fever, cough, and fatigue Dyspnea may occur with the progress of the disease, and acute respiratory distress syndrome may occur in severe cases The CT manifestations of this disease are mainly ground-glass opacity (GGO) in the lung, which may be accompanied by patchy consolidation, and fibrous changes may appear in the lung at the later stage of the disease Combined with typical clinical and imaging findings and positive nucleic acid test results, the disease can be diagnosed We report the first case of novel coronavirus disease (COVED-19) in Heilongjiang Province, China The patient was seriously ill, who felt that he suffered from fever, fatigue, cough, and expectoration and sought medical treatment, with a history of contact with Wuhan The leukocyte count was normal, and the lymphocyte count was decreased CT imaging showed large GGO and partial patchy consolidation in both lungs The patient recovered and was discharged after 26 days of treatment This study is helpful for early diagnosis and timely clinical management by mastering the typical imaging of novel coronavirus disease (COVED-19)", "title": "CT findings of severe novel coronavirus disease (COVID-19): A case report of Heilongjiang Province, China", "pid": "x2z68b45", "bm25_score": 213.69134521484375}, {"text": "In December 2019, the outbreak of novel coronavirus (2019-nCoV) in Wuhan, China, attracting attention worldwidely. The novel coronavirus has the characteristics of rapid transmission, atypical clinical symptoms, and easy to affect both lungs, leading to missed diagnosis and misdiagnosis, as well as difficult to detection and assessment at early stage. Fever, cough, myalgia, weakness, dyspnea and imagings may be helpful for the early detection of novel coronavirus pneumonia. At the same time, the rate of disease progression, fever, CT manifestations, hypoxia degree, age, basic diseases, and laboratory indicators can also be used to evaluate the severity of the novel coronavirus pneumonia.", "title": "[Early detection and disease assessment of patients with novel coronavirus pneumonia].", "pid": "ufvlr7mp", "bm25_score": 213.6902618408203}, {"text": "In December 2019, the outbreak of novel coronavirus (2019- nCoV) in wuhan, China, attracting attention worldwidely. The novel coronavirus has the characteristics of rapid transmission, atypical clinical symptoms, and easy to affect both lungs, leading to missed diagnosis and misdiagnosis, as well as difficult to detection and assessment at early stage. Fever, cough, myalgia, weakness, dyspnea and imagings may be helpful for the early detection of novel coronavirus pneumonia. At the same time, the rate of disease progression, fever, CT manifestations, hypoxia degree, age, basic diseases, and laboratory indicators can also be used to evaluate the severity of the novel coronavirus pneumonia.", "title": "[Early detection and disease assessment of patients with novel coronavirus pneumonia].", "pid": "rzmomxli", "bm25_score": 213.6902618408203}, {"text": "The current outbreak of infections with SARS-CoV-2 is defined as Coronavirus Disease 2019 (COVID-19). The clinical symptoms of COVID-19 include fever, fatigue, cough, breathing difficulty that may lead to respiratory distress; a small population of patients may have diarrhea, nausea or vomiting. The highest infection rate occurs in adults; however, neonates, children, and adolescents can also be infected. As the outbreak continues to spread worldwide, attention has switched toward determinants of clinical manifes- tations and disease severity. The situation surrounding the outbreak is rapidly evolving and the information and recommendations are changing as new information becomes available. This paper summarises the cur- rent findings (April 3,2020) from a systematic literature review on the current knowledge of COVID-19 in adolescents (10-19 years according to the WHO definition) and reports the preliminary epidemiological data stated by the Italian National Institute of Health.", "title": "Coronavirus Disease 2019 (COVID-19) in adolescents: An update on current clinical and diagnostic characteristics", "pid": "9eijle5e", "bm25_score": 213.6866455078125}, {"text": "Since the coronavirus disease 2019 (COVID 19) outbreak was first reported in the Chinese city of Wuhan on December 31, 2019, it has stricken more than 1,000,000 persons worldwide, of whom over 50,000 have died (1). Having been infected by severe acute respiratory syndrome coronavirus 2 (SARS‐COV‐2), patients with COVID‐19 mainly present with fever and respiratory symptoms (2). Isolated sudden onset anosmia has also frequently been reported (3). Less frequently, rhinorrhea, diarrhoea and dysgeusia may be associated. While only a few reports have evoked cutaneous manifestations (4), we read with interest an initial study on the topic entitled “Cutaneous manifestations in COVID‐19: a first perspective ” by Recalcati S. (5).", "title": "Comment on “Cutaneous manifestations in COVID‐19: a first perspective ” by Recalcati S", "pid": "9pn2hvph", "bm25_score": 213.6848907470703}, {"text": "", "title": "Clinical features of covid-19", "pid": "jf8s9nll", "bm25_score": 213.6769256591797}, {"text": "Healthcare workers (n = 803) with mild symptoms were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n = 90 positive) and asked to complete a symptom questionnaire. Anosmia, muscle ache, ocular pain, general malaise, headache, extreme tiredness and fever were associated with positivity. A predictive model based on these symptoms showed moderate discriminative value (sensitivity: 91.2%; specificity: 55.6%). While our models would not justify presumptive SARS-CoV-2 diagnosis without molecular confirmation, it can contribute to targeted screening strategies.", "title": "Strong associations and moderate predictive value of early symptoms for SARS-CoV-2 test positivity among healthcare workers, the Netherlands, March 2020", "pid": "u32huxat", "bm25_score": 213.67233276367188}, {"text": "In early December 2019, the acute respiratory illness began in the Wuhan, China, which quickly spread around the world, that today known as COVID-19. (Sun, Qie, Liu, Ren, & Xi, 2020) Preliminary studies have shown that hospitalized patients have different symptoms, including myalgia, whooping cough, fatigue, and dyspnea and gastrointestinal complains. (Guo et al., 2020; Zhang et al., 2020) In more recent studies, skin manifestations have also been reported in covid-19 patients.", "title": "Oral cavity lesions as a manifestation of the novel virus (COVID-19): a letter-to-editor.", "pid": "ncp2tphr", "bm25_score": 213.66983032226562}, {"text": "OBJECTIVE: To study the clinical characteristics of patients in Zhejiang province, China, infected with the 2019 severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) responsible for coronavirus disease 2019 (covid-2019). DESIGN: Retrospective case series. SETTING: Seven hospitals in Zhejiang province, China. PARTICIPANTS: 62 patients admitted to hospital with laboratory confirmed SARS-Cov-2 infection. Data were collected from 10 January 2020 to 26 January 2020. MAIN OUTCOME MEASURES: Clinical data, collected using a standardised case report form, such as temperature, history of exposure, incubation period. If information was not clear, the working group in Hangzhou contacted the doctor responsible for treating the patient for clarification. RESULTS: Of the 62 patients studied (median age 41 years), only one was admitted to an intensive care unit, and no patients died during the study. According to research, none of the infected patients in Zhejiang province were ever exposed to the Huanan seafood market, the original source of the virus; all studied cases were infected by human to human transmission. The most common symptoms at onset of illness were fever in 48 (77%) patients, cough in 50 (81%), expectoration in 35 (56%), headache in 21 (34%), myalgia or fatigue in 32 (52%), diarrhoea in 3 (8%), and haemoptysis in 2 (3%). Only two patients (3%) developed shortness of breath on admission. The median time from exposure to onset of illness was 4 days (interquartile range 3-5 days), and from onset of symptoms to first hospital admission was 2 (1-4) days. CONCLUSION: As of early February 2020, compared with patients initially infected with SARS-Cov-2 in Wuhan, the symptoms of patients in Zhejiang province are relatively mild.", "title": "Clinical findings in a group of patients infected with the 2019 novel coronavirus (SARS-Cov-2) outside of Wuhan, China: retrospective case series", "pid": "d677ef8l", "bm25_score": 213.66493225097656}, {"text": "Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.", "title": "Clinical Progression of COVID-19 Patient with Extended Incubation Period, Delayed RT-PCR Time-to-positivity, and Potential Role of Chest CT-scan", "pid": "3njzz1yi", "bm25_score": 213.66004943847656}, {"text": "Background With the emergence of 4rd generation transmission, the prevention and treatment of the novel coronavirus disease 2019 (COVID-19) has entered a new period. We aimed to report several changes in the clinical characteristics at admission of patients with COVID-19. Methods Clinical records and laboratory results of patients suffering from COVID-19 were retrospectively reviewed and matched with the admission dates to analyze the changes in characteristics at the onset of illness. Results Of the 89 affected patients, 31 [34.8%] patients were admitted from January 16 to 22, and 58 [65.2%] were admitted from January 23 to 29. Patients were admitted with more systemic symptoms, such as fever (21 [67.7%] of 31), fatigue (13 [41.9%] of 31), and myalgia (7 [22.6%] of 31), before January 23. More patients (10 [32.3%] of 31) admitted before January 23 had a small amount of sputum production compared with a smaller proportion (4 [6.9%] of 58) of the patients admitted after January 23. Other symptoms, such as cough, nausea, diarrhea, and chest tightness, were not significantly different between the two groups. In addition, the group admitted before January 23 had a larger proportion of patients with reduced lymphocyte (13 [54.2%] of 24), CD3 (11 [54.4%] of 21), and CD8 (9 [42.9%] of 21) counts and elevated serum amyloid A (SAA, 18 [75%] of 24). Conclusions The initial symptoms of recently infected patients seem more insidious, indicating that the new coronavirus may gradually evolve into a virus similar to influenza and latent in asymptomatic carriers for a long time.", "title": "Caution: The clinical characteristics of COVID-19 patients at admission are changing", "pid": "zhdjtv4j", "bm25_score": 213.65008544921875}, {"text": "In December 2019, the outbreak of novel coronavirus (2019- nCoV) in wuhan, China, attracting attention worldwidely. The novel coronavirus has the characteristics of rapid transmission, atypical clinical symptoms, and easy to affect both lungs, leading to missed diagnosis and misdiagnosis, as well as difficult to detection and assessment at early stage. Fever, cough, myalgia, weakness, dyspnea and imagings may be helpful for the early detection of novel coronavirus pneumonia. At the same time, the rate of disease progression, fever, CT manifestations, hypoxia degree, age, basic diseases, and laboratory indicators can also be used to evaluate the severity of the novel coronavirus pneumonia.", "title": "[Early detection and disease assessment of patients with novel coronavirus pneumonia]", "pid": "a0kllvh9", "bm25_score": 213.6427764892578}, {"text": "Coronavirus Disease 2019 (COVID-19), previously called 2019-nCoV, is a novel disease caused by SARS- CoV-2 which was first identified as outbreak of unknown respiratory illness in Wuhan, China. COVID- 19 was declared as global health emergency by WHO on March 11, 2020 and quickly elevated to global pandemic on 11 March 2020. COVID-19 symptom is highly various in each patient, with fever, fatigue, shortness of breath, and cough as the main presenting symptoms. Patient with COVID-19 may shows severe symptom with severe pneumonia and ARDS, mild symptom resembling simple upper respiration tract infection, or even completely asymptomatic. Approximately 80% of cases is mild. However the number may changes as more people are getting tested. Some experts are estimating that up to 50% of all cases may be asymptomatic carrier.", "title": "Clinical Progression of COVID-19 Patient with Extended Incubation Period, Delayed RT-PCR Time-to-positivity, and Potential Role of Chest CT-scan.", "pid": "e4uzvmmh", "bm25_score": 213.63473510742188}, {"text": "PURPOSE: To analyse the high-resolution computed tomography (HRCT) early imaging features and the changing trend of coronavirus disease 2019 (COVID-19) pneumonia. MATERIALS AND METHODS: Forty-six patients with COVID-19 pneumonia who had an isolated lesion on the first positive CT were enrolled in this study. The following parameters were recorded for each lesion: sites, sizes, location (peripheral or central), attenuation (ground-glass opacity or consolidation), and other abnormalities (supply pulmonary artery dilation, air bronchogram, interstitial thickening, etc.). The follow-up CT images were compared with the previous CT scans, and the development of the lesions was evaluated. RESULTS: The lesions tended to be peripheral and subpleural. All the lesions exhibited ground-glass opacity with or without consolidation. A higher proportion of supply pulmonary artery dilation (89.13 % [41/46]) and air bronchogram (69.57 % [32/46]) were found. Other findings included thickening of the intralobular interstitium and a halo sign of ground glass around a solid nodule. Cavitation, calcification or lymphadelopathy were not observed. The reticular patterns were noted from the 14 days after symptoms onset in 7 of 20 patients (45 %). At 22-31 days, the lesions were completely absorbed only in 2 of 7 patients (28.57 %). CONCLUSION: The typical early CT features of COVID-19 pneumonia are ground-glass opacity, and located peripheral or subpleural location, and with supply pulmonary artery dilation. Reticulation was evident after the 2nd week and persisted in half of patients evaluated in 4 weeks after the onset. Long-term follow-up is required to determine whether the reticulation represents irreversible fibrosis.", "title": "Early CT features and temporal lung changes in COVID-19 pneumonia in Wuhan, China", "pid": "olzkxfcp", "bm25_score": 213.63238525390625}, {"text": "The current outbreak of infections with SARS-CoV-2 is defined as Coronavirus Disease 2019 (COVID-19). The clinical symptoms of COVID-19 include fever, fatigue, cough, breathing difficulty that may lead to respiratory distress; a small population of patients may have diarrhea, nausea or vomiting. The highest infection rate occurs in adults; however, neonates, children, and adolescents can also be infected. As the outbreak continues to spread worldwide, attention has switched toward determinants of clinical manifes- tations and disease severity. The situation surrounding the outbreak is rapidly evolving and the information and recommendations are changing as new information becomes available. This paper summarises the cur- rent findings (April 3,2020) from a systematic literature review on the current knowledge of COVID-19 in adolescents (10-19 years according to the WHO definition) and reports the preliminary epidemiological data stated by the Italian National Institute of Health.", "title": "Coronavirus Disease 2019 (COVID-19) in adolescents: An update on current clinical and diagnostic characteristics.", "pid": "gj5mfzxz", "bm25_score": 213.62301635742188}, {"text": "INTRODUCTION: Neurological manifestations can occur during coronavirus disease 19 (COVID-19). Several pathogenic mechanisms have been hypothesized, without conclusive results. In this study, we evaluated the most frequent neurological symptoms in a cohort of hospitalized COVID-19 patients, and also investigated the possible relationship between plasmatic inflammatory indices and olfactory disorders (ODs) and between muscle pain and creatine kinase (CK). METHODS: We consecutively enrolled hospitalized COVID-19 patients. A structured questionnaire concerning typical and neurological symptoms, focusing on headache, dizziness, ODs, taste disorders (TDs), and muscle pain, was administrated by telephone interviews. RESULTS: Common neurological symptoms were reported in the early phase of the disease, with a median onset ranging from 1 to 3 days. Headache showed tension-type features and was more frequently associated with a history of headache. Patients with ODs less frequently needed oxygen therapy. Inflammatory indices did not significantly differ between patients with and without ODs. Muscle pain did not show any association with CK level but was more frequently associated with arthralgia and headache. CONCLUSION: In our cohort, ODs were an early symptom of COVID-19, more frequently reported by patients with milder forms of disease. Headache in association with arthralgia and muscle pain seems to reflect the common symptoms of the flu-like syndrome, and not COVID-19 infection-specific.", "title": "Early neurological manifestations of hospitalized COVID-19 patients", "pid": "3l713mue", "bm25_score": 213.61190795898438}, {"text": "PURPOSE: To investigate the chest CT imaging characteristics and clinical manifestations of patients with COVID-19 pneumonia. METHODS: This study included 150 patients with COVID-19 pneumonia diagnosed from January 10 to February 12, 2020 to analyze their clinical and CT imaging characteristics. RESULTS: The period between symptom onset and initial CT examination ranged from 1 to 8 days. There were 83 cases (55.33%) involving both lungs, 67 cases (44.67%) involving a single lung (left 25 cases and right 42 cases). There were 49 cases (32.67%) of single intrapulmonary lesion, 33 cases (22.00%) of multiple intrapulmonary lesions, 68 cases (44.00%) of diffused intrapulmonary lesions, 67 cases (44.67%) of subpleural lesions, 24 cases (16.00%) of lesions localizing along the bronchovascular bundles, and 59 cases (39.33%) with lesions in both locations. There were 18 cases (12.00%) exhibiting ground-glass nodules of < 10 mm, 124 cases (82.67%) of patchy ground-glass opacities with or without consolidation, 8 cases (5.33%) of cord-like lesions, 6 cases (4.00%) of pleural effusion, and 2 cases (1.33%) of enlarged lymph nodes. CONCLUSIONS: The main manifestations of initial chest CT in COVID-19 pneumonia patients was ground-glass opacities, commonly involving single site in patients < 35 years old and multiple sites and extensive area in patients > 60 years old. The common lesion sites were the subpleural region and the posterior basal segments of the lower lobes, mostly showing thickening of the interlobular septum and mixed with consolidation.", "title": "Imaging characteristics of initial chest computed tomography and clinical manifestations of patients with COVID-19 pneumonia", "pid": "pos7shq4", "bm25_score": 213.60379028320312}, {"text": "SUMMARY The COVID-19 outbreak has become a pandemic that is threatening global health. The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Digestive symptoms such as nausea, vomiting, diarrhea, abdominal pain usually accompany respiratory symptoms. However gastrointestinal bleeding as the first symptom is not reported. Here we reported a case of COVID-19 with gastrointestinal bleeding as the initial symptom to the emergency department with a real-time reverse transcriptase polymerase chain reaction test positive, and normal thorax tomography. The case demonstrate that; clinicians should be alerted to patients about COVID-19 when referring to atypical symptoms and every patient undergoing endoscopy should be considered potentially infected or can infect others.", "title": "Uncommon Presentation Of Covid-19: Gastrointestinal Bleeding", "pid": "xgr6r6of", "bm25_score": 213.60108947753906}, {"text": "OBJECTIVE. The purpose of this study was to investigate early clinical and CT manifestations of coronavirus disease (COVID-19) pneumonia. MATERIALS AND METHODS. Patients with COVID-19 pneumonia confirmed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test (reverse transcription-polymerase chain reaction) were enrolled in this retrospective study. The clinical manifestations, laboratory results, and CT findings were evaluated. RESULTS. One hundred eight patients (38 men, 70 women; age range, 21-90 years) were included in the study. The clinical manifestations were fever in 94 of 108 (87%) patients, dry cough in 65 (60%), and fatigue in 42 (39%). The laboratory results were normal WBC count in 97 (90%) patients and normal or reduced lymphocyte count in 65 (60%). High-sensitivity C-reactive protein level was elevated in 107 (99%) patients. The distribution of involved lobes was one lobe in 38 (35%) patients, two or three lobes in 24 (22%), and four or five lobes in 46 (43%). The major involvement was peripheral (97 patients [90%]), and the common lesion shape was patchy (93 patients [86%]). Sixty-five (60%) patients had ground-glass opacity (GGO), and 44 (41%) had GGO with consolidation. The size of lesions varied from smaller than 1 cm (10 patients [9%]) to larger than 3 cm (56 patients [52%]). Vascular thickening (86 patients [80%]), crazy paving pattern (43 patients [40%]), air bronchogram sign (52 patients [48%]), and halo sign (69 [64%]) were also observed in this study. CONCLUSION. The early clinical and laboratory findings of COVID-19 pneumonia are low to midgrade fever, dry cough, and fatigue with normal WBC count, reduced lymphocyte count, and elevated high-sensitivity C-reactive protein level. The early CT findings are patchy GGO with or without consolidation involving multiple lobes, mainly in the peripheral zone, accompanied by halo sign, vascular thickening, crazy paving pattern, or air bronchogram sign.", "title": "Early Clinical and CT Manifestations of Coronavirus Disease 2019 (COVID-19) Pneumonia", "pid": "e3x96o8d", "bm25_score": 213.59637451171875}, {"text": "Typical presentations of Coronavirus Disease 2019 (COVID19) including respiratory symptoms (cough, respiratory distress and hypoxia), fever and dyspnea are considered main symptoms in adults, but atypical presentation children could be a diagnostic challenge We report three children whose initial presentation was gastrointestinal, and in whom COVID-19 infection was found, concluding that cases of acute appendicitis, mesenteric adenitis and flank tenderness may mask and infection with this virus, which should therefore be investigated.", "title": "Atypical and novel presentations of Coronavirus Disease 2019: a case series of three children.", "pid": "1wyh7mrw", "bm25_score": 213.5938720703125}, {"text": "The COVID-19 outbreak has become a pandemic that is threatening global health. The typical clinical manifestations were fever, cough, dyspnea, and myalgia or fatigue. Digestive symptoms such as nausea, vomiting, diarrhea, abdominal pain usually accompany respiratory symptoms. However gastrointestinal bleeding as the first symptom is not reported. Here we reported a case of COVID-19 with gastrointestinal bleeding as the initial symptom to the emergency department with a real-time reverse transcriptase polymerase chain reaction test positive, and normal thorax tomography. The case demonstrate that; clinicians should be alerted to patients about COVID-19 when referring to atypical symptoms and every patient undergoing endoscopy should be considered potentially infected or can infect others.", "title": "Uncommon presentation of COVID-19: Gastrointestinal bleeding", "pid": "99c1wgid", "bm25_score": 213.59231567382812}, {"text": "Abstract Five cases of non-remitting conjunctivitis turned out to be the sole presenting sign and symptom of COVID-19. These patients tested positive on RT-PCR of naso-pharyngeal swabs and developed no fever, malaise, or respiratory symptoms throughout the course of their illness. They all fully recovered. In the current efforts to fight the spread of this virus, authors want to emphasize that atypical clinical presentations of COVID-19 can occur and a high level of suspicion should be maintained. Ocular involvement and transmission of SARS-CoV-2 should never be overlooked. In fact, conjunctival mucosae are susceptible to respiratory viruses and remain an important point of entry. For this reason, eye protection in the form of goggles or a face shield should be considered essential for all healthcare providers, even when taking care of patients who are not showing typical symptoms of COVID-19.", "title": "Conjunctivitis can be the only presenting sign and symptom of COVID-19", "pid": "kjc1jdvz", "bm25_score": 213.5919952392578}, {"text": "BACKGROUND: The amelioration of the current COVID pandemic relies on swift and efficient case finding as well as stringent social distancing measures. Current advice suggests that fever or new onset dry cough are the commonest presenting complaints. METHODOLOGY: We present a case report and case series as well as other evidence that there is an important fourth presenting syndrome, namely isolated sudden onset anosmia (ISOA), which should be considered highly suspicious for SARS-CoV-2. RESULTS: A patient presenting with ISOA who went on to test positive for infection with COVID-19 and did not develop any further symptoms as well as a case series of similar patients although limited by the lack of reliable testing at the moment. CONCLUSIONS: We posit the existence of a fourth common syndrome of COVID-19 infection: isolated sudden onset anosmia (ISOA) and urge the international community to consider this presentation in current management advice.", "title": "Isolated sudden onset anosmia in COVID-19 infection. A novel syndrome?", "pid": "leeak5ct", "bm25_score": 213.58621215820312}, {"text": "The 2019 novel coronavirus (2019-nCoV) epidemic continues, with the number of infections and deaths increasing. The respiratory tract is the main route of transmission of the virus, and the majority of symptoms are respiratory relative. Until now, there has been no reports concerning the nervous system onset. We present a 2019-nCoV patient with the onset of simple dizziness, accompanied by dry throat, no fever, no cough, no headache, no mental abnormality, and no obvious abnormality in the nuclear magnetic resonance imaging (MRI) of the head. Meanwhile, chest computed tomography (CT) scans showed multiple small spot shadows and interstitial changes in the early stage, especially in the extrapulmonary zone. There was a development of multiple ground-glass shadows and infiltrative shadows in both lungs with mild pleural effusion. The nucleic acid gene detection was positive, and thus the diagnosis of 2019-nCoV was confirmed. At last, the prognosis was good after active treatment. After antiviral and anti-infective treatment, the symptoms recovered. We presume that 2019-nCoV can also manifest in the nervous system alone, and lung CT, which has relative specificity, should be used as a routine screening method.", "title": "2019 novel coronavirus pneumonia with onset of dizziness: a case report.", "pid": "cnrzl20a", "bm25_score": 213.577880859375}, {"text": "Background: On 29th December 2019, a cluster of cases displaying the symptoms of a “pneumonia of unknown cause” was identified in Wuhan, Hubei province of China. This systematic review and meta-analysis aims to review the epidemiological and clinical characteristics of COVID-19 cases in the early phase of the COVID-19 pandemic. Methods: The search strategy involved peer-reviewed studies published between 1st January and 11th February 2020 in Pubmed, Google scholar and China Knowledge Resource Integrated database. Publications identified were screened for their title and abstracts according to the eligibility criteria, and further shortlisted by full-text screening. Three independent reviewers extracted data from these studies, and studies were assessed for potential risk of bias. Studies comprising non-overlapping patient populations, were included for qualitative and quantitative synthesis of results. Pooled prevalence with 95% confidence intervals were calculated for patient characteristics. Results: A total of 29 publications were selected after full-text review. This comprised of 18 case reports, three case series and eight cross-sectional studies on patients admitted from mid-December of 2019 to early February of 2020. A total of 533 adult patients with pooled median age of 56 (95% CI: 49–57) and a pooled prevalence of male of 60% (95% CI: 52–68%) were admitted to hospital at a pooled median of 7 days (95% CI: 7–7) post-onset of symptoms. The most common symptoms at admission were fever, cough and fatigue, with a pooled prevalence of 90% (95% CI: 81–97%), 58% (95% CI: 47–68%), and 50% (95% CI: 29–71%), respectively. Myalgia, shortness of breath, headache, diarrhea and sore throat were less common with pooled prevalence of 27% (95% CI: 20–36%), 25% (95% CI: 15–35%), 10% (95% CI: 7–13%), 8% (95% CI: 5–13%), and 7% (95% CI: 1–15%), respectively. ICU patients had a higher proportion of shortness of breath at presentation, as well as pre-existing hypertension, cardiovascular disease and COPD, compared to non-ICU patients in 2 studies (n = 179). Conclusion: This study highlights the key epidemiological and clinical features of COVID-19 cases during the early phase of the COVID-19 pandemic.", "title": "Epidemiological and Clinical Characteristics of Cases During the Early Phase of COVID-19 Pandemic: A Systematic Review and Meta-Analysis", "pid": "vdpaxj4e", "bm25_score": 213.57386779785156}, {"text": "Coronavirus 19 (COVID‐19) was declared as a pandemic viral infection by the World Health organization on March 11(th) 2020. Usual clinical manifestations of COVID‐19 infection include fever, fatigue, myalgia, headache, diarrhea, dry cough, dyspnea that may lead to acute respiratory distress syndrome and death (1). Skin symptoms of COVID‐19 have been poorly described but may include erythematous rash, urticaria and chicken pox like lesions (2‐7). Angiotensin‐converting enzyme 2 (ACE2) is a cellular receptor for COVID‐19.", "title": "Vascular skin symptoms in COVID‐19: a french observational study", "pid": "qreg4emx", "bm25_score": 213.57069396972656}, {"text": "PURPOSE: To summarize the chest CT imaging and clinical features of the initial COVID-19 patients and provide a clinical diagnostic method that is more effective and can be performed earlier. METHODS: This retrospective study investigated the clinical, laboratory and imaging information of 25 patients in the Luoyang area. There were 15 (60%) male and 10 (40%) female patients ranging from 24 to 88 years old (52 ± 19.30). Data were analyzed by Microsoft Excel and are expressed as the mean ± standard deviation or percentage. RESULTS: Thirteen (52%) patients had been in Wuhan or were in contact with people who had been in Wuhan, and ten (40%) patients were infected by their families or colleagues. The median time from initial symptoms to diagnosis was 7 days. Ninety-two percent of patients had respiratory symptoms, and 8% of them had digestive symptoms. Fever (92%), cough (60%) and fatigue (56%) were the most common symptoms. Most patients had a normal or reduced WBC (96%), reduced lymphocyte count (60%), increased CRP (48%) and increased ESR (44%). Ground glass opacity (GGO) was the typical radiological finding on chest CT. CONCLUSION: Characteristic chest CT imaging features could appear earlier than the viral nucleic acid assay results.", "title": "A retrospective study of the initial 25 COVID-19 patients in Luoyang, China", "pid": "tqrjb1fe", "bm25_score": 213.56954956054688}, {"text": "OBJECTIVES: To systematically analyze CT findings during the early and progressive stages of natural course of coronavirus disease 2019 and also to explore possible changes in pulmonary parenchymal abnormalities during these two stages. METHODS: We retrospectively reviewed the initial chest CT data of 62 confirmed coronavirus disease 2019 patients (34 men, 28 women; age range 20-91 years old) who did not receive any antiviral treatment between January 21 and February 4, 2020, in Chongqing, China. Patients were assigned to the early-stage group (onset of symptoms within 4 days) or progressive-stage group (onset of symptoms within 4-7 days) for analysis. CT characteristics and the distribution, size, and CT score of pulmonary parenchymal abnormalities were assessed. RESULTS: In our study, the major characteristic of coronavirus disease 2019 was ground-glass opacity (61.3%), followed by ground-glass opacity with consolidation (35.5%), rounded opacities (25.8%), a crazy-paving pattern (25.8%), and an air bronchogram (22.6%). No patient presented cavitation, a reticular pattern, or bronchial wall thickening. The CT scores of the progressive-stage group were significantly greater than those of the early-stage group (p = 0.004). CONCLUSIONS: Multiple ground-glass opacities with consolidations in the periphery of the lungs were the primary CT characteristic of coronavirus disease 2019. CT score can be used to evaluate the severity of the disease. If these typical alterations are found, then the differential diagnosis of coronavirus disease 2019 must be considered. KEY POINTS: • Multiple GGOs with consolidations in the periphery of the lungs were the primary CT characteristic of COVID-19. • The halo sign may be a special CT feature in the early-stage COVID-19 patients. • Significantly increased CT score may indicate the aggravation of COVID-19 in the progressive stage.", "title": "Coronavirus disease 2019: initial chest CT findings", "pid": "azml9ly3", "bm25_score": 213.56117248535156}, {"text": "We report a case series of 6 patients with confirmed COVID-19 in Wakayama prefecture, Japan. All 6 of the patients tested positive in pharyngeal swab PCR tests, and 2 of the 6 were still positive at 3 weeks after onset. All of the patients exhibited bilateral ground glass opacities (GGO) on computed tomography (CT). This paper also reports narrative information on the spectrum of symptoms collected directly from the patients. It would be difficult to triage patients with COVID-19 based on the typical symptoms of fever and/or cough, although PCR and CT are definitive in diagnosis.", "title": "Clinical characteristics of patients with COVID-19 in Japan: a single-center case series", "pid": "nm12lk2h", "bm25_score": 213.55938720703125}, {"text": "OBJECTIVE. The purpose of this study was to investigate early clinical and CT manifestations of coronavirus disease (COVID-19) pneumonia. MATERIALS AND METHODS. Patients with COVID-19 pneumonia confirmed by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleic acid test (reverse transcription-polymerase chain reaction) were enrolled in this retrospective study. The clinical manifestations, laboratory results, and CT findings were evaluated. RESULTS. One hundred eight patients (38 men, 70 women; age range, 21-90 years) were included in the study. The clinical manifestations were fever in 94 of 108 (87%) patients, dry cough in 65 (60%), and fatigue in 42 (39%). The laboratory results were normal WBC count in 97 (90%) patients and normal or reduced lymphocyte count in 65 (60%). High-sensitivity C-reactive protein level was elevated in 107 (99%) patients. The distribution of involved lobes was one lobe in 38 (35%) patients, two or three lobes in 24 (22%), and four or five lobes in 46 (43%). The major involvement was peripheral (97 patients [90%]), and the common lesion shape was patchy (93 patients [86%]). Sixty-five (60%) patients had ground-glass opacity (GGO), and 44 (41%) had GGO with consolidation. The size of lesions varied from smaller than 1 cm (10 patients [9%]) to larger than 3 cm (56 patients [52%]). Vascular thickening (86 patients [80%]), crazy paving pattern (43 patients [40%]), air bronchogram sign (52 patients [48%]), and halo sign (69 [64%]) were also observed in this study. CONCLUSION. The early clinical and laboratory findings of COVID-19 pneumonia are low to midgrade fever, dry cough, and fatigue with normal WBC count, reduced lymphocyte count, and elevated high-sensitivity C-reactive protein level. The early CT findings are patchy GGO with or without consolidation involving multiple lobes, mainly in the peripheral zone, accompanied by halo sign, vascular thickening, crazy paving pattern, or air bronchogram sign.", "title": "Early Clinical and CT Manifestations of Coronavirus Disease 2019 (COVID-19) Pneumonia.", "pid": "8q6p7495", "bm25_score": 213.54873657226562}, {"text": "INTRODUCTION: Presently the COVID-19 pandemic is raging through the United States and worldwide. This enigmatic virus characteristically affects the respiratory system. Atypical presentations, such as gastrointestinal symptoms, and cases of encephalopathy have also been reported. However, psychiatric symptoms as the initial presenting feature is novel. We describe one such case. CASE PRESENTATION: 53-year-old man with no prior psychiatric or significant medical history was brought to the emergency department after ingesting bleach in an apparent suicide attempt. On initial presentation, the patient was uncooperative and withdrawn, though alert and oriented. He subsequently developed fever, tachycardia, elevated blood urea nitrogen and transaminases. SARS CoV-2 was confirmed on RT-PCR. Neurological examination was non-contributory. As his clinical condition improved, the patient reported that his initial symptom was an auditory hallucination telling him to jump from a bridge or ingest bleach. He reported that the increasing intensity of his auditory hallucinations led him to act upon it. He denied mood symptoms or suicidal ideation. The hallucinations did not recur during the hospital course, but he required 3 doses of antipsychotic medication for agitation. After improvement of his SARS CoV-2 infection, he was free of psychiatric symptoms and was discharged to a subacute rehabilitation center. CONCLUSION: This case indicates that what appears as a sudden onset of a psychiatric illness in the current context may be an initial manifestation of a developing COVID illness.", "title": "Command Suicidal Hallucination as Initial Presentation of Coronavirus Disease 2019 (COVID-19): A Case Report", "pid": "d3qgrjc4", "bm25_score": 213.54136657714844}, {"text": "Objectives: To describe baseline clinical characteristics of adult patients with COVID-19. Methods: We conducted a scoping review of the evidence available at LitCovid, until March 23th, 2020, and selected articles that reported the prevalence of socio-demographic characteristics, symptoms and co-morbidities in adults with COVID-19. Results: In total, 1 572 publications were published on LitCovid. We have included 56 articles in our analysis, with 89% conducted in China, and 75% contained inpatients. Three studies were conducted in North America and one in Europe. Participants age ranged from 28 to 70 years, with balanced gender distribution. Proportion of asymptomatic cases were from 2 to 79%. The most common reported symptoms were fever [4-99%], cough [4-92%], dyspnoea/shortness of breath [1-90%], fatigue 4-89%], myalgia [3-65%], and pharyngalgia [2-61%], while regarding co-morbidities we found cardiovascular disease [1-40%], hypertension [0-40%] and cerebrovascular disease [1-40%]. Such heterogeneity impairs the conduction of meta-analysis. Conclusions: The infection by COVID-19 seems to affect people in a very diverse manner and with different characteristics. With the available data it is not possible to clearly identify those at higher risk of being infected with this condition. Furthermore, the evidence from countries other than China is, at the day, too scarce.", "title": "Identifying baseline clinical features of people with COVID-19", "pid": "eblxpfds", "bm25_score": 213.53575134277344}, {"text": "Objective: To describe the symptom course in outpatients with coronavirus disease 2019 (COVID-19). Design: Retrospective chart review of standardized symptom checklist for patients followed at home by telephone calls during their acute COVID-19 illness. Compile results by day of illness into a single heatmap representation of symptoms. Setting: COVID-19 Virtual Outpatient Management Clinic (VOMC) in Atlanta, Georgia; a practice that follows patients with mild COVID-19 at home. Participants: 272 patients with confirmed COVID-19 by nasopharyngeal PCR, who presented to the VOMC within 10 days of symptom onset and within 5 days of screening PCR test. Main outcome measure: Each symptom is recorded as yes/no for each patient on each day. The total number of yes replies is divided by the total number of patients in VOMC to generate a result for each cell in the heatmap. Patients admitted to the hospital are censored from the denominator. Results: The mean duration of follow-up was 20.2 days. The most commonly reported symptoms in the course of illness were cough (83%), headache (73%) loss of smell or taste (71%), sinus congestion (71%), and body ache (67%). Symptoms remained common at 3 weeks, including cough (41%), shortness of breath on exertion (24%), loss of smell or taste (23%), sinus congestion (23%), and headache (20%). Conclusions: Symptoms of acute COVID-19 frequently last longer than the minimum duration of isolation and patients and healthcare providers should be aware that symptom resolution may be gradual.", "title": "Symptom Course in COVID-19 Outpatients", "pid": "dpyvu6ji", "bm25_score": 213.53533935546875}, {"text": "The coronavirus disease of 2019 or COVID-19 was first identified in Hubei Province in China in November of 2019 and quickly spread to become a global pandemic. The virus, SARS-Coronavirus-2 (2-SARS-CoV-2), is particularly virulent in the elderly who can develop symptoms and become mortally ill within days of contracting the virus. The virus is easily transmitted by droplets (e.g., sneezing, coughing) and communal living settings such as personal care homes can be vulnerable to the spread of the virus. Identifying patients early in the disease process is important to providing appropriate medical interventions. To date, most of the medical literature, including Center for Disease Control guidelines, has relied on three necessary symptoms in making the diagnosis of COVID-19: fever, cough and shortness of breath. We present four cases of elderly patients who developed altered mental status as their presenting symptom without associated fever or respiratory symptoms.", "title": "Altered Mental Status as a Novel Initial Clinical Presentation for COVID-19 Infection in the Elderly", "pid": "78rv366w", "bm25_score": 213.53073120117188}, {"text": "With an increasing number of Coronavirus Disease 2019 (COVID-19) cases outside of Hubei, emergency departments (EDs) and fever clinics are facing challenges posed by the large number of admissions of patients suspected to have COVID-19. Therefore, it is of crucial importance to study the initial clinical features of patients, to better differentiate between infected and uninfected patients outside Hubei. A total of 116 patients suspected of having COVID-19 who presented to two emergency departments in Anhui for the first time between 24 January 2020 and 20 February 2020 were enrolled in the study. The initial clinical data of these patients, such as epidemiological features, symptoms, laboratory results, and chest computed tomography (CT) findings were collected using a standard case report form on admission. Thirty-two patients were diagnosed with COVID-19; the remaining 84 patients were referred to as negative cases. The median age of the diagnosed patients was 46 years, but only 35 years for negative cases. History of exposure to Wuhan or COVID-19 patients in the previous 2 weeks was observed in 63% of the diagnosed and 44% of negative cases. Median time from illness onset to ED admission was 5 days for all patients, diagnosed patients, and negative cases, respectively. Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. Nineteen (59%) diagnosed and 24 (29%) negative cases had lymphopenia on admission in ED. A chest CT scan on admission revealed the presence of pneumonia in the majority of the diagnosed patients (30 out of 32, 94%) and in 56 (67%) negative cases. Bilateral involvement and ground-glass opacity (GGO) were present in 91% and 47% of the diagnosed patients. Thirty-two patients were diagnosed with COVID-19; the remaining 84 patients were referred to as negative cases. The median age of the diagnosed patients was 46 years, but only 35 years for negative cases. History of exposure to Wuhan or COVID-19 patients in the previous 2 weeks was observed in 63% of the diagnosed and 44% of negative cases. Median time from illness onset to ED admission was 5 days for all patients, diagnosed patients, and negative cases, respectively. Fever was observed in 27 (84%) and 57 (68%) diagnosed and negative cases, respectively. Nineteen (59%) diagnosed and 24 (29%) negative cases had lymphopenia on admission in ED. A chest CT scan on admission revealed the presence of pneumonia in the majority of the diagnosed patients (30 out of 32, 94%) and in 56 (67%) negative cases. Bilateral involvement and GGO were present in 91% and 47% of the diagnosed patients.", "title": "Initial clinical features of suspected coronavirus disease 2019 in two emergency departments outside of Hubei, China", "pid": "8tygt4zu", "bm25_score": 213.52664184570312}, {"text": "BACKGROUND The first case of pneumonia subsequently attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei Province on December 8, 2019. The symptoms included fever, coughing, and breathing difficulties. A few patients with this infection may only have atypical symptoms, which could lead to a misdiagnosis and subsequently further facilitate the spread of the virus. CASE SUMMARY A 74-year-old female patient complained of severe diarrhea. She did not have fever, coughing, or breathing difficulties. A physical examination revealed no obvious positive signs. The patient had been hypertensive for more than 10 years. Her blood pressure was well controlled. On January 9, 2020, the patient's son visited a colleague who was later confirmed positive for SARS-CoV-2 and his first close contact with our patient was on January 17. The patient was first diagnosed with gastrointestinal dysfunction. However, considering her indirect contact with a SARS-CoV-2-infected individual, we suggested that an atypical pneumonia virus infection should be ruled out. A computed tomography scan was performed on January 26, and showed ground-glass nodules scattered along the two lungs, suggestive of viral pneumonia. Given the clinical characteristics, epidemiological history, and examination, the patient was diagnosed with coronavirus disease-2019 (COVID-19). CONCLUSION Our patient had atypical symptoms of COVID-19. Careful acquisition of an epidemiological history is necessary to make a correct diagnosis and strategize a treatment plan.", "title": "Atypical presentation of SARS-CoV-2 infection: A case report.", "pid": "demny5pa", "bm25_score": 213.52342224121094}, {"text": "An outbreak of the novel coronavirus disease 2019 (COVID-19) occurred in Wuhan, China, in December 2019, which then rapidly spread to more than 80 countries. However, detailed information on the characteristics of COVID-19 in children is still scarce. Five patients with non-respiratory symptoms as the first manifestation were hospitalized from the emergency department, and were later confirmed to have COVID-19, between 23 January and 20 February 2020, at the Wuhan Children's Hospital. SARS-CoV-2 nucleic acid detection was positive for all the patients. Four of the patients were male and one was female, and their ages ranged from 2-months to 5.6 years. All lived in Wuhan. One patient had a clear history of exposure to SARS-CoV-2, one had a suspected history of exposure, while the others had no exposure history. For three of the five patients, the primary onset disease required an emergency operation or treatment, and included intussusception, acute suppurative appendicitis perforation with local peritonitis, and traumatic subdural hemorrhage with convulsion, while for the other two it was acute gastroenteritis (including one patient with hydronephrosis and a stone in his left kidney). During the course of the disease, four of the five patients had a fever, whereas one case had no fever or cough. Two patients had leukopenia, and one also had lymphopenia. In the two cases of severe COVID-19, the levels of CRP, PCT, serum ferritin, IL-6, and IL-10 were significantly increased, whereas the numbers of CD3+, CD4+, CD8+ T lymphocytes, and CD16 + CD56 natural killer cells were decreased. We also found impaired liver, kidney, and myocardial functions; the presence of hypoproteinemia, hyponatremia, and hypocalcemia; and, in one case, abnormal coagulation function. Except for one patient who had a rotavirus infection, all patients tested negative for common pathogens, including the influenza virus, parainfluenza virus, respiratory syncytial virus, adenovirus, enterovirus, mycoplasma, Chlamydia, and Legionella. Chest CT images of all the patients showed patches or ground-glass opacities in the lung periphery or near the pleura, even large consolidations. This case series is the first report to describe the clinical features of COVID-19 with non-respiratory symptoms as the first manifestation in children.", "title": "Clinical Characteristics of 5 COVID-19 Cases With Non-respiratory Symptoms as the First Manifestation in Children", "pid": "g4250q6l", "bm25_score": 213.51795959472656}, {"text": "Background: Since mid-December 2019, a cluster of pneumonia-like diseases caused by a novel coronavirus, now designated COVID-19 by the WHO, emerged in Wuhan city and rapidly spread throughout China. Here we identify the clinical characteristics of COVID-19 in a cohort of patients in Shanghai. Methods: Cases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, laboratory and radiological features. Results: Of 198 patients, the median duration from disease onset to hospital admission was 4 days. The mean age of the patients was 50.1 years, and 51.0% patients were male. The most common symptom was fever. Less than half of the patients presented with respiratory systems including cough, sputum production, itchy or sore throat, shortness of breath, and chest congestion. 5.6% patients had diarrhoea. On admission, T lymphocytes were decreased in 45.8% patients. Ground glass opacity was the most common radiological finding on chest computed tomography. 9.6% were admitted to the ICU because of the development of organ dysfunction. Compared with patients not treated in ICU, patients treated in the ICU were older, had longer waiting time to admission, fever over 38.5o C, dyspnoea, reduced T lymphocytes, elevated neutrophils and organ failure. Conclusions: In this single centre cohort of COVID-19 patients, the most common symptom was fever, and the most common laboratory abnormality was decreased blood T cell counts. Older age, male, fever over 38.5oC, symptoms of dyspnoea, and underlying comorbidity, were the risk factors most associated with severity of disease. Key words: 2019 novel coronavirus; acute respiratory infection; risk factors for disease severity", "title": "Clinical Features of Patients Infected with the 2019 Novel Coronavirus (COVID-19) in Shanghai, China", "pid": "dmud2zf7", "bm25_score": 213.5106201171875}, {"text": "COVID-19, a new illness secondary to a novel Coronavirus emerged in December 2019 in China. Our early understanding of the clinical features of COVID-19 has been based on case series emerging from the first outbreak in Wuhan. These features included fever, a dry cough, myalgia and dyspnea. Gastrointestinal symptoms were rarely reported as a key feature. We present a case report of a 74-year-old male who presented with symptoms of gastroenteritis and subsequently tested positive for COVID-19. This article aims to highlight an uncommon presentation of COVID-19 and that a high index of suspicion is required for COVID-19 in older people given their greater likelihood of presenting atypically.", "title": "COVID-19 and Gastrointestinal Symptoms—A Case Report", "pid": "e43f1xky", "bm25_score": 213.5070343017578}, {"text": "Objective To evaluate the clinical characteristics and pregnant outcomes of gravidae with COVID-19. Methods This study involved nine gravidae with COVID-19 admitted to the Renmin Hospital of Wuhan University from January 22 to February 1, 2020. Their clinical data, including epidemiological history, clinical symptoms, laboratory examinations, chest CT, treatment, delivery mode, and pregnancy outcomes, were analyzed retrospectively. Specimens of maternal vaginal swab were collected in six pregnant women, and the specimens of amniotic fluid, cord blood, neonatal throat swab and breast milk samples were collected in four pregnant women who had a delivery during our study. All samples were tested for the existence of COVID-19. Descriptive analysis was applied in this study. Results (1) Among the nine cases, five were admitted in the third trimester and four in the second trimester. The median incubation period of COVID-19 was 8 (1-14) d. Fever was presented in all cases on admission, and the other commonly seen symptoms were cough (seven cases) and diarrhea (five cases). Other signs and symptoms were also reported, including shortness of breath, myalgia and fatigue (four cases in each), nasal obstruction, pharyngalgia, chest pain, and headache/dizziness (three cases in each), rash (two cases), and chills and expectoration (one case in each). The most common laboratory abnormalities were a decreased number of lymphocytes (seven cases) and elevated C-reactive protein (six cases). Chest CT scans were performed in seven women, and all showed patchy areas or ground-glass opacity in both lungs. Oligohydramnios was detected in only one case at 37 +5 weeks, which was 7 d after the diagnosis of COVID-19. (2) All nine cases received empiric antibiotic and antiviral therapy with Chinese medicine as adjuvant treatment. Eight patients required oxygen inhalation, and eight were treated with glucocorticoid. Six cases received immunotherapy. (3) Four of the nine cases had delivered, including three cesarean sections and one spontaneous vaginal preterm birth after premature rupture of membranes, and the mother was transferred to the intensive care unit 2 d after delivery due to acute respiratory distress syndrome. One case was terminated at 26 gestational weeks. Of the four neonates, there were two term and two premature babies, and one preterm baby was small-for-gestational-age. No neonatal asphyxia was observed. Serial real-time quantitative reverse transcription-polymerase chain reaction showed negative results in the detection of 2019-novel coronavirus in all samples obtained from amniotic fluid, umbilical cord blood, neonatal nasopharynx, breast milk, and vagina. Maternal conditions were all stable in all cases, including the four continuing pregnancy, and the terminated ones, except the case mentioned above. Conclusions There is no distinguishable clinical feature between pregnant and non-pregnant COVID-19 patients. So far, there is no evidence for vertical transmission or worsening perinatal outcome in mothers and babies.", "title": "Clinical characteristics of COVID-19 in pregnancy: analysis of nine cases/ 中华围产医学杂志", "pid": "g4gll50x", "bm25_score": 213.5048828125}, {"text": "Objective: We aim to summarize reliable evidences of evidence-based medicine for the treatment and prevention of the 2019 novel coronavirus (2019-nCoV) by analyzing all the published studies on the clinical characteristics of patients with 2019-nCoV. Methods: PubMed, Cochrane Library, Embase, and other databases were searched. Several studies on the clinical characteristics of 2019-nCoV infection were collected for Meta-analysis. Results: Ten studies were included in Meta-analysis, including a total number of 50466 patients with 2019-nCoV infection. Meta-analysis shows that, among these patients, the incidence of fever was 89.1%, the incidence of cough was 72.2%, and the incidence of muscle soreness or fatigue was 42.5%. The incidence of acute respiratory distress syndrome (ARDS) was 14.8%, the incidence of abnormal chest computer tomography (CT) was 96.6%, the percentage of severe cases in all infected cases was 18.1%, and the case fatality rate of patients with 2019-nCoV infection was 4.3%. Conclusion: Fever and cough are the most common symptoms in patients with 2019-nCoV infection, and most of these patients have abnormal chest CT examination. Several people have muscle soreness or fatigue as well as ARDS. Diarrhea, hemoptysis, headache, sore throat, shock, and other symptoms only occur in a small number of patients. The case fatality rate of patients with 2019-nCoV infection is lower than that of Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS).", "title": "Clinical characteristics of 50466 patients with 2019-nCoV infection", "pid": "aoi4iqkf", "bm25_score": 213.5028839111328}, {"text": "Background: Since early December 2019, the 2019 novel coronavirus (COVID-19) has emerged in Wuhan and spread rapidly in China. We aimed to describe the clinical characteristics of hospitalized patients with confirmed COVID-19 infection in Shaoxing, and provide an insight into the treatment of COVID-19 across China and elsewhere. Methods: In this retrospective, single-center, study, we enrolled 16 patients with laboratory-confirmed COVID-19 admitted to the Affiliated Hospital of Shaoxing University between February 24 and January 25, 2020. Epidemiological, demographic, clinical, laboratory, radiological feature, and treatment data were all collected. Outcomes were followed up until March 16, 2020. Results: Among the 16 patients with COVID-19 infection, 11 patients (68.8%) had traveled or lived in Wuhan or surrounding areas, and 2 (12.5%) patients had exposure to patients with confirmed COVID-19 infection. The average age of the patients was 44.1 (16.5) years, and there were 10 women (62.5%) and 6 men (37.5%). More than half had chronic diseases [9 (56.3%)]. The most common symptoms at onset of COVID-19 infection were fever [12 (75%)] and cough [8 (50%)]; 11 (68.8%) patients had lymphopenia, and 12 (75%) had elevated C-reactive protein. On admission, abnormalities in computed tomography (CT) or chest X-ray images were revealed among all patients, and 11 (68.8%) of 16 patients had bilateral involvement. All patients were given psychological counseling, 15 (93.8%) patients were administered with antiviral therapy, 8 (50%) received empirical antibiotic treatment, and 5 (31.3%) patients were given systematic corticosteroids. Complications included acute respiratory distress syndrome (ARDS) requiring non-invasive mechanical ventilation [1 (6.3%)], acute respiratory injury [4 (25%)], acute renal injury [1 (6.3%)], septic shock [1 (6.3%)], liver dysfunction [5 (31.3%)], electrolyte disturbance [8 (50.0%)], and hospital-acquired pneumonia [3 (18.8%)]. None of the 16 patients died of COVID-19 pneumonia. Conclusions: Compared with the symptoms of the initial patients with COVID-19 infection in Wuhan, the symptoms of the patients from Shaoxing city were relatively mild. Currently, there is no effective drug treatment or vaccine for COVID-19, and psychological counseling cannot be ignored. Drugs and vaccines against COVID-19 infection need to be developed as soon as possible.", "title": "Clinical characteristics of 16 patients with COVID-19 infection outside of Wuhan, China: A retrospective, single-center study", "pid": "d07f65e8", "bm25_score": 213.501708984375}, {"text": "", "title": "SARS-CoV-2 induced diarrhoea as onset symptom in patient with COVID-19.", "pid": "wrvbtwnw", "bm25_score": 213.4998779296875}, {"text": "The symptoms most commonly reported by patients affected by coronavirus disease (COVID-19) include cough, fever, and shortness of breath. However, other major events usually observed in COVID-19 patients (e.g., high blood pressure, arterial and venous thromboembolism, kidney disease, neurologic disorders, and diabetes mellitus) indicate that the virus is targeting the endothelium, one of the largest organs in the human body. Herein, we report a systematic and comprehensive evaluation of both clinical and preclinical evidence supporting the hypothesis that the endothelium is a key target organ in COVID-19, providing a mechanistic rationale behind its systemic manifestations.", "title": "Hypertension, Thrombosis, Kidney Failure, and Diabetes: Is COVID-19 an Endothelial Disease? A Comprehensive Evaluation of Clinical and Basic Evidence", "pid": "5o540o1i", "bm25_score": 213.49954223632812}, {"text": "", "title": "Hemoptysis as an Initial Presentation of COVID-19 - An Observation", "pid": "5gg4c4np", "bm25_score": 213.49569702148438}, {"text": "BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is a novel pathogen causing the current worldwide coronavirus disease 2019 (COVID-19) pandemic. Due to insufficient diagnostic testing in the United States, there is a need for clinical decision-making algorithms to guide testing prioritization. METHODS: We recruited participants nationwide for a randomized clinical trial. We categorized participants into three groups: 1) those with confirmed SARS-CoV-2 infection, 2) those with probable SARS-CoV-2 infection (pending test or not tested but with a confirmed COVID-19 contact), and 3) those with possible SARS-CoV-2 infection (pending test or not tested and with a contact for whom testing was pending or not performed). We compared the frequency of self-reported symptoms in each group and categorized those reporting symptoms in early infection (0 – 2 days), mid-infection (3 – 5 days), and late infection (>5 days). RESULTS: Among 1,252 symptomatic persons screened, 316 had confirmed, 393 had probable, and 543 had possible SARS-CoV-2 infection. In early infection, those with confirmed and probable SARS-CoV-2 infection shared similar symptom profiles, with fever most likely in confirmed cases (p = 0.002). Confirmed cases did not show any statistically significant differences compared to unconfirmed cases in symptom frequency at any time points. The most commonly reported symptoms in those with confirmed infection were cough (82%), fever (67%), fatigue (62%), and headache (60%), with only 52% reporting both fever and cough. CONCLUSION: Symptomatic persons with probable SARS-CoV-2 infection present similarly to those with confirmed SARS-CoV-2 infection. There was no pattern of symptom frequency over time.", "title": "Symptoms of COVID-19 Outpatients in the United States", "pid": "f507uesq", "bm25_score": 213.47369384765625}, {"text": "", "title": "Arthralgia as an initial presentation of COVID-19: observation", "pid": "nxmbt611", "bm25_score": 213.4722442626953}, {"text": "", "title": "Dyspnea: The vanished warning symptom of COVID-19 pneumonia", "pid": "dzqm5rfn", "bm25_score": 213.4695281982422}, {"text": "", "title": "COVID-19 Related Oral Manifestations, Early Disease Features?", "pid": "y4xn2qfe", "bm25_score": 213.46441650390625}, {"text": "A pandemic outbreak of a novel coronavirus disease (COVID-19) that began in Wuhan, China, in December 2019 has spread rapidly to multiple countries. In the United States, the first confirmed case was reported on January 20, 2020, and since then, the number of cases is rising exponentially on a daily basis. We report a case of COVID-19 infection that presented with symptoms suggestive of pneumonia. Due to the major backlog with an immense number of pending tests, it took 48 hours for the result to come back positive, while the patient went into acute respiratory distress syndrome. We provide an internist’s perspective of the difficulties encountered in terms of the available management options, as the patient progressively deteriorated on the regular medical floor prompting transfer to the intensive care unit.", "title": "Coronavirus Disease 2019 (COVID-19) Complicated by Acute Respiratory Distress Syndrome: An Internist’s Perspective", "pid": "kaf9lp9q", "bm25_score": 213.46177673339844}, {"text": "A 77-year-old gentleman, normally fit and well, was admitted with acute confusion. On admission, Glasgow Coma Scale (GCS) was 14/15, vital signs were within the normal limits and bilateral crepitation at the lung base. Head CT scan was normal. CXR showed some air space opacification. Investigations revealed hyponatraemia, raised CRP, and positive for COVID-19. Treated with antibiotics and intravenous saline, sodium returned to normal. Delirium remained unchanged 4 weeks post-incidence. Neurological manifestations were documented in patients with COVID-19; however no report has shown delirium as a primary manifestation. This case illustrates acute confusion may be the only presenting symptom of COVID-19 without overt lung disease.", "title": "Prolonged confusional state as first manifestation of COVID-19", "pid": "bbg4kjb7", "bm25_score": 213.4452667236328}, {"text": "Objective To assess the prevalence of gastrointestinal symptoms and their correlation with need of non-invasive ventilatory support, intensive care unit admission and death in hospitalized SARS-CoV-2 patients. Design Since February 21th 2020, all individuals referred to our emergency department for suspected SARS-CoV-2 underwent a standardized assessment of body temperature and pulse oximetry, hematological screening, chest X-ray and/or computed tomography (CT), and SARS-CoV-2 assay on nasopharyngeal swab. Medical history and GI symptoms including nausea, vomit, diarrhea, and abdominal pain were recorded. Results GI symptoms were the main presentation in 42 (10.2%) of 411 patients, with a mean onset 4.9 +/-... days before admission. In 5 (1.2%) patients GI symptoms have not been associated with respiratory symptoms or fever. We found an inverse trend for ICU admission and death as compared with patients without GI symptoms. Conclusions GI symptoms can be an early and not negligible feature of Covid-19, and might be correlated with a more benign disease course.", "title": "Gastrointestinal symptoms as Covid-19 onset in hospitalized Italian patients", "pid": "e7v4rfje", "bm25_score": 213.4444122314453}, {"text": "We aimed to describe typical radiological features and progression of Coronavirus disease 2019 (COVID-19) patients. We reviewed the chest CT scans, laboratory findings, and clinical records of 66 COVID-19 patients who were admitted to affiliated hospitals of Nanchang university, Nanchang, China, from Jan 21 to Feb 2, 2020. CT was used to evaluate the radiological characteristics of COVID-19 patients. Only 4 patients (4/66, 6%) claimed their exposure to COVID-19 pneumonia patients. The major symptoms were fever (60/66, 91%) and cough (37/66, 56%). The predominant features of lesion were scattered (43/66, 65%), bilateral (50/66, 76%), ground-glass opacity (64/66, 97%), and air bronchogram sign (47/66, 71%). Forty-eight patients (48/66, 73%) had more than two lobes involved. Right lower lobe (58/66, 88%) and left lower lobe (49/66, 74%) were most likely invaded. Twelve patients (12/66, 18%) had at least one comorbid condition. Pleural traction (29/66, 44%), crazy paving (15/66, 23%), interlobular septal thickening (11/66, 17%), and consolidation (7/66, 11%) were also observed. The typical radiology features of COVID-19 patients are scattered ground-glass opacity in the bilateral lobes. Fever and cough are the major symptoms. Evaluating chest CT, clinical symptoms, and laboratory results could facilitate the early diagnosis of COVID-19, and judge disease progression.", "title": "Typical radiological progression and clinical features of patients with coronavirus disease 2019", "pid": "z4r6acop", "bm25_score": 213.44439697265625}, {"text": "", "title": "Olfactory and taste disorder: The first and only sign in a patient with SARS-CoV-2 pneumonia", "pid": "roobzvha", "bm25_score": 213.44223022460938}]}
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"z0gysxni": 1, "z13aa1wk": 0, "z2n51cet": 1, "khja6hbj": 2, "z4l3pk23": 0, "z5sn1czf": 0, "z7lz9syq": 2, "z7r4n0w7": 0, "z9l8heei": 1, "zblitbo0": 0, "zbzrxuoh": 2, "zdfx3zo3": 0, "zdmof6zb": 2, "7kidc16v": 0, "tax8ncny": 1, "zf9bwk1y": 1, "zgta5ah8": 0, "zhamfmiq": 0, "zhdjtv4j": 1, "zhtbzsyf": 2, "zi98dq1v": 1, "zixnvehs": 2, "zjoyxioy": 2, "zkz8e1vd": 1, "zlzag6a8": 0, "zmqb140l": 1, "zndtddty": 0, "zowo5ojd": 1, "zp4uy1v7": 0, "zpb9jicw": 0, "zph2g27g": 2, "zph6r4il": 0, "zpmwxoep": 2, "zpqgz95r": 1, "zpxwsg08": 2, "zr19c351": 0, "zrufbqke": 1, "v0v0ahjh": 0, "zwb1mn7c": 1, "zxpy9j63": 0, "ciiqqyne": 0, "bdfli7l0": 0}, "bm25_results": [{"text": "Since the outbreak of coronavirus disease 2019 (COVID-19) in late December 2019, it has brought significant harm and challenges to over 200 countries and regions around the world. However, there is increasing evidence that many patients with COVID-19 are asymptomatic or have only mild symptoms, but they are able to transmit the virus to others. There are difficulties in screening for asymptomatic infections, which makes it more difficult for national prevention and control of this epidemic. This article reviews the characteristics, treatment, and outcomes of asymptomatic infections with COVID-19, hoping it would be helpful for early prevention and control of this severe public health threat worldwide.", "title": "A Systematic Review of Asymptomatic Infections with COVID-19", "pid": "xz6pq0v3", "bm25_score": 217.67994689941406}, {"text": "Since the outbreak of coronavirus disease 2019 (COVID-19) in late December 2019, it has brought significant harm and challenges to over 200 countries and regions around the world. However, there is increasing evidence that many patients with COVID-19 are asymptomatic or have only mild symptoms, but they are able to transmit the virus to others. There are difficulties in screening for asymptomatic infections, which makes it more difficult for national prevention and control of this epidemic. This article reviews the characteristics, treatment, and outcomes of asymptomatic infections with COVID-19, hoping it would be helpful for early prevention and control of this severe public health threat worldwide.", "title": "A systematic review of asymptomatic infections with COVID-19", "pid": "hv0cwf6d", "bm25_score": 217.67994689941406}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly throughout the world since the first cases of coronavirus disease 2019 (COVID-19) were observed in December 2019 in Wuhan, China. It has been suspected that infected persons who remain asymptomatic play a significant role in the ongoing pandemic, but their relative number and effect have been uncertain. The authors sought to review and synthesize the available evidence on asymptomatic SARS-CoV-2 infection. Asymptomatic persons seem to account for approximately 40% to 45% of SARS-CoV-2 infections, and they can transmit the virus to others for an extended period, perhaps longer than 14 days. Asymptomatic infection may be associated with subclinical lung abnormalities, as detected by computed tomography. Because of the high risk for silent spread by asymptomatic persons, it is imperative that testing programs include those without symptoms. To supplement conventional diagnostic testing, which is constrained by capacity, cost, and its one-off nature, innovative tactics for public health surveillance, such as crowdsourcing digital wearable data and monitoring sewage sludge, might be helpful.", "title": "Prevalence of Asymptomatic SARS-CoV-2 Infection: A Narrative Review", "pid": "1ay60wzs", "bm25_score": 217.33224487304688}, {"text": "On 31 March 2020, Chinese Health Authorization announced that numbers of asymptomatic cases with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection will be made to the public daily. This was a very important step since different counties have different capacities for the detection of SARS-CoV-2 infection and control strategy for the Coronavirus Disease 2019 outbreak. We summarized the characteristics of asymptomatic SARS-CoV-2 infections and the transmission potential of asymptomatic cases. Then we provided guidelines for the management of asymptomatic cases through quarantine and nucleic acid/serology tests.", "title": "Asymptomatic cases with SARS-CoV-2 infection", "pid": "0r8vo1fa", "bm25_score": 217.06094360351562}, {"text": "Abstract Asymptomatic but infectious people have been reported in many infectious diseases. Asymptomatic and pre-symptomatic carriers would be a hidden reservoir of COVID-19. Aim This review identifies primary empirical evidence about the ability of asymptomatic carriers to infect others with COVID-19 pandemic and reflects on the implications for control measures. Methods A systematic review is followed by a narrative report and commentary inclusion criteria were: studies reporting primary data on asymptomatic or pre-symptomatic patients, who were considered to have passed on COVID-19 infection; and published in indexed journals or in peer review between January 1 and March 31, 2020. Results Nine articles reported on 83 asymptomatic or pre-symptomatic persons. Conclusions The evidence confirms COVID-19 transmission from people who were asymptomatic at the time. A series of implications for health service response are laid out. Keywords: Covid-19, Asymptomatic, Pre-symptomatic, Public Health", "title": "There are asymptomatic and pre-symptomatic patients infected with COVID-19. So what? Pandemic response implications", "pid": "nadzy6lm", "bm25_score": 217.00904846191406}, {"text": "BACKGROUND: Coronavirus Disease 2019 (COVID-19) is characterised by an unpredictable disease course, ranging from asymptomatic infections to severe, life-threating manifestations. Asymptomatic COVID-19 infections have been described, and the aim of this systematic review was to summarise their presentation form. METHODS: We searched PubMed® and Google® (1 December 2019 to 29 March 2020) and extracted age, laboratory findings, and computed tomography (CT) investigations. Pooled incidence rates of clinical characteristics were analysed using random effects models. RESULTS: In total, 506 patients from 34 studies (68 single cases and 438 from case series) with an asymptomatic course were identified. Patients with normal radiology were younger (19.59 ± 17.17 years) than patients with abnormal radiology (39.14 ± 26.70 years) (p value = 0.013). Despite being asymptomatic, CT investigations revealed abnormalities in 62.2% of the cases and ground glass opacities were most frequently observed (43.09% by meta-analysis). Most studies reported normal laboratory findings (61.74% by meta-analysis). CONCLUSIONS: More than half of patients without any symptoms present with CT abnormalities. Asymptomatic patients may be contagious and thus a potential source of transmission of COVID-19.", "title": "Asymptomatic patients as a source of COVID-19 infections: A systematic review and meta-analysis", "pid": "59a0v3sg", "bm25_score": 216.99542236328125}, {"text": "BACKGROUND Coronavirus Disease 2019 (COVID-19) is characterised by an unpredictable disease course, ranging from asymptomatic infections to severe, life-threating manifestations. Asymptomatic COVID-19 infections have been described, and the aim of this systematic review was to summarise their presentation form. METHODS We searched PubMed® and Google® (1 December 2019 to 29 March 2020) and extracted age, laboratory findings, and computed tomography (CT) investigations. Pooled incidence rates of clinical characteristics were analysed using random effects models. RESULTS In total, 506 patients from 34 studies (68 single cases and 438 from case series) with an asymptomatic course were identified. Patients with normal radiology were younger (19.59 ± 17.17 years) than patients with abnormal radiology (39.14 ± 26.70 years) (p value = 0.013). Despite being asymptomatic, CT investigations revealed abnormalities in 62.2% of the cases and ground glass opacities were most frequently observed (43.09% by meta-analysis). Most studies reported normal laboratory findings (61.74% by meta-analysis). CONCLUSIONS More than half of patients without any symptoms present with CT abnormalities. Asymptomatic patients may be contagious and thus a potential source of transmission of COVID-19.", "title": "Asymptomatic patients as a source of COVID-19 infections: A systematic review and meta-analysis.", "pid": "szzd7acz", "bm25_score": 216.964111328125}, {"text": "Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is continuously and rapidly circulating at present. Asymptomatic patients have been proven to be contagious and thus pose a significant infection control challenge. Here we describe the characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, Shandong province, China. A total of 47 patients with confirmed COVID-19 were recruited. Among them, 11 patients were categorized as asymptomatic cases. We found that the asymptomatic patients in Jinan were relatively young and were mainly clustered cases. The laboratory indicators and lung lesion on chest CT were mild. No special factors were found accounting for the presence or absence of symptoms. The presence of asymptomatic patients increased the difficulty of screening. It is necessary to strengthen the identification of such patients in the future.", "title": "Characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, China", "pid": "ffs350f2", "bm25_score": 216.63446044921875}, {"text": "The 2019 novel coronavirus disease, SARS-CoV-2, is now spreading globally and is characterized by person-to-person transmission. However, it has recently been found that individuals infected with SARS-CoV-2 can be asymptomatic, and simultaneously a source of infection in others. The viral load detected in nasopharyngeal swabs of asymptomatic carriers is relatively high, with a great potential for transmission. More attention should be paid to the insidious spread of disease and harm contributed by asymptomatic SARS-CoV-2 carriers. To provide a theoretical basis for the accurate and early clinical identification of asymptomatic patients, this review objectively summarizes the epidemic status, transmission characteristics and clinical features of asymptomatic patients with SARS-CoV-2 infection.", "title": "Transmission and clinical characteristics of asymptomatic patients with SARS-CoV-2 infection", "pid": "m9xifjth", "bm25_score": 216.5906219482422}, {"text": "Abstract Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) is continuously and rapidly circulating at present. Asymptomatic patients have been proven to be contagious and thus pose a significant infection control challenge. Here we describe the characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, Shandong province, China. A total of 47 patients with confirmed COVID-19 were recruited. Among them, 11 patients were categorized as asymptomatic cases. We found that the asymptomatic patients in Jinan were relatively young and were mainly clustered cases. The laboratory indicators and lung lesion on chest CT were mild. No special factors were found accounting for the presence or absence of symptoms. The presence of asymptomatic patients increased the difficulty of screening. It is necessary to strengthen the identification of such patients in the future.", "title": "Characteristics of asymptomatic patients with SARS-CoV-2 infection in Jinan, China", "pid": "xwvtjm6s", "bm25_score": 216.5904541015625}, {"text": "BACKGROUND An ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread around the world. It is debatable whether asymptomatic COVID-19 virus carriers are contagious. We report here a case of the asymptomatic patient and present clinical characteristics of 455 contacts, which aims to study the infectivity of asymptomatic carriers. MATERIAL AND METHODS 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research. They were divided into three groups: 35 patients, 196 family members and 224 hospital staffs. We extracted their epidemiological information, clinical records, auxiliary examination results and therapeutic schedules. RESULTS The median contact time for patients was four days and that for family members was five days. Cardiovascular disease accounted for 25% among original diseases of patients. Apart from hospital staffs, both patients and family members were isolated medically. During the quarantine, seven patients plus one family member appeared new respiratory symptoms, where fever was the most common one. The blood counts in most contacts were within a normal range. All CT images showed no sign of COVID-19 infection. No severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was detected in 455 contacts by nucleic acid test. CONCLUSION In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.", "title": "A study on infectivity of asymptomatic SARS-CoV-2 carriers.", "pid": "7xb7hj9u", "bm25_score": 216.5610809326172}, {"text": "OBJECTIVES Asymptomatic infection of SARS-CoV-2 has become a concern worldwide. This study aims to compare the epidemiology and the clinical characteristics of SARS-CoV-2 infection in asymptomatic and symptomatic individuals. METHODS A total of 511 confirmed SARS-CoV-2 infection cases, including 100 asymptomatic (by the time of the pathogenic tests) and 411 symptomatic individuals were consecutively enrolled from January 25 to February 20, 2020 from hospitals in 21 cities and 47 counties or districts in Sichuan Province. Epidemiological and clinical characteristics were compared. RESULTS Compared to the symptomatic patients, the asymptomatic cases were younger (P < 0.001), had similar co-morbidity percentages (P = 0.609), and came from higher altitude areas with lower population mobility (P < 0.001) with better defined epidemiological history (P < 0.001). 27.4% of well-documented asymptomatic cases developed delayed symptoms after the pathogenic diagnosis. 60% of asymptomatic cases demonstrated findings of pneumonia on the initial chest CT, including well-recognized features of coronavirus disease-19. None of the asymptomatic individuals died. Two elderly individuals with initially asymptomatic infection developed severe symptoms during hospitalization. One case of possible virus transmission by a patient during the incubation period was highly suspected. CONCLUSIONS The epidemiological and clinical findings highlight the significance of asymptomatic infection with SARS-CoV-2. Inspecting the epidemiological history would facilitate the identification of asymptomatic cases. Evidence supports the chest CT scans for confirmed asymptomatic cases to evaluate the extent of lung involvement.", "title": "Comparison of clinical and epidemiological characteristics of asymptomatic and symptomatic SARS-CoV-2 infection: A multi-center study in Sichuan Province, China.", "pid": "gqb0rr5t", "bm25_score": 216.52928161621094}, {"text": "BACKGROUND: An ongoing outbreak of coronavirus disease 2019 (COVID-19) has spread around the world. It is debatable whether asymptomatic COVID-19 virus carriers are contagious. We report here a case of the asymptomatic patient and present clinical characteristics of 455 contacts, which aims to study the infectivity of asymptomatic carriers. MATERIAL AND METHODS: 455 contacts who were exposed to the asymptomatic COVID-19 virus carrier became the subjects of our research. They were divided into three groups: 35 patients, 196 family members and 224 hospital staffs. We extracted their epidemiological information, clinical records, auxiliary examination results and therapeutic schedules. RESULTS: The median contact time for patients was four days and that for family members was five days. Cardiovascular disease accounted for 25% among original diseases of patients. Apart from hospital staffs, both patients and family members were isolated medically. During the quarantine, seven patients plus one family member appeared new respiratory symptoms, where fever was the most common one. The blood counts in most contacts were within a normal range. All CT images showed no sign of COVID-19 infection. No severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections was detected in 455 contacts by nucleic acid test. CONCLUSION: In summary, all the 455 contacts were excluded from SARS-CoV-2 infection and we conclude that the infectivity of some asymptomatic SARS-CoV-2 carriers might be weak.", "title": "A study on infectivity of asymptomatic SARS-CoV-2 carriers", "pid": "yz7goivp", "bm25_score": 216.48965454101562}, {"text": "On 31 March 2020, Chinese Health Authorization announced that numbers of asymptomatic cases with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection will be made to the public daily. This was a very important step since different counties have different capacities for the detection of SARS‐CoV‐2 infection and control strategy for the Coronavirus Disease 2019 outbreak. We summarized the characteristics of asymptomatic SARS‐CoV‐2 infections and the transmission potential of asymptomatic cases. Then we provided guidelines for the management of asymptomatic cases through quarantine and nucleic acid/serology tests.", "title": "Asymptomatic cases with SARS‐CoV‐2 infection", "pid": "eudcs9t2", "bm25_score": 216.46929931640625}, {"text": "", "title": "Asymptomatic SARS-CoV-2 infections: What do we need to know?", "pid": "jwb2hj4y", "bm25_score": 216.44345092773438}, {"text": "OBJECTIVES: Detailed knowledge on the prevalence of asymptomatic cases of coronavirus disease 2019 (COVID-19) and the clinical characteristics of mild COVID-19 is essential for effective control of the COVID-19 pandemic. We determined the prevalence of asymptomatic cases of COVID-19 and characterized the symptoms of patients with mild COVID-19. METHODS: Study participants were recruited from a community facility designated for the isolation of patients without moderate-to-severe symptoms of COVID-19 in South Korea. The prevalence of asymptomatic patients at admission and the detailed symptoms of mild COVID-19 were evaluated through a questionnaire-based survey. Diagnosis of COVID-19 was confirmed by real-time RT-PCR. RESULTS: Of the 213 individuals with COVID-19, 41 (19.2%) were asymptomatic until admission. Among the remaining patients with mild COVID-19, the most common symptom was cough (40.1%; 69/172), followed by hyposmia (39.5%; 68/172) and sputum (39.5%; 68/172). Of the 68 individuals with hyposmia, 61 (90%) had accompanying symptoms such as hypogeusia, nasal congestion or rhinorrhoea. Fever (>37.5°C) was only observed in 20 (11.6%) individuals. CONCLUSIONS: As much as one-fifth of individuals with COVID-19 remained asymptomatic from exposure to admission. Hyposmia was quite frequent among individuals with mild COVID-19, but fever was not. Social distancing should be strongly implemented to prevent disease transmission from asymptomatic individuals or those with mild and inconspicuous symptoms.", "title": "Clinical characteristics of asymptomatic and symptomatic patients with mild COVID-19", "pid": "p76gscn5", "bm25_score": 216.42935180664062}, {"text": "OBJECTIVES: Asymptomatic infection of SARS-CoV-2 has become a concern worldwide. This study aims to compare the epidemiology and the clinical characteristics of SARS-CoV-2 infection in asymptomatic and symptomatic individuals. METHODS: A total of 511 confirmed SARS-CoV-2 infection cases, including 100 asymptomatic (by the time of the pathogenic tests) and 411 symptomatic individuals were consecutively enrolled from January 25 to February 20, 2020 from hospitals in 21 cities and 47 counties or districts in Sichuan Province. Epidemiological and clinical characteristics were compared. RESULTS: Compared to the symptomatic patients, the asymptomatic cases were younger (P < 0.001), had similar co-morbidity percentages (P = 0.609), and came from higher altitude areas with lower population mobility (P < 0.001) with better defined epidemiological history (P < 0.001). 27.4% of well-documented asymptomatic cases developed delayed symptoms after the pathogenic diagnosis. 60% of asymptomatic cases demonstrated findings of pneumonia on the initial chest CT, including well-recognized features of coronavirus disease-19. None of the asymptomatic individuals died. Two elderly individuals with initially asymptomatic infection developed severe symptoms during hospitalization. One case of possible virus transmission by a patient during the incubation period was highly suspected. CONCLUSIONS: The epidemiological and clinical findings highlight the significance of asymptomatic infection with SARS-CoV-2. Inspecting the epidemiological history would facilitate the identification of asymptomatic cases. Evidence supports the chest CT scans for confirmed asymptomatic cases to evaluate the extent of lung involvement.", "title": "Comparison of clinical and epidemiological characteristics of asymptomatic and symptomatic SARS-CoV-2 infection: A multi-center study in Sichuan Province, China", "pid": "h3fnztro", "bm25_score": 216.40504455566406}, {"text": "In this population-based study, we identified 307 confirmed COVID-19 cases from massive surveillance, including 129,551 individuals screened at fever clinics or returning from Hubei and 3710 close contacts of confirmed COVID-19 patients. Among them, 17 patients were asymptomatic at initial clinical assessment. These asymptomatic patients on admission accounted for a small proportion of all patients (5.54%) with relatively weak transmissibility, and the detection rate was 0.35 per 100 close contacts. Moreover, the dynamics of symptoms of the 307 patients showed that the interval from symptom remission to the final negativity of viral nucleic acid was 5.0 days (IQR 2.0 to 11.0 days), with 14 patients (4.56%) having re-detectable viral RNA after discharge. Together, our findings suggested asymptomatic carriers and presymptomatic patients only accounted for a small proportion of COVID-19. Also, the asymptomatic phase in during recovery of COVID-19 urged that negativity in viral RNA is necessary as de-isolation criteria and follow-up is recommended.", "title": "Asymptomatic patients and asymptomatic phases of Coronavirus Disease 2019 (COVID-19): a population-based surveillance study", "pid": "l4n9hwcx", "bm25_score": 216.39935302734375}, {"text": "SARS-CoV-2 spread rapidly within months despite global public health strategies to curb transmission by testing symptomatic patients and encouraging social distancing. Here, we summarize rapidly emerging evidence highlighting transmission by asymptomatic and pre-symptomatic individuals. Viral load of asymptomatic carriers is comparable to symptomatic patients, viral shedding is highest before symptom onset suggesting high transmissibility before symptoms. Within universally tested subgroups, surprisingly high percentages of COVID-19 positive asymptomatic individuals were found. Asymptomatic transmission was reported in several clusters. A Wuhan study showed an alarming rate of intrahospital transmission, and several countries reported higher prevalence among healthcare workers than the general population. This raises concern that health workers could act as silent disease vectors. Therefore, current public health strategies relying solely on 'symptom onset' for infection identification need urgent reassessment. Extensive universal testing irrespective of symptoms may be considered with priority placed on groups with high frequency exposure to positive patients.", "title": "Asymptomatic transmission during the COVID-19 pandemic and implications for public health strategies", "pid": "6ua5txjc", "bm25_score": 216.37551879882812}, {"text": "SARS-CoV-2 spread rapidly within months despite global public health strategies to curb transmission by testing symptomatic patients and encouraging social distancing. Here, we summarize rapidly emerging evidence highlighting transmission by asymptomatic and pre-symptomatic individuals. Viral load of asymptomatic carriers is comparable to symptomatic patients, viral shedding is highest before symptom onset suggesting high transmissibility before symptoms. Within universally tested subgroups, surprisingly high percentages of COVID-19 positive asymptomatic individuals were found. Asymptomatic transmission was reported in several clusters. A Wuhan study showed an alarming rate of intrahospital transmission, and several countries reported higher prevalence among healthcare workers than the general population. This raises concern that health workers could act as silent disease vectors. Therefore, current public health strategies relying solely on ‘symptom onset’ for infection identification need urgent reassessment. Extensive universal testing irrespective of symptoms may be considered with priority placed on groups with high frequency exposure to positive patients.", "title": "Asymptomatic transmission during the COVID-19 pandemic and implications for public health strategies", "pid": "f99itvu9", "bm25_score": 216.3573760986328}, {"text": "Asymptomatic individuals with coronavirus disease (COVID-19) have been identified via nucleic acid testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2); however, the epidemiologic characteristics and viral shedding pattern of asymptomatic patients remain largely unknown. In this study, serological testing was applied when identifying nine asymptomatic cases of COVID-19 who showed persistent negative RT-PCR test results for SARS-CoV-2 nucleic acid and no symptoms of COVID-19. Two asymptomatic cases were presumed to be index patients who had cleared the virus when their close contacts developed symptoms of COVID-19. Three of the asymptomatic cases were local individuals who spontaneously recovered before their presumed index patients developed symptoms of COVID-19. This report presents the epidemiologic and clinical characteristics of asymptomatic individuals with SARS-CoV-2 infection that were undetected on RT-PCR tests in previous epidemiologic investigations probably due to the transient viral shedding duration.", "title": "Identification of RT-PCR-Negative Asymptomatic COVID-19 Patients via Serological Testing", "pid": "mu2v9o1p", "bm25_score": 216.29464721679688}, {"text": "", "title": "Asymptomatic and Presymptomatic Infectors: Hidden Sources of COVID-19 Disease", "pid": "svfmc5y5", "bm25_score": 216.209716796875}, {"text": "At present, the prevention and control of COVID-19 in China has entered a critical period. Recently, various areas outside Hubei Province have gradually begun to resume work and production, but the development of the epidemic situation is still uncertain and complex. A few days ago, researchers gradually began to pay attention to asymptomatic infection of 2019-novel coronavirus and described the disease process of asymptomatic infection and the possibility of being a source of infection. This provided a scientific basis for further optimizing and improving epidemic prevention and control measures. Paying attention to the screening and self-protection of high-risk groups and strengthening the level of detection should be helpful to the detection and management of asymptomatic infection.", "title": "[Screening and management of asymptomatic infection of 2019-novel coronavirus]", "pid": "s28hef1o", "bm25_score": 216.19284057617188}, {"text": "The first cases of Coronavirus of 2019 (COVID‐19) were reported in Wuhan, China in December 2019(1). The literature demonstrates geographical variation with regards to estimates of infection incidence, suggesting that COVID‐19 has been underdiagnosed in certain regions(2,3). The rate of asymptomatic infection has been estimated to be as high as 30.8%, which may help explain variation in incidence, particularly in regions with differing screening practices (3). Transmission of COVID‐19 by asymptomatic carriers has been reported in multiple family units, indicating that this mode of infection is important in understanding disease epidemiology and population risk(4,5).", "title": "Testing Asymptomatic Emergency Department Patients for Coronavirus of 2019 (COVID‐19) in a Low Prevalence Region", "pid": "wzb6qv7y", "bm25_score": 216.1661834716797}, {"text": "", "title": "Asymptomatic Patients with Novel Coronavirus Disease (COVID-19)", "pid": "1ix7mtxd", "bm25_score": 216.14764404296875}, {"text": "At present, the prevention and control of COVID-19 in China has entered a critical period. Recently, various areas outside Hubei Province have gradually begun to resume work and production, but the development of the epidemic situation is still uncertain and complex. A few days ago, researchers gradually began to pay attention to asymptomatic infection of 2019-novel coronavirus and described the disease process of asymptomatic infection and the possibility of being a source of infection. This provided a scientific basis for further optimizing and improving epidemic prevention and control measures. Paying attention to the screening and self-protection of high-risk groups and strengthening the level of detection should be helpful to the detection and management of asymptomatic infection.", "title": "[Screening and management of asymptomatic infection of 2019-novel coronavirus].", "pid": "hkm8yspk", "bm25_score": 216.14337158203125}, {"text": "", "title": "Asymptomatic SARS-CoV-2 infection: the tip or the iceberg?", "pid": "9orjecom", "bm25_score": 216.09329223632812}, {"text": "An epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread unexpectedly in Wuhan, Hubei Province, China, since December 2019. There are few reports about asymptomatic contacts of infected patients identified as positive for SARS-CoV-2 through screening. We studied the epidemiological and clinical outcomes in 55 asymptomatic carriers who were laboratory confirmed to be positive for SARS-CoV-2 through nucleic acid testing of pharyngeal swab samples. The asymptomatic carriers seldom occurred among young people (aged 18-29 years) who had close contact with infected family members. In the majority of patients, the outcome was mild or ordinary 2019 novel coronavirus disease during hospitalization.", "title": "Clinical Outcomes in 55 Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Who Were Asymptomatic at Hospital Admission in Shenzhen, China", "pid": "tj5pv57m", "bm25_score": 216.07260131835938}, {"text": "Following a containment phase of two months, China has transitioned to the mitigation phase. However, China still faces the risk of COVID-19 spreading due to not only to sporadic new cases and imported cases but also asymptomatic carriers. According to daily reports from the National Health Commission of the People's Republic of China from March 31, 2020 to April 7, 2020, the number of new asymptomatic cases reported daily greatly exceeded that of new imported cases. As of 24:00 on April 7, there were a total of 1,095 asymptomatic cases with COVID-19 under medical observation on the Chinese mainland, including 358 imported cases. A growing number of studies have indicated that asymptomatic carriers are infectious to an extent and can potentially transmit COVID-19. At present, China's measures for managing asymptomatic carriers are 14 days of centralized quarantine and observation; in principle, people with two consecutive negative nucleic acid tests (at an interval of at least 24 hours) can be released from quarantine. However, asymptomatic carriers will not be included in confirmed cases unless they develop clinical manifestations while in quarantine. As \"silent spreaders\", asymptomatic carriers warrant attention as part of disease prevention and control. The testing and follow-up of asymptomatic carriers should be expanded to include people in close contact with patients with confirmed COVID-19 and asymptomatic cases, clusters of outbreaks, and key areas and populations with a high risk of infection.", "title": "Asymptomatic carriers of COVID-19 as a concern for disease prevention and control: more testing, more follow-up", "pid": "j0a3tgbd", "bm25_score": 216.05636596679688}, {"text": "Following a containment phase of two months, China has transitioned to the mitigation phase. However, China still faces the risk of COVID-19 spreading due to not only to sporadic new cases and imported cases but also asymptomatic carriers. According to daily reports from the National Health Commission of the People's Republic of China from March 31, 2020 to April 7, 2020, the number of new asymptomatic cases reported daily greatly exceeded that of new imported cases. As of 24:00 on April 7, there were a total of 1,095 asymptomatic cases with COVID-19 under medical observation on the Chinese mainland, including 358 imported cases. A growing number of studies have indicated that asymptomatic carriers are infectious to an extent and can potentially transmit COVID-19. At present, China's measures for managing asymptomatic carriers are 14 days of centralized quarantine and observation; in principle, people with two consecutive negative nucleic acid tests (at an interval of at least 24 hours) can be released from quarantine. However, asymptomatic carriers will not be included in confirmed cases unless they develop clinical manifestations while in quarantine. As \"silent spreaders\", asymptomatic carriers warrant attention as part of disease prevention and control. The testing and follow-up of asymptomatic carriers should be expanded to include people in close contact with patients with confirmed COVID-19 and asymptomatic cases, clusters of outbreaks, and key areas and populations with a high risk of infection.", "title": "Asymptomatic carriers of COVID-19 as a concern for disease prevention and control: more testing, more follow-up.", "pid": "vbg06yyw", "bm25_score": 216.0542449951172}, {"text": "According to the current perception, symptomatic, presymptomatic, and asymptomatic infectious persons can infect the healthy population susceptible to the SARS-Cov-2. More importantly, various reports indicate that the number of asymptomatic cases can be several-fold higher than the reported symptomatic cases. In this article, we take the reported cases in India and various states within the country as the specimen to understand the progression of the COVID-19. Employing a modified SEIRD model, we predict the spread of COVID-19 by the symptomatic as well as asymptomatic infectious population. Considering reported infection primarily due to symptomatic we compare the model predicted results with the available data to estimate the dynamics of the asymptomatically infected population. Our data indicate that in the absence of the asymptomatic infectious population, the number of symptomatic cases would have been much less. Therefore, the current progress of the symptomatic infection can be reduced by quarantining the asymptomatically infectious population via extensive or random testing. This study is motivated strictly towards academic pursuit; this theoretical investigation is not meant for influencing policy decisions or public health practices.", "title": "How the asymptomatic population is influencing the COVID-19 outbreak in India?", "pid": "2ohq74mq", "bm25_score": 215.98318481445312}, {"text": "At the present time, COVID-19 is spreading rapidly [1]. The global prevention and control of COVID-19 is focused on the estimation of the relevant incubation period, basic reproduction number (R0), effective reproduction number (Rt) and death risk. Although the prevention and control of COVID-19 requires a reliable estimation of the relevant incubation period, R0, Rt and death risk. Another key epidemiological parameter-asymptomatic ratio that provides strength and range for social alienation strategies of COVID-19, which is widely defined as the proportion of asymptomatic infections among all disease infections. In fact, the ratio of asymptomatic infection is a useful indicator of the burden of disease and a better measurement of the transmissibility of the virus. So far, people have not paid enough attention to asymptomatic carriers. The asymptomatic carriers discussed in this study are recessive infections, that is, those who have never shown symptoms after onset of infection. We will discuss three aspects: detection, infectivity and proportion of healthy carriers.", "title": "COVID-19: asymptomatic carrier transmission is an underestimated problem", "pid": "32jaz3vz", "bm25_score": 215.98171997070312}, {"text": "Abstract Objectives With the ongoing outbreak of COVID-19 around the world, it has become a worldwide health concern. One previous study reported a family cluster with asymptomatic transmission of COVID-19. Here, we report another series of cases and further demonstrate the repeatability of the transmission of COVID-19 by pre-symptomatic carriers. Methods A familial cluster of five patients associated with COVID-19 was enrolled in the hospital. We collected epidemiological and clinical characteristics, laboratory outcomes from electronic medical records, and also affirmed them with the patients and their families. Results Among them, three family members (Case 3/4/5) had returned from Wuhan. Additionally, two family members, those who had not travelled to Wuhan, also contracted COVID-19 after contacting with the other three family members. Case 1 developed severe pneumonia and was admitted to the ICU. Case 3 and Case 5 presented fever and cough on days 2 through 3 of hospitalization and had ground-glass opacity changes in their lungs. Case 4 presented with diarrhoea and pharyngalgia after admission without radiographic abnormalities. Case 2 presented no clinical or radiographic abnormalities. All the cases had an increasing level of C-reactive protein. Conclusions Our findings indicate that COVID-19 can be transmitted by asymptomatic carriers during the incubation period.", "title": "Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster", "pid": "pgtvx6wb", "bm25_score": 215.97576904296875}, {"text": "Background: There is substantial disagreement about the level of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a population. The disagreement results, in part, from the interpretation of studies that report a proportion of asymptomatic people with SARS-CoV-2 detected at a single point. Review questions: 1. Amongst people who become infected with SARS-CoV-2, what proportion does not experience symptoms at all during their infection? 2. Amongst people with SARS-CoV-2 infection who are asymptomatic when diagnosed, what proportion will develop symptoms later? 3. What proportion of SARS-CoV-2 transmission is accounted for by people who are either asymptomatic throughout infection, or pre-symptomatic? Methods: Rapid living systematic review (protocol https://osf.io/9ewys/). We searched Pubmed, Embase, bioRxiv and medRxiv using a living evidence database of SARS-CoV-2 literature on 25.03.2020. We included studies of people with SARS-CoV-2 diagnosed by reverse transcriptase PCR (RT-PCR) that documented follow-up and symptom status at the beginning and end of follow-up and modelling studies. Study selection, data extraction and bias assessment were done by one reviewer and verified by a second, with disagreement resolved by discussion or a third reviewer. We used a common-effect model to synthesise proportions from comparable studies. Results: We screened 89 studies and included 11. We estimated an upper bound for the proportion of asymptomatic SARS-CoV-2 infections of 29% (95% confidence interval 23 to 37%) in eight studies. Selection bias and likely publication bias affected the family case investigation studies. One statistical modelling study estimated the true proportion of asymptomatic infections at 18% (95% credibility interval 16 to 20%). Estimates of the proportions of pre-symptomatic individual in four studies were too heterogeneous to combine. In modelling studies, 40-60% of all SARS-CoV-2 infections are the result of transmission from pre-symptomatic individuals, with a smaller contribution from asymptomatic individuals. Conclusions: An intermediate contribution of pre-symptomatic and asymptomatic infections to overall SARS-CoV-2 transmission means that combination prevention, with enhanced hand and respiratory hygiene, testing tracing and isolation strategies and social distancing, will continue to be needed. The findings of this systematic review of publications early in the pandemic suggests that most SARS-CoV-2 infections are not asymptomatic throughout the course of infection.", "title": "The role of asymptomatic SARS-CoV-2 infections: rapid living systematic review and meta-analysis", "pid": "c5be70t6", "bm25_score": 215.95208740234375}, {"text": "An epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread unexpectedly in Wuhan, Hubei Province, China, since December 2019. There are few reports about asymptomatic contacts of infected patients identified as positive for SARS-CoV-2 through screening. We studied the epidemiological and clinical outcomes in 55 asymptomatic carriers who were laboratory confirmed to be positive for SARS-CoV-2 through nucleic acid testing of pharyngeal swab samples. The asymptomatic carriers seldom occurred among young people (aged 18–29 years) who had close contact with infected family members. In the majority of patients, the outcome was mild or ordinary 2019 novel coronavirus disease during hospitalization.", "title": "Clinical Outcomes in 55 Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Who Were Asymptomatic at Hospital Admission in Shenzhen, China", "pid": "fjnhoai4", "bm25_score": 215.92599487304688}, {"text": "The pandemic of coronavirus disease 2019 (COVID-19) has threatened the social and economic structure all around the world. Generally, COVID-19 has three possible transmission routes, including pre-symptomatic, symptomatic and asymptomatic transmission, among which the last one has brought a severe challenge for the containment of the disease. One core scientific question is to understand the influence of asymptomatic individuals and of the strength of control measures on the evolution of the disease, particularly on a second outbreak of the disease. To explore these issues, we proposed a novel compartmental model that takes the infection of asymptomatic individuals into account. We get the relationship between asymptomatic individuals and critical strength of control measures theoretically. Furthermore, we verify the reliability of our model and the accuracy of the theoretical analysis by using the real confirmed cases of COVID-19 contamination. Our results, showing the importance of the asymptomatic population on the control measures, would provide useful theoretical reference to the policymakers and fuel future studies of COVID-19.", "title": "The impact of asymptomatic individuals on the strength of public health interventions to prevent the second outbreak of COVID-19", "pid": "w2lf01mg", "bm25_score": 215.92593383789062}, {"text": "Abstract An epidemic caused by SARS-Coronavirus-2 infection has spread unexpectedly in Wuhan, Hubei Province, China since December 2019 It is rarely reported about asymptomatic cases screened from close contacts We study epidemiological and clinical outcome of 55 asymptomatic carriers who were laboratory-confirmed positive for the SARS-Coronavirus-2 by testing the nucleic acid of the pharyngeal swab samples The evidence showed that asymptomatic carriers occurred more often in middle aged people who had close contact with infected family members The majority of the cases developed to be mild and ordinary COVID-19 during hospital", "title": "Clinical outcome of 55 asymptomatic cases at the time of hospital admission infected with SARS-Coronavirus-2 in Shenzhen, China ;The Journal of Infectious Diseases ;Oxford Academic", "pid": "qrf7n7dr", "bm25_score": 215.92323303222656}, {"text": "The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.", "title": "Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections", "pid": "gu3neito", "bm25_score": 215.900390625}, {"text": "Asymptomatic transmission of the coronavirus disease 2019 is an important topic. A recent study in China showed that transmissibility of the asymptomatic cases is comparable to that of symptomatic cases. Here, we discuss that the conclusion may depend on how we interpret the data. To the best of our knowledge, this is the first time the relative transmissibility of asymptomatic COVID-19 infections is quantified.", "title": "The relative transmissibility of asymptomatic COVID-19 infections among close contacts", "pid": "cca7gzjq", "bm25_score": 215.8786163330078}, {"text": "", "title": "Asymptomatic SARS-CoV-2 infection", "pid": "qprzgmwz", "bm25_score": 215.86907958984375}, {"text": "The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy1. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.", "title": "Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections.", "pid": "lzgwxshi", "bm25_score": 215.85189819335938}, {"text": "A total of 565 Japanese citizens were evacuated from Wuhan, China to Japan. All passengers were screened for symptoms and also undertook reverse transcription polymerase chain reaction testing, identifying 5 asymptomatic and 7 symptomatic passengers testing positive for 2019-nCoV. We show that the screening result is suggestive of the asymptomatic ratio at 41.6%.", "title": "Estimation of the asymptomatic ratio of novel coronavirus infections (COVID-19)", "pid": "f3h74j1n", "bm25_score": 215.84681701660156}, {"text": "Abstract Data are limited on the viral load, viral shedding patterns and potential infectivity of asymptomatic patients (APs) with coronavirus disease 2019 (COVID-19). We included 31 adult patients who were virologically confirmed to have COVID-19 but were asymptomatic on admission. Among these 31 patients, 22 presented symptoms after admission and were defined as asymptomatic patients in incubation period (APIs); the other 9 patients remained asymptomatic during hospitalization and were defined as asymptomatic patients (APs). The cycle threshold (Ct) values of APs (39.0, IQR 37.5-39.5) was significantly higher than those of APIs (34.5, IQR 32.2-37.0), which indicated a lower viral load in APs, but the duration of viral shedding remained similar between the two groups (7 days IQR 5-14 vs. 8 days IQR 5-16). The study findings demonstrated that although they have a lower viral load, APs with COVID-19 still have certain period of viral shedding, which suggests the possibility of transmission during their asymptomatic period. Further longitudinal surveillance of these asymptomatic cases via virus nucleic acid tests are warranted.", "title": "Viral dynamics in asymptomatic patients with COVID-19", "pid": "bi3bl5qt", "bm25_score": 215.84133911132812}, {"text": "After an outbreak in Wuhan, China, a growing number of countries are now suffering from an epidemic by SARS-CoV-2, which causes COVID-19. Undoubtedly, reports of the skyrocketing global spread of COVID-19 has shocked people globally, from Japan to the United States. Presently, the World Health Organization indicates that the fatality rate due to COVID-19 is about 2%, inferring that many positive subjects may potentially overcome the illness with mild influenza-like symptoms and no need for hospitalization at intensive-care units. Because COVID-19 is completely new to the human immune system, many throughout the world are likely vulnerable to becoming sick after their initial exposure to SARS-CoV-2. Besides hospitalized cases, many individuals are likely asymptomatic but potentially carry the virus. While our knowledge about carriers and their virus shedding is deficient, some studies modelling the viral transmission have considered the potential contribution of the asymptomatic carriers. Protocols for managing asymptomatic cases, for example for controlling them to restrict their contact with healthy people at public places or private residences, have not been established. In-house quarantine may as well be applicable to asymptomatic cases if they could be identified and diagnosed. Presumably now, the asymptomatic subjects potentially contribute to the transmission of COVID-19 without their knowledge, intention, or being diagnosed as carriers. Thus, managing the asymptomatic subjects, who can carry and likely transmit the virus, is a major healthcare challenge while the pandemic is looming.", "title": "Challenges of managing the asymptomatic carriers of SARS-CoV-2", "pid": "27z0z409", "bm25_score": 215.83944702148438}, {"text": "", "title": "Asymptomatic coronavirus infection: MERS-CoV and SARS-CoV-2 (COVID-19)", "pid": "a1370rjp", "bm25_score": 215.83932495117188}, {"text": "This case series examines clinical characteristics of patients with asymptomatic vs symptomatic coronavirus disease 2019 in Wuhan, China.", "title": "Comparison of Clinical Characteristics of Patients with Asymptomatic vs Symptomatic Coronavirus Disease 2019 in Wuhan, China", "pid": "10v7kfcd", "bm25_score": 215.836181640625}, {"text": "At present, Coronavirus Disease 2019 (COVID-19) is rampaging around the world. However, asymptomatic carriers intensified the difficulty of prevention and management. Here we reported the screening, clinical feathers, and treatment process of a family cluster involving three COVID-19 patients. The discovery of the first asymptomatic carrier in this family cluster depends on the repeated and comprehensive epidemiological investigation by disease control experts. In addition, the combination of multiple detection methods can help clinicians find asymptomatic carriers as early as possible. In conclusion, the prevention and control experience of this family cluster showed that comprehensive rigorous epidemiological investigation and combination of multiple detection methods were of great value for the detection of hidden asymptomatic carriers. This article is protected by copyright. All rights reserved.", "title": "Alert for non-respiratory symptoms of Coronavirus Disease 2019 (COVID-19) patients in epidemic period: A case report of familial cluster with three asymptomatic COVID-19 patients.", "pid": "coac0tz3", "bm25_score": 215.8339385986328}, {"text": "After the outbreak in Wuhan, China, we assessed 29,299 workers screened for severe acute respiratory syndrome coronavirus 2 by reverse transcription PCR. We noted 18 (0.061%) cases of asymptomatic infection; 13 turned negative within 8.0 days, and 41 close contacts tested negative. Among 6 contacts who had serologic tests, none were positive.", "title": "Severe Acute Respiratory Syndrome Coronavirus 2 among Asymptomatic Workers Screened for Work Resumption, China", "pid": "gxta7daq", "bm25_score": 215.81246948242188}, {"text": "OBJECTIVES: With the ongoing outbreak of COVID-19 around the world, it has become a worldwide health concern. One previous study reported a family cluster with an asymptomatic transmission of COVID-19. Here, we report another series of cases and further demonstrate the repeatability of the transmission of COVID-19 by pre-symptomatic carriers. METHODS: A familial cluster of five patients associated with COVID-19 was enrolled in the hospital. We collected epidemiological and clinical characteristics, laboratory outcomes from electronic medical records, and also verified them with the patients and their families. RESULTS: Among them, three family members (Case 3/4/5) had returned from Wuhan. Additionally, two family members, those who had not traveled to Wuhan, also contracted COVID-19 after contacting with the other three family members. Case 1 developed severe pneumonia and was admitted to the ICU. Case 3 and Case 5 presented fever and cough on days two through three of hospitalization and had ground-glass opacity changes in their lungs. Case 4 presented with diarrhea and pharyngalgia after admission without radiographic abnormalities. Case 2 presented no clinical nor radiographic abnormalities. All five cases had an increasing level of C-reactive protein. CONCLUSIONS: Our findings indicate that COVID-19 can be transmitted by asymptomatic carriers during the incubation period.", "title": "Delivery of infection from asymptomatic carriers of COVID-19 in a familial cluster", "pid": "bgoihr3t", "bm25_score": 215.79339599609375}, {"text": "At the present time, COVID-19 is spreading rapidly [1]. The global prevention and control of COVID-19 is focused on the estimation of the relevant incubation period, basic reproduction number (R(0)), effective reproduction number (R(t)) and death risk. Although the prevention and control of COVID-19 requires a reliable estimation of the relevant incubation period, R(0), R(t) and death risk. Another key epidemiological parameter-asymptomatic ratio that provides strength and range for social alienation strategies of COVID-19, which is widely defined as the proportion of asymptomatic infections among all disease infections. In fact, the ratio of asymptomatic infection is a useful indicator of the burden of disease and a better measurement of the transmissibility of the virus. So far, people have not paid enough attention to asymptomatic carriers. The asymptomatic carriers discussed in this study are recessive infections, that is, those who have never shown symptoms after onset of infection. We will discuss three aspects: detection, infectivity and proportion of healthy carriers.", "title": "COVID-19: asymptomatic carrier transmission is an underestimated problem", "pid": "c93j35fl", "bm25_score": 215.7860107421875}, {"text": "The asymptomatic carrier state of COVID-19 has become a topic of concern for preventing a possible epidemic rebound. This review describes and defines the COVID-19 asymptomatic carrier state and outlines methods for identifying counting and reporting these cases. The author elaborates that the asymptomatic carrier state can be further divided into asymptomatic infection and pre-symptomatic infection after extended follow-up based on the nature of disease progression. The author presents the limited available data about infectiousness of asymptomatic and pre-symptomatic cases and their possible contributions to the overall epidemic of COVID-19 observed so far in China. Challenges of a possible second epidemic wave of COVID-19 caused by asymptomatic and pre-symptomatic cases are discussed and suggestions for control strategies and scientific research are provided.", "title": "[Asymptomatic and pre-symptomatic cases of COVID-19 contribution to spreading the epidemic and need for targeted control strategies].", "pid": "ghasrwqc", "bm25_score": 215.78469848632812}, {"text": "", "title": "Should Asymptomatic and Low-Risk Individuals be Tested for SARS-CoV-2?", "pid": "jpcwaffg", "bm25_score": 215.7832489013672}, {"text": "", "title": "Natural History of Asymptomatic SARS-CoV-2 Infection", "pid": "6dk9nwup", "bm25_score": 215.7760009765625}, {"text": "Abstract After an outbreak in Wuhan, China, a growing number of countries are now suffering from an epidemic by SARS-CoV-2, which causes COVID-19. Undoubtedly, reports of the skyrocketing global spread of COVID-19 has shocked people globally, from Japan to the United States.Presently, the World Health Organization indicates that fatality due to COVID-19 is about 2%, inferring that many positive subjects may potentially overcome the illness with mild influenza-like symptoms and no need for hospitalization at intensive-care units. Because COVID-19 is completely new to the human immune system, many throughout the world are likely vulnerable to becoming sick after their initial exposure to SARSCoV-2. Besides hospitalized cases, many individuals are likely asymptomatic but potentially carry the virus. While our knowledge about carriers and their virus shedding is deficient, some studies modelling the viral transmission have considered the potential contribution of the asymptomatic carriers. Protocols for managing asymptomatic cases, for example for controlling them to restrict their contact with healthy people at public places or private residences, have not been established.In-house quarantine may as well be applicable to asymptomatic cases if they could be identified and diagnosed. Presumably now, the asymptomatic subjects potentially contribute to the transmission of COVID-19 without their knowledge, intention or being diagnosed as carriers. Thus, managing the asymptomatic cases, who can carry and likely transmit the virus, is a major healthcare challenge while a pandemic is looming.", "title": "Challenges of managing the asymptomatic carriers of SARS-CoV-2", "pid": "c5q7l7en", "bm25_score": 215.7694091796875}, {"text": "Few studies reported the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infected patients with completely asymptomatic throughout the disease course. We investigated the epidemiological and clinical features of patients infected by SARS-CoV-2 without any symptoms. Patients with confirmed SARS-CoV-2 infection were retrospectively recruited. The demographic characteristics, clinical data, treatment, and outcomes of SARS-CoV-2 infected patients without any symptoms were analyzed. Fifteen (4.4%) of 342 SARS-CoV-2 infected patients did not develop any symptom during the course of the disease. The median time from exposure to diagnosis was 7.0 days (interquartile range [IQR]: 1.0-15.0 days). Of the 15 patients, 14 patients were diagnosed by tested positive for SARS-CoV-2 in throat swabs, while one patient was only tested positive for SARS-CoV-2 in anal swabs. During hospitalization, only 1 (6.7%) patient developed lymphopenia. Abnormalities of chest computed tomography examinations were detected in 8 (53.4%) patients on admission. As of 8 March 2020, all patients have been discharged. The median time of SARS-CoV-2 tested negative from admission was 7.0 days (IQR: 4.0-9.0 days). Patients without any symptoms but with SARS-CoV-2 exposure should be closely monitored and tested for SARS-CoV-2 both in anal and throat swabs to excluded the infection. Asymptomatic patients infected by SARS-CoV-2 have favorable outcomes.", "title": "Epidemiological and clinical features of asymptomatic patients with SARS-CoV-2 infection", "pid": "dud6dzp6", "bm25_score": 215.761962890625}, {"text": "The novel coronavirus SARS-CoV-2 infection is spreading worldwide, and there are many reports of acute respiratory distress syndrome caused by this infection. However, asymptomatic lung involvement has not been reported. We hereby present the case of a 44-year-old health-care worker, who was found to be infected with the SARS-CoV-2 virus after a CT-scan performed for an unrelated condition revealed a lesion in the lung field compatible with COVID-19 infection. His condition deteriorated initially, but eventually improved with supportive treatment and the compassionate use of antivirals and antimalarials and is now in a stable condition.", "title": "Lung Involvement Found on Chest CT Scan in a Pre-Symptomatic Person with SARS-CoV-2 Infection: A Case Report", "pid": "rymfx50v", "bm25_score": 215.7565460205078}, {"text": "BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, resulting in the coronavirus disease COVID-19) is highly transmissible among people. Asymptomatic infections are also an important source of infection. Here, we aimed to further clarify the epidemiologic and clinical characteristics of asymptomatic SARS-CoV-2 infections. METHODS: We identified close contacts of confirmed COVID-19 cases in northeast Chongqing who were RT-PCR+ yet remained asymptomatic throughout their infections. We stratified this cohort by normal versus abnormal findings on chest CT, and compared the strata regarding comorbidities, demographics, laboratory findings, viral transmission and other factors. RESULTS: Between January and March, 2020, we identified and hospitalized 279 RT-PCR+ contacts of COVID-19 patients. Of these, 63 (23%) remained asymptomatic until discharge; 29 had abnormal and 34 had normal chest CT findings. The mean cohort age was 39.3 years, and 87.3% had no comorbidities. Mean time to diagnosis after close contact with a COVID-19 index patient was 16.0 days (range 1 to 29), and 13.4 days and 18.7 days for those with abnormal and normal CT findings, respectively (p < 0.05). Nine subjects (14.3%) transmitted the virus to others; 4 and 5 were in the abnormal and normal CT strata, respectively. The median length of nucleic acid turning negative in asymptomatic COVID-19 patients was 13 days, compared to 10.4 days in those with normal chest CT (p < 0.05). CONCLUSIONS: A portion of these asymptomatic individuals, with and without abnormal chest CT scans, were capable of transmitting the virus to others. Given the frequency and potential infectiousness of asymptomatic infections, testing of traced contacts is essential. Studies of the impact of treatment on asymptomatic RT-PCR+ individuals on disease progression and transmission should be undertaken.", "title": "Characterization of an asymptomatic cohort of SARS-COV-2 infected individuals outside of Wuhan, China", "pid": "we4kfb8u", "bm25_score": 215.75082397460938}, {"text": "At present, Coronavirus Disease 2019 (COVID-19) is rampaging around the world. However, asymptomatic carriers intensified the difficulty of prevention and management. Here we reported the screening, clinical feathers, and treatment process of a family cluster involving three COVID-19 patients. The discovery of the first asymptomatic carrier in this family cluster depends on the repeated and comprehensive epidemiological investigation by disease control experts. In addition, the combination of multiple detection methods can help clinicians find asymptomatic carriers as early as possible. In conclusion, the prevention and control experience of this family cluster showed that comprehensive rigorous epidemiological investigation and combination of multiple detection methods were of great value for the detection of hidden asymptomatic carriers. This article is protected by copyright. All rights reserved.", "title": "Alert for non-respiratory symptoms of Coronavirus Disease 2019 (COVID-19) patients in epidemic period: A case report of familial cluster with three asymptomatic COVID-19 patients", "pid": "v9e4is5j", "bm25_score": 215.7490997314453}, {"text": "Background: Up to 80% of active SARS-CoV-2 infections are proposed to be asymptomatic based on cross-sectional studies. However, accurate estimates of the asymptomatic proportion require systematic detection and follow-up to differentiate between truly asymptomatic and pre-symptomatic cases. We conducted a rapid review and meta-analysis of current evidence regarding the asymptomatic proportion of PCR-confirmed SARS-CoV-2 infections based on methodologically-appropriate studies in community settings. Methods: We searched Medline and EMBASE for peer-reviewed articles, and BioRxiv and MedRxiv for pre-prints published prior to 05/05/2020. We included studies based in community settings that involved systematic PCR testing on participants and follow-up symptom monitoring regardless of symptom status. We extracted data on study characteristics, frequencies of PCR-confirmed infections by symptom status, and (if available) cycle threshold values and/or duration of viral shedding by symptom status. We computed estimates of the asymptomatic proportion and 95% confidence intervals for each study and overall using random effect meta-analysis. Findings: We screened 270 studies and included 6. The pooled estimate for the asymptomatic proportion of SARS-CoV-2 infections was 11% (95% CI 4%-18%). Estimates of baseline viral load appeared to be similar for asymptomatic and symptomatic cases based on available data in three studies, though detailed reporting of cycle threshold values and natural history of viral shedding by symptom status was limited. Interpretation: The asymptomatic proportion of SARS-CoV-2 infections is relatively low when estimated from methodologically-appropriate studies. Further investigation into the degree and duration of infectiousness for asymptomatic infections is warranted. Funding: Medical Research Council", "title": "A Rapid Review of the Asymptomatic Proportion of PCR-Confirmed SARS-CoV-2 Infections in Community Settings", "pid": "plut8jl1", "bm25_score": 215.7443389892578}, {"text": "After the outbreak in Wuhan, China, we assessed 29,299 workers screened for severe acute respiratory syndrome coronavirus 2 by reverse transcription PCR. We noted 18 (0.061%) cases of asymptomatic infection; 13 turned negative within 8.0 days, and 41 close contacts tested negative. Among 6 contacts who had serologic tests, none were positive.", "title": "Severe Acute Respiratory Syndrome Coronavirus 2 among Asymptomatic Workers Screened for Work Resumption, China.", "pid": "rpdlk1b6", "bm25_score": 215.74301147460938}, {"text": "COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of \"the degree to which presymptomatic or asymptomatic infections can transmit\" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.", "title": "[Advances on presymptomatic or asymptomatic carrier transmission of COVID-19]", "pid": "3fd81ovn", "bm25_score": 215.70716857910156}, {"text": "Background: SARS-CoV-2 has been a global pandemic, but the emergence of asymptomatic patients has caused difficulties in the prevention of the epidemic. Therefore, it is significant to understand the epidemiological characteristics of asymptomatic patients with SARS-CoV-2 infection. Methods: In this single-center, retrospective and observational study, we collected data from 167 patients with SARS-CoV-2 infection treated in Chongqing Public Health Medical Center (Chongqing, China) from January to March 2020. The epidemiological characteristics and variable of these patients were collected and analyzed. Findings: 82.04% of the SARS-CoV-2 infected patients had a travel history in Wuhan or a history of contact with returnees from Wuhan, showing typical characteristics of imported cases, and the proportion of severe Covid-19 patients was 13.2%, of which 59% were imported from Wuhan. For the patients who was returnees from Wuhan, 18.1% was asymptomatic patients. In different infection periods, compared with the proportion after 1/31/2020, the proportion of asymptomatic patient among SARS-CoV-2 infected patient was higher(19% VS 1.5%). In different age groups, the proportion of asymptomatic patient was the highest(28.6%) in children group under 14, next in elder group over 70 (27.3%). Compared with mild and common Covid-19 patients, the mean latency of asymptomatic was longer (11.25 days VS 8.86 days), but the hospital length of stay was shorter (14.3 days VS 16.96 days) . Conclusion: The SARS-CoV-2 prevention needs to focus on the screening of asymptomatic patients in the community with a history of contact with the imported population, especially for children and the elderly population.", "title": "High incidence of asymptomatic SARS-CoV-2 infection, Chongqing, China", "pid": "7w1bhaz6", "bm25_score": 215.6938934326172}, {"text": "", "title": "Covid-19: four fifths of cases are asymptomatic, China figures indicate.", "pid": "wwam0ebo", "bm25_score": 215.6923828125}, {"text": "We conducted a study among healthcare workers (HCWs) exposed to patients with severe acute respiratory syndrome (SARS) before infection control measures were instituted. Of all exposed HCWs, 7.5% had asymptomatic SARS-positive cases. Asymptomatic SARS was associated with lower SARS antibody titers and higher use of masks when compared to pneumonic SARS.", "title": "Asymptomatic SARS Coronavirus Infection among Healthcare Workers, Singapore", "pid": "xcu80tcp", "bm25_score": 215.688720703125}, {"text": "PURPOSE: Aimed to characterize the CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia. METHODS: Asymptomatic cases with COVID-19 pneumonia confirmed by SARS-COV-2 nucleic acid testing in Renmin Hospital of Wuhan University were retrospectively enrolled. The characteristics of CT imaging and clinical feature were collected and analyzed. RESULTS: 58 asymptomatic cases with COVID-19 pneumonia admitted to our hospital between Jan 1, 2020 and Feb 23, 2020 were enrolled. All patients had history of exposure to SARS-CoV-2. On admission, patients had no symptoms and laboratory findings were normal. The predominant feature of CT findings in this cohort was ground glass opacity (GGO) (55, 94.8%) with peripheral (44, 75.9%) distribution, unilateral location (34, 58.6%) and mostly involving one or two lobes (38, 65.5%), often accompanied by characteristic signs. After short-term follow-up, 16 patients (27.6%) presented symptoms with lower lymphocyte count and higher CRP, mainly including fever, cough and fatigue. The evolution of lesions on CT imaging were observed in 10 patients (17.2%). The average days of hospitalization was19.80±10.82 days, and was significantly longer in progression patients (28.60±7.55 day). CONCLUSION: CT imaging of asymptomatic cases with COVID-19 pneumonia has definite characteristics. Since asymptomatic infections as \"covert transmitter\", and some patients can progress rapidly in the short term. It is essential to pay attention to the surveillance of asymptomatic patients with COVID-19. CT scan has great value in screening and detecting patients with COVID-19 pneumonia, especially in the highly suspicious, asymptomatic cases with negative nucleic acid testing.", "title": "CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan, China", "pid": "5daqr7ff", "bm25_score": 215.6839141845703}, {"text": "", "title": "Asymptomatic and Pre-Symptomatic COVID-19 in China", "pid": "r6as6syi", "bm25_score": 215.68353271484375}, {"text": "BACKGROUND: Limited information is available about COVID-19 infections among health care workers. Sensitive detection of COVID-19 cases in health care workers is crucial for hospital infection prevention policy, particularly for those who work with vulnerable patients. The aim of this study is to describe the prevalence of positive COVID-19 among asymptomatic health care workers who took care of patients with COVID-19 during the pandemic. METHODS: This retrospective study included all health care workers at King Abdullah University Hospital who take care of patients infected with COVID-19 patients from March 18, 2020 to April 29, 2020. They were tested for COVID-19 infection by use of real-time reverse-transcriptase rRT-PCR on samples from nasopharyngeal swabs. RESULTS: A total number of 370 health care workers were screened. The majority were nurses followed by physicians and other personnel. This study showed that all asymptomatic health care workers were tested negative for COVID-19Q. CONCLUSION: Unexpectedly, the prevalence of positive COVID-19 among asymptomatic health care workers who take care of patients infected with the novel coronavirus was 0%. This result must be cautiously interpreted. Further studies are needed in order to find effective strategy of screening health care workers to insure a safe working environment.", "title": "Prevalence of positive COVID-19 among asymptomatic health care workers who care patients infected with the novel coronavirus: A retrospective study", "pid": "hvo5smwx", "bm25_score": 215.68270874023438}, {"text": "Patients with coronavirus disease 2019 (COVID-19) with variable clinical presentations are encountered in the perioperative setting. While some have already been diagnosed and are symptomatic, others have undiagnosed, asymptomatic COVID-19. The latter group poses the greatest risk of transmission. Given limited capacities in most health care systems, diagnostic testing is mainly performed in symptomatic patients or those with relevant exposure. We report an intraoperative diagnosis of COVID-19 in an asymptomatic patient, prompted by clinical signs. To control a pandemic such as COVID-19, a high index of suspicion is pivotal when caring for asymptomatic patients in the perioperative setting.", "title": "Intraoperative Diagnosis of Coronavirus Disease 2019 in an Asymptomatic Patient: A Case Report", "pid": "d06wt817", "bm25_score": 215.67987060546875}, {"text": "2019 novel coronavirus pneumonia (COVID-19) is an ongoing global pandemic with a worldwide death toll of over 416,000 as of June 10, 2020. Although the first documented cases in Wuhan, China were patients with severe respiratory symptoms including cough, fever, fatigue, and shortness of breath, the disease process can also be asymptomatic. In this case report, an asymptomatic 63-year old male with Lynch syndrome undergoing a routine staging fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) was found to have typical radiologic features of COVID-19 with marked pulmonary FDG uptake and was subsequently diagnosed via RT-PCR. Many studies have described the appearance of COVID-19 on chest radiography and CT with the most common imaging features being bilateral, peripheral, and basilar predominant ground glass opacities and consolidation. Although these findings are typically nonspecific for an atypical lung infection, early recognition of COVID-19 in the setting of a global pandemic (even in the asymptomatic patient) is critical in order to limit the spread of disease.", "title": "COVID-19 in an asymptomatic patient undergoing FDG PET/CT", "pid": "w3fomrg8", "bm25_score": 215.67575073242188}, {"text": "Recent epidemiologic, virologic, and modeling reports support the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission from persons who are presymptomatic (SARS-CoV-2 detected before symptom onset) or asymptomatic (SARS-CoV-2 detected but symptoms never develop). SARS-CoV-2 transmission in the absence of symptoms reinforces the value of measures that prevent the spread of SARS-CoV-2 by infected persons who may not exhibit illness despite being infectious. Critical knowledge gaps include the relative incidence of asymptomatic and symptomatic SARS-CoV-2 infection, the public health interventions that prevent asymptomatic transmission, and the question of whether asymptomatic SARS-CoV-2 infection confers protective immunity.", "title": "Evidence Supporting Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 While Presymptomatic or Asymptomatic", "pid": "g12i1jig", "bm25_score": 215.65997314453125}, {"text": "Background: Some key gaps in the understanding of SARS-CoV-2 infection remain. One of them is the contribution to transmission from individuals experiencing asymptomatic infections. We aimed to characterise the proportion and infectiousness of asymptomatic infections using data from the outbreak on the Diamond Princess cruise ship. Methods: We used a transmission model of COVID-19 with asymptomatic and presymptomatic states calibrated to outbreak data from the Diamond Princess, to quantify the contribution of asymptomatic infections to transmission. Data available included the date of symptom onset for symptomatic disease for passengers and crew, the number of symptom agnostic tests done each day, and date of positive test for asymptomatic and presymptomatic individuals. Findings: On the Diamond Princess 74% (70-78%) of infections proceeded asymptomatically, i.e. a 1:3.8 case-to-infection ratio. Despite the intense testing 53%, (51-56%) of infections remained undetected, most of them asymptomatic. Asymptomatic individuals were the source for 69% (20-85%) of all infections. While the data did not allow identification of the infectiousness of asymptomatic infections, assuming no or low infectiousness resulted in posterior estimates for the net reproduction number of an individual progressing through presymptomatic and symptomatic stages in excess of 15. Interpretation: Asymptomatic SARS-CoV-2 infections may contribute substantially to transmission. This is essential to consider for countries when assessing the potential effectiveness of ongoing control measures to contain COVID-19.", "title": "The contribution of asymptomatic SARS-CoV-2 infections to transmission - a model-based analysis of the Diamond Princess outbreak", "pid": "eerqrqwk", "bm25_score": 215.652587890625}, {"text": "In a family experiencing coronavirus disease 2019, the parents and 2 children aged 2 and 5 years became infected but the youngest child was not infected. Both children initially shed infectious virus, but cleared the virus after 5 to 6 days in the nasopharynx. However, viral RNA was continuously detected in the children’s stool for more than 4 weeks.", "title": "Clinical and Epidemiological Features of a Family Cluster of Symptomatic and Asymptomatic Severe Acute Respiratory Syndrome Coronavirus 2 Infection", "pid": "zz5bpas1", "bm25_score": 215.63511657714844}, {"text": "BACKGROUND: Little is known about the natural history of asymptomatic SARS-CoV-2 infection or its contribution to infection transmission. METHODS: We conducted a prospective study at a quarantine center for COVID-19 in Ho Chi Minh City, Vietnam. We enrolled quarantined people with RT-PCR-confirmed SARS-CoV-2 infection, collecting clinical data, travel and contact history, and saliva at enrolment and daily nasopharyngeal throat swabs (NTS) for RT-PCR testing. We compared the natural history and transmission potential of asymptomatic and symptomatic individuals. RESULTS: Between March 10(th) and April 4(th), 2020, 14,000 quarantined people were tested for SARS-CoV-2; 49 were positive. Of these, 30 participated in the study: 13(43%) never had symptoms and 17(57%) were symptomatic. 17(57%) participants acquired their infection outside Vietnam. Compared with symptomatic individuals, asymptomatic people were less likely to have detectable SARS-CoV-2 in NTS samples collected at enrolment (8/13 (62%) vs. 17/17 (100%) P=0.02). SARS-CoV-2 RNA was detected in 20/27 (74%) available saliva; 7/11 (64%) in the asymptomatic and 13/16 (81%) in the symptomatic group (P=0.56). Analysis of the probability of RT-PCR positivity showed asymptomatic participants had faster viral clearance than symptomatic participants (P<0.001 for difference over first 19 days). This difference was most pronounced during the first week of follow-up. Two of the asymptomatic individuals appeared to transmit the infection to up to four contacts. CONCLUSIONS: Asymptomatic SARS-CoV-2 infection is common and can be detected by analysis of saliva or NTS. NTS viral loads fall faster in asymptomatic individuals, but they appear able to transmit the virus to others.", "title": "The natural history and transmission potential of asymptomatic SARS-CoV-2 infection", "pid": "bfe8e0wu", "bm25_score": 215.62673950195312}, {"text": "COVID-19 is rapidly spreading. Patients in incubation period and healthy carriers are possible sources for transmission. However, such sources of infection cannot be effectively identified due to the symptoms absent. The research evidence is very lacking so far, although there are a few studies suggesting that presymptomatic or asymptomatic carrier may cause COVID-19 transmission. Nearly half of the literature is in the state of preprint without peer review. The question of \"the degree to which presymptomatic or asymptomatic infections can transmit\" is not fully understood. There is an urgent need to screen infected carriers in larger close contacts or in the general population, and assess their risk for transmission.", "title": "[Advances on presymptomatic or asymptomatic carrier transmission of COVID-19].", "pid": "xbv0b96w", "bm25_score": 215.6238250732422}, {"text": "Abstract Purpose Aimed to characterize the CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia. Methods Asymptomatic cases with COVID-19 pneumonia confirmed by SARS-COV-2 nucleic acid testing in Renmin Hospital of Wuhan University were retrospectively enrolled. The characteristics of CT imaging and clinical feature were collected and analyzed. Results 58 asymptomatic cases with COVID-19 pneumonia admitted to our hospital between Jan 1, 2020 and Feb 23, 2020 were enrolled. All patients had history of exposure to SARS-CoV-2. On admission, patients had no symptoms and laboratory findings were normal. The predominant feature of CT findings in this cohort was ground glass opacity (GGO) (55, 94.8%) with peripheral (44, 75.9%) distribution, unilateral location (34, 58.6%) and mostly involving one or two lobes (38, 65.5%), often accompanied by characteristic signs. After short-term follow-up, 16 patients (27.6%) presented symptoms with lower lymphocyte count and higher CRP, mainly including fever, cough and fatigue. The evolution of lesions on CT imaging were observed in 10 patients (17.2%). The average days of hospitalization was19.80±10.82 days, and was significantly longer in progression patients (28.60±7.55 day). Conclusion CT imaging of asymptomatic cases with COVID-19 pneumonia has definite characteristics. Since asymptomatic infections as “covert transmitter”, and some patients can progress rapidly in the short term. It is essential to pay attention to the surveillance of asymptomatic patients with COVID-19. CT scan has great value in screening and detecting patients with COVID-19 pneumonia, especially in the highly suspicious, asymptomatic cases with negative nucleic acid testing.", "title": "CT imaging and clinical course of asymptomatic cases with COVID-19 pneumonia at admission in Wuhan, China", "pid": "zbzrxuoh", "bm25_score": 215.6216278076172}, {"text": "Coronavirus disease 2019 (COVID-19) is a novel human respiratory disease caused by the SARS-CoV-2 virus. Asymptomatic carriers of the virus display no clinical symptoms but are known to be contagious. Recent evidence reveals that this sub-population, as well as persons with mild, represent a major contributor in the propagation of COVID-19. The asymptomatic sub-population frequently escapes detection by public health surveillance systems. Because of this, the currently accepted estimates of the basic reproduction number (Ro) of the virus are inaccurate. It is unlikely that a pathogen can blanket the planet in three months with an Ro in the vicinity of 3, as reported in the literature. In this manuscript, we present a mathematical model taking into account asymptomatic carriers. Our results indicate that an initial value of the effective reproduction number could range from 5.5 to 25.4, with a point estimate of 15.4, assuming mean parameters. The first three weeks of the model exhibit exponential growth, which is in agreement with average case data collected from thirteen countries with universal health care and robust communicable disease surveillance systems; the average rate of growth in the number of reported cases is 23.3% per day during this period.", "title": "Investigating the Impact of Asymptomatic Carriers on COVID-19 Transmission", "pid": "tg5wbwf9", "bm25_score": 215.6199493408203}, {"text": "The current pandemic of COVID-19 has generated many challenging questions for the scientific community, ranging from queries about the origin of the virus to its pathogenesis and clinical management. This article is protected by copyright. All rights reserved.", "title": "Higher prevalence of asymptomatic or mild COVID‐19 in children, claims and clues", "pid": "n15i01tn", "bm25_score": 215.61294555664062}, {"text": "", "title": "An Asymptomatic Patient with COVID-19", "pid": "ls6cdive", "bm25_score": 215.6087188720703}, {"text": "Previously we showed that 31/1,032 (3%) asymptomatic healthcare workers (HCW) from a large teaching hospital in Cambridge UK tested positive for SARS-CoV-2 in April 2020. 26/169 (15%) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive (Rivett et al., 2020). Here we show that the proportion of both asymptomatic and symptomatic HCWs testing positive rapidly declined to near-zero between 25th April and 24th May 2020, corresponding with a decline in patient admissions with COVID-19 during the ongoing UK 'lockdown'. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent 'hubs' of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organisations in other sectors may be able to resume on-site work safely.", "title": "Effective control of SARS-CoV-2 transmission between healthcare workers during a period of diminished community prevalence of COVID-19", "pid": "p64gwyiu", "bm25_score": 215.60263061523438}, {"text": "Data are limited on the viral load, viral shedding patterns, and potential infectivity of asymptomatic patients (APs) with coronavirus disease 2019 (COVID-19). This study included 31 adult patients who were virologically confirmed to have COVID-19 but were asymptomatic on admission. Among these 31 patients, 22 presented symptoms after admission and were defined as asymptomatic patients in the incubation period (APIs); the other nine patients remained asymptomatic during hospitalization and were defined as asymptomatic patients (APs). The median cycle threshold (Ct) value of APs (39.0, interquartile range (IQR) 37.5-39.5) was significantly higher than that of APIs (34.5, IQR 32.2-37.0), indicating a lower viral load in APs. However, the duration of viral shedding remained similar in the two groups (7 days, IQR 5-14 days vs. 8 days, IQR 5-16 days). The study findings demonstrated that although APs with COVID-19 have a lower viral load, they still have certain period of viral shedding, which suggests the possibility of transmission during their asymptomatic period. Further longitudinal surveillance of these asymptomatic cases via virus nucleic acid testing are warranted.", "title": "Viral dynamics in asymptomatic patients with COVID-19", "pid": "thftzde3", "bm25_score": 215.59942626953125}, {"text": "Background: Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Methods: Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. Findings: None of the 24 asymptomatic cases presented any obvious symptoms before nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue and etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and five (20.8%) presented stripe shadowing in the lungs. The remaining seven (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These seven cases were younger (median age: 14.0 years; P = 0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Interpretation: The asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.", "title": "Clinical Characteristics of 24 Asymptomatic Infections with COVID-19 Screened among Close Contacts in Nanjing, China", "pid": "ofoqk100", "bm25_score": 215.5971221923828}, {"text": "Background: The prevalence of true asymptomatic COVID-19 cases is critical to policy makers considering the effectiveness of mitigation measures against the SARS-CoV-2 pandemic. We aimed to synthesize all available research on the asymptomatic rates and transmission rates where possible. Methods: We searched PubMed, Embase, Cochrane COVID-19 trials, and European PMC for pre-print platforms such as MedRxiv. We included primary studies reporting on asymptomatic prevalence where: (a) the sample frame includes at-risk population, and (b) there was sufficiently long follow up to identify pre-symptomatic cases. Meta-analysis used fixed effect and random effects models. Results: We screened 571 articles and included five low risk-of-bias studies from three countries (China (2), USA (2), Italy (1)) that tested 9,242 at-risk people, of which 413 were positive and 65 were asymptomatic. Diagnosis in all studies was confirmed using a RT-qPCR test. The proportion of asymptomatic cases ranged from 6% to 41%. Meta-analysis (fixed effect) found that the proportion of asymptomatic cases was 16% (95% CI: 12% - 20%) overall; higher in non-aged care 19% (15% - 24%), and lower in long-term aged care 8% (4% - 14%). Two studies provided direct evidence of forward transmission of the infection by asymptomatic cases but suggested lower rates than symptomatic cases. Conclusion: Our estimates of the prevalence of asymptomatic COVID-19 cases are lower than many highly publicized studies, but still substantial. Further robust epidemiological evidence is urgently needed, including in sub-populations such as children, to better understand the importance of asymptomatic cases for driving spread of the pandemic.", "title": "Estimating the extent of true asymptomatic COVID-19 and its potential for community transmission: systematic review and meta-analysis", "pid": "li8kvzdh", "bm25_score": 215.58050537109375}, {"text": "Asymptomatic infection occurs for numerous respiratory viral diseases, including influenza and COVID-19. We seek to clarify confusion in three areas: age-specific risks of transmission and/or disease; various definitions for the COVID-19 \"mortality rate\", each useful for specific purposes; and implications for student return strategies from pre-school through university settings.", "title": "Asymptomatic transmission and the infection fatality risk for COVID-19: Implications for school reopening", "pid": "401kxcmi", "bm25_score": 215.579345703125}, {"text": "Abstract From 78 laboratory-confirmed cases, we found 2 asymptomatic infections. One patient was discharged within 14 days after treatment. Another patient was discharged 25 days after treatment, and his TR-PCR test was still positive on the 15th day. We found that there may be virus carriers in asymptomatic population with epidemiological contact history. After 14 days of isolation, asymptomatic infection may still carry the virus, which means the risk of transmission and present a new challenge to home isolation.", "title": "The enlightenment from two cases of asymptomatic infection with SARS-CoV-2: is it safe after 14 days of isolation?", "pid": "h3imi4tk", "bm25_score": 215.53903198242188}, {"text": "Asymptomatic infection occurs for numerous respiratory viral diseases, including influenza and COVID-19. We seek to clarify confusion in three areas: age-specific risks of transmission and/or disease; various definitions for the COVID-19 “mortality rate”, each useful for specific purposes; and implications for student return strategies from pre-school through university settings.", "title": "Asymptomatic transmission and the infection fatality risk for COVID-19: Implications for school reopening", "pid": "e995ev2w", "bm25_score": 215.53102111816406}, {"text": "", "title": "COVID-19 transmission through asymptomatic carriers is a challenge to containment", "pid": "a4gbe42z", "bm25_score": 215.52960205078125}, {"text": "Among 78 laboratory-confirmed cases, we found two asymptomatic infections. One patient was discharged within 14 days after treatment. Another patient was discharged 25 days after treatment, and his RT-PCR test was still positive on the 15th day. We found that there may be virus carriers in the asymptomatic population with an epidemiological contact history. After 14 days of isolation, those with asymptomatic infection may still carry the virus, which means a risk of transmission, presenting a new challenge for the management of home isolation.", "title": "Evidence from two cases of asymptomatic infection with SARS-CoV-2: Are 14 days of isolation sufficient?", "pid": "exket0xs", "bm25_score": 215.52691650390625}, {"text": "", "title": "Asymptomatic COVID-19 transmission: the importance of avoiding official miscommunication", "pid": "vs01f85s", "bm25_score": 215.5242462158203}, {"text": "Coronavirus disease 2019 (COVID-19) is an infectious disease with a high asymptomatic incidence. Asymptomatic infections within a population will inevitably lead to diagnosis via unrelated medical imaging. We report the case of an asymptomatic patient undergoing a spine CT examination for trauma who was incidentally found to have lung abnormalities later confirmed to be COVID-19. We aim to familiarize neuroradiologists with the spectrum of COVID-19 pulmonary manifestations that are likely to be observed on neck and spine CT imaging.", "title": "Asymptomatic COVID-19: What the Neuroradiologist Needs to Know about Pulmonary Manifestations.", "pid": "t0mqh9m0", "bm25_score": 215.51950073242188}, {"text": "Coronavirus disease 2019 (COVID-19) is an infectious disease with a high asymptomatic incidence. Asymptomatic infections within a population will inevitably lead to diagnosis via unrelated medical imaging. We report the case of an asymptomatic patient undergoing a spine CT examination for trauma who was incidentally found to have lung abnormalities later confirmed to be COVID-19. We aim to familiarize neuroradiologists with the spectrum of COVID-19 pulmonary manifestations that are likely to be observed on neck and spine CT imaging.", "title": "Asymptomatic COVID-19: What the Neuroradiologist Needs to Know about Pulmonary Manifestations", "pid": "5j6uu16i", "bm25_score": 215.5170135498047}, {"text": "Data concerning the transmission of the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) in paucisymptomatic patients are lacking. We report an Italian paucisymptomatic case of coronavirus disease 2019 with multiple biological samples positive for SARS-CoV-2. This case was detected using the World Health Organization protocol on cases and contact investigation. Current discharge criteria and the impact of extra-pulmonary SARS-CoV-2 samples are discussed.", "title": "Coronavirus disease (COVID-19) in a paucisymptomatic patient: epidemiological and clinical challenge in settings with limited community transmission, Italy, February 2020", "pid": "uptx84we", "bm25_score": 215.5147705078125}, {"text": "", "title": "Clinical Features and Outcomes of Asymptomatic Cases of SARS-CoV-2 Infection", "pid": "kj92cr7r", "bm25_score": 215.50064086914062}, {"text": "Whether severe acute respiratory syndrome–associated coronavirus (SARS-CoV) infection can be asymptomatic is unclear. We examined the seroprevalence of SARS-CoV among 674 healthcare workers from a hospital in which a SARS outbreak had occurred. A total of 353 (52%) experienced mild self-limiting illnesses, and 321 (48%) were asymptomatic throughout the course of these observations. None of these healthcare workers had antibody to SARS CoV, indicating that subclinical or mild infection attributable to SARS CoV in adults is rare.", "title": "Severe Acute Respiratory Syndrome–associated Coronavirus Infection", "pid": "wivzfv6t", "bm25_score": 215.49920654296875}, {"text": "", "title": "Asymptomatic COVID-19 transmission: the importance of avoiding official miscommunication.", "pid": "d4ujcv2g", "bm25_score": 215.49703979492188}, {"text": "", "title": "Letter to the Editor concerning A study on infectivity of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) carriers by Gao et al", "pid": "ypenda9f", "bm25_score": 215.48292541503906}, {"text": "Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged.", "title": "Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China", "pid": "nubzfw13", "bm25_score": 215.47927856445312}, {"text": "Previous studies have showed clinical characteristics of patients with the 2019 novel coronavirus disease (COVID-19) and the evidence of person-to-person transmission. Limited data are available for asymptomatic infections. This study aims to present the clinical characteristics of 24 cases with asymptomatic infection screened from close contacts and to show the transmission potential of asymptomatic COVID-19 virus carriers. Epidemiological investigations were conducted among all close contacts of COVID-19 patients (or suspected patients) in Nanjing, Jiangsu Province, China, from Jan 28 to Feb 9, 2020, both in clinic and in community. Asymptomatic carriers were laboratory-confirmed positive for the COVID-19 virus by testing the nucleic acid of the pharyngeal swab samples. Their clinical records, laboratory assessments, and chest CT scans were reviewed. As a result, none of the 24 asymptomatic cases presented any obvious symptoms while nucleic acid screening. Five cases (20.8%) developed symptoms (fever, cough, fatigue, etc.) during hospitalization. Twelve (50.0%) cases showed typical CT images of ground-glass chest and 5 (20.8%) presented stripe shadowing in the lungs. The remaining 7 (29.2%) cases showed normal CT image and had no symptoms during hospitalization. These 7 cases were younger (median age: 14.0 years; P=0.012) than the rest. None of the 24 cases developed severe COVID-19 pneumonia or died. The median communicable period, defined as the interval from the first day of positive nucleic acid tests to the first day of continuous negative tests, was 9.5 days (up to 21 days among the 24 asymptomatic cases). Through epidemiological investigation, we observed a typical asymptomatic transmission to the cohabiting family members, which even caused severe COVID-19 pneumonia. Overall, the asymptomatic carriers identified from close contacts were prone to be mildly ill during hospitalization. However, the communicable period could be up to three weeks and the communicated patients could develop severe illness. These results highlighted the importance of close contact tracing and longitudinally surveillance via virus nucleic acid tests. Further isolation recommendation and continuous nucleic acid tests may also be recommended to the patients discharged. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available for this article at 10.1007/s11427-020-1661-4 and is accessible for authorized users.", "title": "Clinical characteristics of 24 asymptomatic infections with COVID-19 screened among close contacts in Nanjing, China", "pid": "iff8cuum", "bm25_score": 215.47927856445312}, {"text": "", "title": "Covid-19: Nine in 10 pregnant women with infection when admitted for delivery are asymptomatic, small study finds.", "pid": "baiim35r", "bm25_score": 215.475341796875}, {"text": "BACKGROUND: The ongoing COVID-19 pandemic is a global threat. Identification of markers for symptom onset and disease progression is a pressing issue. We described the clinical features of people infected on board the Diamond Princess cruise ship who were diagnosed with asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or mild or severe COVID-19, on admission to the Self-Defense Forces Central Hospital (Tokyo, Japan) and at the end of observation. METHODS: This retrospective, single-centre study included participants with laboratory-detected SARS-CoV-2 infection who were admitted to the Self-Defense Forces Central Hospital from Feb 11 to Feb 25, 2020. Clinical records, laboratory data, and radiological findings were analysed. Clinical outcomes were followed up until discharge or Feb 26, 2020, whichever came first. We defined asymptomatic infection as SARS-CoV-2 infection with no history of clinical signs and symptoms, severe COVID-19 as clinical symptoms of pneumonia (dyspnoea, tachypnoea, peripheral capillary oxygen saturation <93%, and need for oxygen therapy), and mild COVID-19 as all other symptoms. Clinical features on admission were compared among patients with different disease severity, including asymptomatic infection, at the end of observation. We used univariable analysis to identify factors associated with symptomatic illness among asymptomatic people infected with SARS-CoV-2 and disease progression in patients with COVID-19. FINDINGS: Among the 104 participants included in the final analysis, the median age was 68 years (IQR 47-75) and 54 (52%) were male. On admission, 43 (41%) participants were classified as asymptomatic, 41 (39%) as having mild COVID-10, and 20 (19%) as having severe COVID-19. At the end of observation, 33 (32%) participants were confirmed as being asymptomatic, 43 (41%) as having mild COVID-19, and 28 (27%) as having severe COVID-19. Serum lactate hydrogenase concentrations were significantly higher in the ten participants who were asymptomatic on admission but developed symptomatic COVID-19 compared with the 33 participants who remained asymptomatic throughout the observation period (five [50%] vs four [12%] participants; odds ratio 7·25, 95% CI 1·43-36·70; p=0·020). Compared with patients with mild disease at the end of observation, patients with severe COVID-19 were older (median age 73 years [IQR 55-77] vs 60 years [40-71]; p=0·028) and had more frequent consolidation on chest CT (13 [46%] of 28 vs nine [21%] of 43; p=0·035) and lymphopenia (16 [57%] vs ten [23%]; p=0·0055) on admission. INTERPRETATION: Older age, consolidation on chest CT images, and lymphopenia might be risk factors for disease progression of COVID-19 and contribute to improved clinical management. FUNDING: None.", "title": "Clinical characteristics of COVID-19 in 104 people with SARS-CoV-2 infection on the Diamond Princess cruise ship: a retrospective analysis", "pid": "2i1q54nd", "bm25_score": 215.47503662109375}, {"text": "Objectives: The objective of the study was to conduct a follow-up investigation of 10 asymptomatic patients at diagnosis among the 98 confirmed COVID-19 cases reported in Busan between February 21 and March 13, 2020 to determine whether asymptomatic infection and transmission during asymptomatic period are possible. Methods: The study analyzed 10 asymptomatic, confirmed COVID-19 cases to determine whether asymptomatic infection is possible. We conducted in-depth interviews with patients and guardians; interviews with primary physicians; review of medical records and drug utilization review (DUR) reports; and base station-based location tracking. Results: Among the 98, confirmed COVID-19 cases reported in Busan, the study analyzed 10 (10.2%) asymptomatic patients at diagnosis. The Results confirmed that two (2.0%) patients reported to be asymptomatic during the initial epidemiological investigation, but turned symptomatic before diagnosis as per the in-depth interview results. Four cases (4.0%) of early detection led to confirmed diagnosis during the incubation period and presentation of symptoms after diagnosis. In addition, the remaining four patients (4.0%), having no subjective symptoms nor specific findings on chest radiography and Computed Tomography, remained asymptomatic until the isolation order was lifted. With regard to whether transmission during the asymptomatic period is possible, it was found that one out of 23 household contacts of the confirmed patients was identified as an additional confirmed case after coming in close contact with an index patient during the presymptomatic period. Conclusion: Among the 98 confirmed cases, asymptomatic infection was confirmed in four cases (4.0%). In addition, there was one additional confirmed case in which the patient was a family member who came in close contact with an index patient during the incubation period, thereby confirming that transmission during the asymptomatic period is possible. The possibility of transmission during the asymptomatic period has been confirmed; therefore, it is necessary to review the measures for expanding contact tracing that is currently being applied starting one day prior to the onset of symptoms.", "title": "Follow up investigation of asymptomatic COVID-19 cases at diagnosis in Busan, Korea", "pid": "op7ohlv3", "bm25_score": 215.4635009765625}]}
{"idx": 27, "qid": "28", "q_text": "what evidence is there for the value of hydroxychloroquine in treating Covid-19?", "qrels": {"01s21vh0": 1, "03eifdr1": 2, "pl9ht0d0": 0, "063hs3u1": 2, "06k7pknx": 0, "06yilajc": 2, "07tdrd4w": 2, "08ds967z": 0, "08j87r2u": 0, "yzr7ifbj": 1, "brqby02y": 0, "0cvoeiy0": 0, "0dav52vr": 2, "0dut550o": 0, "0eizsamh": 0, "0ewcptub": 1, "0gozdv43": 2, "0gss1knb": 2, "0hrmk77p": 1, "0ikvdwkz": 2, "0jr31q5g": 2, "0kss5r7u": 0, "0lk8eujq": 2, "0mciznu2": 0, "0n52x2z7": 0, "0nh58odf": 0, "0oxo2awm": 2, "0pi3wcv5": 2, "0piwihfs": 2, "jn2or2a2": 2, "0qwwycnc": 0, "0qy1nngs": 0, "0sm0r4v8": 0, "0sy3j2oc": 2, "0ti403i4": 0, "0tkx7aas": 0, "2bl0q0b1": 2, "0u4ar3b5": 2, "0uengr9t": 0, "0wpzsmoy": 1, "qo39xyhq": 2, "11sxecb3": 0, "12ikum8s": 2, "12th7nja": 2, "1n6d1gco": 1, "13h5i2nw": 0, "13n2ks4l": 2, "14he8n3u": 0, "cussiba2": 0, "1zutvba1": 0, "16ff3c7m": 1, "kdd9bggz": 2, "195h4ofw": 2, "1aal6njl": 0, "1b4qkn36": 2, "1bapn9w0": 0, "1dhj7ixu": 2, "1fgnfh62": 0, 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We aim to provide evidence to support clinical decision-making regarding medication for the treatment of COVID-19 by carrying out a systematic review of the literature. The electronic databases MEDLINE, EMBASE, Global Health, and HMIC were searched up to April 2020. Eligible study outcomes included: extubation or patient recovery. Relevant data were extracted and analysed by narrative synthesis. Our results included six studies in the review of which four studies were of good or fair quality. All eligible studies included were for coronavirus involving the use of either chloroquine or hydroxychloroquine to treat common symptoms such as fever, cough, shortness of breath and fatigue. Outcomes most commonly reported were improved lung function, viral clearance, and hospital discharge. Strong evidence to support the use of chloroquine and hydroxychloroquine in the treatment of COVID-19 is lacking. Fast track trials are riddled with bias and may not conform to rigorous guidelines which may lead to inadequate data being reported. The use of these drugs in combination with other medications may be useful but without knowing which groups they are suited for and when they may cause more harm than good.", "title": "Chloroquine and hydroxychloroquine effectiveness in human subjects during coronavirus: a systematic review", "pid": "w1au4pyl", "bm25_score": 220.51370239257812}, {"text": "Hydroxychloroquine (HCQ) has sparked much interest in the therapeutics of the Coronavirus Disease 2019 (COVID-19) pandemic. Its antiviral properties have been studied for years; regarding the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), it has been shown that HCQ may act at multiple levels. These extend from the initial attachment of the virus to the respiratory epithelium to the inhibition of its replication by the alkalinisation of the phagolysosome's microenvironment and the post-translational modification of certain viral proteins. Preliminary clinical evidence from China and France showed significant virological and clinical benefit in HCQ-treated patients, while other studies, mostly including critically ill patients, did not show favorable results. In this review, we critically appraise the existing evidence on HCQ against SARS-CoV-2 with particular emphasis on its protective and therapeutic role. Safety concerns that are relevant to the short-term HCQ use are also discussed. In the context of the rapid evolution of the COVID-19 pandemic that strains the health care systems worldwide and considering limited population-wide testing rates in most of the vulnerable countries, early empiric short-term administration of HCQ in symptomatic individuals, may be a promising, safe and low-cost strategy.", "title": "Hydroxychloroquine against COVID-19: A critical appraisal of the existing evidence.", "pid": "an28gfe4", "bm25_score": 220.31956481933594}, {"text": "BACKGROUNDS AND AIMS: The role of hydroxychloroquine (HCQ) in the treatment of COVID-19 is not fully known. We studied the efficacy of HCQ compared to the control in COVID-19 subjects on a. viral clearance measured by reverse transcriptase polymerase chain reaction (RT-PCR) and, b. death due to all cause. METHODS: PubMed, Scopus, Cochrane and MedRxiv database were searched using the specific keywords up to April 30, 2020. Studies that met our objectives were assessed for the risk of bias applying various tools as indicated. Three studies each that reported the outcome of viral clearance by RT-PCR and death due to all cause, were meta-analyzed by applying inverse variance-weighted averages of logarithmic risk ratio (RR) using a random effects model. Heterogeneity and publication bias were assessed using the I(2) statistic and funnel plots, respectively. RESULTS: Meta-analysis of 3 studies (n = 210) on viral clearance assessed by RT-PCR showed no benefit (RR, 1.05; 95% CI, 0.79 to 1.38; p = 0.74), although with a moderate heterogeneity (I(2) = 61.7%, p = 0.07). While meta-analysis of 3 studies (n = 474) showed a significant increase in death with HCQ, compared to the control (RR, 2.17; 95% 1.32 to 3.57; p = 0.002), without any heterogeneity (I(2) = 0.0%, p = 0.43). CONCLUSIONS: No benefit on viral clearance but a significant increase in mortality was observed with HCQ compared to control in patients with COVID-19.", "title": "“Hydroxychloroquine in patients with COVID-19: A Systematic Review and meta-analysis.”", "pid": "95zrth5d", "bm25_score": 220.24246215820312}, {"text": "Hydroxychloroquine (HCQ) has sparked much interest in the therapeutics of the Coronavirus Disease 2019 (COVID-19) pandemic. Its antiviral properties have been studied for years; regarding the Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2), it has been shown that HCQ may act at multiple levels. These extend from the initial attachment of the virus to the respiratory epithelium to the inhibition of its replication by the alkalinisation of the phagolysosome's microenvironment and the post-translational modification of certain viral proteins. Preliminary clinical evidence from China and France showed significant virological and clinical benefit in HCQ-treated patients, while other studies, mostly including critically ill patients, did not show favorable results. In this review, we critically appraise the existing evidence on HCQ against SARS-CoV-2 with particular emphasis on its protective and therapeutic role. Safety concerns that are relevant to the short-term HCQ use are also discussed. In the context of the rapid evolution of the COVID-19 pandemic that strains the health care systems worldwide and considering limited population-wide testing rates in most of the vulnerable countries, early empiric short-term administration of HCQ in symptomatic individuals, may be a promising, safe and low-cost strategy.", "title": "Hydroxychloroquine against COVID-19: A critical appraisal of the existing evidence", "pid": "5jafu8tw", "bm25_score": 220.16262817382812}, {"text": "Background: There is no effective therapy for COVID-19. Hydroxychloroquine (HCQ) and chloroquine (CQ) have been used for its treatment but their safety and efficacy remain uncertain. Objective: We performed a systematic review to synthesize the available data on the efficacy and safety of CQ and HCQ for the treatment of COVID-19. Methods: Two reviewers searched for published and pre-published relevant articles between December 2019 to 8th June 2020. The data from the selected studies were abstracted and analyzed for efficacy and safety outcomes. Critical appraisal of the evidence was done by Cochrane risk of bias tool and Newcastle Ottawa scale. The quality of evidence was graded as per the GRADE approach. Results: We reviewed 12 observational and 3 randomized trials which included 10659 patients of whom 5713 received CQ/HCQ and 4966 received only standard of care. The efficacy of CQ/HCQ for COVID-19 was inconsistent across the studies. Meta-analysis of included studies revealed no significant reduction in mortality with HCQ use [RR 0.98 95% CI 0.66-1.46] , time to fever resolution [mean difference -0.54 days (-1.19-011)] or clinical deterioration/development of ARDS with HCQ [RR 0.90 95% CI 0.47-1.71]. There was a higher risk of ECG abnormalities/arrhythmia with HCQ/CQ [RR 1.46 95% CI 1.04 to 2.06]. The quality of evidence was graded as very low for these outcomes. Conclusions: The available evidence suggests that CQ or HCQ does not improve clinical outcomes in COVID-19. Well-designed randomized trials are required for assessing the efficacy and safety of HCQ and CQ for COVID-19.", "title": "Chloroquine and Hydroxychloroquine for the treatment of COVID-19: A Systematic Review and Meta-analysis", "pid": "uf32cq68", "bm25_score": 220.1573486328125}, {"text": "The severity of COVID-19 disease has led to an urgent need for the discovery of new treatments. Thus, global stocks of hydroxychloroquine (HCQ) have been put under pressure with a study of 26 patients treated with HCQ during their infection with SARS-CoV-2. Despite the study's lack of quality, several countries' medicines agencies subsequently issued guidelines for the use of HCQ for COVID-19. This review aims to elucidate potential mechanisms, which make HCQ treatment interesting in the fight against SARS-CoV-2 infection, as well as the current evidence for clinical use of HCQ to treat COVID-19.", "title": "[Lack of clinical evidence for the use of hydroxychloroquine to treat SARS-CoV-2 infection].", "pid": "hjl6vdwy", "bm25_score": 220.14212036132812}, {"text": "BACKGROUNDS AND AIMS: The role of hydroxychloroquine (HCQ) in the treatment of COVID-19 is not fully known. We studied the efficacy of HCQ compared to the control in COVID-19 subjects on - a. viral clearance measured by reverse transcriptase polymerase chain reaction (RT-PCR) and, b. death due to all cause. METHODS: PubMed, Scopus, Cochrane and MedRxiv database were searched using the specific keywords up to April 30, 2020. Studies that met our objectives were assessed for the risk of bias applying various tools as indicated. Three studies each that reported the outcome of viral clearance by RT-PCR and death due to all cause, were meta-analyzed by applying inverse variance-weighted averages of logarithmic risk ratio (RR) using a random effects model. Heterogeneity and publication bias were assessed using the I2 statistic and funnel plots, respectively. RESULTS: Meta-analysis of 3 studies (n = 210) on viral clearance assessed by RT-PCR showed no benefit (RR, 1.05; 95% CI, 0.79 to 1.38; p = 0.74), although with a moderate heterogeneity (I2 = 61.7%, p = 0.07). While meta-analysis of 3 studies (n = 474) showed a significant increase in death with HCQ, compared to the control (RR, 2.17; 95% 1.32 to 3.57; p = 0.002), without any heterogeneity (I2 = 0.0%, p = 0.43). CONCLUSIONS: No benefit on viral clearance but a significant increase in mortality was observed with HCQ compared to control in patients with COVID-19.", "title": "\"Hydroxychloroquine in patients with COVID-19: A Systematic Review and meta-analysis.\"", "pid": "dapkxiyy", "bm25_score": 220.12538146972656}, {"text": "Chloroquine and Hydroxychloroquine are drugs which have been widely used in malaria and rheumatoid arthritis respectively for over 50 years. There was anecdotal evidence of their efficacy in the earlier SARS outbreak in 2003. This prompted physicians from across the world to use them in the present SARS-CoV- 2 pandemic that is currently sweeping the globe, with 5 million people already infected to date. These drugs are already in widespread use for the treatment of COVID-19 in India, mainly because they are cheap and easily available, and because of the absence of any readily available alternative therapy. This timely review discusses the pre-clinical evidence, and data from the eight available clinical trials. We emphasise that careful monitoring for cardiac toxicity is required when these drugs are used. Finally, we conclude that current data does not allow us to recommend for or against the use of these drugs. Results of two large RCTs, one from the NIH and the other from WHO (Solidarity) are eagerly awaited before the role of these drugs in COVID-19 can be definitively established.", "title": "Hydroxychloroquine for COVID-19: What is our Current State of Knowledge?", "pid": "b6aeu1ph", "bm25_score": 220.11056518554688}, {"text": "The severity of COVID-19 disease has led to an urgent need for the discovery of new treatments. Thus, global stocks of hydroxychloroquine (HCQ) have been put under pressure with a study of 26 patients treated with HCQ during their infection with SARS-CoV-2. Despite the study's lack of quality, several countries' medicines agencies subsequently issued guidelines for the use of HCQ for COVID-19. This review aims to elucidate potential mechanisms, which make HCQ treatment interesting in the fight against SARS-CoV-2 infection, as well as the current evidence for clinical use of HCQ to treat COVID-19.", "title": "[Lack of clinical evidence for the use of hydroxychloroquine to treat SARS-CoV-2 infection]", "pid": "v5qhqn9o", "bm25_score": 220.08250427246094}, {"text": "At present, there are no studies demonstrating the clinical efficacy of hydroxychloroquine for the prophylaxis or treatment of COVID-19 infection.", "title": "Hydroxychloroquine use during the COVID-19 pandemic 2020.", "pid": "svwkpcme", "bm25_score": 220.02467346191406}, {"text": "BACKGROUND: On the 11 March 2020, the World Health Organization (WHO) declared that COVID-19 was a pandemic. To date, there are no medical treatments for COVID-19 with proven effectiveness. Novel treatments and/or vaccines will take time to be developed and distributed to patients. In light of this, there has been growing interest in the use of existing medications, such as chloroquine (CQ) and hydroxychloroquine (HCQ), as potential treatments of this disease. AIM: To establish the current evidence for the effectiveness of CQ and HCQ in treating COVID-19. DESIGN & SETTING: A rapid review of the literature was conducted. METHOD: Electronic searches in PubMed and Google Scholar were conducted on 21 March 2020. A further search was conducted in Google for relevant literature on 28 March 2020. RESULTS: There is limited evidence of in vitro activity of CQ/HCQ against SARS-CoV-2. A number of in vivo clinical trials are underway. The empirical data available from two of these trials reveal conflicting results. Both trials are characterised by small numbers of participants (n = 30 and n = 36) and suffer methodological limitations. No medium or long-term follow-up data is available. CONCLUSION: At present, there is insufficient evidence to determine whether CQ/HCQ are safe and effective treatments for COVID-19. High quality, adequately powered randomised clinical trials in primary and secondary care settings are urgently required to guide policymakers and clinicians. These studies should report medium- and long-term follow-up results, and safety data.", "title": "Should chloroquine and hydroxychloroquine be used to treat COVID-19? A rapid review", "pid": "86h5ptxm", "bm25_score": 220.02008056640625}, {"text": "Background: Coronavirus Disease 2019 (COVID-19) has become a major global issue with rising the number of infected individuals and mortality in recent months. Among all therapeutic approaches, arguments have raised about hydroxychloroquine efficacy in treatment of COVID-19. We aimed to overcome the controversies regarding effectiveness of hydroxychloroquine in treatment of COVID-19, using a systematic review and meta-analysis. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science, Google Scholar and medRxiv pre-print database using all available MeSH terms for COVID-19 and hydroxychloroquine. Two authors selected and assessed the quality of studies independently using related checklists. Data have been extracted from included studies and analyzed using CMA v. 2.2.064. heterogeneity was also assessed using I-squared test. Results: Seven studies including four clinical trials and three observational studies have entered into the study. The results of meta-analysis of clinical trials showed that there were no significant differences between patients who received the standard treatment with HCQ regimen and the patients that received the standard treatment without HCQ (RR: 1.44, 95% CI, 0.80-2.59). CT-Scan findings improved in 59% (95% CI 0.15-0.92) and nasopharyngeal culture following RT-PCR resulted negative in 76% (95% CI 0.56-0.89) of patients received hydroxychloroquine. Meta-analysis of observational studies showed 75% (95% CI, 0.54-0.88) of patients were discharged from the hospital, 34% (95% CI, 0.07-0.14) admitted to intensive care unit and 1.5% (95% CI, 0.03-0.83) have expired. Conclusion: This study indicated no clinical benefits regarding HCQ for treatment of COVID-19 patients. However, further large clinical trials should be taken into account in order to achieve more reliable findings.", "title": "Hydroxychloroquine Versus COVID-19: A Rapid Systematic Review and Meta-Analysis", "pid": "ujomta30", "bm25_score": 219.9713592529297}, {"text": "Hydroxychloroquine (HCQ) has multiple potential antiviral mechanisms of action that differ according to the pathogen studied (eg, Chikungunya, Dengue virus, human immunodeficiency virus, poliovirus, Zika virus). Data on HCQ for treatment of coronavirus disease 2019 (COVID-19) are rapidly evolving. To date, there is no evidence from randomized controlled trials that HCQ, or any single therapy, improves outcomes in patients infected with COVID-19. There are also no clinical trial data supporting prophylactic HCQ therapy in COVID-19. Use of HCQ in patients with COVID-19 is being investigated for prophylaxis, postexposure prophylaxis, and treatment.", "title": "Hydroxychloroquine use in the COVID-19 patient", "pid": "1x9vqepb", "bm25_score": 219.93203735351562}, {"text": "", "title": "Hydroxychloroquine in the treatment of COVID-19: how to use it waiting for conclusive scientific evidence()", "pid": "hpgrbhkl", "bm25_score": 219.93060302734375}, {"text": "Background: Coronavirus pandemic is currently a global public health emergency. At present, no pharmacological treatment is known to treat this condition, and there is a need to review the available treatments. Objective: While there have been studies to describe the role of chloroquine and hydroxychloroquine in various viral conditions, there is limited information about the use of them in COVID-19. This systematic review aims to summarize the available evidence regarding the role of chloroquine in treating coronavirus infection. Methods: The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used for this review. A literature search was performed using PUBMED & Google Scholar to find articles about the role of CQ in COVID-19 patients. Results: We included 19 publications (Five published articles, three letters/correspondence, one commentary, five pre-proofs of accepted articles, one abstract of yet to be published article, and four were pre-prints (not yet peer-reviewed) articles) in this systematic review. All the articles mentioned about the role of chloroquine and /or hydroxychloroquine in limiting the infection with SARS-CoV-2 (the virus causing COVID-19). Conclusions: There is theoretical, experimental, preclinical and clinical evidence of the effectiveness of chloroquine in patients affected with COVID-19. There is adequate evidence of drug safety from the long-time clinical use of chloroquine and hydroxychloroquine in other indications. More data from ongoing and future trials will add more insight into the role of chloroquine and hydroxychloroquine in COVID-19 infection.", "title": "Role of Chloroquine and Hydroxychloroquine in the Treatment of COVID-19 Infection- A Systematic Literature Review", "pid": "0lk8eujq", "bm25_score": 219.87710571289062}, {"text": "Hydroxychloroquine (HCQ) has multiple potential antiviral mechanisms of action that differ according to the pathogen studied (eg, Chikungunya, Dengue virus, human immunodeficiency virus, poliovirus, Zika virus). Data on HCQ for treatment of coronavirus disease 2019 (COVID-19) are rapidly evolving. To date there is no evidence from randomized controlled trials that any single therapy improves outcomes in patients infected with COVID-19. There are also no clinical trial data supporting prophylactic HCQ therapy in COVID-19. Hydroxychloroquine (HCQ) use in patients with COVID-19 is being investigated examining prophylaxis, postexposure prophylaxis, and treatment regimens.", "title": "Hydroxychloroquine use in the COVID-19 patient.", "pid": "7ttesiuu", "bm25_score": 219.871337890625}, {"text": "BACKGROUND AND OBJECTIVE: The world is currently experiencing the Coronavirus Disease-19 (COVID-19) pandemic. There is no approved drug for the definitive treatment of the disease. Various drugs are being tried for the treatment of COVID-19, including hydroxychloroquine (HCQ). This study was performed to systematically review the therapeutic role of HCQ in COVID-19 from the available literature. METHODS: PubMed, Embase, ClinicalTrials.gov, ICTRP (WHO), Cochrane Library databases, and two pre-print servers (medRxiv.org and Research Square) were searched for clinical studies that evaluated the therapeutic role of HCQ on COVID-19 until 10 May 2020. The available studies were critically analyzed and the data were extracted. RESULTS: A total of 663 articles were screened and 12 clinical studies (seven peer-reviewed and published studies and five non-peer-reviewed studies from pre-print servers) with a total sample size of 3543 patients were included. Some of the clinical studies demonstrated good virological and clinical outcomes with HCQ alone or in combination with azithromycin in COVID-19 patients, although the studies had major methodological limitations. Some of the other studies showed negative results with HCQ therapy along with the risk of adverse reactions. CONCLUSION: The results of efficacy and safety of HCQ in COVID-19, as obtained from the clinical studies, are not satisfactory, although many of these studies had major methodological limitations. Stronger evidence from well-designed robust randomized clinical trials is required before conclusively determining the role of HCQ in the treatment of COVID-19. Clinical prudence is required in advocating HCQ as a therapeutic armamentarium in COVID-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40261-020-00927-1) contains supplementary material, which is available to authorized users.", "title": "An Updated Systematic Review of the Therapeutic Role of Hydroxychloroquine in Coronavirus Disease-19 (COVID-19)", "pid": "ne8k1vez", "bm25_score": 219.865966796875}, {"text": "The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019. As similar cases rapidly emerged around the world(1–3), the World Health Organization (WHO) declared a public health emergency of international concern on January 30, 2020 and pronounced the rapidly spreading coronavirus outbreak as a pandemic on March 11, 2020(4). The virus has reached almost all countries of the globe. As of June 3, 2020, the accumulated confirmed cases reached 6,479,405 with more than 383,013 deaths worldwide. The urgent and emergency care of COVID-19 patients calls for effective drugs, in addition to the beneficial effects of remdesivir(5), to control the disease and halt the pandemic.", "title": "Is hydroxychloroquine beneficial for COVID-19 patients?", "pid": "hqkrer9m", "bm25_score": 219.85659790039062}, {"text": "Chloroquine and closely related structural analogs, employed initially for the treatment of malaria, are now gaining worldwide attention due to the rapidly spreading pandemic caused by severe acute respiratory syndrome-coronavirus-2, named coronavirus disease (COVID) of 2019 (COVID-19). Although much of this attention has a mechanistic basis, the hard efficacy data for chloroquine/hydroxychloroquine in the management of the clinical syndrome of COVID-19 have been limited thus far. This review aims to present the available in vitro and clinical data for the role of chloroquine/hydroxychloroquine in COVID-19 and attempts to put them into perspective, especially in relation to the different risks/benefits particular to each patient who may require treatment.", "title": "Chloroquine and hydroxychloroquine in the context of COVID-19", "pid": "tkqmu1va", "bm25_score": 219.82882690429688}, {"text": "In less than six months, COVID-19 has spread from a marketplace in Wuhan, China to over 150 countries and territories of the world. Therapeutics are desperately needed to reduce the morbidity and mortality of this pandemic disease. It has been reported that hydroxychloroquine (HCQ) is active against SARS-CoV-2 in vitro, and this finding was quickly supported by an open label non-randomized clinical trial that provided the first published clinical evidence HCQ may be a treatment option.", "title": "Hydroxychloroquine for Treatment of SARS‐CoV‐2 Infection? Improving Our Confidence in a Model‐Based Approach to Dose Selection", "pid": "248de4cj", "bm25_score": 219.82229614257812}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging viral infection causing coronavirus disease 2019 (COVID-19). Hydroxychloroquine and chloroquine have garnered unprecedented attention as potential therapeutic agents against COVID-19 following several small clinical trials, uncontrolled case series, and public figure endorsements. While there is a growing body of scientific data, there is also concern for harm, particularly QTc prolongation and cardiac arrhythmias. Here, we perform a rapid narrative review and discuss the strengths and limitations of existing in vitro and clinical studies. We call for additional randomized controlled trial evidence prior to the widespread incorporation of hydroxychloroquine and chloroquine into national and international treatment guidelines.", "title": "Review: Hydroxychloroquine and Chloroquine for Treatment of SARS-CoV-2 (COVID-19)", "pid": "wmpjfc02", "bm25_score": 219.81768798828125}, {"text": "BACKGROUND AND OBJECTIVE: The world is currently experiencing the Coronavirus Disease-19 (COVID-19) pandemic. There is no approved drug for the definitive treatment of the disease. Various drugs are being tried for the treatment of COVID-19, including hydroxychloroquine (HCQ). This study was performed to systematically review the therapeutic role of HCQ in COVID-19 from the available literature. METHODS: PubMed, Embase, ClinicalTrials.gov, ICTRP (WHO), Cochrane Library databases, and two pre-print servers (medRxiv.org and Research Square) were searched for clinical studies that evaluated the therapeutic role of HCQ on COVID-19 until 10 May 2020. The available studies were critically analyzed and the data were extracted. RESULTS: A total of 663 articles were screened and 12 clinical studies (seven peer-reviewed and published studies and five non-peer-reviewed studies from pre-print servers) with a total sample size of 3543 patients were included. Some of the clinical studies demonstrated good virological and clinical outcomes with HCQ alone or in combination with azithromycin in COVID-19 patients, although the studies had major methodological limitations. Some of the other studies showed negative results with HCQ therapy along with the risk of adverse reactions. CONCLUSION: The results of efficacy and safety of HCQ in COVID-19, as obtained from the clinical studies, are not satisfactory, although many of these studies had major methodological limitations. Stronger evidence from well-designed robust randomized clinical trials is required before conclusively determining the role of HCQ in the treatment of COVID-19. Clinical prudence is required in advocating HCQ as a therapeutic armamentarium in COVID-19.", "title": "An Updated Systematic Review of the Therapeutic Role of Hydroxychloroquine in Coronavirus Disease-19 (COVID-19)", "pid": "5gvdddeh", "bm25_score": 219.8153839111328}, {"text": "At present, there are no studies demonstrating the clinical efficacy of hydroxychloroquine for the prophylaxis or treatment of COVID-19 infection.", "title": "Hydroxychloroquine use during the COVID-19 pandemic 2020", "pid": "o3ggu5qf", "bm25_score": 219.74859619140625}, {"text": "Hydroxychloroquine (HCQ), an antimalarial has been proposed as possible treatment for coronavirus disease-2019 (COVID-19). India has approved the use of HCQ for prophylaxis of asymptomatic health workers treating suspected or confirmed COVID-19 cases, and asymptomatic household contacts of confirmed patients. The U.S. Food and Drug Administration has issued Emergency Use Authorization for the use of HCQ to treat COVID-19 in adolescents and adults. In this review, we go over the available evidence for and against HCQ's use as prophylaxis or treatment for COVID-19, especially in the Indian context.", "title": "Hydroxychloroquine as prophylaxis or treatment for COVID-19: What does the evidence say?", "pid": "9eo0leey", "bm25_score": 219.71273803710938}, {"text": "BACKGROUND: Hydroxychloroquine and chloroquine are widely used to treat hospitalized COVID-19 patients primarily based on antiviral activity in in vitro studies. Our objective was to systematically evaluate their efficacy and safety in hospitalized patients with COVID-19. METHODS: We systematically reviewed PubMed, ClinicalTrials.gov, and Medrxviv for studies of hydroxychloroquine and chloroquine in COVID-19 hospitalized patients on April 26, 2020. We evaluated the quality of trials and observational studies using the Jadad criteria and Newcastle Ottawa Scale, respectively. RESULTS: After a review of 175 citations, we included 5 clinical trials (total of 345 patients), 9 observational studies (n = 2529), and 6 additional studies (n = 775) reporting on the QT interval. Three studies reported treatment benefits including two studies reporting benefit on virologic outcomes, which was statistically significant in one study, and another reported significant improvement on cough symptoms. Three studies reported that treatment was potentially harmful, including an significantly increased risk of mortality in two studies and increased need for respiratory support in another. Eight studies were unable to detect improvements on virologic outcomes (n = 3) or pneumonia or transfer to ICU/death (n = 5). The proportion of participants with critical QTc intervals of [≥] 500 ms or an increase of [≥] 60 ms from baseline ranged from 8.3% to 36% (n = 8). One clinical trial and six observational studies were of good quality. The remaining studies were of poor quality. CONCLUSIONS: Our systematic review of reported clinical studies did not identify substantial evidence to support the efficacy of hydroxychloroquine or chloroquine in hospitalized COVID-19 patients and raises questions about potential harm from QT prolongation and increased mortality.", "title": "Efficacy and Safety of Hydroxychloroquine and Chloroquine for COVID-19: A systematic review", "pid": "2txzi7kb", "bm25_score": 219.69898986816406}, {"text": "The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in December 2019. As similar cases rapidly emerged around the world1-3, the World Health Organization (WHO) declared a public health emergency of international concern on January 30, 2020 and pronounced the rapidly spreading coronavirus outbreak as a pandemic on March 11, 20204. The virus has reached almost all countries of the globe. As of June 3, 2020, the accumulated confirmed cases reached 6,479,405 with more than 383,013 deaths worldwide. The urgent and emergency care of COVID-19 patients calls for effective drugs, in addition to the beneficial effects of remdesivir5, to control the disease and halt the pandemic.", "title": "Is hydroxychloroquine beneficial for COVID-19 patients?", "pid": "gme9pxbo", "bm25_score": 219.6932373046875}, {"text": "Drugs that are specifically efficacious against SARS-CoV-2 have yet to be established. Chloroquine and hydroxychloroquine have garnered considerable attention for their potential to treat coronavirus disease 2019 (COVID-19). Increasing evidence obtained from completed clinical studies indicates the prospects for chloroquine/hydroxychloroquine to treat COVID-19. More randomized control clinical studies are warranted to determine the feasibility of these two drugs in treating COVID-19.", "title": "Update on use of chloroquine/hydroxychloroquine to treat coronavirus disease 2019 (COVID-19).", "pid": "px2o98cv", "bm25_score": 219.66273498535156}, {"text": "", "title": "Shining a light on the evidence for hydroxychloroquine in SARS-CoV-2", "pid": "6l3j83br", "bm25_score": 219.64126586914062}, {"text": "Hydroxychloroquine and chloroquine are medications that have been used for a long time. Their most common use is for the treatment and prophylaxis of malaria. However, these antimalarial drugs are known to also have anti-inflammatory and antiviral effects and are used for several chronic diseases such as systemic lupus erythematosus with low adverse effects. The antiviral action of hydroxychloroquine and chloroquine has been a point of interest to different researchers due to its mechanism of action. Several in vitro studies have proven their effectiveness on severe acute respiratory syndrome virus and currently both in vitro and in vivo studies have been conducted on 2019 novel coronavirus (covid-19). The purpose of this article is to review the history and mechanism of actions of these drugs and the potential use they can have on the current covid-19 pandemic.", "title": "Hydroxychloroquine and covid-19.", "pid": "qv2wup1o", "bm25_score": 219.6405029296875}, {"text": "", "title": "Hydroxychloroquine for the Prevention of Covid-19 - Searching for Evidence", "pid": "16d0zvot", "bm25_score": 219.63485717773438}, {"text": "As the time for finding a definitive and safe cure as a vaccine for novel Corona Virus Disease 2019 (Covid-19) is still far, there is need to study in depth about the other potential drugs, which can save millions of lives due to Covid-19 pandemic. Right at the center of the debate is the use of drug “Hydroxychloroquine” as a prophylaxis as well as a treatment strategy against Covid-19 in conjunction with azithromycin. In this review, we will study the cellular and molecular aspects of hydroxychloroquine, which had driven its use in Covid-19 patients, as well as its chemistry and pharmacokinetics along with clinical trials going on worldwide using hydroxychloroquine against Covid-19. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12291-020-00900-x) contains supplementary material, which is available to authorized users.", "title": "Hydroxychloroquine and Covid-19: A Cellular and Molecular Biology Based Update", "pid": "0gozdv43", "bm25_score": 219.6296844482422}, {"text": "Hydroxychloroquine and chloroquine are medications that have been used for a long time. Their most common use is for the treatment and prophylaxis of malaria. However, these antimalarial drugs are known to also have anti-inflammatory and antiviral effects and are used for several chronic diseases such as systemic lupus erythematosus with low adverse effects. The antiviral action of hydroxychloroquine and chloroquine has been a point of interest to different researchers due to its mechanism of action. Several in vitro studies have proven their effectiveness on severe acute respiratory syndrome virus and currently both in vitro and in vivo studies have been conducted on 2019 novel coronavirus (covid-19). The purpose of this article is to review the history and mechanism of actions of these drugs and the potential use they can have on the current covid-19 pandemic.", "title": "Hydroxychloroquine and covid-19", "pid": "fg2yt2o0", "bm25_score": 219.6247100830078}, {"text": "The emerging COVID-19 pandemic poses a threat to the global health care system. Given the lack of antiviral therapies or vaccines for the disease, the antimalarial drug hydroxychloroquine (HCQ) obtained much attention as a treatment for COVID-19. However, there are limited and uncertain clinical data to support the beneficial effect of this drug in COVID-19 treatment. HCQ has several side effects and warnings, including blindness, heart failure, and renal toxicity, even with recommended doses. For severe cases of COVID-19 or in patients with preexisting conditions, administering such a drug could be fatal, particularly when taken at high doses or in combination with other antibiotics. However, further well-designed studies that would address the optimal dose, duration of treatment, possible side effects, and long-term usage outcomes are needed to make the final decision. In this paper, we aim to discuss the risk of using HCQ in treating COVID-19 patients, including its possible side effects.", "title": "Risk of using hydroxychloroquine as a treatment of COVID-19.", "pid": "p88auycu", "bm25_score": 219.6157684326172}, {"text": "", "title": "The Role of Hydroxychloroquine in Coronavirus Disease 2019. A Versatile Tool at the Service of Humanity", "pid": "zby7eclc", "bm25_score": 219.60842895507812}, {"text": "BACKGROUND: Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads. PATIENTS AND METHODS: French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. RESULTS: Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. CONCLUSION: Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.", "title": "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial", "pid": "mkne71q7", "bm25_score": 219.58987426757812}, {"text": "", "title": "Hydroxychloroquine for the Prevention of Covid-19 — Searching for Evidence", "pid": "xx8snj1h", "bm25_score": 219.58734130859375}, {"text": "Aims: Studies have indicated that chloroquine (CQ) shows antagonism against COVID-19 in vitro. However, evidence regarding its effects in patients is limited. This study aims to evaluate the efficacy of hydroxychloroquine (HCQ) in the treatment of patients with COVID-19. Main methods: From February 4 to February 28, 2020, 62 patients suffering from COVID-19 were diagnosed and admitted to Renmin Hospital of Wuhan University. All participants were randomized in a parallel-group trial, 31 patients were assigned to receive an additional 5-day HCQ (400 mg/d) treatment, Time to clinical recovery (TTCR), clinical characteristics, and radiological results were assessed at baseline and 5 days after treatment to evaluate the effect of HCQ. Key findings: For the 62 COVID-19 patients, 46.8% (29 of 62) were male and 53.2% (33 of 62) were female, the mean age was 44.7 (15.3) years. No difference in the age and sex distribution between the control group and the HCQ group. But for TTCR, the body temperature recovery time and the cough remission time were significantly shortened in the HCQ treatment group. Besides, a larger proportion of patients with improved pneumonia in the HCQ treatment group (80.6%, 25 of 31) compared with the control group (54.8%, 17 of 31). Notably, all 4 patients progressed to severe illness that occurred in the control group. However, there were 2 patients with mild adverse reactions in the HCQ treatment group. Significance: Among patients with COVID-19, the use of HCQ could significantly shorten TTCR and promote the absorption of pneumonia.", "title": "Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial", "pid": "q8l3ra55", "bm25_score": 219.58441162109375}, {"text": "Abstract The rapidly spreading Coronavirus Disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents an unprecedented serious challenge to the global public health community. The extremely rapid international spread of the disease with significant morbidity and mortality made finding possible therapeutic interventions a global priority. While approved specific antiviral drugs against SARS-CoV-2 are still lacking, a large number of existing drugs are being explored as a possible treatment for COVID-19 infected patients. Recent publications have re-examined the use of Chloroquine (CQ) and/or Hydroxychloroquine (HCQ) as a potential therapeutic option for these patients. In an attempt to explore the evidence that supports their use in COVID-19 patients, we comprehensively reviewed the previous studies which used CQ or HCQ as an antiviral treatment. Both CQ and HCQ demonstrated promising in vitro results, however, such data have not yet been translated into meaningful in vivo studies. While few clinical trials have suggested some beneficial effects of CQ and HCQ in COVID-19 patients, most of the reported data are still preliminary. Given the current uncertainty, it is worth being mindful of the potential risks and strictly rational the use of these drugs in COVID-19 patients until further high quality randomized clinical trials are available to clarify their role in the treatment or prevention of COVID-19.", "title": "Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review", "pid": "5yvjbr5q", "bm25_score": 219.57557678222656}, {"text": "", "title": "Does Hydroxychloroquine Combat COVID-19? A Timeline of Evidence", "pid": "z434n5k1", "bm25_score": 219.57070922851562}, {"text": "", "title": "Does hydroxychloroquine combat COVID-19? A timeline of evidence", "pid": "fpn9y7e6", "bm25_score": 219.57070922851562}, {"text": "Background The antimalarial agents, chloroquine (CQ) and hydroxychloroquine (HCQ) show promising SARS-CoV-2 anti-viral activity in vitro; however, clinical studies have reported conflicting results. We sought to systematically evaluate the effect of CQ and HCQ with or without azithromycin (AZ) on outcomes of COVID-19 patients. Methods We performed a systematic review and meta-analysis of studies published through July 7, 2020. We searched Medline, Embase, EBM Reviews, Scopus, Web of Science, preprints and grey literature. We included studies that assessed COVID-19 patients treated with CQ or HCQ, with or without AZ. We pooled only adjusted effect estimates of mortality using a random effect model and estimated between studies heterogeneity using I2 statistic. We summarized the effect of CQ or HCQ on viral clearance and ICU admission/ mechanical ventilation. Results Out of 1463 citations screened for eligibility, five RCTs and 14 cohort studies were included (20,263 patients, all hospitalized but with a variable disease severity spectrum). Thirteen studies (1 RCT and 12 cohorts) with 19,573 patients examined the effect of HCQ on short term mortality. The pooled adjusted OR was 1.05 (95% CI 0.96-1.15, I2=0 %, p=0.647). Six cohort studies examined the effect of HCQ and AZ combination among 3430 patients. After excluding a study that examined only patients with cancers, the pooled adjusted OR was (1.15, 95% CI 0.99-1.34, I2=0.0%). Two cohort studies and three RCTs found no significant effect of HCQ on viral clearance. One RCT with 48 patients demonstrated improved viral clearance in patients treated with CQ and HCQ. Three cohort studies found that HCQ with or without AZ had no significant effect on mechanical ventilation/ ICU admission. Conclusion Moderate certainty evidence suggests that HCQ, with or without AZ, lacks efficacy in reducing short-term mortality in patients hospitalized with COVID-19. Our findings are consistent with the recommendations from medical societies that HCQ should only be used to treat COVID-19 patients in the context of clinical trials. Trials of HCQ as pre-exposure prophylaxis are ongoing.", "title": "Efficacy of Chloroquine or Hydroxychloroquine in COVID-19 Patients: A Systematic Review and Meta-Analysis", "pid": "o013tpxz", "bm25_score": 219.552734375}, {"text": "Abstract Background Since the onset of the new coronavirus pandemic, the world is facing a public health emergency. Repositioning hydroxychloroquine (HQ) seems to be a promising option. Many emerging evidences have converged on the effectiveness of HQ in the treatment of Covid-19 infection. In a recent paper, Gautret et al. suggested that further works are needed to determine if HQ antiviral prophylaxis is useful, especially for healthcare workers. Methods The purpose of this paper is to assess the Covid-19 exposure and risks level among caregivers. For this, we performed research on internet and PubMed by crossing the following keywords: healthcare givers, healthcare workers, doctors, nurses, coronavirus, Covid-19, mortality, infection rate, chloroquine, hydroxychloroquine. Results Data on healthcare worker's infection and mortality by Covid-19 are partial and are not systematically published. However, it seems that the infection rate varies between 3.8% and 9% depending on the country. Moreover, the mean age of this population is relatively old, especially in the OECD area. Conclusions Anti-Covid-19 HQ prophylaxis should be urgently accessed, especially for healthcare workers. It is to be hoped that HQ prophylaxis reduces the morbidity and mortality from Covid-19 infection among this population which is particularly exposed and relatively old.", "title": "Hydroxychloroquine as antiviral prophylaxis for exposed caregivers to Covid-19: an urgent appraisal is needed", "pid": "9r1sjbtl", "bm25_score": 219.53517150878906}, {"text": "BACKGROUND Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). PURPOSE To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate 500 mg once or twice daily with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine. LIMITATION There were few controlled studies, and control for confounding was inadequate in observational studies. CONCLUSION Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting. PRIMARY FUNDING SOURCE Agency for Healthcare Research and Quality.", "title": "Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review.", "pid": "fanupn22", "bm25_score": 219.5260467529297}, {"text": "", "title": "Does Adding of Hydroxychloroquine to the Standard Care Provide any Benefit in Reducing the Mortality among COVID-19 Patients?: a Systematic Review", "pid": "ai0rgelv", "bm25_score": 219.4977569580078}, {"text": "Our coalition of public health experts, doctors, and scientists worldwide want to draw attention to the need for high-quality evaluation protocols of the potential beneficial effect of hydroxychloroquine (HCQ) as a post-exposure drug for exposed people, meaning people with close contact with positive tested patients, including home and medical caregivers. We have reviewed the mechanisms of antiviral effect of HCQ, the risk-benefit ratio taking into consideration the PK/PD of HCQ and the thresholds of efficacy. We have studied its use as an antimalarial, an antiviral, and an immunomodulating drug and concluded that the use of HCQ at does matching that of the standard treatment of Systemic Lupus erythematous, which has proven safety and efficacy in terms of HCQ blood and tissue concentration adapted to bodyweight (2,3), at 6 mg/kg/day 1 (loading dose) followed by 5 mg/kg/day, with a maximum limit of 600 mg/day in all cases should swiftly be clinically evaluated as a post-exposure drug for exposed people.", "title": "Coalition: Advocacy for prospective clinical trials to test the post-exposure potential of hydroxychloroquine against COVID-19", "pid": "etpmevun", "bm25_score": 219.49188232421875}, {"text": "", "title": "Hydroxychloroquine in the management of critically ill patients with COVID-19: the need for an evidence base", "pid": "r8q9ucb3", "bm25_score": 219.48300170898438}, {"text": "Drugs that are specifically efficacious against SARS-CoV-2 have yet to be established. Chloroquine and hydroxychloroquine have garnered considerable attention for their potential to treat coronavirus disease 2019 (COVID-19). Increasing evidence obtained from completed clinical studies indicates the prospects for chloroquine/hydroxychloroquine to treat COVID-19. More randomized control clinical studies are warranted to determine the feasibility of these two drugs in treating COVID-19.", "title": "Update on use of chloroquine/hydroxychloroquine to treat coronavirus disease 2019 (COVID-19)", "pid": "n3cg3w9v", "bm25_score": 219.48135375976562}, {"text": "The controversy surrounding the use of hydroxychloroquine (HCQ), an antimalarial drug, for COVID-19 has raised numerous ethical and policy problems. Since the suggestion that HCQ has potential for COVID-19, there have been varying responses from clinicians and healthcare institutions, ranging from adoption of protocols using HCQ for routine care to the conduct of randomised controlled trials to an effective system-wide prohibition on its use for COVID-19. In this article, we argue that the concept of 'disease public profile' has become a prominent, if not the sole, determinant in decision-making across various healthcare responses to the pandemic. In the case of COVID-19, the disease's public profile is based on clinical and non-clinical factors that include contagiousness, clinical presentation and media coverage. In particular, we briefly examine the dangers of a heightened public profile in magnifying the inequality of diseases and undermining three key ethical concepts, namely (1) evidence-based practice, (2) sustainable allocation and (3) meaningful consent.", "title": "Hydroxychloroquine and COVID-19: critiquing the impact of disease public profile on policy and clinical decision-making", "pid": "m7z23lps", "bm25_score": 219.46578979492188}, {"text": "We would like to share ideas on the report \"Hydroxychloroquine in Patients with Rheumatic Disease Complicated by COVID-19: Clarifying Target Exposures and the Need for Clinical Trials\"1 Balevic noted that \"well-designed clinical trials that include patients with rheumatic disease are urgently needed to characterize the efficacy, safety, and target exposures for hydroxychloroquine1\".", "title": "Evidence of Protective Effect of Hydroxychloroquine on COVID-19", "pid": "ondv8c78", "bm25_score": 219.4638671875}, {"text": "BACKGROUND: Since the onset of the new coronavirus pandemic, the world is facing a public health emergency. Repositioning hydroxychloroquine (HQ) seems to be a promising option. Many emerging evidences have converged on the effectiveness of HQ in the treatment of Covid-19 infection. In a recent paper, Gautret et al. suggested that further works are needed to determine if HQ antiviral prophylaxis is useful, especially for healthcare workers. METHODS: The purpose of this paper is to assess the Covid-19 exposure and risks level among caregivers. For this, we performed research on internet and PubMed by crossing the following keywords: healthcare givers, healthcare workers, doctors, nurses, coronavirus, Covid-19, mortality, infection rate, chloroquine, hydroxychloroquine. RESULTS: Data on healthcare worker's infection and mortality by Covid-19 are partial and are not systematically published. However, it seems that the infection rate varies between 3.8% and 9% depending on the country. Moreover, the mean age of this population is relatively old, especially in the OECD area. CONCLUSIONS: Anti-Covid-19 HQ prophylaxis should be urgently accessed, especially for healthcare workers. It is to be hoped that HQ prophylaxis reduces the morbidity and mortality from Covid-19 infection among this population which is particularly exposed and relatively old.", "title": "Hydroxychloroquine as antiviral prophylaxis for exposed caregivers to Covid-19: An urgent appraisal is needed", "pid": "66ocolzl", "bm25_score": 219.46331787109375}, {"text": "Abstract Our coalition of public health experts, doctors, and scientists worldwide want to draw attention to the need for high-quality evaluation protocols of the potential beneficial effect of hydroxychloroquine (HCQ) as a post-exposure drug for exposed people, meaning people with close contact with positive tested patients, including home and medical caregivers. We have reviewed the mechanisms of antiviral effect of HCQ, the risk-benefit ratio taking into consideration the PK/PD of HCQ and the thresholds of efficacy. We have studied its use as an antimalarial, an antiviral, and an immunomodulating drug and concluded that the use of HCQ at does matching that of the standard treatment of Systemic Lupus erythematous, which has proven safety and efficacy in terms of HCQ blood and tissue concentration adapted to bodyweight (2,3), at 6 mg/kg/day 1 (loading dose) followed by 5 mg/kg/day, with a maximum limit of 600 mg/day in all cases should swiftly be clinically evaluated as a post-exposure drug for exposed people.", "title": "Coalition: Advocacy for prospective clinical trials to test the post-exposure potential of hydroxychloroquine against COVID-19", "pid": "tedurmyb", "bm25_score": 219.46249389648438}, {"text": "", "title": "No evidence so far on the protective effect of hydroxychloroquine to prevent COVID-19: response to the comment by Joob and Wiwanitkit", "pid": "hz0vj0a2", "bm25_score": 219.45399475097656}, {"text": "The rapidly spreading Coronavirus Disease (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus (SARS-CoV-2), represents an unprecedented serious challenge to the global public health community. The extremely rapid international spread of the disease with significant morbidity and mortality made finding possible therapeutic interventions a global priority. While approved specific antiviral drugs against SARS-CoV-2 are still lacking, a large number of existing drugs are being explored as a possible treatment for COVID-19 infected patients. Recent publications have re-examined the use of Chloroquine (CQ) and/or Hydroxychloroquine (HCQ) as a potential therapeutic option for these patients. In an attempt to explore the evidence that supports their use in COVID-19 patients, we comprehensively reviewed the previous studies which used CQ or HCQ as an antiviral treatment. Both CQ and HCQ demonstrated promising in vitro results, however, such data have not yet been translated into meaningful in vivo studies. While few clinical trials have suggested some beneficial effects of CQ and HCQ in COVID-19 patients, most of the reported data are still preliminary. Given the current uncertainty, it is worth being mindful of the potential risks and strictly rationalise the use of these drugs in COVID-19 patients until further high quality randomized clinical trials are available to clarify their role in the treatment or prevention of COVID-19.", "title": "Therapeutic use of chloroquine and hydroxychloroquine in COVID-19 and other viral infections: A narrative review", "pid": "7habtj4m", "bm25_score": 219.44845581054688}, {"text": "Abstract Background Chloroquine and hydroxychloroquine have been found to be efficient on SARS-CoV-2, and reported to be efficient in Chinese COV-19 patients. We evaluate the role of hydroxychloroquine on respiratory viral loads. Patients and methods French Confirmed COVID-19 patients were included in a single arm protocol from early March to March 16th, to receive 600mg of hydroxychloroquine daily and their viral load in nasopharyngeal swabs was tested daily in a hospital setting. Depending on their clinical presentation, azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative controls. Presence and absence of virus at Day6-post inclusion was considered the end point. Results Six patients were asymptomatic, 22 had upper respiratory tract infection symptoms and eight had lower respiratory tract infection symptoms. Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D6-post inclusion compared to controls, and much lower average carrying duration than reported of untreated patients in the literature. Azithromycin added to hydroxychloroquine was significantly more efficient for virus elimination. Conclusion Despite its small sample size our survey shows that hydroxychloroquine treatment is significantly associated with viral load reduction/disappearance in COVID-19 patients and its effect is reinforced by azithromycin.", "title": "Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial", "pid": "5o9bbspc", "bm25_score": 219.43289184570312}, {"text": "The controversy surrounding the use of hydroxychloroquine (HCQ), an antimalarial drug, for COVID-19 has raised numerous ethical and policy problems. Since the suggestion that HCQ has potential for COVID-19, there have been varying responses from clinicians and healthcare institutions, ranging from adoption of protocols using HCQ for routine care to the conduct of randomised controlled trials to an effective system-wide prohibition on its use for COVID-19. In this article, we argue that the concept of 'disease public profile' has become a prominent, if not the sole, determinant in decision-making across various healthcare responses to the pandemic. In the case of COVID-19, the disease's public profile is based on clinical and non-clinical factors that include contagiousness, clinical presentation and media coverage. In particular, we briefly examine the dangers of a heightened public profile in magnifying the inequality of diseases and undermining three key ethical concepts, namely (1) evidence-based practice, (2) sustainable allocation and (3) meaningful consent.", "title": "Hydroxychloroquine and COVID-19: critiquing the impact of disease public profile on policy and clinical decision-making.", "pid": "8m4930bc", "bm25_score": 219.4256591796875}, {"text": "BACKGROUND: Hydroxychloroquine and chloroquine have antiviral effects in vitro against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). PURPOSE: To summarize evidence about the benefits and harms of hydroxychloroquine or chloroquine for the treatment or prophylaxis of coronavirus disease 2019 (COVID-19). DATA SOURCES: PubMed (via MEDLINE), EMBASE (via Ovid), Scopus, Web of Science, Cochrane Library, bioRxiv, Preprints, ClinicalTrials.gov, World Health Organization International Clinical Trials Registry Platform, and the Chinese Clinical Trials Registry from 1 December 2019 until 8 May 2020. STUDY SELECTION: Studies in any language reporting efficacy or safety outcomes from hydroxychloroquine or chloroquine use in any setting in adults or children with suspected COVID-19 or at risk for SARS-CoV-2 infection. DATA EXTRACTION: Independent, dually performed data extraction and quality assessments. DATA SYNTHESIS: Four randomized controlled trials, 10 cohort studies, and 9 case series assessed treatment effects of the medications, but no studies evaluated prophylaxis. Evidence was conflicting and insufficient regarding the effect of hydroxychloroquine on such outcomes as all-cause mortality, progression to severe disease, clinical symptoms, and upper respiratory virologic clearance with antigen testing. Several studies found that patients receiving hydroxychloroquine developed a QTc interval of 500 ms or greater, but the proportion of patients with this finding varied among the studies. Two studies assessed the efficacy of chloroquine; 1 trial, which compared higher-dose (600 mg twice daily for 10 days) with lower-dose (450 mg twice daily on day 1 and once daily for 4 days) therapy, was stopped owing to concern that the higher dose therapy increased lethality and QTc interval prolongation. An observational study that compared adults with COVID-19 receiving chloroquine phosphate 500 mg once or twice daily with patients not receiving chloroquine found minor fever resolution and virologic clearance benefits with chloroquine. LIMITATION: There were few controlled studies, and control for confounding was inadequate in observational studies. CONCLUSION: Evidence on the benefits and harms of using hydroxychloroquine or chloroquine to treat COVID-19 is very weak and conflicting. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.", "title": "Hydroxychloroquine or Chloroquine for Treatment or Prophylaxis of COVID-19: A Living Systematic Review", "pid": "fs8r5ze0", "bm25_score": 219.42465209960938}, {"text": "Background Chloroquine and Hydroxychloroquine have been found to be efficient on COV-19, and reported to be efficient in Chinese patients infected by this virus. We evaluate the role of Hydroxychloroquine on respiratory viral loads. Patients and methods Patients were included in a single arm protocol to receive 600mg of hydroxychloroquine daily and their viral load in nasal swabs was tested daily. Depending on their clinical presentation azithromycin was added to the treatment. Untreated patients from another center and cases refusing the protocol were included as negative control. Presence and absence of virus at Day-6 was considered the end point. Results Twenty cases were treated in this study and showed a significant reduction of the viral carriage at D-6 compared to controls, and much lower than reported average carrying duration of untreated patients in the literature. Azithromycin added to Hydroxychloroquine was significantly more efficient for virus elimination. Conclusion : Hydroxychloroquine is significantly associated with viral load reduction/disappearance in patients with COVID-19 and its effect is reinforced by Azithromycin.", "title": "Hydroxychloroquine and Azithromycin as a treatment of COVID-19: preliminary results of an open-label non-randomized clinical trial", "pid": "tdlcb9bf", "bm25_score": 219.41392517089844}, {"text": "The emerging COVID-19 pandemic poses a threat to the global health care system. Given the lack of antiviral therapies or vaccines for the disease, the antimalarial drug hydroxychloroquine (HCQ) obtained much attention as a treatment for COVID-19. However, there are limited and uncertain clinical data to support the beneficial effect of this drug in COVID-19 treatment. HCQ has several side effects and warnings, including blindness, heart failure, and renal toxicity, even with recommended doses. For severe cases of COVID-19 or in patients with preexisting conditions, administering such a drug could be fatal, particularly when taken at high doses or in combination with other antibiotics. However, further well-designed studies that would address the optimal dose, duration of treatment, possible side effects, and long-term usage outcomes are needed to make the final decision. In this paper, we aim to discuss the risk of using HCQ in treating COVID-19 patients, including its possible side effects.", "title": "Risk of using hydroxychloroquine as a treatment of COVID-19", "pid": "xv6g05zk", "bm25_score": 219.40896606445312}, {"text": "Hydroxychloroquine has been promoted for its use in treatment of COVID-19 patients based on in-vitro evidences. We searched the databases to include randomized and observational studies evaluating the effect of Hydroxychloroquine on mortality in COVID-19 patients. The outcome was summarized as odds ratios (OR) with a 95% confidence interval (CI).We used the inverse-variance method with a random effect model and assessed the heterogeneity using I(2) test. We used ROBINS-I tool to assess methodological quality of the included studies. We performed the meta-analysis using ‘Review manager software version 5.3’. We identified 6 observationalstudies satisfying the selection criteria. In all studies, Hydroxychloroquine was given as add on to the standard care and effect was compared with the standard care alone. A pooled analysis observed 251 deaths in 1331 participants of the Hydroxychloroquine arm and 363 deaths in 1577 participants of the control arm. There was no difference in odds of mortality events amongst Hydroxychloroquine and supportive care arm [1.25 (95% CI: 0.65, 2.38); I(2) = 80%]. A similar trend was observed with moderate risk of bias studies [0.95 (95% CI: 0.44, 2.06); I(2) = 85%]. The odds of mortality were significantly higher in patients treated with Hydroxychloroquine + Azithromycin than supportive care alone [2.34 (95% CI: 1.63, 3.34); I(2) = 0%]. A pooled analysis of recently published studies suggests no additional benefit for reducing mortality in COVID-19 patients when Hydroxychloroquine is given as add-on to the standard care. [Figure: see text] ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s11481-020-09930-x) contains supplementary material, which is available to authorized users.", "title": "Does Adding of Hydroxychloroquine to the Standard Care Provide any Benefit in Reducing the Mortality among COVID-19 Patients?: a Systematic Review", "pid": "uljaj8gd", "bm25_score": 219.402099609375}, {"text": "BACKGROUND: Data from non-randomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against Covid-19. METHODS: We conducted an observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe Covid-19 in a French university hospital. Patients who received hydroxychloroquine (200mg tid dosage for 10 days) on a compassionate basis in addition to SOCwere compared to patients without contraindications to hydroxychloroquine who received SOCalone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission &#8804; 7 days, Charlson comorbidity index, medical history of arterial hypertension, and obesity, NEWS2 score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first. RESULTS: Data from 89 patients with laboratory-confirmed Covid-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOCalone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxycholoroquine was not associated with a significantly reduced risk of unfavorable outcome (HR 0.90 [0.38; 2.1], p = 0.81). Overall survival was not significantly different between the two groups (HR 0.89 [0.23; 3.47], p = 1). CONCLUSION: In hospitalized adults with Covid-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to standard of care. Unmeasured confounders may however have persisted despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of Covid-19.", "title": "Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital", "pid": "fbnge94q", "bm25_score": 219.39466857910156}, {"text": "", "title": "No evidence so far on the protective effect of hydroxychloroquine to prevent COVID-19: response to the comment by Joob and Wiwanitkit.", "pid": "nyvvah7u", "bm25_score": 219.38046264648438}, {"text": "We read with great interest the very thoughtful commentary by Joob and Wiwanitkit1 We agree with the authors that, despite conflicting clinical data to date, it is possible that hydroxychloroquine (HCQ) may have a protective effect in the setting of the coronavirus disease 2019 (COVID­19).", "title": "Dr. Balevic, et al, reply", "pid": "s4wa298y", "bm25_score": 219.37930297851562}, {"text": "We remain largely without effective prophylactic/therapeutic interventions for COVID-19. Although many human clinical trials are ongoing, there remains a deficiency of supportive preclinical drug efficacy studies. Here we assessed the prophylactic/therapeutic efficacy of hydroxychloroquine (HCQ), a drug of interest for COVID-19 management, in two animal models. When used for prophylaxis or treatment neither the standard human malaria dose (6.5 mg/kg) nor a high dose (50 mg/kg) of HCQ had any beneficial effect on clinical disease or SARS-CoV-2 kinetics (replication/shedding) in the Syrian hamster disease model. Similarly, HCQ prophylaxis/treatment (6.5 mg/kg) did not significantly benefit clinical outcome nor reduce SARS-CoV-2 replication/shedding in the upper and lower respiratory tract in the rhesus macaque disease model. In conclusion, our preclinical animal studies do not support the use of HCQ in prophylaxis/treatment of COVID-19.", "title": "Hydroxychloroquine Proves Ineffective in Hamsters and Macaques Infected with SARS-CoV-2", "pid": "y5cbp2yz", "bm25_score": 219.35848999023438}, {"text": "Backgrounds. Since COVID-19 outbreak, various agents have been tested but no proven effective therapies have been identified. This has led to a lot of controversies among associated researches. Hence, in order to address the issue of using hydroxychloroquine in treating COVID-19 patients, we conducted a systematic review and meta-analysis. Methods. A thorough search was carried out to find relevant studies in MEDLINE, medRxiv, PubMed, Cochrane Database, China Academic Journals Full-text Database and Web of Science. Two investigators independently reviewed 274 abstracts and 23 articles. The trials which evaluated hydroxychloroquine for treatment of COVID-19 were included for this systematic review. Two investigators assessed quality of the studies and data extraction was done by one reviewer and cross checked by the other. Results. Five trials involving 677 patients were included while conducting the meta-analysis. Compared with the control group, hydroxychloroquine with or without azithromycin showed benefits in positive-to-negative conversion of SARS-CoV-2 (odds ratio [OR], 1.95 [95% CI,0.19 to 19.73] and a reduction in progression rate (OR, 0.89 [95% CI, 0.58 to 1.37]), but without demonstrating any statistical significance. This systematic review has also suggested a possible synergistic effect of the combination therapy which included hydroxychloroquine and azithromycin. However, the use of hydroxychloroquine alone was associated with increased mortality in COVID-19 patients. Conclusion. The use of hydroxychloroquine with or without azithromycin for treatment of COVID-19 patients, seems to be effective. The combination of hydroxychloroquine and azithromycin has shown synergic effects. However, mortality rate was increased when the treatment was conducted with hydroxychloroquine.", "title": "Systematic Review and Meta-analysis of the Effectiveness and Safety of Hydroxychloroquine in COVID-19.", "pid": "2f6nj4to", "bm25_score": 219.35833740234375}, {"text": "INTRODUCTION: Several months into the COVID-19 pandemic, safe and effective treatments against this global health disaster have yet to be identified. Clinical research trials around the world are underway testing a wide array of possible medications. In particular, the off-label use of hydroxychloroquine for COVID-19 prophylaxis and treatment has created many unprecedented challenges for the scientific community and the public. AREAS COVERED: We critically assessed major events from February - May 2020 that contributed to widespread use of hydroxychloroquine for the treatment and prophylaxis of COVID-19. We aimed to explore how opinions towards hydroxychloroquine may shift from early enthusiasm (based on in vitro and preliminary clinical data) to the hope for a miracle cure (through communication and promotion of questionable results) and, finally, to a rise of skepticism as more in-depth analyses are emerging. EXPERT OPINION: Mindful and rigorous acquisition of data, as well as its interpretation, are essential to an effective pandemic response. The rapid and premature promotion of results has had major implications for global crisis management, even creating distrust among the public. It is crucial for the medical and scientific community to incorporate the lessons learned from this situation.", "title": "Swinging the pendulum: lessons learned from public discourse concerning hydroxychloroquine and COVID-19", "pid": "salxq8ir", "bm25_score": 219.33218383789062}, {"text": "OBJECTIVES: The emergence of SARS-CoV-2 has presented clinicians with a difficult therapeutic dilemma. With supportive care as the current mainstay of treatment, the fatality rate of COVID-19 is 6.9%. There are currently several trials assessing the efficacy of different antivirals as treatment. Of these, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have garnered the most attention. METHODS: In this study, the literature currently available on CQ and HCQ as treatment of COVID-19 was surveyed using EMBASE, PubMed, Cochrane Library, MedRxiv, and one clinical trial registry. Upon gathering published and preprint trials, risk of bias was assessed using Cochrane Risk of Bias Tool 2.0. RESULTS: There are currently seven completed clinical trials and 29 registered clinical trials focusing on HCQ or CQ as a therapeutic avenue for COVID-19. Of these, five of seven trials have shown favorable outcomes for patients using CQ or HCQ and two of seven have shown no change compared to control. However, all seven trials carried varying degrees of bias and poor study design. CONCLUSION: There are currently not enough data available to support the routine use of HCQ and CQ as therapies for COVID-19. Pending further results from more extensive studies with more stringent study parameters, clinicians should defer from routine use of HCQ and CQ. There are several clinical trials currently under way with results expected soon.", "title": "A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID-19", "pid": "bfui91w7", "bm25_score": 219.33050537109375}, {"text": "INTRODUCTION Several months into the COVID-19 pandemic, safe and effective treatments against this global health disaster have yet to be identified. Clinical research trials around the world are underway testing a wide array of possible medications. In particular, the off-label use of hydroxychloroquine for COVID-19 prophylaxis and treatment has created many unprecedented challenges for the scientific community and the public. AREAS COVERED We critically assessed major events from February - May 2020 that contributed to widespread use of hydroxychloroquine for the treatment and prophylaxis of COVID-19. We aimed to explore how opinions towards hydroxychloroquine may shift from early enthusiasm (based on in vitro and preliminary clinical data) to the hope for a miracle cure (through communication and promotion of questionable results) and, finally, to a rise of skepticism as more in-depth analyses are emerging. EXPERT OPINION Mindful and rigorous acquisition of data, as well as its interpretation, are essential to an effective pandemic response. The rapid and premature promotion of results has had major implications for global crisis management, even creating distrust among the public. It is crucial for the medical and scientific community to incorporate the lessons learned from this situation.", "title": "Swinging the pendulum: lessons learned from public discourse concerning hydroxychloroquine and COVID-19.", "pid": "ilu5oskk", "bm25_score": 219.3065185546875}, {"text": "OBJECTIVE: To assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen. DESIGN: Comparative observational study using data collected from routine care. SETTING: Four French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020. PARTICIPANTS: 181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care. INTERVENTIONS: Hydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group). MAIN OUTCOME MEASURES: The primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting. RESULTS: In the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment. CONCLUSIONS: Hydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.", "title": "Clinical efficacy of hydroxychloroquine in patients with covid-19 pneumonia who require oxygen: observational comparative study using routine care data", "pid": "d7vpwb8h", "bm25_score": 219.30337524414062}, {"text": "Following the demonstration of the efficacy of hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 in vitro, many trials started to evaluate its efficacy in clinical settings. However, no systematic review and meta-analysis have addressed the issue of the safety and efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019. We conducted a systematic review and meta-analysis with the objectives of evaluation of safety and efficacy of HCQ alone or in combination in terms of \"time to clinical cure,\" \"virological cure,\" \"death or clinical worsening of disease,\" \"radiological progression,\" and safety. RevMan was used for meta-analysis. We searched 16 literature databases out of which seven studies (n = 1358) were included in the systematic review. In terms of clinical cure, two studies reported possible benefit in \"time to body temperature normalization\" and one study reported less \"cough days\" in the HCQ arm. Treatment with HCQ resulted in less number of cases showing the radiological progression of lung disease (odds ratio [OR], 0.31, 95% confidence interval [CI], 0.11-0.9). No difference was observed in virological cure (OR, 2.37, 95% CI, 0.13-44.53), death or clinical worsening of disease (OR, 1.37, 95% CI, 1.37-21.97), and safety (OR, 2.19, 95% CI, 0.59-8.18), when compared with the control/conventional treatment. Five studies reported either the safety or efficacy of HCQ + azithromycin. Although seems safe and effective, more data are required for a definitive conclusion. HCQ seems to be promising in terms of less number of cases with radiological progression with a comparable safety profile to control/conventional treatment. We need more data to come to a definite conclusion.", "title": "Virological and clinical cure in COVID-19 patients treated with hydroxychloroquine: A systematic review and meta-analysis", "pid": "8fnvufmc", "bm25_score": 219.3001708984375}, {"text": "Hydroxychloroquine (HCQ) garnered scientific attention in early February following publication of reports showing in vitro activity of chloroquine (CQ) against COVID‐19. While studies are mixed on this topic, the therapeutic effect of HCQ or CQ still need more valid clinical evidence. In this descriptive observational study, we aimed to discuss the treatment response of HCQ in COVID‐19 infected patients and 30 cases were included. The demographic, treatment, laboratory parameters of C‐reactive protein (CRP) and interleukin‐6 (IL‐6) before and after HCQ therapy and clinical outcome in the 30 COVID‐19 patients were assessed. In order to evaluate the effect of mediation time point, we also divided these cases into two groups, patients began administrated with HCQ within 7 days hospital (defined as early delivery group) and 7 days after hospital (defined as later delivery group). We found that, the elevated IL‐6, a risk factor in severe patients were reduced to normal level after HCQ treatment. More importantly, patients treated with HCQ at the time of early hospital recovered faster than those who treated later or taken as second line choose for their obvious shorter hospitalization time. In summary, early use of HCQ was better than later use and the effect of IL‐6 and CRP level can not be ruled out. This article is protected by copyright. All rights reserved.", "title": "Hydroxychloroquine treatment in COVID‐19: a descriptive observational analysis of 30 cases from a single center in Wuhan, China", "pid": "hd5yvs5x", "bm25_score": 219.2802276611328}, {"text": "Background Treatments are urgently needed to prevent respiratory failure and deaths from coronavirus disease 2019 (COVID-19). Hydroxychloroquine (HCQ) has received worldwide attention because of positive results from small studies. Methods We used data collected from routine care of all adults in 4 French hospitals with documented SARS-CoV-2 pneumonia and requiring oxygen ≥ 2 L/min to emulate a target trial aimed at assessing the effectiveness of HCQ at 600 mg/day. The composite primary endpoint was transfer to intensive care unit (ICU) within 7 days from inclusion and/or death from any cause. Analyses were adjusted for confounding factors by inverse probability of treatment weighting. Results This study included 181 patients with SARS-CoV-2 pneumonia; 84 received HCQ within 48 hours of admission (HCQ group) and 97 did not (no-HCQ group). Initial severity was well balanced between the groups. In the weighted analysis, 20.2% patients in the HCQ group were transferred to the ICU or died within 7 days vs 22.1% in the no-HCQ group (16 vs 21 events, relative risk [RR] 0.91, 95% CI 0.47-1.80). In the HCQ group, 2.8% of the patients died within 7 days vs 4.6% in the no-HCQ group (3 vs 4 events, RR 0.61, 95% CI 0.13-2.89), and 27.4% and 24.1%, respectively, developed acute respiratory distress syndrome within 7 days (24 vs 23 events, RR 1.14, 95% CI 0.65-2.00). Eight patients receiving HCQ (9.5%) experienced electrocardiogram modifications requiring HCQ discontinuation. Interpretation These results do not support the use of HCQ in patients hospitalised for documented SARS-CoV-2-positive hypoxic pneumonia.", "title": "No evidence of clinical efficacy of hydroxychloroquine in patients hospitalized for COVID-19 infection with oxygen requirement: results of a study using routinely collected data to emulate a target trial", "pid": "otp1atui", "bm25_score": 219.2689208984375}, {"text": "The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic poses a serious threat to public health and local economies around the globe. This has created an urgent need to identify effective medications for its prevention and treatment (1). Among these treatments, the off-label use of hydroxychloroquine (HCQ), a less toxic derivate of chloroquine, has become a common practice among clinicians, including pediatricians, despite lack of evidence of its clinical efficacy for this indication (especially for pediatric patients) at present time (2).", "title": "Efficacy, safety and cost‐effectiveness of hydroxychloroquine in children with COVID‐19: A call for evidence", "pid": "tovty20e", "bm25_score": 219.26736450195312}, {"text": "Abstract Background Hydroxychloroquine is being administered among patients with COVID19 infection in many healthcare systems across the world considering its in vitro effect against the SARS CoV 2 virus. In spite of several observational studies and a few randomized controlled trials, the effect of hydroxychloroquine on patients with COVID 19 infection remains unclear. We undertook this systematic review with meta-analysis to evaluate the efficacy and safety of hydroxychloroquine among patients with COVID 19 infection. Methods We searched PubMed, Embase, the Cochrane Library, Web of Science, medRxiv, and other relevant resources until May 13, 2020. We included randomized controlled trials and observational studies in which hydroxychloroquine was adminstered and compared to a control group. Data were extracted, and quality assessment of the studies was carried out. We evaluated symptomatic progression, mortality, viral clearance, the evolution of changes on chest CT imaging, and adverse events. A fixed or random-effects model was used depending on outcome heterogeneity. Results We included eleven studies including, three randomized controlled trials and eight observational studies. Among these, 2354 patients received hydroxychloroquine alone or in combination, while 1952 did not. Mortality was reported at different points of time. The overall mortality was not significantly different among patients who received hydroxychloroquine compared to the control group (OR: 1.41, 95% CI: 0.76 to 2.62; p = 0.28). Clinical worsening or lack of symptomatic improvement did not differ between patients who received hydroxychloroquine compared to those who did not (OR 1.1, 95% CI: 0.6 to 2.02; p = 0.76). Viral clearance, assessed by RT-PCR, did not differ significantly between the hydroxychloroquine and the control groups (OR: 1.13, CI: 0.26 to 5.01; p = 0.87). The evolution of changes on chest CT imaging was reported only in two studies; a more pronounced improvement was observed with the use of hydroxychloroquine compared to standard care (OR: 2.68, CI: 1.1 to 6.6; P = 0.03). The incidence of adverse events was significantly higher with hydroxychloroquine (OR: 4.1, CI: 1.42 to 11.88; p = 0.009). Conclusions Our meta-analysis does not suggest improvement in clinical progression, mortality, or viral clearance by RT PCR among patients with COVID 19 infection who are treated with hydroxychloroquine. There was a significantly higher incidence of adverse events with hydroxychloroquine use.", "title": "Hydroxychloroquine in COVID-19: A systematic review and meta-analysis", "pid": "qxgpehuy", "bm25_score": 219.26522827148438}, {"text": "Chloroquine and hydroxychloroquine are drugs that have shown in vitro activity on the replication of certain coronaviruses. In the context of the SARS-Cov-2 epidemic, the virus responsible for the novel coronavirus disease (COVID-19), these two drugs have been proposed as possible treatments. The results of the first clinical studies evaluating the effect of hydroxychloroquine do not support any efficacy of this drug in patients with COVID-19, due to major methodological weaknesses. Yet, these preliminary studies have aroused considerable media interest, raising fears of massive and uncontrolled use. In the absence of evidence of clinical benefits, the main risk is of exposing patients unnecessarily to the well-known adverse effects of hydroxychloroquine, with a possibly increased risk in the specific setting of COVID-19. In addition, widespread use outside of any recommendation risks compromising the completion of good quality clinical trials. The chloroquine hype, fueled by low-quality studies and media announcements, has yielded to the implementation of more than 150 studies worldwide. This represents a waste of resources and a loss of opportunity for other drugs to be properly evaluated. In the context of emergency, rigorous trials are more than ever needed in order to have, as soon as possible, reliable data on drugs that are possibly effective against the disease. Meanwhile, serious adverse drug reactions have been reported in patients with COVID-19 receiving hydroxychloroquine, justifying to limit its prescription, and to perform suitable cardiac and therapeutic drug monitoring.", "title": "Chloroquine and hydroxychloroquine in the management of COVID-19: Much kerfuffle but little evidence", "pid": "gjmvw8l2", "bm25_score": 219.2640380859375}, {"text": "PURPOSE: To assess efficacy and safety of chloroquine (CQ)/hydroxychloroquine (HCQ) for treatment or prophylaxis of COVID-19 in adult humans. MATERIALS AND METHODS: MEDLINE, PubMed, EMBASE and two pre-print repositories (bioRxiv, medRxiv) were searched from inception to 8th June 2020 for RCTs and nonrandomized studies (retrospective and prospective, including single-arm, studies) addressing the use of CQ/HCQ in any dose or combination for COVID-19. RESULTS: Thirty-two studies were included (6 RCTs, 26 nonrandomized, 29,192 participants). Two RCTs had high risk, two ‘some concerns’ and two low risk of bias (Rob2). Among nonrandomized studies with comparators, nine had high risk and five moderate risk of bias (ROBINS-I). Data synthesis was not possible. Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low. CONCLUSIONS: Patients with COVID-19 should be treated with CQ/HCQ only if monitored and within the context of high quality RCTs. High quality data about efficacy/safety are urgently needed.", "title": "Update I. A systematic review on the efficacy and safety of chloroquine/hydroxychloroquine for COVID-19", "pid": "w1785lap", "bm25_score": 219.25167846679688}, {"text": "Summary Chloroquine and hydroxychloroquine are drugs that have shown in vitro activity on the replication of certain coronaviruses. In the context of the SARS-Cov-2 epidemic, the virus responsible for the novel coronavirus disease (COVID-19), these two drugs have been proposed as possible treatments. The results of the first clinical studies evaluating the effect of hydroxychloroquine do not support any efficacy of this drug in patients with COVID-19, due to major methodological weaknesses. Yet, these preliminary studies have aroused considerable media interest, raising fears of massive and uncontrolled use. In the absence of evidence of clinical benefits, the main risk is of exposing patients unnecessarily to the well-known adverse effects of hydroxychloroquine, with a possibly increased risk in the specific setting of COVID-19. In addition, widespread use outside of any recommendation risks compromising the completion of good quality clinical trials. The chloroquine hype, fueled by low-quality studies and media announcements, has yielded to the implementation of more than 150 studies worldwide. This represents a waste of resources and a loss of opportunity for other drugs to be properly evaluated. In the context of emergency, rigorous trials are more than ever needed in order to have, as soon as possible, reliable data on drugs that are possibly effective against the disease. Meanwhile, serious adverse drug reactions have been reported in patients with COVID-19 receiving hydroxychloroquine, justifying to limit its prescription, and to perform suitable cardiac and therapeutic drug monitoring.", "title": "Chloroquine and hydroxychloroquine in the management of COVID-19: much kerfuffle but little evidence", "pid": "pdvqdgsw", "bm25_score": 219.23776245117188}, {"text": "Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10%. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 h after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.", "title": "Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection", "pid": "pbhzmaju", "bm25_score": 219.20875549316406}, {"text": "OBJECTIVES: The emergence of SARS‐CoV‐2 has presented clinicians with a difficult therapeutic dilemma. With supportive care as the current mainstay of treatment, the fatality rate of COVID‐19 is 6.9%. There are currently several trials assessing the efficacy of different antivirals as treatment. Of these, chloroquine (CQ) and its derivative hydroxychloroquine (HCQ) have garnered the most attention. METHODS: In this study, the literature currently available on CQ and HCQ as treatment of COVID‐19 was surveyed using EMBASE, PubMed, Cochrane Library, MedRxiv, and one clinical trial registry. Upon gathering published and preprint trials, risk of bias was assessed using Cochrane Risk of Bias Tool 2.0. RESULTS: There are currently seven completed clinical trials and 29 registered clinical trials focusing on HCQ or CQ as a therapeutic avenue for COVID‐19. Of these, five of seven trials have shown favorable outcomes for patients using CQ or HCQ and two of seven have shown no change compared to control. However, all seven trials carried varying degrees of bias and poor study design. CONCLUSION: There are currently not enough data available to support the routine use of HCQ and CQ as therapies for COVID‐19. Pending further results from more extensive studies with more stringent study parameters, clinicians should defer from routine use of HCQ and CQ. There are several clinical trials currently under way with results expected soon.", "title": "A Rapid Systematic Review of Clinical Trials Utilizing Chloroquine and Hydroxychloroquine as a Treatment for COVID‐19", "pid": "4stz2t7s", "bm25_score": 219.20643615722656}, {"text": "", "title": "Do we have enough evidence to use chloroquine/hydroxychloroquine as a public health panacea for COVID-19?", "pid": "4bkinsuo", "bm25_score": 219.1942138671875}, {"text": "We would like to share ideas on the report on \"Hydroxychloroquine in Patients with Rheumatic Disease Complicated by COVID-19: Clarifying Target Exposures and the Need for Clinical Trials [1].\"Balevic noted that \"well-designed clinical trials that include patients with rheumatic disease are urgently needed to characterize the efficacy, safety, and target exposures for hydroxychloroquine [1].\"", "title": "Evidence of protective effect of hydroxychloroquine to prevent COVID-19.", "pid": "4ch5dmj8", "bm25_score": 219.1925506591797}, {"text": "Purpose: The COVID-19 Pandemic has literally left the world breathless in the chase for Pharmacotherapy. With the vaccine approval likely more than a year away and novel drugs in early clinical trials, repurposing of existing drugs takes the center stage. A potential drug discussed both in geopolitical and global scientific community is hydroxychloroquine (HCQ). We intend to systematically weigh and analyze the existing evidence of HCQ in the light of published and pre-print data available so far. Methods: PubMed Ovid MEDLINE, EMBASE, Google scholar databases and official clinical trial Registries of the United States, China, WHO ICTRP were electronically searched for studies for the use of HCQ in patients with COVID-19. Pre-proof article repositories like MedRxiv, BioRxiv, and ChemRxiv were also included in the search. The literature was critically appraised. Results: Total 71 articles were available as of 15 th April of which articles of relevance (three invitro studies, two open label non-randomized trials, two open label randomized control trials, one follow-up study, three reviews, ten short communications) and 88 clinical trials registered in three clinical trial registries were analyzed. HCQ seems to be efficient in inhibiting of SARS CoV-2 in in-vitro cell lines; there is lack of strong evidence from human studies. Conclusions: The in-vitro cell culture based data of viral inhibition does not suffice for the use of hydroxychloroquine in the patients with COVID-19. Currently literature shows inadequate, low level evidence in human studies. Scarcity of safety and efficacy data warrants medical communities, health care agencies and governments across the world against the widespread use of HCQ in COVID-19 prophylaxis and treatment, until robust evidence becomes available. Keywords: Hydroxychloroquine, SARS-CoV-2, COVID-19, Corona virus, nCov2, systematic review", "title": "Hydroxychloroquine for the management of COVID-19: Hope or Hype? A Systematic review of the current evidence", "pid": "0u4ar3b5", "bm25_score": 219.1893310546875}, {"text": "The current pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calls urgently for effective therapies. Anti-malarial medicine chloroquine (CQ) and particularly its chemical analogue hydroxychloroquine (HCQ) have been recommended as promising candidate therapeutics that are now under either compassionate off-label use or clinical trials for the treatment of COVID-19 patients. However, there are public concerns and disputes about both the safety and efficacy of CQ and HCQ for this new application. Given the fact that for decades HCQ has been approved as an immunomodulatory drug for the long term treatment of chronic rheumatic diseases, as experienced rheumatologists, we would like to share our thoughts in this regard and trigger a brainstorm among clinical care providers for exchanging their diverse opinions on this urgent topic.", "title": "Rheumotologitsts' view on the use of hydroxychloroquine to treat COVID-19", "pid": "f3mebese", "bm25_score": 219.1779327392578}, {"text": "", "title": "Lack of efficacy of hydroxychloroquine in covid-19.", "pid": "o91ew9sl", "bm25_score": 219.1732177734375}, {"text": "Coronavirus disease 2019 (COVID-19) is a pandemic with no specific drugs and high fatality. The most urgent need is to find effective treatments. We sought to determine whether hydroxychloroquine (HCQ) application may reduce the death risk of critically ill COVID-19 patients. In this retrospective study, we included 550 critically ill COVID-19 patients who need mechanical ventilation in Tongji Hospital, Wuhan, from February 1, 2020 to April 4, 2020. All 550 patients received comparable basic treatments including antiviral drugs and antibiotics, and 48 of them were treated with oral HCQ treatment (200 mg twice a day for 7-10 days) in addition to the basic treatments. Primary endpoint is fatality of patients, and inflammatory cytokine levels were compared between HCQ and non-hydroxychloroquine (NHCQ) treatments. We found that fatalities are 18.8% (9/48) in HCQ group, which is significantly lower than 47.4% (238/502) in the NHCQ group (P<0.001). The time of hospital stay before patient death is 15 (10-21) days and 8 (4-14) days for the HCQ and NHCQ groups, respectively (P<0.05). The levels of inflammatory cytokine IL-6 were significantly reduced from 22.2 (8.3-118.9) pg mL-1 at the beginning of the treatment to 5.2 (3.0-23.4) pg mL-1 (P<0.05) at the end of the treatment in the HCQ group but there is no change in the NHCQ group. These data demonstrate that addition of HCQ on top of the basic treatments is highly effective in reducing the fatality of critically ill patients of COVID-19 through attenuation of inflammatory cytokine storm. Therefore, HCQ should be prescribed as a part of treatment for critically ill COVID-19 patients, with possible outcome of saving lives. hydroxychloroquine, IL-6, mortalities, COVID-19.", "title": "Low dose of hydroxychloroquine reduces fatality of critically ill patients with COVID-19", "pid": "lfq1znzm", "bm25_score": 219.16586303710938}, {"text": "OBJECTIVE: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called COVID-19, has caused a pandemic which has swiftly involved the entire world and raised great public health concerns. The scientific community is actively exploring treatments that would potentially be effective in combating COVID-19. Hydroxychloroquine has been demonstrated to limit the replication of SARS-CoV-2 virus in vitro. In malarial pandemic countries, chloroquine is widely used to treat malaria. In malarial non-pandemic nations, chloroquine is not widely used. Chloroquine and hydroxychloroquine share similar chemical structures and mechanisms of action. The aim of this study was to indirectly investigate the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 by determining the prevalence of COVID-19 in malaria pandemic and non-pandemic nations. We sought evidence to support or refute the hypothesis that these drugs could show efficacy in the treatment of COVID-19. MATERIALS AND METHODS: We reviewed in vitro studies, in vivo studies, original studies, clinical trials, and consensus reports, that were conducted to evaluate the antiviral activities of chloroquine and hydroxychloroquine. The studies on \"COVID-19 and its allied treatment were found from World Health Organization (WHO), ISI-Web of Science, PubMed, EMBASE, Scopus, Google Scholar, and clinical trial registries. The search was based on keywords: antiviral drugs, chloroquine, hydroxychloroquine, COVID-19, COVID-19 treatment modalities, and coronavirus. In addition, we analyzed the prevalence of COVID-19 in malaria pandemic and non-pandemic countries. The review and analyses were performed on March 28, 2020. RESULTS: For this study, we identified a total of 09 published articles: 03 clinical trials with sample size 150; 03 in vitro studies and 03 expert consensus reports. These studies were all suggestive that chloroquine and hydroxychloroquine can successfully treat COVID-19 infections. We found that COVID-19 infections are highly pandemic in countries where malaria is least pandemic and are least pandemic in nations where malaria is highly pandemic. CONCLUSIONS: Chloroquine and hydroxychloroquine have antiviral characteristics in vitro. The findings support the hypothesis that these drugs have efficacy in the treatment of COVID-19. People are currently using these drugs for malaria. It is reasonable, given the hypothetical benefit of these two drugs, that they are now being tested in clinical trials to assess their effectiveness to combat this global health crisis.", "title": "Efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19", "pid": "hf5b7gxf", "bm25_score": 219.15676879882812}, {"text": "BACKGROUND: Data from non-randomized studies have suggested that hydroxychloroquine could be an effective therapeutic agent against Covid-19. METHODS: We conducted an observational, retrospective cohort study involving hospitalized adult patients with confirmed, mild to severe Covid-19 in a French university hospital. Patients who received hydroxychloroquine (200mg tid dosage for 10 days) on a compassionate basis in addition to SOCwere compared to patients without contraindications to hydroxychloroquine who received SOCalone. A propensity score-weighted analysis was performed to control for confounders: age, sex, time between symptom onset and admission ≤ 7 days, Charlson comorbidity index, medical history of arterial hypertension, and obesity, NEWS2 score at admission, and pneumonia severity. The primary endpoint was time to unfavorable outcome, defined as: death, admission to an intensive care unit, or decision to withdraw or withhold life-sustaining treatments, whichever came first. RESULTS: Data from 89 patients with laboratory-confirmed Covid-19 were analyzed, 84 of whom were considered in the primary analysis; 38 patients treated with hydroxychloroquine and 46 patients treated with SOCalone. At admission, the mean age of patients was 66 years, the median Charlson comorbidity index was 3, and the median NEWS2 severity score was 3. After propensity score weighting, treatment with hydroxycholoroquine was not associated with a significantly reduced risk of unfavorable outcome (HR 0.90 [0.38; 2.1], p = 0.81). Overall survival was not significantly different between the two groups (HR 0.89 [0.23; 3.47], p = 1) CONCLUSION: In hospitalized adults with Covid-19, no significant reduction of the risk of unfavorable outcomes was observed with hydroxychloroquine in comparison to standard of care. Unmeasured confounders may however have persisted despite careful propensity-weighted analysis and the study might be underpowered. Ongoing controlled trials in patients with varying degrees of initial severity on a larger scale will help determine whether there is a place for hydroxychloroquine in the treatment of Covid-19.", "title": "Compassionate use of hydroxychloroquine in clinical practice for patients with mild to severe Covid-19 in a French university hospital", "pid": "k9aorukq", "bm25_score": 219.13987731933594}, {"text": "Purpose: This study aims to critically assess the published studies of Chloroquine (CQ) and hydroxychloroquine (HCQ) for the treatment of COVID-19 and provide recommendations for future clinical trials for the COVID-19 pandemic. Method: A rapid systematic review was conducted by searching the PubMed, Embase, and China National Knowledge Infrastructure databases on April 13, 2020. Three clinical trial registry platforms, including ClinicalTrials.gov, the EU Clinical Trials Register, and the Chinese Clinical Trial Register were also complementarily searched. Results: A total of 10 clinical studies were identified, including 3 randomized controlled trials (RCTs), 1 comparative nonrandomized trial, 5 single-arm trials, and 1 interim analysis. The heterogeneity among studies of the baseline disease severity and reported endpoints made a pooled analysis impossible. CQ and HCQ (with or without azithromycin) showed significant therapeutic benefit in terms of virologic clearance rate, improvement in symptoms and imaging findings, time to clinical recovery, and length of hospital stay in 1 RCT, 4 single-arm trials, and the interim analysis, whereas no treatment benefit of CQ or HCQ was observed in the remaining 4 studies. Limitations of the included studies ranged from small sample size, to insufficient information concerning baseline patient characteristics, to potential for selection bias without detailing the rationale for exclusion, and presence of confounding factors. Conclusion: Based on the studies evaluated, there still lacked solid evidence supporting the efficacy and safety of HCQ and CQ as a treatment for COVID-19 with or without azithromycin. This emphasized the importance of robust RCTs investing HCQ/CQ to address the evidence uncertainties. Keywords: COVID-19, Systematic review, Clinical trial, Chloroquine, Hydroxychloroquine", "title": "Rapid systematic review on clinical evidence of chloroquine and hydroxychloroquine in COVID-19: critical assessment and recommendation for future clinical trials", "pid": "y9wuszu5", "bm25_score": 219.13250732421875}, {"text": "Following the demonstration of the efficacy of hydroxychloroquine against severe acute respiratory syndrome coronavirus 2 in vitro, many trials started to evaluate its efficacy in clinical settings. However, no systematic review and meta‐analysis have addressed the issue of the safety and efficacy of hydroxychloroquine (HCQ) in coronavirus disease 2019. We conducted a systematic review and meta‐analysis with the objectives of evaluation of safety and efficacy of HCQ alone or in combination in terms of “time to clinical cure,” “virological cure,” “death or clinical worsening of disease,” “radiological progression,” and safety. RevMan was used for meta‐analysis. We searched 16 literature databases out of which seven studies (n = 1358) were included in the systematic review. In terms of clinical cure, two studies reported possible benefit in “time to body temperature normalization” and one study reported less “cough days” in the HCQ arm. Treatment with HCQ resulted in less number of cases showing the radiological progression of lung disease (odds ratio [OR], 0.31, 95% confidence interval [CI], 0.11‐0.9). No difference was observed in virological cure (OR, 2.37, 95% CI, 0.13‐44.53), death or clinical worsening of disease (OR, 1.37, 95% CI, 1.37‐21.97), and safety (OR, 2.19, 95% CI, 0.59‐8.18), when compared with the control/conventional treatment. Five studies reported either the safety or efficacy of HCQ + azithromycin. Although seems safe and effective, more data are required for a definitive conclusion. HCQ seems to be promising in terms of less number of cases with radiological progression with a comparable safety profile to control/conventional treatment. We need more data to come to a definite conclusion.", "title": "Virological and clinical cure in COVID‐19 patients treated with hydroxychloroquine: A systematic review and meta‐analysis", "pid": "3tio10sx", "bm25_score": 219.12774658203125}, {"text": "The Indian Council of Medical Research (ICMR), recommended the use of hydroxychloroquine (HCQ) as a prophylactic against COVID‐19 among health care workers and asymptomatic contacts of laboratory confirmed cases of COVID. This is widely criticised as a hastily taken step with political inclination and minimal evidence backing. In the current scenario, where there is mass fear against COVID‐19, this recommendation has made the people to believe that it will kill the viruses. This has important public health implications which are discussed below. Better communication should have been planned to ensure everyone does not go out and buy it. However, as a nation of 1.3 billion, we need to capitalize on this opportunity to generate data and valuable evidence on the use of HCQ to beat this pandemic. All health care workers taking this drug should volunteer themselves to be part of a trial/observational study and get registered online to generate useful data related to its safety and efficacy and guide future recommendations. The other risk group which includes asymptomatic contacts of laboratory confirmed COVID‐19 patients are under surveillance by the state and local health authorities and could also be roped into this study to generate robust evidence. Of course, pandemic does not just justify the use of HCQ, but pandemic is the time to innovate, think out of box and generate evidence to prove the same so that we can lives. This article is protected by copyright. All rights reserved.", "title": "Does pandemic justify the use of Hydroxychloroquine for treatment and prevention of COVID‐19 in India?", "pid": "vtiwj788", "bm25_score": 219.10748291015625}, {"text": "OBJECTIVE The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also called COVID-19, has caused a pandemic which has swiftly involved the entire world and raised great public health concerns. The scientific community is actively exploring treatments that would potentially be effective in combating COVID-19. Hydroxychloroquine has been demonstrated to limit the replication of SARS-CoV-2 virus in vitro. In malarial pandemic countries, chloroquine is widely used to treat malaria. In malarial non-pandemic nations, chloroquine is not widely used. Chloroquine and hydroxychloroquine share similar chemical structures and mechanisms of action. The aim of this study was to indirectly investigate the efficacy of chloroquine and hydroxychloroquine for the treatment of COVID-19 by determining the prevalence of COVID-19 in malaria pandemic and non-pandemic nations. We sought evidence to support or refute the hypothesis that these drugs could show efficacy in the treatment of COVID-19. MATERIALS AND METHODS We reviewed in vitro studies, in vivo studies, original studies, clinical trials, and consensus reports, that were conducted to evaluate the antiviral activities of chloroquine and hydroxychloroquine. The studies on \"COVID-19 and its allied treatment were found from World Health Organization (WHO), ISI-Web of Science, PubMed, EMBASE, Scopus, Google Scholar, and clinical trial registries. The search was based on keywords: antiviral drugs, chloroquine, hydroxychloroquine, COVID-19, COVID-19 treatment modalities, and coronavirus. In addition, we analyzed the prevalence of COVID-19 in malaria pandemic and non-pandemic countries. The review and analyses were performed on March 28, 2020. RESULTS For this study, we identified a total of 09 published articles: 03 clinical trials with sample size 150; 03 in vitro studies and 03 expert consensus reports. These studies were all suggestive that chloroquine and hydroxychloroquine can successfully treat COVID-19 infections. We found that COVID-19 infections are highly pandemic in countries where malaria is least pandemic and are least pandemic in nations where malaria is highly pandemic. CONCLUSIONS Chloroquine and hydroxychloroquine have antiviral characteristics in vitro. The findings support the hypothesis that these drugs have efficacy in the treatment of COVID-19. People are currently using these drugs for malaria. It is reasonable, given the hypothetical benefit of these two drugs, that they are now being tested in clinical trials to assess their effectiveness to combat this global health crisis.", "title": "Efficacy of chloroquine and hydroxychloroquine in the treatment of COVID-19.", "pid": "fgxbyb7l", "bm25_score": 219.104736328125}, {"text": "Abstract Covid-19 is a new coronavirus disease first described in December 2019. This respiratory illness is severe and potentially fatal. Severe cases make up to 15%, lethality ranges between 1.5 and more than 10 %. What is urgently needed is an efficient pharmacological treatment for the treatment of severe cases. During the infection of alveolar epithelial cells of the lung, the ACE2 receptor has a central function. The antimalarial drugs chloroquine phosphate (CQ) and hydroxychloroquine (HCQ) impair in vitro the terminal glycosylation of ACE2 without significant change of cell-surface ACE2 and, therefore, might be potent inhibitors of SARS-CoV-2 infections. Starting inhibition at 0.1 µM, CQ completely prevented in vitro infections at 10 µM, suggesting a prophylactic effect and preventing the virus spread 5 hours after infection. In a first clinical trial, CQ was effective in inhibiting exacerbation of pneumonia, improving lung imaging findings, promotion of virus-negative conversion, and shortening the disease. In addition, HCQ, which is three times more potent than CQ in SARS-CoV-2 infected cells (EC50 0.72 µM), was significantly associated with viral load reduction/disappearance in COVID-19 patients compared to controls. Theoretically, CQ and HCQ could thus be effectively used in the treatment of SARS-CoV pneumonia. From a pharmacological standpoint, however, the major problems of oral treatment with these drugs are possible severe side effects and toxicity. Concretely, this relates to (a) the inconsistent individual bioavailability of these drugs at the alveolar target cells, depending on intestinal resorption, hepatic first-pass metabolism and accumulation in liver, spleen and lung, and (b) the need for a relatively high concentration of 1-5 µM at the alveolar surface. Therefore, we propose in a first dose estimation the use of HCQ as an aerosol in a dosage of 2-4 mg per inhalation in order to reach sufficient therapeutic levels at the alveolar epithelial cells. By using a low-dose non-systemic aerosol, adverse drug reactions will markedly be reduced compared with oral application. This increase in tolerability enables a broader use for prevention and after contact with an infected person, which would be an advantage especially for the high-risk, often multi-morbid and elderly patients. Empirical data on self-medication with a one-week aerosol application by two of the authors is presented. Inhalation was well tolerated without relevant side effects.", "title": "Hydroxychloroquine as an aerosol might markedly reduce and even prevent severe clinical symptoms after SARS-CoV-2 infection", "pid": "a62k3lma", "bm25_score": 219.10447692871094}, {"text": "", "title": "An independent appraisal and re-analysis of hydroxychloroquine treatment trial for COVID-19.", "pid": "2clz993c", "bm25_score": 219.1027374267578}, {"text": "BACKGROUND: As the number of severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) infected people is skyrocketing worldwide, the international medical situation becomes very serious. Potential therapeutic drugs, vaccine and stem cell replacement methods are emerging, it is urgent to find specific therapeutic drugs and the best treatment regimens. After the publication of hydroxychloroquine (HCQ) with anti-SARS-COV-2 activity in vitro, a small, non-randomized, open-label clinical trial showed that HCQ treatment was significantly associated with reduced viral load in patients with coronavirus disease-19 (COVID-19). Meanwhile, a large prophylaxis study of HCQ sulfate for COVID-19 has been initiated in the United States. HCQ offered a promising efficacy in the treatment of COVID-19, but the optimal administration is still being explored. METHODS: Use the keyword 'Hydroxychloroquine' to conduct a literature search in PubMed to collect relevant literature on the mechanism of action of HCQ, clinical efficacy and safety, pharmacokinetic characteristics, precautions for clinical use and drug interactions, and extract and organize information. RESULTS: This paper reviews the mechanism, clinical efficacy and safety, pharmacokinetic characteristics, exposure-response relationship and precautions and drug interactions of HCQ, and summarized dosage recommendations for HCQ sulfate. CONCLUSION: It has been proved that HCQ, which has an established safety profile, is effective against SARS-CoV-2 with sufficient pre-clinical rationale and evidence. Data from high-quality clinical trials are urgently needed worldwide.", "title": "Review on the clinical pharmacology of hydroxychloroquine sulfate for the treatment of COVID-19", "pid": "u2zu2oet", "bm25_score": 219.08193969726562}, {"text": "Hydroxychloroquine has been promoted for its use in treatment of COVID-19 patients based on in-vitro evidences. We searched the databases to include randomized and observational studies evaluating the effect of Hydroxychloroquine on mortality in COVID-19 patients. The outcome was summarized as odds ratios (OR) with a 95% confidence interval (CI).We used the inverse-variance method with a random effect model and assessed the heterogeneity using I2 test. We used ROBINS-I tool to assess methodological quality of the included studies. We performed the meta-analysis using 'Review manager software version 5.3'. We identified 6 observationalstudies satisfying the selection criteria. In all studies, Hydroxychloroquine was given as add on to the standard care and effect was compared with the standard care alone. A pooled analysis observed 251 deaths in 1331 participants of the Hydroxychloroquine arm and 363 deaths in 1577 participants of the control arm. There was no difference in odds of mortality events amongst Hydroxychloroquine and supportive care arm [1.25 (95% CI: 0.65, 2.38); I2 = 80%]. A similar trend was observed with moderate risk of bias studies [0.95 (95% CI: 0.44, 2.06); I2 = 85%]. The odds of mortality were significantly higher in patients treated with Hydroxychloroquine + Azithromycin than supportive care alone [2.34 (95% CI: 1.63, 3.34); I2 = 0%]. A pooled analysis of recently published studies suggests no additional benefit for reducing mortality in COVID-19 patients when Hydroxychloroquine is given as add-on to the standard care. Graphical Abstract.", "title": "Does Adding of Hydroxychloroquine to the Standard Care Provide any Benefit in Reducing the Mortality among COVID-19 Patients?: a Systematic Review", "pid": "wuv1kafa", "bm25_score": 219.0802764892578}, {"text": "Coronavirus disease 2019 (COVID-19) has been declared a pandemic by the World Health Organization. The United States Food and Drug Administration has not approved any drug or vaccine for the treatment of COVID-19; however, reports have emerged from different parts of the world about the potential therapeutic benefits of existing drugs. Chloroquine and phosphate hydroxychloroquine are the drugs currently in the limelight, and recently, the National Task Force for COVID-19 constituted by the Indian Council of Medical Research has recommended the use of antimalarial drug hydroxychloroquine for prophylaxis of severe acute respiratory syndrome-coronavirus 2 infection in selected high-risk individuals. This short write-up explores the potential efficacy and established safety of chloroquine in COVID-19.", "title": "Chloroquine: Can it be a Novel Drug for COVID-19", "pid": "fxqseibh", "bm25_score": 219.07980346679688}, {"text": "The current pandemic coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) calls urgently for effective therapies. Anti-malarial medicine chloroquine (CQ) and particularly its chemical analogue hydroxychloroquine (HCQ) have been recommended as promising candidate therapeutics that are now under either compassionate off-label use or clinical trials for the treatment of COVID-19 patients. However, there are public concerns and disputes about both the safety and efficacy of CQ and HCQ for this new application. Given the fact that for decades HCQ has been approved as an immunomodulatory drug for the long term treatment of chronic rheumatic diseases, as experienced rheumatologists, we would like to share our thoughts in this regard and trigger a brainstorm among clinical care providers for exchanging their diverse opinions on this urgent topic.", "title": "Rheumotologitsts’ view on the use of hydroxychloroquine to treat COVID-19", "pid": "isxasd9b", "bm25_score": 219.07568359375}, {"text": "The pandemic of the new coronavirus, known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has urged the nations to an unprecedented world-wide reaction, including an accelerated exploration of therapeutic options. In the absence of a vaccine and specifically designed antivirals, the medical community has proposed the use of various previously available medications in order to reduce the number of patients requiring prolonged hospitalizations, oxygen therapy, and mechanical ventilation and to decrease mortality from coronavirus disease 2019 (COVID-19). Hydroxychloroquine and chloroquine are among the proposed drugs and are the most widely used so far, despite the lack of robust evidence on their usefulness. The objective of this article is to review and discuss the possible role of these drugs in the therapy of COVID-19.", "title": "Hydroxychloroquine and chloroquine in COVID-19: should they be used as standard therapy?", "pid": "kwvgj5jf", "bm25_score": 219.05389404296875}, {"text": "", "title": "Does pandemic justify the use of hydroxychloroquine for treatment and prevention of COVID-19 in India?", "pid": "12ikum8s", "bm25_score": 219.0444793701172}, {"text": "Gautret and colleagues reported results of a non-randomised open-label case series which examined the effects of hydroxychloroquine and azithromycin on viral load in the upper respiratory tract of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patients. The authors report that hydroxychloroquine (HCQ) had significant virus reducing effects, and that dual treatment of both HCQ and azithromycin further enhanced virus reduction. This data has triggered speculation whether these drugs should be considered as candidates for the treatment of severe COVID-19. However, questions have been raised regarding the study's data integrity, statistical analyses, and experimental design. We therefore reanalysed the original data to interrogate the main claims of the paper. Here we apply Bayesian statistics to assess the robustness of the original papers claims by testing four variants of the data: 1) The original data; 2) Data including patients who deteriorated; 3) Data including patients who deteriorated with exclusion of untested patients in the comparison group; 4) Data that includes patients who deteriorated with the assumption that untested patients were negative. To ask if HCQ monotherapy is effective, we performed an A/B test for a model which assumes a positive effect, compared to a model of no effect. We find that the statistical evidence is highly sensitive to these data variants. Statistical evidence for the positive effect model ranged from strong for the original data (BF ~11), to moderate when including patients who deteriorated (BF ~4.35), to anecdotal when excluding untested patients (BF ~2), and to anecdotal negative evidence if untested patients were assumed positive (BF ~0.6). To assess whether HCQ is more effective when combined with AZ, we performed the same tests, and found only anecdotal evidence for the positive effect model for the original data (BF ~2.8), and moderate evidence for all other variants of the data (BF ~5.6). Our analyses only explore the effects of different assumptions about excluded and untested patients. These assumptions are not adequately reported, nor are they justified in the original paper, and we find that varying them causes substantive changes to the evidential support for the main claims of the original paper. This statistical uncertainty is exacerbated by the fact that the treatments were not randomised, and subject to several confounding variables including the patients' consent to treatment, different care centres, and clinical decision-making. Furthermore, while the viral load measurements were noisy, showing multiple reversals between test outcomes, there is greater certainty around other clinical outcomes such as the 4 patients who seriously deteriorated. The fact that all of these belonged to the HCQ monotherapy group should be assigned greater weight when evaluating the potential clinical efficacy of HCQ. Randomised controlled trials are currently underway, and will be critical in resolving this uncertainty as to whether HCQ and AZ are effective as a treatment for COVID-19.", "title": "A Bayesian reanalysis of the effects of hydroxychloroquine and azithromycin on viral carriage in patients with COVID-19", "pid": "tg8kfiot", "bm25_score": 219.04379272460938}, {"text": "", "title": "Hydroxychloroquine for Treatment of SARS-CoV-2 Infection? Improving Our Confidence in a Model-Based Approach to Dose Selection", "pid": "dwn1h7rz", "bm25_score": 219.03640747070312}]}
{"idx": 28, "qid": "29", "q_text": "which SARS-CoV-2 proteins-human proteins interactions indicate potential for drug targets. Are there approved drugs that can be repurposed based on this information?", "qrels": {"02bik024": 0, "02q9y011": 2, "03eifdr1": 0, "03isjlif": 2, "043w3zgy": 2, "047xpt2c": 0, "05fiqpeg": 1, "pl9ht0d0": 0, "084o1dmp": 0, "08ds967z": 0, "08yraaz7": 0, "yzr7ifbj": 2, "0d77ojnb": 2, "0ec2xunt": 0, "0ewcptub": 0, "0hwbmf8k": 0, "0hxan9rw": 0, "0ikvdwkz": 0, "0j8rvapz": 1, "0jr31q5g": 2, "0lk8eujq": 1, "0lvgqhwo": 2, "0m5umout": 1, "0nh58odf": 0, "0nm7wgf5": 0, "0nqz5y20": 0, "0o6agnrc": 1, "74pj3vho": 0, "0qihw3bn": 0, "0qwveb68": 2, "0sdjy80s": 1, "0u4ar3b5": 2, "0wfaggvo": 0, "0wh7x410": 2, "100ir651": 1, "100pko8b": 1, "11edrkav": 0, "12san3m7": 0, "12th7nja": 1, "13jupb26": 1, "15drpph0": 0, "161ck1i9": 0, "17oac3bg": 0, "1b3x7p6u": 1, "1c47w4q5": 2, "1fgnfh62": 0, "1fxrmuzl": 1, "ij8wk06v": 2, "1icxzdnm": 1, "1intktsf": 2, "1kyrptgx": 0, "ldyg241o": 2, "1lc2xf7u": 1, "1mmqfp7g": 1, "1nnqx1g9": 0, "f6xhrpi8": 2, "1qniriu0": 1, "1rhy8td0": 0, "1sxhza50": 2, "1t4ykc01": 1, "u7j2gicv": 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"zsr5zz2k": 0, "zult69f2": 0, "zv0ysi8m": 2, "zx02gxw0": 1, "zzkqb0u2": 0}, "bm25_results": [{"text": "An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption(1,2). There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity- purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral therapeutics against SARS-CoV-2 and other deadly coronavirus strains.", "title": "A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing", "pid": "38d6gb7o", "bm25_score": 222.76275634765625}, {"text": "The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.", "title": "A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.", "pid": "eje3i558", "bm25_score": 222.74609375}, {"text": "Motivated by the critical need to identify new treatments for COVID-19, we present a genome-scale, systems-level computational approach to prioritize drug targets based on their potential to regulate host-virus interactions or their downstream signaling targets. We adapt and specialize network label propagation methods to this end. We demonstrate that these techniques can predict human-SARS-CoV-2 protein interactors with high accuracy. The top-ranked proteins that we identify are enriched in host biological processes that are potentially coopted by the virus. We present cases where our methodology generates promising insights such as the potential role of HSPA5 in viral entry. We highlight the connection between endoplasmic reticulum stress, HSPA5, and anti-clotting agents. We identify tubulin proteins involved in ciliary assembly that are targeted by anti-mitotic drugs. Drugs that we discuss are already undergoing clinical trials to test their efficacy against COVID-19. Our prioritized list of human proteins and drug targets is available as a general resource for biological and clinical researchers who are repositioning existing and approved drugs or developing novel therapeutics as anti-COVID-19 agents.", "title": "Identifying Human Interactors of SARS-CoV-2 Proteins and Drug Targets for COVID-19 using Network-Based Label Propagation", "pid": "qrfx165d", "bm25_score": 222.6595001220703}, {"text": "A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption1,2. There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein-protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19.", "title": "A SARS-CoV-2 protein interaction map reveals targets for drug repurposing", "pid": "7qd8z5e7", "bm25_score": 221.871826171875}, {"text": "SARS-CoV-2 has caused tens of thousands of infections and more than one thousand deaths. There are currently no registered therapies for treating coronavirus infections. Because of time consuming process of new drug development, drug repositioning may be the only solution to the epidemic of sudden infectious diseases. We systematically analyzed all the proteins encoded by SARS-CoV-2 genes, compared them with proteins from other coronaviruses, predicted their structures, and built 19 structures that could be done by homology modeling. By performing target-based virtual ligand screening, a total of 21 targets (including two human targets) were screened against compound libraries including ZINC drug database and our own database of natural products. Structure and screening results of important targets such as 3-chymotrypsin-like protease (3CLpro), Spike, RNA-dependent RNA polymerase (RdRp), and papain like protease (PLpro) were discussed in detail. In addition, a database of 78 commonly used anti-viral drugs including those currently on the market and undergoing clinical trials for SARS-CoV-2 was constructed. Possible targets of these compounds and potential drugs acting on a certain target were predicted. This study will provide new lead compounds and targets for further in vitro and in vivo studies of SARS-CoV-2, new insights for those drugs currently ongoing clinical studies, and also possible new strategies for drug repositioning to treat SARS-CoV-2 infections.", "title": "Analysis of therapeutic targets for SARS-CoV-2 and discovery of potential drugs by computational methods", "pid": "i1lyno9g", "bm25_score": 221.82711791992188}, {"text": "We previously presented the protein-protein interaction network - the ‘HoP’ or the host protein interactome - of 332 host proteins that were identified to interact with 27 nCoV19 viral proteins by Gordon et al. Here, we studied drugs targeting the proteins in this interactome to identify whether any of them may potentially be repurposable against SARS-CoV-2. We studied each of the drugs using the BaseSpace Correlation Engine and identified those that induce gene expression profiles negatively correlated with SARS-associated expression profile. This analysis resulted in 20 drugs whose differential gene expression (drug versus normal) had an anti-correlation with differential expression for SARS (viral infection versus normal). These included drugs that were already being tested for their clinical activity against SARS-CoV-2, those with proven activity against SARS-CoV/MERS-CoV, broad-spectrum antiviral drugs, and those identified/prioritized by other computational re-purposing studies. In summary, our integrated computational analysis of the HoP interactome in conjunction with drug-induced transcriptomic data resulted in drugs that may be repurposable for COVID-19.", "title": "Potentially repurposable drugs for COVID-19 identified from SARS-CoV-2 Host Protein Interactome", "pid": "yv2gjjzg", "bm25_score": 221.38961791992188}, {"text": "The SARS-CoV-2 pandemic, declared as a global health emergency by the WHO in February 2020, has currently infected more than 6 million people with fatalities near 371,000 and increasing exponentially, in absence of vaccines and drugs. The pathogenesis of SARS-CoV-2 is still being elucidated. Identifying potential targets and repurposing drugs as therapeutic options is the need of the hour. In this review, we focus on potential druggable targets and suitable therapeutics, currently being explored in clinical trials, to treat SARS-CoV-2 infection. A brief understanding of the complex interactions of both viral as well as host targets, and the possible repurposed drug candidates are described with an emphasis on understanding the mechanisms at the molecular level.", "title": "Tackling SARS-CoV-2: proposed targets and repurposed drugs", "pid": "4tis2he4", "bm25_score": 221.10275268554688}, {"text": "Herein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was to solvate the isolated S-protein in water for molecular dynamics (MD) simulation, being observed a transition from \"up\" to \"down\" conformation of receptor-binding domain (RBD) of the S-protein with angle of 54.3 and 43.0 degrees, respectively. The RBD region was more exposed to the solvent and to the possible drugs due to its enhanced surface area. From the equilibrated MD structure, virtual screening by docking calculations were performed using a library contained 9091 FDA approved drugs. Among them, 24 best-scored ligands (14 traditional herbal isolate and 10 approved drugs) with the binding energy below -8.1 kcal/mol were selected as potential candidates to inhibit the SARS-CoV-2 S-protein, preventing the human cell infection and their replication. For instance, the ivermectin drug (present in our list of promise candidates) was recently used successful to control viral replication in vitro. MD simulations were performed for the three best ligands@S-protein complexes and the binding energies were calculated using the MM/PBSA approach. Overall, it is highlighted an important strategy, some key residues, and chemical groups which may be considered on clinical trials for COVID-19 outbreak.", "title": "Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening", "pid": "5vgfliv0", "bm25_score": 220.9130096435547}, {"text": "The prevalence of respiratory illness caused by the novel SARS-CoV-2 associated with multiple organ failures is spreading rapidly due to its contagious human-to-human transmission and inadequate global healthcare systems. Pharmaceutical re-use, reflecting an effective drug development technique using existing drugs, could shorten the time and reduce the costs relative to de novo drug discovery. We have performed virtual screening of antiviral compounds targeting the spike glycoprotein (S), main protease (M(pro)), and the SARS-CoV-2 RBD-ACE2 complex of SARS-CoV-2. PC786, an antiviral polymerase inhibitor, showed improved binding affinity toward all the targets. Furthermore, the post-fusion conformation of the trimeric S protein RBD domain with ACE2 revealed conformational changes associated with the PC786 drug binding. The proposed T cell and B cell epitope identification using the immunoinformatics approach could direct the experimental study with a higher probability of discovering appropriate vaccine candidates with fewer experiments and higher reliability.", "title": "Structure-based drug designing and immunoinformatics approach for SARS-CoV-2", "pid": "ty27die9", "bm25_score": 220.87850952148438}, {"text": "COVID-19 has created a global pandemic with high morbidity and mortality in 2020. Novel coronavirus (nCoV), also known as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2), is responsible for this deadly disease. International Committee on Taxonomy of Viruses (ICTV) has declared that nCoV is highly genetically similar to SARS-CoV epidemic in 2003 (89% similarity). Limited number of clinically validated Human-nCoV protein interaction data is available in the literature. With this hypothesis, the present work focuses on developing a computational model for nCoV-Human protein interaction network, using the experimentally validated SARS-CoV-Human protein interactions. Initially, level-1 and level-2 human spreader proteins are identified in SARS-CoV-Human interaction network, using Susceptible-Infected-Susceptible (SIS) model. These proteins are considered as potential human targets for nCoV bait proteins. A gene-ontology based fuzzy affinity function has been used to construct the nCoV-Human protein interaction network at 99.98% specificity threshold. This also identifies the level-1 human spreaders for COVID-19 in human protein-interaction network. Level-2 human spreaders are subsequently identified using the SIS model. The derived host-pathogen interaction network is finally validated using 7 potential FDA listed drugs for COVID-19 with significant overlap between the known drug target proteins and the identified spreader proteins.", "title": "Computational modeling of Human-nCoV protein-protein interaction network", "pid": "k4f79dr4", "bm25_score": 220.8402099609375}, {"text": "The mapping of SARS-CoV-2 human protein-protein interactions by Gordon and colleagues revealed druggable targets that are hijacked by the virus. Here, we highlight several oncogenic pathways identified at the host-virus interface of SARS-CoV-2 to enable cancer biologists to apply their knowledge for rapid drug repurposing to treat COVID-19, and help inform the response to potential long-term complications of the disease.", "title": "The Landscape of Human Cancer Proteins Targeted by SARS-CoV-2", "pid": "2cvvkrx9", "bm25_score": 220.8226318359375}, {"text": "WHO has declared the outbreak of COVID-19 as a public health emergency of international concern. The ever-growing new cases have called for an urgent emergency for specific anti-COVID-19 drugs. Three structural proteins (Membrane, Envelope and Nucleocapsid protein) play an essential role in the assembly and formation of the infectious virion particles. Thus, the present study was designed to identify potential drug candidates from the unique collection of 548 anti-viral compounds (natural and synthetic anti-viral), which target SARS-CoV-2 structural proteins. High-end molecular docking analysis was performed to characterize the binding affinity of the selected drugs-the ligand, with the SARS-CoV-2 structural proteins, while high-level Simulation studies analyzed the stability of drug-protein interactions. The present study identified rutin, a bioflavonoid and the antibiotic, doxycycline, as the most potent inhibitor of SARS-CoV-2 envelope protein. Caffeic acid and ferulic acid were found to inhibit SARS-CoV-2 membrane protein while the anti-viral agent's simeprevir and grazoprevir showed a high binding affinity for nucleocapsid protein. All these compounds not only showed excellent pharmacokinetic properties, absorption, metabolism, minimal toxicity and bioavailability but were also remain stabilized at the active site of proteins during the MD simulation. Thus, the identified lead compounds may act as potential molecules for the development of effective drugs against SARS-CoV-2 by inhibiting the envelope formation, virion assembly and viral pathogenesis.", "title": "Identification of potential inhibitors against SARS-CoV-2 by targeting proteins responsible for envelope formation and virion assembly using docking based virtual screening, and pharmacokinetics approaches", "pid": "j92mfwkj", "bm25_score": 220.79354858398438}, {"text": "A new Coronavirus strain, named SARS-CoV-2, suddenly emerged in early December 2019. SARS-CoV-2 resulted in being dramatically infectious, with thousands of people infected. In this scenario, and without effective vaccines available, the importance of an immediate tool to support patients and against viral diffusion becomes evident. In this study, we exploit the molecular docking approach to analyze the affinity between different viral proteins and several inhibitors, originally developed for other viral infections. Our data show that, in some cases, a relevant binding can be detected. These findings support the hypothesis to develop new antiviral agents against COVID-19, on the basis of already established therapies.", "title": "Molecular Investigation of SARS-CoV-2 Proteins and Their Interactions with Antiviral Drugs", "pid": "jg9vlpu1", "bm25_score": 220.76136779785156}, {"text": "Herein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was to solvate the isolated S-protein in water for molecular dynamics (MD) simulation, being observed a transition from “up” to “down” conformation of receptor-binding domain (RBD) of the S-protein with angle of 54.3 and 43.0 degrees, respectively. The RBD region was more exposed to the solvent and to the possible drugs due to its enhanced surface area. From the equilibrated MD structure, virtual screening by docking calculations were performed using a library contained 9091 FDA approved drugs. Among them, 24 best-scored ligands (14 traditional herbal isolate and 10 approved drugs) with the binding energy below –8.1 kcal/mol were selected as potential candidates to inhibit the SARS-CoV-2 S-protein, preventing the human cell infection and their replication. For instance, the ivermectin drug (present in our list of promise candidates) was recently used successful to control viral replication in vitro. MD simulations were performed for the three best ligands@S-protein complexes and the binding energies were calculated using the MM/PBSA approach. Overall, it is highlighted an important strategy, some key residues, and chemical groups which may be considered on clinical trials for COVID-19 outbreak.", "title": "Repurposing approved drugs as inhibitors of SARS-CoV-2 S-protein from molecular modeling and virtual screening", "pid": "74xvvwrw", "bm25_score": 220.70516967773438}, {"text": "Non-structural protein 1 (nsp1) is found in all Betacoronavirus genus, an important viral group that causes severe respiratory human diseases. This protein has significant role in pathogenesis and it is considered a probably major virulence factor. As it is absent in humans, it becomes an interesting target of study, especially when it comes to the rational search for drugs, since it increases the specificity of the target and reduces possible adverse effects that may be caused to the patient. Using approaches in silico we seek to study the behavior of nsp1 in solution to obtain its most stable conformation and find possible drugs with affinity to all of them. For this purpose, complete model of nsp1 of SARS-CoV-2 were predicted and its stability analyzed by molecular dynamics simulations in five different replicas. After main pocket validation using two control drugs and the main conformations of nsp1, molecular docking based on virtual screening were performed to identify novel potential inhibitors from DrugBank database. It has been found 16 molecules in common to all five nsp1 replica conformations. Three of them was ranked as the best compounds among them and showed better energy score than control molecules that have in vitro activity against nsp1 from SARS-CoV-2. The results pointed out here suggest new potential drugs for therapy to aid the rational drug search against COVID-19. Communicated by Ramaswamy H. Sarma.", "title": "Identification of potential drugs against SARS-CoV-2 non-structural protein 1 (nsp1).", "pid": "h4occy7h", "bm25_score": 220.65957641601562}, {"text": "The mapping of SARS-CoV-2 human protein–protein interactions by Gordon and colleagues revealed druggable targets that are hijacked by the virus. Here, we highlight several oncogenic pathways identified at the host–virus interface of SARS-CoV-2 to enable cancer biologists to apply their knowledge for rapid drug repurposing to treat COVID-19, and help inform the response to potential long-term complications of the disease.", "title": "The Landscape of Human Cancer Proteins Targeted by SARS-CoV-2", "pid": "uuy94dwa", "bm25_score": 220.65780639648438}, {"text": "A new Coronavirus strain, named SARS-CoV-2, suddenly emerged in early December 2019. SARS-CoV-2 resulted in being dramatically infectious, with thousands of people infected. In this scenario, and without effective vaccines available, the importance of an immediate tool to support patients and against viral diffusion becomes evident. In this study, we exploit the molecular docking approach to analyze the affinity between different viral proteins and several inhibitors, originally developed for other viral infections. Our data show that, in some cases, a relevant binding can be detected. These findings support the hypothesis to develop new antiviral agents against COVID-19, on the basis of already established therapies.", "title": "Molecular Investigation of SARS–CoV-2 Proteins and Their Interactions with Antiviral Drugs", "pid": "ftyj42bz", "bm25_score": 220.6140594482422}, {"text": "Coronavirus Disease 2019 (COVID-19) has been creating a worldwide pandemic situation. Repurposing drugs, already shown to be free of harmful side effects, for the treatment of COVID-19 patients is an important option in launching novel therapeutic strategies. Therefore, reliable molecule interaction data are a crucial basis, where drug-/protein-protein interaction networks establish invaluable, year-long carefully curated data resources. However, these resources have not yet been systematically exploited using high-performance artificial intelligence approaches. Here, we combine three networks, two of which are year-long curated, and one of which, on SARS-CoV-2-human host-virus protein interactions, was published only most recently (30th of April 2020), raising a novel network that puts drugs, human and virus proteins into mutual context. We apply Variational Graph AutoEncoders (VGAEs), representing most advanced deep learning based methodology for the analysis of data that are subject to network constraints. Reliable simulations confirm that we operate at utmost accuracy in terms of predicting missing links. We then predict hitherto unknown links between drugs and human proteins against which virus proteins preferably bind. The corresponding therapeutic agents present splendid starting points for exploring novel host-directed therapy (HDT) options.", "title": "Predicting potential drug targets and repurposable drugs for COVID-19 via a deep generative model for graphs", "pid": "2lmwnfda", "bm25_score": 220.6019744873047}, {"text": "Given the severity of the SARS-CoV-2 pandemic, a major challenge is to rapidly repurpose existing approved drugs for clinical interventions. While a number of data-driven and experimental approaches have been suggested in the context of drug repurposing, a platform that systematically integrates available transcriptomic, proteomic and structural data is missing. More importantly, given that SARS-CoV-2 pathogenicity is highly age-dependent, it is critical to integrate aging signatures into drug discovery platforms. We here take advantage of large-scale transcriptional drug screens combined with RNA-seq data of the lung epithelium with SARS-CoV-2 infection as well as the aging lung. To identify robust druggable protein targets, we propose a principled causal framework that makes use of multiple data modalities. Our analysis highlights the importance of serine/threonine and tyrosine kinases as potential targets that intersect the SARS-CoV-2 and aging pathways. By integrating transcriptomic, proteomic and structural data that is available for many diseases, our drug discovery platform is broadly applicable. Rigorous in vitro experiments as well as clinical trials are needed to validate the identified candidate drugs.", "title": "Causal Network Models of SARS-CoV-2 Expression and Aging to Identify Candidates for Drug Repurposing", "pid": "ofmjtri8", "bm25_score": 220.57827758789062}, {"text": "[Image: see text] Currently, humans are immersed in a pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which threatens public health worldwide. To date, no drug or vaccine has been approved to treat the severe disease caused by this coronavirus, COVID-19. In this paper, we will focus on the main virus-based and host-based targets that can guide efforts in medicinal chemistry to discover new drugs for this devastating disease. In principle, all CoV enzymes and proteins involved in viral replication and the control of host cellular machineries are potentially druggable targets in the search for therapeutic options for SARS-CoV-2. This Perspective provides an overview of the main targets from a structural point of view, together with reported therapeutic compounds with activity against SARS-CoV-2 and/or other CoVs. Also, the role of innate immune response to coronavirus infection and the related therapeutic options will be presented.", "title": "COVID-19: Drug Targets and Potential Treatments", "pid": "2kfmgr7k", "bm25_score": 220.45970153808594}, {"text": "The recent outbreak of coronavirus disease-19 (COVID-19) continues to drastically affect healthcare throughout the world. To date, no approved treatment regimen or vaccine is available to effectively attenuate or prevent the infection. Therefore, collective and multidisciplinary efforts are needed to identify new therapeutics or to explore effectiveness of existing drugs and drug-like small molecules against SARS-CoV-2 for lead identification and repurposing prospects. This study addresses the identification of small molecules that specifically bind to any of the three essential proteins (RdRp, 3CL-protease and helicase) of SARS-CoV-2. By applying computational approaches we screened a library of 4574 compounds also containing FDA-approved drugs against these viral proteins. Shortlisted hits from initial screening were subjected to iterative docking with the respective proteins. Ranking score on the basis of binding energy, clustering score, shape complementarity and functional significance of the binding pocket was applied to identify the binding compounds. Finally, to minimize chances of false positives, we performed docking of the identified molecules with 100 irrelevant proteins of diverse classes thereby ruling out the non-specific binding. Three FDA-approved drugs showed binding to 3CL-protease either at the catalytic pocket or at an allosteric site related to functionally important dimer formation. A drug-like molecule showed binding to RdRp in its catalytic pocket blocking the key catalytic residues. Two other drug-like molecules showed specific interactions with helicase at a key domain involved in catalysis. This study provides lead drugs or drug-like molecules for further in vitro and clinical investigation for drug repurposing and new drug development prospects.", "title": "Identification of potential inhibitors of three key enzymes of SARS-CoV2 using computational approach", "pid": "eja8fkwv", "bm25_score": 220.38031005859375}, {"text": "The present pandemic of SARS-CoV-2 has been a tough task for the whole world to deal with. With the absence of specific drugs or vaccines against SARS-CoV-2, the situation is very difficult to control. Apart from the absence of specific therapies, the lack of knowledge about potential therapeutic targets and individual perception is adding to the complications. The present review describes the novel SARS-CoV-2 structure, surface proteins, asymptomatic and symptomatic transmission in addition to the genotype and phenotype of SARS-CoV-2 along with genetic strains and similarity between SARS, MERS and SARS-CoV-2. Therapeutic strategies such as inhibition of the endocytic pathway and suppressing RNA polymerase activity by metal ions, which could be quite beneficial for controlling COVID-19, are outlined. The drug repurposing for SARS-CoV-2 is discussed in detail along with therapeutic classes such as antivirals, antibiotics, and amino quinolones and their probable role in suppressing SARS-CoV-2 with reference to case studies. The ongoing clinical trials both with respect to drug repurposing and vaccines are summarized along with a brief description. The recent advancements and future perspective of ongoing research for therapy and detection of SARS-CoV-2 are provided. The review, in brief, summarizes epidemiology, therapy and the current scenario for combating SARS-CoV-2.", "title": "Potential therapeutic targets for combating SARS-CoV-2: Drug repurposing, clinical trials and recent advancements", "pid": "0wh7x410", "bm25_score": 220.31204223632812}, {"text": "COVID-19 is one of the most impactful pandemics in recorded history. As such, the identification of inhibitory drugs against its etiological agent, SARS-CoV-2, is of utmost importance, and in particular, repurposing may provide the fastest route to curb the disease. As the first step in this route, we sought to identify an attractive and viable target in the virus for pharmaceutical inhibition. Using three bacteria-based assays that were tested on known viroporins, we demonstrate that one of its essential components, the E protein, is a potential ion channel and, therefore, is an excellent drug target. Channel activity was demonstrated for E proteins in other coronaviruses, providing further emphasis on the importance of this functionally to the virus’ pathogenicity. The results of a screening effort involving a repurposing drug library of ion channel blockers yielded two compounds that inhibit the E protein: Gliclazide and Memantine. In conclusion, as a route to curb viral virulence and abate COVID-19, we point to the E protein of SARS-CoV-2 as an attractive drug target and identify off-label compounds that inhibit it.", "title": "SARS-CoV-2 E protein is a potential ion channel that can Be inhibited by Gliclazide and Memantine", "pid": "cjq0ep4f", "bm25_score": 220.2744140625}, {"text": "The outbreak of novel coronavirus pneumonia (COVID-19) caused thousands of deaths worldwide, and the number of total infections is still rising. However, the development of effective vaccine for this novel virus would take a few months. Thus it is urgent to identify some potentially effective old drugs that can be used immediately. Fortunately, some compounds that can inhibit coronavirus in vitro have been reported. In this study, the coronavirus-specific dataset was used to fine-tune our pre-trained multi-task deep model. Next we used the re-trained model to select available commercial drugs against targeted proteins of SARS-CoV-2. The results show that abacavir, a powerful nucleoside analog reverse transcriptase inhibitor used to treat HIV, is predicted to have high binding affinity with several proteins of SARS-CoV-2. Almitrine mesylate and roflumilast which are used for respiratory diseases such as chronic obstructive pulmonary disease are also predicted to have inhibitory effect. Overall, ten drugs are listed as potential inhibitors and the important sites for these binding by our model are exhibited. We hope these results would be useful in the fight against SARS-CoV-2.", "title": "Prediction of potential commercially inhibitors against SARS-CoV-2 by multi-task deep model", "pid": "2fs8oui2", "bm25_score": 220.2625732421875}, {"text": "SARS-CoV-2 has been widely spread around the world and COVID-19 was declared a global pandemic by the World Health Organization. Limited clinically effective antiviral drugs are available now. The development of anti-SARS-CoV-2 drugs has become an urgent work worldwide. At present, potential therapeutic targets and drugs for SARS-CoV-2 are continuously reported, and many repositioning drugs are undergoing extensive clinical research, including remdesivir and chloroquine. On the other hand, structures of many important viral target proteins and host target proteins, including that of RdRp and Mpro were constantly reported, which greatly promoted structure-based drug design. This paper summarizes the current research progress and challenges in the development of anti-SARS-CoV-2 drugs, and proposes novel short-term and long-term drug research strategies.", "title": "Research progress on repositioning drugs and specific therapeutic drugs for SARS-CoV-2", "pid": "xb5p25gk", "bm25_score": 220.25650024414062}, {"text": "The current pandemic SARS-CoV-2 has wreaked havoc in the world, and neither drugs nor vaccine is available for the treatment of this disease. Thus, there is an immediate need for novel therapeutics that can combat this deadly infection. In this study, we report the therapeutic assessment of azurin and its peptides: p18 and p28 against the viral structural S-protein and non-structural 3CLpro and PLpro proteins. Among the analyzed complexes, azurin docked relatively well with the S2 domain of S-protein compared to the other viral proteins. The derived peptide p18 bound to the active site domain of the PLpro protein; however, in other complexes, lesser interactions were recorded. The second azurin derived peptide p28, fared the best among the docked proteins. p28 interacted with all the three viral proteins and the host ACE-2 receptor by forming several electrostatic and hydrogen bonds with the S-protein, 3CLpro, and PLpro. MD simulations indicated that p28 exhibited a strong affinity to S-protein and ACE-2 receptor, indicating a possibility of p28 as a protein-protein interaction inhibitor. Our data suggest that the p28 has potential as an anti-SARS-CoV-2 agent and can be further exploited to establish its validity in the treatment of current and future SARS-CoV crisis.Communicated by Ramaswamy H. Sarma.", "title": "Bacterial protein azurin and derived peptides as potential anti-SARS-CoV-2 agents: insights from molecular docking and molecular dynamics simulations.", "pid": "pb0wvujy", "bm25_score": 220.21897888183594}, {"text": "The World Health Organization (WHO) has declared the coronavirus disease 2019 (COVID-19) caused by the novel coronavirus SARS-CoV-2 a pandemic. There is, however, no confirmed anti-COVID-19 therapeutic currently. In order to assist structure-based discovery efforts for repurposing drugs against this disease, we constructed knowledge-based models of SARS-CoV-2 proteins and compared the ligand molecules in the template structures with approved/experimental drugs and components of natural medicines. Our theoretical models suggest several drugs, such as carfilzomib, sinefungin, tecadenoson, and trabodenoson, that could be further investigated for their potential for treating COVID-19.", "title": "Knowledge-based structural models of SARS-CoV-2 proteins and their complexes with potential drugs", "pid": "onskc3u9", "bm25_score": 220.21255493164062}, {"text": "This is a further study on the severe acute respiratory syndrome (SARS) using the probabilistic models. The purpose was to define the potential targets for anti-SARS drugs in the structural proteins from human SARS related coronavirus (SARS-CoV) while knowing little about the functional sites and possible mutations in these proteins. From a probabilistic viewpoint, we can theoretically select the amino acid pairs as potential candidates for anti-SARS drugs. These candidates have a greater chance of colliding with anti-SARS drugs, are more likely to link with the protein functions and are less vulnerable to mutations.", "title": "Potential targets for anti-SARS drugs in the structural proteins from SARS related coronavirus", "pid": "amzmyqys", "bm25_score": 220.20108032226562}, {"text": "The recent pandemic associated with SARS-CoV-2, a virus of the Coronaviridae family, has resulted in an unprecedented number of infected people. The highly contagious nature of this virus makes it imperative for us to identify promising inhibitors from pre-existing antiviral drugs. Two druggable targets, namely 3C-like proteinase (3CLpro) and 2'-O-ribose methyltransferase (2'-O-MTase) were selected in this study due to their indispensable nature in the viral life cycle. 3CLpro is a cysteine protease responsible for the proteolysis of replicase polyproteins resulting in the formation of various functional proteins, whereas 2'-O-MTase methylates the ribose 2'-O position of the first and second nucleotide of viral mRNA, which sequesters it from the host immune system. The selected drug target proteins were screened against an in-house library of 123 antiviral drugs. Two promising drug molecules were identified for each protein based on their estimated free energy of binding (&#916;G), the orientation of drug molecules in the active site and the interacting residues. The selected protein-drug complexes were then subjected to MD simulation, which consists of various structural parameters to equivalently reflect their physiological state. From the virtual screening results, two drug molecules were selected for each drug target protein [Paritaprevir (&#916;G = -9.8 kcal/mol) & Raltegravir (&#916;G = -7.8 kcal/mol) for 3CLpro and Dolutegravir (&#916;G = -9.4 kcal/mol) and Bictegravir (&#916;G = -8.4 kcal/mol) for 2'-OMTase]. After the extensive computational analysis, we proposed that Raltegravir, Paritaprevir, Bictegravir and Dolutegravir are excellent lead candidates for these crucial proteins and they could become potential therapeutic drugs against SARS-CoV-2. Communicated by Ramaswamy H. Sarma.", "title": "Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2'-O-ribose methyltransferase", "pid": "sd40c03b", "bm25_score": 220.19235229492188}, {"text": "We propose a novel numerical method able to determine efficiently and effectively the relationship of complementarity between portions of protein surfaces. This innovative and general procedure, based on the representation of the molecular iso-electron density surface in terms of 2D Zernike polynomials, allows the rapid and quantitative assessment of the geometrical shape complementarity between interacting proteins, that was unfeasible with previous methods. We first tested the method with a large dataset of known protein complexes obtaining an overall area under the ROC curve of 0.76 in the blind recognition of binding sites and then applied it to investigate the features of the interaction between the Spike protein of SARS-CoV-2 and human cellular receptors. Our results indicate that SARS-CoV-2 uses a dual strategy: its spike protein could also interact with sialic acid receptors of the cells in the upper airways, in addition to the known interaction with Angiotensin-converting enzyme 2.", "title": "In-Silico evidence for two receptors based strategy of SARS-CoV-2", "pid": "ob37jivi", "bm25_score": 220.17213439941406}, {"text": "Abstract The recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear, threatening global health security. To date, no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are underway to test possible therapies. During this urgency situation, computational drug discovery methods provide an alternative to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has indicated highest potential towards antiviral drug discovery. In this work, we present potential compounds that specifically target SARS-CoV-2 vital proteins, including the main protease, Nsp12 RNA polymerase and Nsp13 helicase. An integrative virtual screening and molecular dynamics simulations approach led to the identification of potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.", "title": "Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase", "pid": "0nqz5y20", "bm25_score": 220.15283203125}, {"text": "We propose a novel numerical method able to determine efficiently and effectively the relationship of complementarity between portions of proteins surfaces. This innovative and general procedure, based on the representation of the molecular iso-electron density surface in terms of 2D Zernike polynomials, allows the rapid and quantitative assessment of the geometrical shape complementarity between interacting proteins, that was unfeasible with previous methods. We first tested the method with a large dataset of known protein complexes obtaining an overall area under the ROC curve of 0.76 in the blind recognition of binding sites and then applied it to investigate the features of the interaction between the Spike protein of SARS-Cov-2 and human cellular receptors. Our results indicate that SARS-CoV-2 uses a dual strategy: its spike protein could also interact with sialic acid receptors of the cells in the upper airways, in addition to the known interaction with Angiotensin-converting enzyme 2.", "title": "In-Silico evidence for two receptors based strategy of SARS-CoV-2", "pid": "mdtehi97", "bm25_score": 220.14208984375}, {"text": "The recently emerged SARS-CoV-2 caused a major outbreak of coronavirus disease 2019 (COVID-19) and instigated a widespread fear, threatening global health security. To date, no licensed antiviral drugs or vaccines are available against COVID-19 although several clinical trials are underway to test possible therapies. During this urgency situation, computational drug discovery methods provide an alternative to tiresome high-throughput screening, particularly in the hit-to-lead-optimization stage. Identification of small molecules that specifically target viral replication apparatus has indicated highest potential towards antiviral drug discovery. In this work, we present potential compounds that specifically target SARS-CoV-2 vital proteins, including the main protease, Nsp12 RNA polymerase and Nsp13 helicase. An integrative virtual screening and molecular dynamics simulations approach led to the identification of potential binding modes and favourable molecular interaction profile of corresponding compounds. Moreover, the identification of structurally important binding site residues in conserved motifs located inside the active site highlights relative importance of ligand binding based on residual energy decomposition analysis. Although the current study lacks experimental validation, the structural information obtained from this computational study has paved way for the design of targeted inhibitors to combat COVID-19 outbreak.", "title": "Structural elucidation of SARS-CoV-2 vital proteins: Computational methods reveal potential drug candidates against main protease, Nsp12 polymerase and Nsp13 helicase", "pid": "jznszeo7", "bm25_score": 220.1180877685547}, {"text": "Beside socio-economic issues, coronavirus pandemic COVID-19, the infectious disease caused by the newly discovered coronavirus SARS-CoV-2, has caused a deep impact in the scientific community, that has considerably increased its effort to discover the infection strategies of the new virus. Among the extensive and crucial research that has been carried out in the last few months, the analysis of the virus-host relationship plays an important role in drug discovery. Virus-host protein-protein interactions are the active agents in virus replication, and the analysis of virus-host protein-protein interaction networks is fundamental to the study of the virus-host relationship. We have adapted and implemented a recent integer linear programming model for protein-protein interaction network alignment to virus-host networks, and obtained a consensus alignment of the SARS-CoV-1 and SARS-CoV-2 virus-host protein-protein interaction networks. Despite the lack of shared human proteins in these virus-host networks and the low number of preserved virus-host interactions, the consensus alignment revealed aligned human proteins that share a function related to viral infection, as well as human proteins of high functional similarity that interact with SARS-CoV-1 and SARS-CoV-2 proteins, whose alignment would preserve these virus-host interactions.", "title": "Alignment of virus-host protein-protein interaction networks by integer linear programming: SARS-CoV-2", "pid": "iynga1d9", "bm25_score": 220.1153564453125}, {"text": "As of April 9, 2020, a novel coronavirus (SARS-CoV-2) had caused 89,931 deaths and 1,503,900 confirmed cases worldwide, which indicates an increasingly severe and uncontrollable situation. Initially, little was known about the virus. As research continues, we now know the genome structure, epidemiological and clinical characteristics, and pathogenic mechanisms of SARS-CoV-2. Based on this knowledge, potential targets involved in the processes of virus pathogenesis need to be identified, and the discovery or development of drugs based on these potential targets is the most pressing need. Here, we have summarized the potential therapeutic targets involved in virus pathogenesis and discuss the advances, possibilities, and significance of drugs based on these targets for treating SARS-CoV-2. This review will facilitate the identification of potential targets and provide clues for drug development that can be translated into clinical applications for combating SARS-CoV-2.", "title": "Potential therapeutic targets and promising drugs for combating SARS-CoV-2", "pid": "zl1d3gf2", "bm25_score": 220.10931396484375}, {"text": "The global emergency caused by COVID-19 makes the discovery of drugs capable of inhibiting SARS-CoV-2 a priority, to reduce the mortality and morbidity of this disease. Repurposing approved drugs can provide therapeutic alternatives that promise rapid and ample coverage because they have a documented safety record, as well as infrastructure for large-scale production. The main protease of SARS-CoV-2 (Mpro) is an excellent therapeutic target because it is critical for viral replication; however, Mpro has a highly flexible active site that must be considered when performing computer-assisted drug discovery. In this work, potential inhibitors of the main protease (Mpro) of SARS-Cov-2 were identified through a docking-assisted virtual screening procedure. A total of 4384 drugs, all approved for human use, were screened against three conformers of Mpro. The ligands were further studied through molecular dynamics simulations and binding free energy analysis. A total of nine currently approved molecules are proposed as potential inhibitors of SARS-CoV-2. These molecules can be further tested to speed the development of therapeutics against COVID-19.", "title": "Virtual screening of approved drugs as potential SARS-CoV-2 main protease inhibitors", "pid": "jnw0pnfu", "bm25_score": 220.1061248779297}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into the cells through its spike proteins binding to human angiotensin-converting enzyme 2 (ACE2) protein and causes virus infection in host cells. Until now, there are no available antiviral drugs have been reported that can effectively block virus infection. The study aimed to discover the potential compounds to prevent viral spike proteins to bind to the human ACE2 proteins from Taiwan Database of Extracts and Compounds (TDEC) by structure-based virtual screening. In this study, to rapidly discover potential inhibitors against SARS-CoV-2 spike proteins, the molecular docking calculation was performed by AutoDock Vina program. Herein, we found that 39 potential compounds may have good binding affinities and can respectively bind to the viral receptor-binding domain (RBD) of spike protein in the prefusion conformation and spike-ACE2 complex protein in silico. Among those compounds, especially natural products thioflexibilolide A and candidine that were respectively isolated from the soft corals Sinularia flexibilis and Phaius mishmensis may have better binding affinity than others. This study provided the predictions that these compounds may have the potential to prevent SARS-CoV-2 spike protein from entry into cells.", "title": "The discovery of potential natural products for targeting SARS-CoV-2 spike protein by virtual screening", "pid": "4skamxby", "bm25_score": 220.1057586669922}, {"text": "The current pandemic SARS-CoV-2 has wreaked havoc in the world, and neither drugs nor vaccine is available for the treatment of this disease. Thus, there is an immediate need for novel therapeutics that can combat this deadly infection. In this study, we report the therapeutic assessment of azurin and its peptides: p18 and p28 against the viral structural S-protein and non-structural 3CLpro and PLpro proteins. Among the analyzed complexes, azurin docked relatively well with the S2 domain of S-protein compared to the other viral proteins. The derived peptide p18 bound to the active site domain of the PLpro protein; however, in other complexes, lesser interactions were recorded. The second azurin derived peptide p28, fared the best among the docked proteins. p28 interacted with all the three viral proteins and the host ACE-2 receptor by forming several electrostatic and hydrogen bonds with the S-protein, 3CLpro, and PLpro. MD simulations indicated that p28 exhibited a strong affinity to S-protein and ACE-2 receptor, indicating a possibility of p28 as a protein-protein interaction inhibitor. Our data suggest that the p28 has potential as an anti-SARS-CoV-2 agent and can be further exploited to establish its validity in the treatment of current and future SARS-CoV crisis.Communicated by Ramaswamy H. Sarma.", "title": "Bacterial protein azurin and derived peptides as potential anti-SARS-CoV-2 agents: insights from molecular docking and molecular dynamics simulations", "pid": "812vjcr7", "bm25_score": 220.1005096435547}, {"text": "The worldwide CoVid-19 pandemic has led to an unprecedented push across the whole of the scientific community to develop a potent antiviral drug and vaccine as soon as possible. Existing academic, governmental and industrial institutions and companies have engaged in large-scale screening of existing drugs, in vitro, in vivo and in silico. Here, we are using in silico modelling of SARS-CoV-2 drug targets, i.e. SARS-CoV-2 protein structures as deposited on the Protein Databank (PDB). We study their flexibility, rigidity and mobility, an important first step in trying to ascertain their dynamics for further drug-related docking studies. We are using a recent protein flexibility modelling approach, combining protein structural rigidity with possible motion consistent with chemical bonds and sterics. For example, for the SARS-CoV-2 spike protein in the open configuration, our method identifies a possible further opening and closing of the S1 subunit through movement of SB domain. With full structural information of this process available, docking studies with possible drug structures are then possible in silico. In our study, we present full results for the more than 200 thus far published SARS-CoV-2-related protein structures in the PDB.", "title": "Flexibility and mobility of SARS-CoV-2-related protein structures", "pid": "w62xaa4f", "bm25_score": 220.0908966064453}, {"text": "There are an urgent need for antivirals to treat the newly emerged SARS-CoV-2. To identify new candidates we screened a repurposing library of ~3,000 drugs. Screening in Vero cells found few antivirals, while screening in human Huh7.5 cells validated 23 diverse antiviral drugs. Extending our studies to lung epithelial cells, we found that there are major differences in drug sensitivity and entry pathways used by SARS-CoV-2 in these cells. Entry in lung epithelial Calu-3 cells is pH-independent and requires TMPRSS2, while entry in Vero and Huh7.5 cells requires low pH and triggering by acid-dependent endosomal proteases. Moreover, we found 9 drugs are antiviral in lung cells, 7 of which have been tested in humans, and 3 are FDA approved including Cyclosporine which we found is targeting Cyclophilin rather than Calcineurin for its antiviral activity. These antivirals reveal essential host targets and have the potential for rapid clinical implementation.", "title": "Drug repurposing screens reveal FDA approved drugs active against SARS-Cov-2", "pid": "hsc2x36j", "bm25_score": 220.08041381835938}, {"text": "World over, people are looking for solutions to tackle the pandemic coronavirus disease (COVID-19) caused by the virus SARS-CoV-2/nCoV-19. Notable contributions in biomedical field have been characterizing viral genomes, host transcriptomes and proteomes, repurposable drugs and vaccines. In one such study, 332 human proteins targeted by nCoV19 were identified. We expanded this set of host proteins by constructing their protein interactome, including in it not only the known protein-protein interactions (PPIs) but also novel, hitherto unknown PPIs predicted with our High-precision Protein-Protein Interaction Prediction (HiPPIP) model that was shown to be highly accurate. In fact, one of the earliest discoveries made possible by HiPPIP is related to activation of immunity upon viral infection. We found that several interactors of the host proteins are differentially expressed upon viral infection, are related to highly relevant pathways, and that the novel interaction of NUP98 with CHMP5 may activate an antiviral mechanism leading to disruption of viral budding. We are making the interactions available as downloadable files to facilitate future systems biology studies and also on a web-server at http://hagrid.dbmi.pitt.edu/corona that allows not only keyword search but also queries such as “PPIs where one protein is associated with ‘virus’ and the interactors with ‘pulmonary’”.", "title": "Interactome of SARS-CoV-2 / nCoV19 modulated host proteins with computationally predicted PPIs", "pid": "jk01nq02", "bm25_score": 220.05722045898438}, {"text": "The outbreak of a novel human coronavirus (SARS-CoV-2) has evolved into global health emergency, infecting hundreds of thousands of people worldwide. We have identified experimental data on the inhibitory activity of compounds tested against closely related (96% sequence identity, 100% active site conservation) protease of SARS-CoV and employed this data to build QSAR models for this dataset. We employed these models for virtual screening of all drugs from DrugBank, including compounds in clinical trials. Molecular docking and similarity search approaches were explored in parallel with QSAR modeling, but molecular docking failed to correctly discriminate between experimentally active and inactive compounds. As a result of our studies, we recommended 41 approved, experimental, or investigational drugs as potential agents against SARS-CoV-2 acting as putative inhibitors of Mpro. Ten compounds with feasible prices were purchased and are awaiting the experimental validation..", "title": "Computational Models Identify Several FDA Approved or Experimental Drugs as Putative Agents Against SARS-CoV-2.", "pid": "hchioraj", "bm25_score": 220.0203399658203}, {"text": "The most rapid path to discovering treatment options for the novel coronavirus SARS-CoV-2 is to find existing medications that are active against the virus. We have focused on identifying repurposing candidates for the transmembrane serine protease family member II (TMPRSS2), which is critical for entry of coronaviruses into cells. Using known 3D structures of close homologs, we created seven homology models. We also identified a set of serine protease inhibitor drugs, generated several conformations of each, and docked them into our models. We used three known chemical (non-drug) inhibitors and one validated inhibitor of TMPRSS2 in MERS as benchmark compounds and found six compounds with predicted high binding affinity in the range of the known inhibitors. We also showed that a previously published weak inhibitor, Camostat, had a significantly lower binding score than our six compounds. All six compounds are anticoagulants with significant and potentially dangerous clinical effects and side effects. Nonetheless, if these compounds significantly inhibit SARS-CoV-2 infection, they could represent a potentially useful clinical tool.", "title": "Homology Modeling of TMPRSS2 Yields Candidate Drugs That May Inhibit Entry of SARS-CoV-2 into Human Cells.", "pid": "97l3r5tv", "bm25_score": 219.96768188476562}, {"text": "A novel coronavirus [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), or 2019 novel coronavirus] has been identified as the pathogen of coronavirus disease 2019. The main protease (Mpro , also called 3-chymotrypsin-like protease) of SARS-CoV-2 is a potential target for treatment of COVID-19. A Mpro homodimer structure suitable for docking simulations was prepared using a crystal structure (PDB ID: 6Y2G; resolution 2.20 Å). Structural refinement was performed in the presence of peptidomimetic &#945;-ketoamide inhibitors, which were previously disconnected from each Cys145 of the Mpro homodimer, and energy calculations were performed. Structure-based virtual screenings were performed using the ChEMBL database. Through a total of 1 485 144 screenings, 64 potential drugs (11 approved, 14 clinical, and 39 preclinical drugs) were predicted to show high binding affinity with Mpro . Additional docking simulations for predicted compounds with high binding affinity with Mpro suggested that 28 bioactive compounds may have potential as effective anti-SARS-CoV-2 drug candidates. The procedure used in this study is a possible strategy for discovering anti-SARS-CoV-2 drugs from drug libraries that may significantly shorten the clinical development period with regard to drug repositioning.", "title": "Potential anti-SARS-CoV-2 drug candidates identified through virtual screening of the ChEMBL database for compounds that target the main coronavirus protease", "pid": "md75mnh8", "bm25_score": 219.9515380859375}, {"text": "The integration of machine learning methods into bioinformatics provides particular benefits in identifying how therapeutics effective in one context might have utility in an unknown clinical context or against a novel pathology. We aim to discover the underlying associations between viral proteins and antiviral therapeutics that are effective against them by employing neural network models. Using the National Center for Biotechnology Information virus protein database and the DrugVirus database, which provides a comprehensive report of broad-spectrum antiviral agents (BSAAs) and viruses they inhibit, we trained ANN models with virus protein sequences as inputs and antiviral agents deemed safe-in-humans as outputs. Model training excluded SARS-CoV-2 proteins and included only Phases II, III, IV and Approved level drugs. Using sequences for SARS-CoV-2 (the coronavirus that causes COVID-19) as inputs to the trained models produces outputs of tentative safe-in-human antiviral candidates for treating COVID-19. Our results suggest multiple drug candidates, some of which complement recent findings from noteworthy clinical studies. Our in-silico approach to drug repurposing has promise in identifying new drug candidates and treatments for other viruses.", "title": "Machine-Learning Driven Drug Repurposing for COVID-19", "pid": "1nnqx1g9", "bm25_score": 219.95111083984375}, {"text": "Currently, humans are immersed in a pandemic caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which threatens public health worldwide. To date, no drug or vaccine has been approved to treat the severe disease caused by this coronavirus, COVID-19. In this paper, we will focus on the main virus-based and host-based targets that can guide efforts in medicinal chemistry to discover new drugs for this devastating disease. In principle, all CoV enzymes and proteins involved in viral replication and the control of host cellular machineries are potentially druggable targets in the search for therapeutic options for SARS-CoV-2. This Perspective provides an overview of the main targets from a structural point of view, together with reported therapeutic compounds with activity against SARS-CoV-2 and/or other CoVs. Also, the role of innate immune response to coronavirus infection and the related therapeutic options will be presented.", "title": "COVID-19: Drug Targets and Potential Treatments", "pid": "f6xhrpi8", "bm25_score": 219.9117889404297}, {"text": "SARS-CoV-2 Spike protein was predicted by molecular docking to bind the host cell surface GRP78, which was suggested as a putative good molecular target to inhibit Covid-19. We aimed to confirm that GRP78 gene expression was increased in blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients. In addition, we aimed to identify drugs that could be repurposed to inhibit GRP78, thus with potential anti-SARS-CoV-2 activity. Gene expression studies were performed in 10 SARS-CoV-2 (−) and 24 SARS-CoV-2 (+) pneumonia patients. A structure-based virtual screen was performed with 10,761 small molecules retrieved from DrugBank, using the GRP78 nucleotide binding domain and substrate binding domain as molecular targets. Results indicated that GRP78 mRNA levels were approximately four times higher in the blood of SARS-CoV-2 (+) versus SARS-CoV-2 (−) pneumonia patients, further suggesting that GRP78 might be a good molecular target to treat Covid-19. In addition, a total of 409 compounds were identified with potential as GRP78 inhibitors. In conclusion, we found preliminary evidence that further proposes GRP78 as a possible molecular target to treat Covid-19 and that many clinically approved drugs bind GRP78 as an off-target effect. We suggest that further work should be urgently carried out to confirm if GRP78 is indeed a good molecular target and if some of those drugs have potential to be repurposed for SARS-CoV-2 antiviral activity.", "title": "Preliminary Virtual Screening Studies to Identify GRP78 Inhibitors Which May Interfere with SARS-CoV-2 Infection", "pid": "l7ohbk7c", "bm25_score": 219.8935089111328}, {"text": "Molecular mimicry is a general strategy used by pathogens to infect the host cells. The emergence of SARS-CoV-2 virus has resulted in more than 6,700,000 infections and 390,000 deaths worldwide. Coronavirus disease (COVID-19) is an infectious disease caused by this virus. In this project concept, we aim to focus on the peptide-protein interaction analysis using two important drug targets in SARS-CoV-2 such as spike (S) protein and nucleocapsid (N) protein. These proteins play an important role in the virus entry and encapsidation of the viral particles. Motifs or functional regions in these two proteins must be sharing sequence homology with human protein (ACE2) which may be involved in the binding mechanism. The results will show a set of motif regions which can disrupt the viral infection. Once we identify these sets of antigenic determinant regions, antibody binding activity studies can be performed by in vitro methods. Our results from this study may suggest the existence of antigenic mimicry between SARS-CoV-2 and host proteins. The hit peptide components will have therapeutic applications to be developed into a wide variety of medicinal formulations against SARS-CoV-2 such as vaccine, intranasal and inhalation formulations. Also, the choice of conserved regions will lead to development of cross protective therapeutics against wide range of coronaviruses.", "title": "En route to Peptide Therapeutics for COVID 19: Harnessing Potential Antigenic Mimicry Between Viral and Human Proteins", "pid": "qj81xbn0", "bm25_score": 219.8619384765625}, {"text": "Specific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of>2500 coronaviruses and computed>100000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that the 3 and 5 prime ends are the most structured elements in the viral genome and the 5 prime end has the strongest propensity to associate with human proteins. The domain encompassing nucleotides 23000-24000 is highly conserved both at the sequence and structural level, while the region upstream varies significantly. These two sequences code for a domain of the viral protein Spike S that interacts with the human receptor angiotensin-converting enzyme 2 (ACE2) and has the potential to bind sialic acids. Our predictions indicate that the first 1000 nucleotides in the 5 prime end can interact with proteins involved in viral RNA processing such as double-stranded RNA specific editases and ATP-dependent RNA-helicases, in addition to other high-confidence candidate partners. These interactions, previously reported to be also implicated in HIV, reveal important information on host-virus interactions. The list of transcriptional and post-transcriptional elements recruited by SARS-CoV-2 genome provides clues on the biological pathways associated with gene expression changes in human cells.", "title": "Structural analysis of SARS-CoV-2 and prediction of the human interactome", "pid": "26n22jbx", "bm25_score": 219.85150146484375}, {"text": "A novel coronavirus was recently discovered and termed SARS-CoV-2. Human infection can cause coronavirus disease 2019 (COVID-19), which has been rapidly spreading around the globe1,2. SARS-CoV-2 shows some similarities to other coronaviruses. However, treatment options and a cellular understanding of SARS-CoV-2 infection are lacking. Here we identify the host cell pathways modulated by SARS-CoV-2 infection and show that inhibition of these pathways prevent viral replication in human cells. We established a human cell culture model for infection with SARS-CoV-2 clinical isolate. Employing this system, we determined the SARS-CoV-2 infection profile by translatome3 and proteome proteomics at different times after infection. These analyses revealed that SARS-CoV-2 reshapes central cellular pathways, such as translation, splicing, carbon metabolism and nucleic acid metabolism. Small molecule inhibitors targeting these pathways prevented viral replication in cells. Our results reveal the cellular infection profile of SARS-CoV-2 and led to the identification of drugs inhibiting viral replication. We anticipate our results to guide efforts to understand the molecular mechanisms underlying host cell modulation upon SARS-CoV-2 infection. Furthermore, our findings provide insight for the development of therapy options for COVID-19.", "title": "Proteomics of SARS-CoV-2-infected host cells reveals therapy targets", "pid": "9ldwlix3", "bm25_score": 219.83895874023438}, {"text": "Human Coronaviruses (HCoVs), including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle east respiratory syndrome coronavirus (MERS-CoV), and 2019 novel coronavirus (2019-nCoV), lead global epidemics with high morbidity and mortality. However, there are currently no effective drugs targeting 2019-nCoV. Drug repurposing, represented as an effective drug discovery strategy from existing drugs, could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we present an integrative, antiviral drug repurposing methodology implementing a systems pharmacology-based network medicine platform, quantifying the interplay between the HCoV-host interactome and drug targets in the human protein-protein interaction network. Phylogenetic analyses of 15 HCoV whole genomes reveal that 2019-nCoV has the highest nucleotide sequence identity with SARS-CoV (79.7%) among the six other known pathogenic HCoVs. Specifically, the envelope and nucleocapsid proteins of 2019-nCoV are two evolutionarily conserved regions, having the sequence identities of 96% and 89.6%, respectively, compared to SARS-CoV. Using network proximity analyses of drug targets and known HCoV-host interactions in the human protein-protein interactome, we computationally identified 135 putative repurposable drugs for the potential prevention and treatment of HCoVs. In addition, we prioritized 16 potential anti-HCoV repurposable drugs (including melatonin, mercaptopurine, and sirolimus) that were further validated by enrichment analyses of drug-gene signatures and HCoV-induced transcriptomics data in human cell lines. Finally, we showcased three potential drug combinations (including sirolimus plus dactinomycin, mercaptopurine plus melatonin, and toremifene plus emodin) captured by the Complementary Exposure pattern: the targets of the drugs both hit the HCoV-host subnetwork, but target separate neighborhoods in the human protein-protein interactome network. In summary, this study offers powerful network-based methodologies for rapid identification of candidate repurposable drugs and potential drug combinations toward future clinical trials for HCoVs.", "title": "Network-based Drug Repurposing for Human Coronavirus", "pid": "b4mdiont", "bm25_score": 219.79127502441406}, {"text": "The rapid global spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has created an unprecedented healthcare crisis. The treatment for the severe respiratory illness caused by this virus is primarily symptomatic at this point, although the usage of a broad antiviral drug Remdesivir has been allowed on emergency basis by the Food and Drug Administration (FDA).The ever-increasing death toll highlights an urgent need for development of specific antivirals. In this work, we have utilized docking and simulation methods to identify small molecule inhibitors of SARS-CoV-2 Membrane (M) and Envelope (E) proteins, which are essential for virus assembly and budding. A total of 70 compounds from an Indian medicinal plant source (Azadirachta indica or Neem) were virtually screened against these two proteins and further analyzed with molecular dynamics simulations, which resulted in the identification of a few common compounds with strong binding to both structural proteins. The compounds bind to biologically critical regions of M and E, indicating their potential to inhibit the functionality of these components. We hope that our computational approach may result in the identification of effective inhibitors of SARS-CoV-2 assembly.", "title": "A computational prediction of SARS-CoV-2 structural protein inhibitors from Azadirachta indica (Neem)", "pid": "67evoqls", "bm25_score": 219.79049682617188}, {"text": "There is little or no research initiated on enlightening Nigerians about the pathogenesis, targets for drug development, and drug repositioning for SARS-CoV-2 infection. COVID-19 is a viral infection causing symptoms like dry cough, sore throat, nasal congestion, tiredness, fever, loss of taste and smell etc. Th disease was first reported in Wuhan, China, in December 2019. The infection is caused by SARS-CoV-2, which is the third introduction of a highly pathogenic coronavirus into the human population. Coronaviruses are viruses with a positive RNA envelope assigned to α, β, γ, and δ genera. Moreover, SARS-CoV-2 belongs to the β genus. The four structural proteins of β coronavirus are membrane (M), envelope (E), spike (S), and nucleocapsid (N) protein, mediation of coronavirus host infection is established by spike (S) protein. Therefore, the search for drug development targets and repositioning of existing therapeutics is essential for fighting the present pandemic. It was reviewed that therapeutics targeting SARS-CoV-2 binding to ACE2 receptor, viral RNA synthesis and replication, 3CLpro, RdRp, and helicase will play a crucial role in the development of treatment for SARS-CoV-2 infection. Furthermore, the RdRp and spike protein of SARS-CoV-2 are the most promising targets for drug development and repositioning and vaccine development. Remdesivir combination with chloroquine/hydroxychloroquine are promising drug repositioning for the treatment of COVID-19, and mRNA-1273 targeting spike protein is the promising vaccine. However, as patient management and drug repositioning are taking place, it is imperative to identify other promising targets used by SARS-CoV-2 to establish infection, to develop novel therapeutics.", "title": "Molecular targets for COVID-19 drug development: Enlightening Nigerians about the pandemic and future treatment", "pid": "ddt5qmls", "bm25_score": 219.78790283203125}, {"text": "BACKGROUND Cell entry of SARS-CoV-2, the novel coronavirus causing COVID-19, is facilitated by host cell angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2). We aimed to identify and characterize genes that are co-expressed with ACE2 and TMPRSS2, and to further explore their biological functions and potential as druggable targets. METHODS Using the gene expression profiles of 1,038 lung tissue samples, we performed a weighted gene correlation network analysis (WGCNA) to identify modules of co-expressed genes. We explored the biology of co-expressed genes using bioinformatics databases, and identified known drug-gene interactions. RESULTS ACE2 was in a module of 681 co-expressed genes; 12 genes with moderate-high correlation with ACE2 (r>0.3, FDR<0.05) had known interactions with existing drug compounds. TMPRSS2 was in a module of 1,086 co-expressed genes; 15 of these genes were enriched in the gene ontology biologic process ‘Entry into host cell’, and 53 TMPRSS2-correlated genes had known interactions with drug compounds. CONCLUSION Dozens of genes are co-expressed with ACE2 and TMPRSS2, many of which have plausible links to COVID-19 pathophysiology. Many of the co-expressed genes are potentially targetable with existing drugs, which may help to fast-track the development of COVID-19 therapeutics.", "title": "Gene Expression Network Analysis Provides Potential Targets Against SARS-CoV-2", "pid": "par7lp1z", "bm25_score": 219.779052734375}, {"text": "The emergence and rapid worldwide spread of the novel coronavirus disease, COVID-19, has prompted concerted efforts to find successful treatments. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses its spike (S) protein to gain entry into host cells. Therefore, the S protein presents a viable target to develop a directed therapy. Here, we deployed an integrated artificial intelligence with molecular dynamics simulation approach to provide new details of the S protein structure. Based on a comprehensive structural analysis of S proteins from SARS-CoV-2 and previous human coronaviruses, we found that the protomer state of S proteins is structurally flexible. Without the presence of a stabilizing beta sheet from another protomer chain, two regions in the S2 domain and the hinge connecting the S1 and S2 subunits lose their secondary structures. Interestingly, the region in the S2 domain was previously identified as an immunodominant site in the SARS-CoV-1 S protein. We anticipate that the molecular details elucidated here will assist in effective therapeutic development for COVID-19.", "title": "Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets", "pid": "klb8oe9q", "bm25_score": 219.7763671875}, {"text": "Objective: Total 186 biologically important phenylpropanoids and polyketides compounds from different Indian medicinal plants and dietary sources were screened to filter potential compounds that bind at the active site of the therapeutic target proteins of SARS-CoV-2. Method: The molecular docking studies were carried out by using the Autodock Vina. The in silico ADMET and drug-likeness properties of the compounds were predicted from SwissADME server. Result: The molecular docking study of the 186 compounds with the therapeutic target proteins (Mpro, PLpro, RdRp, SGp and ACE2) of SARS-CoV-2 resulted 40 compounds that bind at the active site with dock score above -8.0 kcal/mol. Conclusion: Based on the in silico ADMET study and drug-likeness prediction of 40 compounds, we proposed petunidin, baicalein, cyanidin, 7-hydroxy-3',4'-methylenedioxyflavan, quercetin and ellagic acid among the 186 biologically important phenylpropanoids and polyketides as potential lead compounds, which can further be investigated pharmacologically and clinically to formulate therapeutic approaches for the COVID-19.", "title": "Protein-ligand interaction study to identify potential dietary compounds binding at the active site of therapeutic target proteins of SARS-CoV-2", "pid": "28wu1oyy", "bm25_score": 219.77069091796875}, {"text": "Global coronavirus disease pandemic (COVID-19) caused by newly identified SARS- CoV-2 coronavirus continues to claim the lives of thousands of people worldwide. The unavailability of specific medications to treat COVID-19 has led to drug repositioning efforts using various approaches, including computational analyses. Such analyses mostly rely on molecular docking and require the 3D structure of the target protein to be available. In this study, we utilized a set of machine learning algorithms and trained them on a dataset of RNA-dependent RNA polymerase (RdRp) inhibitors to run inference analyses on antiviral and anti-inflammatory drugs solely based on the ligand information. We also performed virtual screening analysis of the drug candidates predicted by machine learning models and docked them against the active site of SARS- CoV-2 RdRp, a key component of the virus replication machinery. Based on the ligand information of RdRp inhibitors, the machine learning models were able to identify candidates such as remdesivir and baloxavir marboxil, molecules with documented activity against RdRp of the novel coronavirus. Among the other identified drug candidates were beclabuvir, a non-nucleoside inhibitor of the hepatitis C virus (HCV) RdRp enzyme, and HCV protease inhibitors paritaprevir and faldaprevir. Further analysis of these candidates using molecular docking against the SARS-CoV-2 RdRp revealed low binding energies against the enzyme active site. Our approach also identified anti-inflammatory drugs lupeol, lifitegrast, antrafenine, betulinic acid, and ursolic acid to have potential activity against SARS-CoV-2 RdRp. We propose that the results of this study are considered for further validation as potential therapeutic options against COVID-19.", "title": "Predicting inhibitors for SARS-CoV-2 RNA-dependent RNA polymerase using machine learning and virtual screening", "pid": "0s1vgu85", "bm25_score": 219.76385498046875}, {"text": "We dissect the mechanism of SARS-CoV-2 in human lung host from the initial phase of receptor binding to viral replication machinery. We constructed two independent lung protein interactome to reveal the signaling process on receptor activation and host protein hijacking machinery in the pathogenesis of virus. Further, we test the functional role of the hubs derived from both interactome. Most hubs proteins were differentially regulated on SARS-CoV-2 infection. Also, the proteins of viral replication hubs were related with cardiovascular disease, diabetes and hypertension confirming the vulnerability and severity of infection in the risk individual. Additionally, the hub proteins were closely linked with other viral infection, including MERS and HCoVs which suggest similar infection pattern in SARS-CoV-2. We identified five interconnecting cascades between hubs of both networks that show the preparation of optimal environment in the host for viral replication process upon receptor attachment. Interestingly, we propose that seven potential miRNAs, targeting the intermediate phase that connects receptor and viral replication process a better choice as a drug for SARS-CoV-2.", "title": "Interplay of host regulatory network on SARS-CoV-2 binding and replication machinery", "pid": "vb53bih9", "bm25_score": 219.7484588623047}, {"text": "Abstract The infection of a novel coronavirus found in Wuhan of China (SARS-CoV-2) is rapidly spreading, and the incidence rate is increasing worldwide. Due to the lack of effective treatment options for SARS-CoV-2, various strategies are being tested in China, including drug repurposing. In this study, we used our pre-trained deep learning-based drug-target interaction model called Molecule Transformer-Drug Target Interaction (MT-DTI) to identify commercially available drugs that could act on viral proteins of SARS-CoV-2. The result showed that atazanavir, an antiretroviral medication used to treat and prevent the human immunodeficiency virus (HIV), is the best chemical compound, showing an inhibitory potency with Kd of 94.94 nM against the SARS-CoV-2 3C-like proteinase, followed by remdesivir (113.13 nM), efavirenz (199.17 nM), ritonavir (204.05 nM), and dolutegravir (336.91 nM). Interestingly, lopinavir, ritonavir, and darunavir are all designed to target viral proteinases. However, in our prediction, they may also bind to the replication complex components of SARS-CoV-2 with an inhibitory potency with Kd < 1,000 nM. In addition, we also found that several antiviral agents, such as Kaletra (lopinavir/ritonavir), could be used for the treatment of SARS-CoV-2. Overall, we suggest that the list of antiviral drugs identified by the MT-DTI model should be considered, when establishing effective treatment strategies for SARS-CoV-2.", "title": "Predicting commercially available antiviral drugs that may act on the novel coronavirus (SARS-CoV-2) through a drug-target interaction deep learning model", "pid": "zb434ve3", "bm25_score": 219.73590087890625}, {"text": "For patients with COVID-19 caused by SARS-CoV-2, the damages to multiple organs have been clinically observed. Since most of current investigations for virus-host interaction are based on cell level, there is an urgent demand to probe tissue-specific features associated with SARS-CoV-2 infection. Based on collected proteomic datasets from human lung, colon, kidney, liver and heart, we constructed a virus-receptor network, a virus-interaction network and a virus-perturbation network. In the tissue-specific networks associated with virus-host crosstalk, both common and different key hubs are revealed in diverse tissues. Ubiquitous hubs in multiple tissues such as BRD4 and RIPK1 would be promising drug targets to rescue multi-organ injury and deal with inflammation. Certain tissue-unique hubs such as REEP5 might mediate specific olfactory dysfunction. The present analysis implies that SARS-CoV-2 could affect multi-targets in diverse host tissues, and the treatment of COVID-19 would be a complex task.", "title": "Proteome-wide Data Analysis Reveals Tissue-specific Network Associated with SARS-CoV-2 Infection.", "pid": "3ntn4iwl", "bm25_score": 219.72271728515625}, {"text": "A new coronavirus identified as SARS-CoV-2 virus has brought the world to a state of crisis, causing a major pandemic, claiming more than 433,000 lives and instigating major financial damage to the global economy. Despite current efforts, developing safe and effective treatments remains a major challenge. Moreover, new strains of the virus are likely to emerge in the future. To prevent future pandemics, several drugs with various mechanisms of action are required. Drug discovery efforts against the virus fall into two main categories: (a) monoclonal antibodies targeting the spike protein of the virus and blocking it from entry; (b) small molecule inhibitors targeting key proteins of the virus, interfering with replication and translation of the virus. In this study, we are presenting a computational investigation of a potential drug candidate that targets SARS-CoV-2 protease, a viral protein critical for replication and translation of the virus.", "title": "A small molecule drug candidate targeting SARS-CoV-2 main protease", "pid": "2rczhxp2", "bm25_score": 219.71640014648438}, {"text": "A novel coronavirus (SARS-CoV-2) has caused a major outbreak in humans all over the world, and it is the latest pandemic in the series of other infectious diseases. The concept of drug repurposing has been used successfully for many years for known diseases. Considering the emergency and urgency, drug repurposing concept is being explored for coronavirus disease (COVID-19) as well. Recently, the combination of three known drugs, lopinavir, oseltamivir and ritonavir has been proposed to control the virulence to a great extent in COVID-19 affected patients within 48 hours. Hence, we tried to understand the effect of synergism of these drugs against the SARS-CoV-2 protease using sequential docking studies. As a result, combination of three drugs showed a better binding energy than that of individual drugs. Further, the complex was subjected to molecular dynamics simulations to get insights into the stability of the complex, considering the simultaneous interactions between three drugs and the protein. The protein complexed with three drugs remained stable during the simulations. Hence, these drugs can be explored further for drug repurposing against the successful inhibition of COVID-19.", "title": "Computational studies of drug repurposing and synergism of lopinavir, oseltamivir and ritonavir binding with SARS-CoV-2 Protease against COVID-19.", "pid": "s953j62y", "bm25_score": 219.69679260253906}, {"text": "For patients with COVID-19 caused by SARS-CoV-2, the damages to multiple organs have been clinically observed. Since most of current investigations for virus-host interaction are based on cell level, there is an urgent demand to probe tissue-specific features associated with SARS-CoV-2 infection. Based on collected proteomic datasets from human lung, colon, kidney, liver and heart, we constructed a virus-receptor network, a virus-interaction network and a virus-perturbation network. In the tissue-specific networks associated with virus-host crosstalk, both common and different key hubs are revealed in diverse tissues. Ubiquitous hubs in multiple tissues such as BRD4 and RIPK1 would be promising drug targets to rescue multi-organ injury and deal with inflammation. Certain tissue-unique hubs such as REEP5 might mediate specific olfactory dysfunction. The present analysis implies that SARS-CoV-2 could affect multi-targets in diverse host tissues, and the treatment of COVID-19 would be a complex task.", "title": "Proteome-wide Data Analysis Reveals Tissue-specific Network Associated with SARS-CoV-2 Infection", "pid": "z2biippi", "bm25_score": 219.69332885742188}, {"text": "MOTIVATION: Since December 2019, the newly identified coronavirus SARS-CoV-2 has caused a massive health crisis worldwide and resulted in over 70 000 COVID-19 infections so far. Clinical drugs targeting SARS-CoV-2 are urgently needed to decrease the high fatality rate of confirmed COVID-19 patients. Traditional de novo drug discovery needs more than 10 years, so drug repurposing seems the best option currently to find potential drugs for treating COVID-19. RESULTS: Compared with traditional non-covalent drugs, covalent drugs have attracted escalating attention recent years due to their advantages in potential specificity upon careful design, efficiency and patient burden. We recently developed a computational protocol named as SCAR (steric-clashes alleviating receptors) for discovering covalent drugs. In this work, we used the SCAR protocol to identify possible covalent drugs (approved or clinically tested) targeting the main protease (3CLpro) of SARS-CoV-2. We identified 11 potential hits, among which at least six hits were exclusively enriched by the SCAR protocol. Since the preclinical or clinical information of these identified drugs is already available, they might be ready for being clinically tested in the treatment of COVID-19. CONTACT: senliu.ctgu@gmail.com.", "title": "Potential covalent drugs targeting the main protease of the SARS-CoV-2 coronavirus", "pid": "rddq8bi3", "bm25_score": 219.66162109375}, {"text": "COVID-19 outbreak is still threatening the public health. Therefore, in the middle of the pandemic, all kind of knowledge on SARS-CoV-2 may help us to find the solution. Determining the 3D structures of the proteins involved in host-pathogen interactions are of great importance in the fight against infection. Besides, post-translational modifications of the protein on 3D structure should be revealed in order to understand the protein function since these modifications are responsible for the host-pathogen interaction. Based on these, we predicted O-glycosylation and phosphorylation positions using full amino acid sequence of S1 protein. Candidate positions were further analyzed with enzyme binding activity, solvent accessibility, surface area parameters and the positions determined with high accuracy rate were used to design full 3D glycoprotein structure of the S1 protein using carbohydrate force field. In addition, the interaction between the C-type lectin CD209L and α-mannose residues was examined and carbohydrate recognition positions were predicted. We suggest these positions as a potential target for the inhibition of the initial binding of SARS-CoV-2 S1 protein to the host cell.", "title": "Glycoinformatics approach for identifying target positions to inhibit initial binding of SARS-CoV-2 S1 protein to the host cell", "pid": "x8jgcqts", "bm25_score": 219.64691162109375}, {"text": "The unprecedented pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is threatening global health. The virus emerged in late 2019 and can cause a severe disease associated with significant mortality. Several vaccine development and drug discovery campaigns are underway. The SARS-CoV-2 main protease is considered a promising drug target, as it is dissimilar to human proteases. Sequence and structure of the main protease are closely related to those from other betacoronaviruses, facilitating drug discovery attempts based on previous lead compounds. Covalently binding peptidomimetics and small molecules are investigated. Various compounds show antiviral activity in infected human cells.", "title": "The SARS-CoV-2 main protease as drug target", "pid": "f8aolprb", "bm25_score": 219.63926696777344}, {"text": "A novel coronavirus was recently discovered and termed SARS-CoV-2. Human infection can cause coronavirus disease 2019 (COVID-19), which has been rapidly spreading around the globe1,2. SARS-CoV-2 shows some similarities to other coronaviruses. However, treatment options and a cellular understanding of SARS-CoV-2 infection are lacking. Here we identify the host cell pathways modulated by SARS-CoV-2 infection and show that inhibition of these pathways prevent viral replication in human cells. We established a human cell culture model for infection with SARS-CoV-2 clinical isolate. Employing this system, we determined the SARS-CoV-2 infection profile by translatome3 and proteome proteomics at different times after infection. These analyses revealed that SARS-CoV-2 reshapes central cellular pathways, such as translation, splicing, carbon metabolism and nucleic acid metabolism. Small molecule inhibitors targeting these pathways prevented viral replication in cells. Our results reveal the cellular infection profile of SARS-CoV-2 and led to the identification of drugs inhibiting viral replication. We anticipate our results to guide efforts to understand the molecular mechanisms underlying host cell modulation upon SARS-CoV-2 infection. Furthermore, our findings provide insight for the development of therapy options for COVID-19.", "title": "Proteomics of SARS-CoV-2-infected host cells reveals therapy targets.", "pid": "to6b17cb", "bm25_score": 219.63504028320312}, {"text": "The rapid global spread of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has created an unprecedented healthcare crisis. The treatment for the severe respiratory illness caused by this virus is primarily symptomatic at this point, although the usage of a broad antiviral drug Remdesivir has been allowed on emergency basis by the Food and Drug Administration (FDA). The ever-increasing death toll highlights an urgent need for development of specific antivirals. In this work, we have utilized docking and simulation methods to identify small molecule inhibitors of SARS-CoV-2 Membrane (M) and Envelope (E) proteins, which are essential for virus assembly and budding. A total of 70 compounds from an Indian medicinal plant source (Azadirachta indica or Neem) were virtually screened against these two proteins and further analyzed with molecular dynamics simulations, which resulted in the identification of a few common compounds with strong binding to both structural proteins. The compounds bind to biologically critical regions of M and E, indicating their potential to inhibit the functionality of these components. We hope that our computational approach may result in the identification of effective inhibitors of SARS-CoV-2 assembly. Communicated by Ramaswamy H. Sarma", "title": "A computational prediction of SARS-CoV-2 structural protein inhibitors from Azadirachta indica (Neem)", "pid": "c9qs4ny7", "bm25_score": 219.6234588623047}, {"text": "A new coronavirus was recently discovered and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection with SARS-CoV-2 in humans causes coronavirus disease 2019 (COVID-19) and has been rapidly spreading around the globe1,2. SARS-CoV-2 shows some similarities to other coronaviruses; however, treatment options and an understanding of how SARS-CoV-2 infects cells are lacking. Here we identify the host cell pathways that are modulated by SARS-CoV-2 and show that inhibition of these pathways prevents viral replication in human cells. We established a human cell-culture model for infection with a clinical isolate of SARS-CoV-2. Using this cell-culture system, we determined the infection profile of SARS-CoV-2 by translatome3 and proteome proteomics at different times after infection. These analyses revealed that SARS-CoV-2 reshapes central cellular pathways such as translation, splicing, carbon metabolism, protein homeostasis (proteostasis) and nucleic acid metabolism. Small-molecule inhibitors that target these pathways prevented viral replication in cells. Our results reveal the cellular infection profile of SARS-CoV-2 and have enabled the identification of drugs that inhibit viral replication. We anticipate that our results will guide efforts to understand the molecular mechanisms that underlie the modulation of host cells after infection with SARS-CoV-2. Furthermore, our findings provide insights for the development of therapies for the treatment of COVID-19.", "title": "Proteomics of SARS-CoV-2-infected host cells reveals therapy targets", "pid": "shgvlfmn", "bm25_score": 219.60260009765625}, {"text": "The computational strategies like molecular docking, simulation, in silico ADMET and drug-likeness prediction were adopted to search potential compounds that can inhibit the effects of SARS-CoV-2. Considering the published literatures on medicinal importance, total 154 phytochemicals with analogous structure from limonoids and triterpenoids were selected to search potential inhibitors for the five protein targets of SARS-CoV-2, i.e., 3CLpro (main protease), PLpro (papain like protease), SGp-RBD (spike glycoprotein-receptor binding domain), RdRp (RNA dependent RNA polymerase, ACE2 (angiotensin converting enzyme 2). Analyses of the in silico computational results and reported medicinal uses, the phytochemicals such as 7-deacetyl-7-benzoylgedunin, epoxyazadiradione, limonin, maslinic acid, glycyrrhizic acid and ursolic acid were found to be effective against the target proteins of SARS-CoV-2. The protein-ligand interaction study revealed that these phytochemicals bind at the main active site of the target proteins. Therefore, the core structure of these potential hits can be used for further lead optimization to design drugs for SARS-CoV-2. Also, the plants extracts like neem, tulsi, citrus and olives containing these phytochemicals can be used to formulate suitable therapeutics approaches in traditional medicines.", "title": "In silico ADMET and molecular docking study on searching potential inhibitors from limonoids and triterpenoids for COVID-19", "pid": "onereai5", "bm25_score": 219.5980224609375}, {"text": "Covid-19, a serious respiratory complications caused by SARS-CoV-2 has become one of the global threat to human healthcare system. The present study evaluated the possibility of plant originated approved 117 therapeutics against the main protease protein (MPP), RNA-dependent RNA polymerase (RdRp) and spike protein (S) of SARS-CoV-2 including drug surface analysis by using molecular docking through drug repurposing approaches. The molecular interaction study revealed that Rifampin (-16.3 kcal/mol) were topmost inhibitor of MPP where Azobechalcone were found most potent plant therapeutics for blocking the RdRp (-15.9 kcal /mol) and S (-14.4 kcal/mol) protein of SARS-CoV-2. After the comparative analysis of all docking results, Azobechalcone, Rifampin, Isolophirachalcone, Tetrandrine and Fangchinoline were exhibited as the most potential inhibitory plant compounds for targeting the key proteins of SARS-CoV-2. However, amino acid positions; H41, C145, and M165 of MPP played crucial roles for the drug surface interaction where F368, L371, L372, A375, W509, L514, Y515 were pivotal for RdRP. In addition, the drug interaction surface of S proteins also showed similar patterns with all of its maximum inhibitors. ADME analysis also strengthened the possibility of screened plant therapeutics as the potent drug candidates against SARS-C with the highest drug friendliness.", "title": "Virtual Screening of Plant Metabolites against Main protease, RNA-dependent RNA polymerase and Spike protein of SARS-CoV-2: Therapeutics option of COVID-19", "pid": "oyc2djxk", "bm25_score": 219.58506774902344}, {"text": "Specific elements of viral genomes regulate interactions within host cells. Here, we calculated the secondary structure content of >2500 coronaviruses and computed >100000 human protein interactions with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We found that the 3’ and 5’ are the most structured elements in the viral genome and the 5’ has the strongest propensity to associate with human proteins. The domain encompassing nucleotides 23000 – 24000 is highly conserved both at the sequence and structural level, while the region upstream varies significantly. These two sequences code for a domain of the viral protein Spike S that interacts with the human receptor angiotensin-converting enzyme 2 (ACE2) and has the potential to bind sialic acids. Our predictions indicate that the first 1000 nucleotides in the 5’ can interact with proteins involved in viral RNA processing such as double-stranded RNA specific editases and ATP-dependent RNA-helicases, in addition to other high-confidence candidate partners. These interactions, previously reported to be also implicated in HIV, reveal important information on hostvirus interactions. The list of transcriptional and post-transcriptional elements recruited by SARS-CoV-2 genome provides clues on the biological pathways associated with gene expression changes in human cells.", "title": "Structural analysis of SARS-CoV-2 and predictions of the human interactome", "pid": "ewvdl06h", "bm25_score": 219.56314086914062}, {"text": "The steep climbing of victims caused by the new coronavirus disease 2019 (COVID-19) throughout the planet is sparking an unprecedented effort to identify effective therapeutic regimens to tackle the pandemic. The SARS-CoV-2 virus is known to gain entry into various cell types through the binding of one of its surface proteins (spike) to the host Angiotensin Converting Enzyme 2 (ACE2). Thus, the spike-ACE2 interaction represents a major target for vaccines and antiviral drugs. We recently described a novel method to pharmacologically down-regulate the expression of target proteins at the post-translational level. This technology builds on computational advancements in the simulation of folding mechanisms to rationally block protein expression by targeting folding intermediates, hence hampering the folding process. Here, we report the all-atom simulation of the entire sequence of events underlying the folding pathway of ACE2. Our data reveal the existence of a folding intermediate showing druggable pockets hidden in the native conformation. Both pockets were targeted by a virtual screening repurposing campaign aimed at quickly identifying drugs capable to decrease the expression of ACE2. Importantly, among the different virtual hits, we identified mefloquine, a quinoline-derivative belonging to a class of antimalaria agents (e.g. chloroquine and hydroxychloroquine) recently described for their effects on ACE2 maturation. Thus, our results suggest that these drugs could act against SARS-CoV-2 by altering the folding pathway of its receptor ACE2.", "title": "Identification of a Druggable Intermediate along the Folding Pathway of the SARS-CoV-2 Receptor ACE2", "pid": "blhzq7oo", "bm25_score": 219.55386352539062}, {"text": "The sudden global emergence of SARS-CoV-2 urgently requires an in-depth understanding of molecular functions of viral proteins and their interactions with the host proteome. Several omics studies have extended our knowledge of COVID-19 pathophysiology, including some focused on proteomic aspects1–3. To understand how SARS-CoV-2 and related coronaviruses manipulate the host we here characterized interactome, proteome and signaling processes in a systems-wide manner. This identified connections between the corresponding cellular events, revealed functional effects of the individual viral proteins and put these findings into the context of host signaling pathways. We investigated the closely related SARS-CoV-2 and SARS-CoV viruses as well as the influence of SARS-CoV-2 on transcriptome, proteome, ubiquitinome and phosphoproteome of a lung-derived human cell line. Projecting these data onto the global network of cellular interactions revealed relationships between the perturbations taking place upon SARS-CoV-2 infection at different layers and identified unique and common molecular mechanisms of SARS coronaviruses. The results highlight the functionality of individual proteins as well as vulnerability hotspots of SARS-CoV-2, which we targeted with clinically approved drugs. We exemplify this by identification of kinase inhibitors as well as MMPase inhibitors with significant antiviral effects against SARS-CoV-2.", "title": "Multi-level proteomics reveals host-perturbation strategies of SARS-CoV-2 and SARS-CoV", "pid": "zf096duh", "bm25_score": 219.5382537841797}, {"text": "COV spike (S) glycoprotein and Mpro are two key targets that have been identified for vaccines and drug development against the COVID-19 disease. Virtual screening of some compounds of plants origin that have shown antiviral activities were carried out on the two targets, 6lu7 and 6vsb by docking with the PyRx software. The binding affinities were compared with other compounds and drugs already identified as potential ligands for 6lu7 and 6vsb as well as Chloroquine and hydroxychloroquine. The docked compounds with best binding affinities were also filtered for drug likeness using the SwissADME and PROTOX platforms on the basis of Physicochemical properties and toxicity respectively. The docking results revealed that scopodulcic acid and dammarenolic acid had the best binding affinity on the s-glycoprotein and Mpro protein targets respectively. Silybinin also demonstrated a good binding affinity to both protein targets making it a potential candidate for further evaluation as repurposed candidate for SARS COV2 with likelihood of having a multitarget activity.", "title": "Molecular Docking Analysis Of Some Phytochemicals On Two SARS-CoV-2 Targets: Potential Lead Compounds Against Two Target Sites of SARS-CoV-2 Obtained from Plants", "pid": "w84qtud6", "bm25_score": 219.5357666015625}, {"text": "BACKGROUND: The Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) outbreak originating in Wuhan, China, has raised global health concerns and the pandemic has now been reported on all inhabited continents. Hitherto, no antiviral drug is available to combat this viral outbreak. METHODS: Keeping in mind the urgency of the situation, the current study was designed to devise new strategies for drug discovery and/or repositioning against SARS-CoV-2. In the current study, RNA-dependent RNA polymerase (RdRp), which regulates viral replication, is proposed as a potential therapeutic target to inhibit viral infection. RESULTS: Evolutionary studies of whole-genome sequences of SARS-CoV-2 represent high similarity (> 90%) with other SARS viruses. Targeting the RdRp active sites, ASP760 and ASP761, by antiviral drugs could be a potential therapeutic option for inhibition of coronavirus RdRp, and thus viral replication. Target-based virtual screening and molecular docking results show that the antiviral Galidesivir and its structurally similar compounds have shown promise against SARS-CoV-2. CONCLUSIONS: The anti-polymerase drugs predicted here—CID123624208 and CID11687749—may be considered for in vitro and in vivo clinical trials.", "title": "Analysis of SARS-CoV-2 RNA-dependent RNA polymerase as a potential therapeutic drug target using a computational approach", "pid": "61nwk2sg", "bm25_score": 219.53146362304688}, {"text": "The coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by the severe acute respiratory syndrome coronavirus (SARS)-CoV-2. In the light of the urgent need to identify novel approaches to be used in the emergency phase, a largely explored strategy has been the repurpose of clinically available drugs as new antivirals, by targeting different viral proteins. In this paper, we describe a drug repurposing strategy based on a virtual screening of druggable pockets located in the central β-sheet core of the SARS-CoV-2 Spike protein RBD supported by in vitro tests identifying several steroidal derivatives as SARS-CoV-2 entry inhibitors. Our results demonstrate that several potential binding sites exist in the SARS CoV-2 S protein, and that the occupancy of these pockets reduces the ability of the S protein RBD to bind to the ACE2 consensus in vitro. In particular, natural occurring and clinically available steroids as glycyrrhetinic and oleanolic acids, as well as the bile acids derivatives glyco-UDCA and obeticholic acid have been shown to be effective in preventing virus entry in the case of low viral load. All together, these results might help to define novel approaches to reduce the viral load by using SARS-CoV-2 entry inhibitors.", "title": "Hijacking SARS-Cov-2/ACE2 receptor interaction by natural and semi-synthetic steroidal agents acting on functional pockets on receptor binding region", "pid": "l41lq2sc", "bm25_score": 219.51840209960938}, {"text": "The worldwide spread of COVID-19 highlights the need for an efficient approach to rapidly develop therapeutics and prophylactics against SARS-CoV-2. The SARS-CoV-2 spike protein, containing the receptor-binding domain (RBD) and S1 subunit involved in receptor engagement, is a potential therapeutic target. We describe the development of a phage-displayed single-domain antibody library by grafting naive complementarity-determining regions (CDRs) into framework regions of a human germline immunoglobulin heavy chain variable region (IGHV) allele. Panning this library against SARS-CoV-2 RBD and S1 subunit identified fully human single-domain antibodies targeting five distinct epitopes on SARS-CoV-2 RBD with subnanomolar to low nanomolar affinities. Some of these antibodies neutralize SARS-CoV-2 by targeting a cryptic epitope located in the spike trimeric interface. Collectively, this work presents a versatile platform for rapid antibody isolation and identifies promising therapeutic anti-SARS-CoV-2 antibodies as well as the diverse immogneic profile of the spike protein.", "title": "Identification of Human Single-Domain Antibodies against SARS-CoV-2", "pid": "ppdsgi9o", "bm25_score": 219.51022338867188}, {"text": "The world is confronting a dire situation due to the recent pandemic of the novel coronavirus disease (SARS-CoV-2) with the mortality rate passed over 470,000. Attaining efficient drugs evolve in parallel to the understanding of the SARS-CoV-2 pathogenesis. The current drugs in the pipeline and some plausible drugs are overviewed in this paper. Although different types of antiviral targets are applicable for SARS-CoV-2 drug screenings, the more promising targets can be considered as 3C-like main protease (3CL protease) and RNA polymerase. The remdesivir could be considered the closest bifunctional drug to the provisional clinical administration for SARS-CoV-2. The known molecular targets of the SARS-CoV-2 include fourteen targets while four molecules of angiotensin-converting enzyme 2 (ACE2), cathepsin L, 3CL protease and RNA-dependent RNA polymerase (RdRp) are suggested as more promising potential targets. Accordingly, dual-acting drugs as an encouraging solution in drug discovery are suggested. Emphasizing the potential route of SARS-CoV-2 infection and virus entry related factors like integrins, cathepsin and ACE2 seems valuable. The potential molecular targets of each phase of the SARS-CoV-2 life cycle are discussed and highlighted in this paper. Much progress in understanding the SARS-CoV-2 and molecular details of its life cycle followed by the identification of new therapeutic targets are needed to lead us to an efficient approach in anti-SARS-CoV-2 drug discovery.", "title": "Hypothetical targets and plausible drugs of Coronavirus infection caused by SARS-CoV-2.", "pid": "bq0hm89l", "bm25_score": 219.5008544921875}, {"text": "The COVID-19 pandemic triggered by SARS-CoV-2 is a worldwide health disaster. Main protease is an attractive drug target among coronaviruses, due to its vital role in processing the polyproteins that are translated from the viral RNA. There is presently no exact drug or treatment for this diseases caused by SARS-CoV-2. In the present study, we report the potential inhibitory activity of some FDA approved drugs against SARS-CoV-2 main protease by molecular docking study to investigate their binding affinity in protease active site. Docking studies revealed that drug Oseltamivir (anti-H1N1 drug), Rifampin (anti-TB drug), Maraviroc, Etravirine, Indinavir, Rilpivirine (anti-HIV drugs) and Atovaquone, Quinidine, Halofantrine, Amodiaquine, Tetracylcine, Azithromycin, hydroxycholoroquine (anti-malarial drugs) among others binds in the active site of the protease with similar or higher affinity. However, the in-silico abilities of the drug molecules tested in this study, further needs to be validated by carrying out in vitro and in vivo studies. Moreover, this study spreads the potential use of current drugs to be considered and used to comprise the fast expanding SARS-CoV-2 infection.", "title": "In silico identification of clinically approved medicines against the main protease of SARS-CoV-2, causative agent of covid-19", "pid": "w9mij6c6", "bm25_score": 219.49673461914062}, {"text": "MOTIVATION: Since December 2019, the newly identified coronavirus SARS-CoV-2 has caused a massive health crisis worldwide and resulted in over 70,000 COVID-19 infections so far. Clinical drugs targeting SARS-CoV-2 are urgently needed to decrease the high fatality rate of confirmed COVID-19 patients. Traditional de novo drug discovery needs more than 10 years, so drug repurposing seems the best option currently to find potential drugs for treating COVID-19. RESULTS: Compared with traditional non-covalent drugs, covalent drugs have attracted escalating attention recent years due to their advantages in potential specificity upon careful design, efficiency, and patient burden. We recently developed a computational protocol named as SCAR for discovering covalent drugs. In this work, we used the SCAR protocol to identify possible covalent drugs (approved or clinically tested) targeting the main protease (3CLpro) of SARS-CoV-2. We identified 11 potential hits, among which at least 6 hits were exclusively enriched by the SCAR protocol. Since the preclinical or clinical information of these identified drugs is already available, they might be ready for being clinically tested in the treatment of COVID-19.", "title": "Potential covalent drugs targeting the main protease of the SARS-CoV-2 coronavirus", "pid": "sywk7014", "bm25_score": 219.49465942382812}, {"text": "The COVID-19 respiratory disease is caused by the novel coronavirus SARS-CoV-2, which uses the enzyme ACE2 to entry human cells. This disease is characterized by important damages at multi-organ level, partially due to the abundant expression of ACE2 in practically all human tissues. However, not every organ in which ACE2 is abundant is affected by SARS CoV-2, which suggests the existence of other multi-organ routes for transmitting the perturbations produced by the virus. We consider here diffusive processes through the protein-protein interaction (PPI) network of proteins targeted by SARS CoV-2 as such alternative route. We found a subdiffusive regime that allows the propagation of virus perturbations through the PPI network at a significant rate. By following the main subdiffusive routes across the PPI network we identify proteins mainly expressed in the heart, cerebral cortex, thymus, testis, lymph node, kidney, among others of the organs reported to be affected by COVID-19.", "title": "Analyzing the impact of SARS CoV-2 on the human proteome", "pid": "yakmicn0", "bm25_score": 219.49229431152344}, {"text": "A novel coronavirus recently identified in Wuhan, China (SARS-CoV-2) has expanded the number of highly pathogenic coronaviruses affecting humans. The SARS-CoV-2 represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging SARS-CoV-2 is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Actin protein was also suggested as a host factor that participates in cell entry and pathogenesis of SARS-CoV-2; therefore, drugs modulating biological activity of this protein (e.g. ibuprofen) were suggested as potential candidates for treatment of this viral infection. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the SARS-CoV-2, and that domain 288-330 of S1 protein from the SARS-CoV-2 represents promising therapeutic and/or vaccine target.", "title": "Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target", "pid": "3bc72zgr", "bm25_score": 219.47607421875}, {"text": "PURPOSE: Recently, the world has been dealing with a new type of coronavirus called COVID-19 that in terms of symptoms is similar to the SARS coronavirus. Unfortunately, researchers could not find a registered therapy to treat the infection related to the virus yet. Regarding the fact that drug repurposing is a good strategy for epidemic viral infection, we applied the drug repurposing strategy using virtual screening to identify therapeutic options for COVID-19. For this purpose, five proteins of COVID-19 (3-chymotrypsin-like protease (3CLpro), Papain-Like protease (PLpro), cleavage site, HR1 and RBD in Spike protein) were selected as target proteins for drug repositioning. METHODS: First, five proteins of COVID-19 were built by homology modeling. Then FDA-approved drugs (2471 drugs) were screened against cleavage site and RBD in Spike protein via virtual screening. One hundred and twenty-eight FDA-approved drugs with the most favorable free-binding energy were attached to the cleavage site and RBD in Spike protein. Of these 128 drugs, 18 drugs have either been used currently as antiviral or have been reported to possess antiviral effects. Virtual screening was then performed for the 18 selected drugs with ACE2, 3CLpro and PLpro and HR1 and TMPRSS2. RESULTS: According to the results, glecaprevir, paritaprevir, simeprevir, ledipasvir, glycyrrhizic acid, TMC-310911, and hesperidin showed highly favorably free binding energies with all tested target proteins. CONCLUSION: The above-mentioned drugs can be regarded as candidates to treat COVID-19 infections, but further study on the efficiency of these drugs is also necessary.", "title": "Drug repurposing using computational methods to identify therapeutic options for COVID-19", "pid": "03isjlif", "bm25_score": 219.4707794189453}, {"text": "The recent pandemic associated with SARS-CoV-2, a virus of the Coronaviridae family, has resulted in an unprecedented number of infected people. The highly contagious nature of this virus makes it imperative for us to identify promising inhibitors from pre-existing antiviral drugs. Two druggable targets, namely 3C-like proteinase (3CLpro) and 2′-O-ribose methyltransferase (2′-O-MTase) were selected in this study due to their indispensable nature in the viral life cycle. 3CLpro is a cysteine protease responsible for the proteolysis of replicase polyproteins resulting in the formation of various functional proteins, whereas 2′-O-MTase methylates the ribose 2′-O position of the first and second nucleotide of viral mRNA, which sequesters it from the host immune system. The selected drug target proteins were screened against an in-house library of 123 antiviral drugs. Two promising drug molecules were identified for each protein based on their estimated free energy of binding (ΔG), the orientation of drug molecules in the active site and the interacting residues. The selected protein-drug complexes were then subjected to MD simulation, which consists of various structural parameters to equivalently reflect their physiological state. From the virtual screening results, two drug molecules were selected for each drug target protein [Paritaprevir (ΔG = −9.8 kcal/mol) & Raltegravir (ΔG = −7.8 kcal/mol) for 3CLpro and Dolutegravir (ΔG = −9.4 kcal/mol) and Bictegravir (ΔG = −8.4 kcal/mol) for 2′-OMTase]. After the extensive computational analysis, we proposed that Raltegravir, Paritaprevir, Bictegravir and Dolutegravir are excellent lead candidates for these crucial proteins and they could become potential therapeutic drugs against SARS-CoV-2. Communicated by Ramaswamy H. Sarma", "title": "Targeting SARS-CoV-2: a systematic drug repurposing approach to identify promising inhibitors against 3C-like proteinase and 2′-O-ribose methyltransferase", "pid": "tzsm1t44", "bm25_score": 219.4671630859375}, {"text": "The recent severe acute respiratory syndrome, known as Corona Virus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim we performed an in silico comparative modeling analysis, which allows to gain new insights about the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor binding domain (RBD), along interactions with human cells angiotensin converting enzyme 2 (ACE2) receptor, that favour human cell invasion. Furthermore, our analysis provides i) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, for preventing interactions with the human ACE2, and ii) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico a high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high affinity antibodies against present and future coronavirus able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnosis kits and other treatments based on the usage or the targeting of SARS-CoV-2 spike protein.", "title": "Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies", "pid": "mswmkgl4", "bm25_score": 219.4596710205078}, {"text": "The COVID-19 pandemic, caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is a current global threat for which there is an urgent need to search for an effective therapy. The transmembrane spike (S) glycoprotein of SARS-CoV-2 directly binds to the host angiotensin-converting enzyme 2 (ACE2) and mediates viral entrance, which is therefore considered as a promising drug target. Considering that new drug development is a time-consuming process, drug repositioning may facilitate rapid drug discovery dealing with sudden infectious diseases. Here, we compared the differences between the virtual structural proteins of SARS-CoV-2 and SARS-CoV, and selected a pocket mainly localizing in the fusion cores of S2 domain for drug screening. A virtual drug design algorithm screened the Food and Drug Administration-approved drug library of 1234 compounds, and 13 top scored compounds were obtained through manual screening. Through in vitro molecular interaction experiments, eltrombopag was further verified to possess a high binding affinity to S protein plus human ACE2 and could potentially affect the stability of the ACE2-S protein complex. Hence, it is worth further exploring eltrombopag as a potential drug for the treatment of SARS-CoV-2 infection.", "title": "Eltrombopag is a potential target for drug intervention in SARS-CoV-2 spike protein", "pid": "ogiicyik", "bm25_score": 219.45460510253906}, {"text": "A bright spot in the SARS-CoV-2 (CoV-2) coronavirus pandemic has been the immediate mobilization of the biomedical community, working to develop treatments and vaccines for COVID-19. Rational drug design against emerging threats depends on well-established methodology, mainly utilizing X-ray crystallography, to provide accurate structure models of the macromolecular drug targets and of their complexes with candidates for drug development. In the current crisis, the structural biological community has responded by presenting structure models of CoV-2 proteins and depositing them in the Protein Data Bank (PDB), usually without time embargo and before publication. Since the structures from the first-line research are produced in an accelerated mode, there is an elevated chance of mistakes and errors, with the ultimate risk of hindering, rather than speeding up, drug development. In the present work, we have used model-validation metrics and examined the electron density maps for the deposited models of CoV-2 proteins and a sample of related proteins available in the PDB as of April 1, 2020. We present these results with the aim of helping the biomedical community establish a better-validated pool of data. The proteins are divided into groups according to their structure and function. In most cases, no major corrections were necessary. However, in several cases significant revisions in the functionally sensitive area of protein-inhibitor complexes or for bound ions justified correction, re-refinement, and eventually reversioning in the PDB. The re-refined coordinate files and a tool for facilitating model comparisons are available at https://covid-19.bioreproducibility.org. DATABASE: Validated models of CoV-2 proteins are available in a dedicated, publicly accessible web service https://covid-19.bioreproducibility.org.", "title": "Ligand-centered assessment of SARS-CoV-2 drug target models in the Protein Data Bank", "pid": "jt989p2x", "bm25_score": 219.4537353515625}, {"text": "Currently, the world suffers from a new coronavirus SARS-CoV-2 that causes COVID-19. Therefore, there is a need for the urgent development of novel drugs and vaccines for COVID-19. Since it can take years to develop new drugs against this disease, here we used a hybrid combined molecular modeling approach in virtual drug screening repurposing study to identify new compounds against this disease. One of the important SARS-CoV-2 targets namely type 2 transmembrane serine protease (TMPRSS2) was screened with NPC’s NIH small molecule library which includes approved drugs by FDA and compounds in clinical investigation. We used 6654 small molecules in molecular docking and top-50 docking scored compounds were initially used in short (10-ns) molecular dynamics (MD) simulations. Based on average MM/GBSA binding free energy results, long (100-ns) MD simulations were employed for the identified hits. Both binding energy results as well as crucial residues in ligand binding were also compared with a positive control TMPRSS2 inhibitor, Camostat mesylate. Based on these numerical calculations we proposed a compound (benzquercin) as strong TMPRSS2 inhibitor. If these results can be validated by in vitro and in vivo studies, benzquercin can be considered to be used as inhibitor of TMPRSS2 at the clinical studies.", "title": "Virtual drug repurposing study against SARS-CoV-2 TMPRSS2 target", "pid": "cl3nu5cm", "bm25_score": 219.44114685058594}, {"text": "Currently, the pandemic coronavirus disease 2019 (COVID-19) has unprecedentedly captivated its human hosts by causing respiratory illnesses because of evolution of the genetic makeup of novel coronavirus (CoV) known as severe acute respiratory syndrome coronavirus-2 (SARS CoV-2). As much as the researchers are inundated for the quest of effective treatments from available drugs, the discovery and trials of new experimental drugs are also at a threshold for clinical trials. There has been much concern regarding the new and targeted drugs considering the comprehensive ambiguity regarding the mechanism and pathway of the drug action with respect to the new and unpredictable structural and nonstructural proteins (NSPs) of SARS CoV-2. This study was aimed to discuss functional pathways related to NSPs in CoVs with updated knowledge regarding SARS CoV-2, mechanisms of action of certain approved and investigational drugs for correct orientation regarding the treatment strategies, including nucleotide analog mechanism, receptor analog mechanism, and peptide-peptide interactions, along with the impact of COVID-19 on a global scale. Although there is a dire need for targeted drugs against SARS CoV-2, the practical achievement of its cure is possible by only using effective drugs with appropriate mechanisms to eliminate the disease.", "title": "Therapeutic dilemma in the repression of severe acute respiratory syndrome coronavirus-2 proteome.", "pid": "btk6u9j4", "bm25_score": 219.4302215576172}, {"text": "Knowledge of structural details is very much essential from the drug-design perspective. In the systematic review, we systematically reviewed the structural basis of different target proteins of SARS-corona virus (CoV2) from a viral life cycle and from drug design perspective. We searched four literature (PubMed, EMBASE, NATURE, and Willey online library) databases and one structural database (RCSB.org) with appropriate keywords till April 18, and finally, 26 articles were included in the systematic review. The published literature mainly centered upon the structural details of \"spike protein,\" \"main protease/M Pro/3CL pro,\" \"RNA-dependent RNA polymerase,\" and \"nonstructural protein 15 Endoribonuclease\" of SARS-CoV-2. However, inhibitor bound structures were very less. We need better structures elucidating the interactions between different targets and their inhibitors which will help us in understanding the atomic level importance of different amino acid residues in the functionality of the target structures. To summarize, we need structures with fine resolution, co-crystallized structures with biologically validated inhibitors, and functional characterization of different target proteins. Some other routes of entry of SARS-CoV-2 are also mentioned (e.g., CD147); however, these findings are not structurally validated. This review may pave way for better understanding of SARS-CoV-2 life cycle from structural biology perspective.", "title": "Update on the target structures of SARS-CoV-2: A systematic review", "pid": "wak7ie3q", "bm25_score": 219.42843627929688}, {"text": "Abstract The SARS-associated coronavirus (SARS-CoV) main proteinase is a key enzyme in viral polyprotein processing. To allow structure-based design of drugs directed at SARS-CoV main proteinase, we predicted its binding pockets and affinities with existing HIV, psychotic and parasite drugs (lopinavir, ritonavir, niclosamide and promazine), which show signs of inhibiting the replication of SARS-CoV. Our results suggest that these drugs and another two HIV inhibitors (PNU and UC2) could be used as templates for designing SARS-CoV proteinase inhibitors.", "title": "Old drugs as lead compounds for a new disease? Binding analysis of SARS coronavirus main proteinase with HIV, psychotic and parasite drugs", "pid": "d4loia11", "bm25_score": 219.41778564453125}, {"text": "SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.", "title": "SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals", "pid": "sygnmiun", "bm25_score": 219.41778564453125}, {"text": "Aim: Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2), a pernicious viral disease, causes acute respiratory distress responsible for mortality and morbidity worldwide. To screen different immunomodulatory medicinal compounds to unravel their interaction with SARS-COV-2 viral proteins. Materials & methods: A library of immunomodulatory medicinal compounds with antiviral capability were analyzed against SARS proteases, spike protein and nonstructural proteins (NSP-9, 15) using Autodock vina. Results: Out of more than 300 medicinal compounds, only six compounds: arzanol, ferulic acid, genistein, resveratrol, rosmanol and thymohydroquinone showed significant interaction with the SARS viral proteins by forming hydrogen bonds with the active site residues with low binding energy. Further ADMET (absorption, distribution, metabolism, excretion and toxicity) analysis showed good pharmacokinetic properties and low acute toxicity of these compounds. Conclusion: The current study provides convincing evidence that these medicinal compounds exert antiviral activity against the SARS-COV-2 virus and could be further exploited for the treatment of this disease.", "title": "Virtual screening of immunomodulatory medicinal compounds as promising anti-SARS-COV-2 inhibitors", "pid": "201ac32t", "bm25_score": 219.4163818359375}, {"text": "The current global pandemic COVID-19 caused by the SARS-CoV-2 virus has already inflicted insurmountable damage both to the human lives and global economy. There is an immediate need for identification of effective drugs to contain the disastrous virus outbreak. Global efforts are already underway at a war footing to identify the best drug combination to address the disease. In this review, an attempt has been made to understand the SARS-CoV-2 life cycle, and based on this information potential druggable targets against SARS-CoV-2 are summarized. Also, the strategies for ongoing and future drug discovery against the SARSCoV- 2 virus are outlined. Given the urgency to find a definitive cure, ongoing drug repurposing efforts being carried out by various organizations are also described. The unprecedented crisis requires extraordinary efforts from the scientific community to effectively address the issue and prevent further loss of human lives and health.", "title": "Drug targets for COVID-19 therapeutics: Ongoing global efforts.", "pid": "ovvyq18n", "bm25_score": 219.4144744873047}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing global pandemic that has infected more than 6 million people in more than 180 countries worldwide. Like other coronaviruses, SARS-CoV-2 is thought to have been transmitted to humans from wild animals. Given the scale and widespread geographical distribution of the current pandemic, the question emerges whether human-to-animal transmission is possible and if so, which animal species are most at risk. Here, we investigated the structural properties of several ACE2 orthologs bound to the SARS-CoV-2 spike protein. We found that species known not to be susceptible to SARS-CoV-2 infection have non-conservative mutations in several ACE2 amino acid residues that disrupt key polar and charged contacts with the viral spike protein. Our models also predict affinity-enhancing mutations that could be used to design ACE2 variants for therapeutic purposes. Finally, our study provides a blueprint for modeling viral-host protein interactions and highlights several important considerations when designing these computational studies and analyzing their results.", "title": "Insights on cross-species transmission of SARS-CoV-2 from structural modeling", "pid": "mtq6yh25", "bm25_score": 219.41287231445312}, {"text": "The current coronavirus (SARS-COV-2) pandemic and phenomenal spread to every nook and cranny of the world has raised major apprehensions about the modern public health care system. So far as a result of this epidemic, 4,434,653 confirmed cases and 302,169 deaths are reported. The growing infection rate and death toll demand the use of all possible approaches to design novel drugs and vaccines to curb this disease. In this study, we combined drugs repurposing and virtual drug screening strategies to target 3CLpro, which has an essential role in viral maturation and replication. A total of 31 FDA approved anti-HIV drugs, and Traditional Chinese medicines (TCM) database were screened to find potential inhibitors. As a result, Saquinavir, and five drugs (TCM5280805, TCM5280445, TCM5280343, TCM5280863, and TCM5458190) from the TCM database were found as promising hits. Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. Thus, we suggest that these compounds should be tested experimentally against the SARS-COV-2 as Saquinavir has been reported to inhibit HIV protease experimentally. Considering the intensity of coronavirus dissemination, the present research is in line with the idea of discovering the latest inhibitors against the coronavirus essential pathways to accelerate the drug development cycle. Communicated by Ramaswamy H. Sarma.", "title": "Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro)", "pid": "pwi48i20", "bm25_score": 219.410400390625}, {"text": "The current coronavirus (SARS-COV-2) pandemic and phenomenal spread to every nook and cranny of the world has raised major apprehensions about the modern public health care system. So far as a result of this epidemic, 4,434,653 confirmed cases and 302,169 deaths are reported. The growing infection rate and death toll demand the use of all possible approaches to design novel drugs and vaccines to curb this disease. In this study, we combined drugs repurposing and virtual drug screening strategies to target 3CLpro, which has an essential role in viral maturation and replication. A total of 31 FDA approved anti-HIV drugs, and Traditional Chinese medicines (TCM) database were screened to find potential inhibitors. As a result, Saquinavir, and five drugs (TCM5280805, TCM5280445, TCM5280343, TCM5280863, and TCM5458190) from the TCM database were found as promising hits. Furthermore, results from molecular dynamics simulation and total binding free energy revealed that Saquinavir and TCM5280805 target the catalytic dyad (His41 and Cys145) and possess stable dynamics behavior. Thus, we suggest that these compounds should be tested experimentally against the SARS-COV-2 as Saquinavir has been reported to inhibit HIV protease experimentally. Considering the intensity of coronavirus dissemination, the present research is in line with the idea of discovering the latest inhibitors against the coronavirus essential pathways to accelerate the drug development cycle.Communicated by Ramaswamy H. Sarma.", "title": "Combined drug repurposing and virtual screening strategies with molecular dynamics simulation identified potent inhibitors for SARS-CoV-2 main protease (3CLpro)", "pid": "qp54spam", "bm25_score": 219.410400390625}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global health pandemic. The lack of effective treatments, coupled with its etiology, has resulted in more than 400,000 deaths at the time of writing. The SARS-CoV-2 genome is highly homologous to that of SARS-CoV, the causative agent behind the 2003 SARS outbreak. Based on prior reports, clinicians have pursued the off-label use of several antiviral drugs, while the scientific community has responded by seeking agents against traditional targets, especially viral proteases. However, several avenues remain unexplored, including disrupting E and M protein oligomerization, outcompeting host glycan-virus interactions, interfering with the heparan sulfate proteoglycans-virus interaction, and others. In this review, we highlight some of these opportunities while summarizing the drugs currently in use against coronavirus 2019 (COVID-19).", "title": "Discovering small-molecule therapeutics against SARS-CoV-2", "pid": "cpg4q29v", "bm25_score": 219.40997314453125}, {"text": "While vaccine development will hopefully quell the global pandemic of COVID-19 caused by SARS-CoV-2, small molecule drugs that can effectively control SARS-CoV-2 infection are urgently needed. Here inhibitors of two coronavirus spike proteins (S) were identified by screening a library of approved drugs with SARS-S and MERS-S pseudotyped particle entry assays. Using high-throughput screening technology, we discovered three compounds (cepharanthine, abemaciclib and trimipramine) to be broad spectrum inhibitors for spike-mediated entry. This work should contribute to the development of effective treatments against the initial stage of viral infection, thus reducing viral burden in COVID-19 patients.", "title": "Identifying SARS-CoV-2 entry inhibitors through drug repurposing screens of SARS- S and MERS-S pseudotyped particles", "pid": "n1aphggl", "bm25_score": 219.39649963378906}]}
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Remdesivir had been proposed as a promising option for treating coronavirus disease 2019 (COVID-19). We provided a rapid review to critically assess the potential anti-coronavirus effect of remdesivir on COVID-19 and other coronaviruses based on the most up-to-date evidence. Even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification.", "title": "Rapid review for the anti-coronavirus effect of remdesivir.", "pid": "4el6qq3n", "bm25_score": 220.48025512695312}, {"text": "Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5-9 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. Graphical abstract.", "title": "Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit", "pid": "r0znh1bi", "bm25_score": 220.4622802734375}, {"text": "Remdesivir is one of the most promising drugs to treat COVID-19 based on the following facts: remdesivir has a broad-spectrum antiviral mechanism of action; it demonstrated in vitro activity against SARS-CoV-2 and in vivo efficacy in animal models against the similar coronavirus MERS-CoV; its safety profile has been tested in Ebola patients and in compassionate use in COVID-19 patients. Currently, remdesivir is being investigated in ten randomized controlled trials against COVID-19. The dose regimen of remdesivir is an IV loading dose of 200 mg on day 1 followed by daily IV maintenance doses of 100 mg for 5–9 days. Based on our data analysis, however, remdesivir with IV administration alone is unlikely to achieve excellent clinical efficacy. This analysis is based on the following observations: plasma exposures of remdesivir and its active metabolite are unlikely to be correlated with its clinical efficacy; remdesivir and its active metabolites are unlikely to be adequate in the lung to kill the SARS-CoV-2 virus. Even if remdesivir demonstrates benefits in the current randomized controlled trials, its efficacy may be limited. We suggest that a combination of an IV and pulmonary delivery dose regimen should be studied immediately to realize a potentially more effective antiviral therapy against COVID-19. [Figure: see text]", "title": "Remdesivir for Treatment of COVID-19: Combination of Pulmonary and IV Administration May Offer Aditional Benefit", "pid": "4178ui2c", "bm25_score": 220.26930236816406}, {"text": "The outbreak of SARS-CoV-2 rapidly spread across China and worldwide. Remdesivir had been proposed as a promising option for treating coronavirus disease 2019 (COVID-19). We provided a rapid review to critically assess the potential anti-coronavirus effect of remdesivir on COVID-19 and other coronaviruses based on the most up-to-date evidence. Even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification.", "title": "Rapid review for the anti-coronavirus effect of remdesivir", "pid": "a0drmmf7", "bm25_score": 220.141845703125}, {"text": "", "title": "Remdesivir for the Treatment of Covid-19 - Preliminary Report.", "pid": "40vtvseh", "bm25_score": 220.00692749023438}, {"text": "", "title": "Remdesivir for the Treatment of Covid-19 - Preliminary Report", "pid": "zlmv67ia", "bm25_score": 220.0009002685547}, {"text": "", "title": "Remdesivir as a possible therapeutic option for the COVID-19", "pid": "wcdq0fqj", "bm25_score": 219.91049194335938}, {"text": "Remdesivir (GS-5734), a viral RNA-dependent RNA polymerase (RdRP) inhibitor that can be used to treat a variety of RNA virus infections, is expected to be an effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. On May 1, 2020, The U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for remdesivir to treat COVID-19 patients. In light of the COVID-19 pandemic, this review presents comprehensive information on remdesivir, including information regarding the milestones, intellectual properties, anti-coronavirus mechanisms, preclinical research and clinical trials, and in particular, the chemical synthesis, pharmacology, toxicology, pharmacodynamics and pharmacokinetics of remdesivir. Furthermore, perspectives regarding the use of remdesivir for the treatment of COVID-19 are also discussed.", "title": "A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir.", "pid": "bz1lz2ze", "bm25_score": 219.86834716796875}, {"text": "Background Effective therapeutics to treat COVID-19 are urgently needed. Remdesivir is a nucleotide prodrug with in vitro and in vivo efficacy against coronaviruses. Here, we tested the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection. Methods To evaluate the effect of remdesivir treatment on SARS-CoV-2 disease outcome, we used the recently established rhesus macaque model of SARS-CoV-2 infection that results in transient lower respiratory tract disease. Two groups of six rhesus macaques were infected with SARS-CoV-2 and treated with intravenous remdesivir or an equal volume of vehicle solution once daily. Clinical, virological and histological parameters were assessed regularly during the study and at necropsy to determine treatment efficacy. Results In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs. Virus titers in bronchoalveolar lavages were significantly reduced as early as 12hrs after the first treatment was administered. At necropsy on day 7 after inoculation, lung viral loads of remdesivir-treated animals were significantly lower and there was a clear reduction in damage to the lung tissue. Conclusions Therapeutic remdesivir treatment initiated early during infection has a clear clinical benefit in SARS-CoV-2-infected rhesus macaques. These data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to severe pneumonia.", "title": "Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2", "pid": "p6uliadr", "bm25_score": 219.79075622558594}, {"text": "Remdesivir (GS-5734), a viral RNA-dependent RNA polymerase (RdRP) inhibitor that can be used to treat a variety of RNA virus infections, is expected to be an effective treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. On May 1, 2020, The U.S. Food and Drug Administration (FDA) has granted Emergency Use Authorization (EUA) for remdesivir to treat COVID-19 patients. In light of the COVID-19 pandemic, this review presents comprehensive information on remdesivir, including information regarding the milestones, intellectual properties, anti-coronavirus mechanisms, preclinical research and clinical trials, and in particular, the chemical synthesis, pharmacology, toxicology, pharmacodynamics and pharmacokinetics of remdesivir. Furthermore, perspectives regarding the use of remdesivir for the treatment of COVID-19 are also discussed.", "title": "A promising antiviral candidate drug for the COVID-19 pandemic: A mini-review of remdesivir", "pid": "ygbfvjz8", "bm25_score": 219.74180603027344}, {"text": "The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV-induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.", "title": "Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection", "pid": "x1fzgiy6", "bm25_score": 219.73873901367188}, {"text": "", "title": "Arguments in favour of remdesivir for treating SARS-CoV-2 infections", "pid": "107lb1bd", "bm25_score": 219.62554931640625}, {"text": "The continued emergence of Middle East Respiratory Syndrome (MERS) cases with a high case fatality rate stresses the need for the availability of effective antiviral treatments. Remdesivir (GS-5734) effectively inhibited MERS coronavirus (MERS-CoV) replication in vitro, and showed efficacy against Severe Acute Respiratory Syndrome (SARS)-CoV in a mouse model. Here, we tested the efficacy of prophylactic and therapeutic remdesivir treatment in a nonhuman primate model of MERS-CoV infection, the rhesus macaque. Prophylactic remdesivir treatment initiated 24 h prior to inoculation completely prevented MERS-CoV−induced clinical disease, strongly inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions. Therapeutic remdesivir treatment initiated 12 h postinoculation also provided a clear clinical benefit, with a reduction in clinical signs, reduced virus replication in the lungs, and decreased presence and severity of lung lesions. The data presented here support testing of the efficacy of remdesivir treatment in the context of a MERS clinical trial. It may also be considered for a wider range of coronaviruses, including the currently emerging novel coronavirus 2019-nCoV.", "title": "Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection", "pid": "x50tvq3a", "bm25_score": 219.62310791015625}, {"text": "The pandemic of COVID-19 (Coronavirus Disease-2019) is an extremely contagious respiratory illness due to a novel coronavirus, SARS-CoV-2. Certain drugs have several protein targets and many illnesses share overlapping molecular paths. In such cases, reusing drugs for more than one objective and finding their novice uses can considerably decrease the time in finding new cures for unforeseen diseases. Remdesivir has been recently a strong candidate for the treatment of Covid-19. In this commentary, we have portrayed the structure of the coronavirus in a simple way as well as the site where remdesivir acts. We have also displayed the ongoing clinical trials, as well as a published study that was conducted on compassionate base. The covid-19 pandemic might wean down by the end of summer 2020, but the risk of seasonality exists. Therefore, future disposal of agents such as remdesivir might be crucial for ensuring an efficient treatment, decrease mortality and allow early discharge. Communicated by Ramaswamy H. Sarma", "title": "Remdesivir in the treatment of coronavirus disease 2019 (COVID-19): a simplified summary", "pid": "np6nfvf2", "bm25_score": 219.59445190429688}, {"text": "Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.", "title": "Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2", "pid": "jxbch44o", "bm25_score": 219.50259399414062}, {"text": "Effective therapeutics to treat COVID-19 are urgently needed. While many investigational, approved, and repurposed drugs have been suggested, preclinical data from animal models can guide the search for effective treatments by ruling out treatments without in vivo efficacy. Remdesivir (GS-5734) is a nucleotide analog prodrug with broad antiviral activity1,2, that is currently investigated in COVID-19 clinical trials and recently received Emergency Use Authorization from the US Food and Drug Administration3,4. In animal models, remdesivir treatment was effective against MERS-CoV and SARS-CoV infection.2,5,6 In vitro, remdesivir inhibited replication of SARS-CoV-2.7,8 Here, we investigated the efficacy of remdesivir treatment in a rhesus macaque model of SARS-CoV-2 infection9. In contrast to vehicle-treated animals, animals treated with remdesivir did not show signs of respiratory disease and had reduced pulmonary infiltrates on radiographs and reduced virus titers in bronchoalveolar lavages 12hrs after the first treatment administration. Virus shedding from the upper respiratory tract was not reduced by remdesivir treatment. At necropsy, lung viral loads of remdesivir-treated animals were lower and there was a reduction in damage to the lungs. Thus, therapeutic remdesivir treatment initiated early during infection had a clinical benefit in SARS-CoV-2-infected rhesus macaques. Although the rhesus macaque model does not represent the severe disease observed in a proportion of COVID-19 patients, our data support early remdesivir treatment initiation in COVID-19 patients to prevent progression to pneumonia.", "title": "Clinical benefit of remdesivir in rhesus macaques infected with SARS-CoV-2.", "pid": "1cph1uij", "bm25_score": 219.45999145507812}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as responsible for the COVID-19 outbreak worldwide. Data on treatment are scare and parallels are made between SARS-CoV-2 and other coronavirus. Remdesivir is a broad spectrum antiviral with efficient in vitro activity against SARS-CoV-2 and controversial evidence of clinical improvement in severe COVID-19 patients. We aimed to describe the clinical outcome and virological monitoring of the first five COVID-19 patients admitted in ICU for severe pneumonia related to SARS-CoV-2 and treated with remdesivir in the University hospital of Bichat, Paris, France. SARS-CoV-2 RT-qPCR in blood plasma, lower and upper respiratory tract were monitored. Among the five treated patients, two needed mechanical ventilation and one high flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load from upper respiratory tract was observed in most cases but two died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted for side effects among four patients, including 2 ALT elevations (3 to 5 N) and 2 renal failures requiring renal replacement. This case series of five COVID-19 patients requiring ICU for a respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.", "title": "Case reports study of the first five patients COVID-19 treated with remdesivir in France", "pid": "oc0m6r5c", "bm25_score": 219.41519165039062}, {"text": "Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been identified as responsible for the COVID-19 outbreak worldwide. Data on treatment are scare and parallels are made between SARS-CoV-2 and other coronavirus. Remdesivir is a broad spectrum antiviral with efficient in vitro activity against SARS-CoV-2 and controversial evidence of clinical improvement in severe COVID-19 patients. We aimed to describe the clinical outcome and virological monitoring of the first five COVID-19 patients admitted in ICU for severe pneumonia related to SARS-CoV-2 and treated with remdesivir in the University hospital of Bichat, Paris, France. SARS-CoV-2 RT-qPCR in blood plasma, lower and upper respiratory tract were monitored. Among the five treated patients, two needed mechanical ventilation and one high flow cannula oxygen. A significant decrease in SARS-CoV-2 viral load from upper respiratory tract was observed in most cases but two died with active SARS-CoV-2 replication in the lower respiratory tract. Plasma samples were positive for SARS-CoV-2 in only one patient. Remdesivir was interrupted for side effects among four patients, including 2 ALT elevations (3 to 5 N) and 2 renal failures requiring renal replacement. This case series of five COVID-19 patients requiring ICU for a respiratory distress and treated with remdesivir, highlights the complexity of remdesivir use in such critically ill patients.", "title": "Case reports study of the first five patients COVID-19 treated with remdesivir in France", "pid": "m69ceq2t", "bm25_score": 219.3577880859375}, {"text": "", "title": "Remdesivir in covid-19", "pid": "928lhz2l", "bm25_score": 219.33026123046875}, {"text": "", "title": "Remdesivir in covid-19.", "pid": "m2k6usaz", "bm25_score": 219.2325439453125}, {"text": "Remdesivir is a novel therapeutic with known activity against SARS CoV-2 and related coronaviruses. Remdesivir, as well as convalescent plasma therapy, are currently under investigation as potential therapies for patients with Coronavirus Disease 19 (COVID-19). In this case report we summarize the use of convalescent plasma therapy and then remdesivir as a late addition in the treatment of a critically ill obstetric patient with COVID-19. The patient subsequently improved, was extubated 5 days after initiation of remdesivir, was transitioned to room air 24 h later, and discharged at the completion of remdesivir therapy.", "title": "The use of convalescent plasma therapy and remdesivir in the successful management of a critically ill obstetric patient with novel coronavirus 2019 infection: A case report", "pid": "6wwmbgw7", "bm25_score": 219.13134765625}, {"text": "Remdesivir is a novel therapeutic with known activity against SARS CoV-2 and related coronaviruses. Remdesivir, as well as convalescent plasma therapy, are currently under investigation as potential therapies for patients with Coronavirus Disease 19 (COVID-19). In this case report we summarize the use of convalescent plasma therapy and then remdesivir as a late addition in the treatment of a critically ill obstetric patient with COVID-19. The patient subsequently improved, was extubated 5 days after initiation of remdesivir, was transitioned to room air 24 h later, and discharged at the completion of remdesivir therapy.", "title": "The use of convalescent plasma therapy and remdesivir in the successful management of a critically ill obstetric patient with novel coronavirus 2019 infection: A case report", "pid": "fxi8ss2s", "bm25_score": 219.083984375}, {"text": "Abstract Recent international epidemics of coronavirus-associated illnesses underscore the urgent medical and public health need for vaccine development and regulatory body approved therapies. In particular, the current coronavirus disease 2019 (COVID-19) pandemic has quickly intensified interest in developing treatment options to mitigate impact on human life. Remdesivir (GS-5734™) is a broad-spectrum antiviral drug that is now being tested as a potential treatment for COVID-19 in international, multi-site clinical trials. Currently available evidence about the antiviral effects of remdesivir against coronaviruses is primarily based on in vitro and in vivo studies (including some on a chemically related compound, GS-441524™), which have demonstrated largely favorable findings. As the pandemic progresses, information from human compassionate use cases will continue to accumulate before the clinical trials are concluded. It is imperative for public health practitioners and the One Health community to stay up to date on the most promising potential therapeutic options that are under investigation. Thus, the purpose of this review is to synthesize the knowledge to date about remdesivir as a therapeutic option for coronaviruses, with a special focus on information relevant to the One Health community.", "title": "Current knowledge about the antivirals remdesivir (GS-5734) and GS-441524 as therapeutic options for coronaviruses", "pid": "95fc828i", "bm25_score": 219.07965087890625}, {"text": "At present, there is no definitive antiviral treatment for coronavirus disease 2019 (COVID-19). We describe our early experience with remdesivir in four critically ill COVID-19 patients. Patients received a 200 mg loading dose, followed by 100 mg daily intravenously for up to 10 days. All patients had been previously treated with other antivirals before remdesivir initiation. One patient experienced a torsade de pointes requiring cardiac resuscitation and one died due to multiple organ failure. Three patients showed biochemical signs of liver injury. Lymphocyte count increased in all patients soon after remdesivir initiation. Nasal swab SARS-CoV-2 RNA became negative in three of four patients after 3 days of therapy. We observed an in vivo virological effect of remdesivir in four critically ill, COVID-19 patients, coupled with a significant burden of adverse events. Although limited by the low number of subjects studied, our preliminary experience may be relevant for clinicians treating COVID-19.", "title": "Early experience with remdesivir in SARS-CoV-2 pneumonia", "pid": "mp3qb33p", "bm25_score": 219.05221557617188}, {"text": "COVID-19 is now pandemic throughout the world. Scientist, doctors are searching for effective therapy of this diseases. The remdesivir, an antiviral drug, is appeared as 'molecule of hope' for the treatment of this disease. USFDA gave emergency approval to this drug for the treatment of COVID-19. The molecular mechanism is unknown. In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2. However, more detail mechanism is needed to understand mechanism of action of remdesivir.", "title": "Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More", "pid": "8n6eybze", "bm25_score": 219.0402069091797}, {"text": "Remdesivir is a nucleoside antiviral recently studied in several randomized trials for treatment of COVID-19. The available observational and prospective data are conflicting, requiring clinicians to critically evaluate and reconcile results to determine patient populations that may optimally benefit from remdesivir therapy, especially while drug supply is scarce. In this review, we analyze pertinent clinical remdesivir data for patients with COVID-19 from January 1, 2020, through May 31, 2020.", "title": "That Escalated Quickly: Remdesivir's Place in Therapy for COVID-19", "pid": "ioqvxhar", "bm25_score": 219.03428649902344}, {"text": "[Image: see text] The global pandemic of SARS-CoV-2, the causative viral pathogen of COVID-19, has driven the biomedical community to action—to uncover and develop antiviral interventions. One potential therapeutic approach currently being evaluated in numerous clinical trials is the agent remdesivir, which has endured a long and winding developmental path. Remdesivir is a nucleotide analogue prodrug that perturbs viral replication, originally evaluated in clinical trials to thwart the Ebola outbreak in 2014. Subsequent evaluation by numerous virology laboratories demonstrated the ability of remdesivir to inhibit coronavirus replication, including SARS-CoV-2. Here, we provide an overview of remdesivir’s discovery, mechanism of action, and the current studies exploring its clinical effectiveness.", "title": "Remdesivir: A Review of Its Discovery and Development Leading to Emergency Use Authorization for Treatment of COVID-19", "pid": "zdfx3zo3", "bm25_score": 218.9680938720703}, {"text": "Background Coronavirus disease 2019 (COVID-19), caused by the novel coronavirus SARS-CoV-2, has led to significant global mortality and morbidity. Until now, no treatment has proven to be effective in COVID-19. To explore whether the use of remdesivir, initially an experimental broad-spectrum antiviral, is effective in the treatment of hospitalized patients with COVID-19, we conducted a systematic review and meta-analysis of randomized, placebo-controlled trials investigating its use. Methods A rapid search of the MEDLINE and EMBASE medical databases was conducted for randomized controlled trials. A systematic approach was used to screen, abstract, and critically appraise the studies. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method was applied to rate the certainty and quality of the evidence reported per study. Results Two RCTs studies were identified (n=1,299). A fixed-effects meta-analysis revealed reductions in mortality (RR=0.69, 0.49 to 0.99), time to clinical improvement (3.95 less days, from 3.86 days less to 4.05 less days ), serious adverse events (RR=0.77, 0.63 to 0.94) and all adverse events (RR=0.87, 0.79 to 0.96). Conclusion In this rapid systematic review, we present pooled evidence from the 2 included RCT studies that reveal that remdesivir has a modest yet significant reduction in mortality and significantly improves the time to recovery, as well as significantly reduced risk in adverse events and serious adverse events. It is more than likely that as an antiviral, remdesivir is not sufficient on its own and may be suitable in combination with other antivirals or treatments such as convalescent plasma. Research is ongoing to clarify and contextual these promising findings.", "title": "Remdesivir use in patients with coronavirus COVID-19 disease: a systematic review and meta-analysis", "pid": "7xc47la7", "bm25_score": 218.9417724609375}, {"text": "", "title": "Uncertainty about the Efficacy of Remdesivir on COVID-19", "pid": "twn38v3a", "bm25_score": 218.91432189941406}, {"text": "We present a case of late initiation of remdesivir antiviral therapy in the successful treatment of a patient with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a mixed medical intensive care unit of a community teaching hospital. A previously healthy 40-year-old man was admitted to the hospital 3 days after the onset of coronavirus disease 2019 (COVID-19) symptoms including dry cough, fever, and shortness of breath progressing to intubation and increased mechanical ventilator support. A request for compassionate use remdesivir was submitted on the same hospital day as the positive COVID-19 polymerase chain reaction result. Supportive measures, in addition to a 5-day course of hydroxychloroquine, were maintained until remdesivir could be supplied on day 9 of hospitalization, 13 days after symptom onset. Sixty hours after initiating remdesivir, the patient was successfully extubated and able to transition to room air within 24 hours of extubation. Late initiation of remdesivir may be effective in treating SARS-CoV-2, unlike antivirals utilized for different disease states, such as oseltamivir, that are most effective when started as soon as possible following symptom onset. Urgent action is needed by regulatory agencies to work with drug manufacturers to expedite the study and approval of investigational agents targeting SARS-CoV-2 as well as to meet manufacturing demands.", "title": "Delayed Initiation of Remdesivir in a COVID-19-Positive Patient", "pid": "jql4n0td", "bm25_score": 218.86746215820312}, {"text": "The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has created an urgent need for effective antivirals. Remdesivir (formerly GS-5734) is a nucleoside analogue pro-drug currently being evaluated in COVID-19 clinical trials. Its unique structural features allow high concentrations of the active triphosphate metabolite to be delivered intracellularly and it evades proofreading to successfully inhibit viral RNA synthesis. In pre-clinical models, remdesivir has demonstrated potent antiviral activity against diverse human and zoonotic ß-coronaviruses, including SARS-CoV-2. In this article, we critically review available data on remdesivir with an emphasis on biochemistry, pharmacology, pharmacokinetics, and in vitro activity against coronaviruses as well as clinical experience and current progress in COVID-19 clinical trials.", "title": "Remdesivir: Review of Pharmacology, Pre-clinical Data, and Emerging Clinical Experience for COVID-19", "pid": "gk2p9w2d", "bm25_score": 218.80690002441406}, {"text": "BACKGROUND Remdesivir, an inhibitor of viral RNA-dependent RNA polymerases, has been identified as a candidate for COVID-19 treatment. However, the therapeutic effect of remdesivir is controversial. METHODS We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials, from inception to June 11, 2020 for randomized controlled trials on the clinical efficacy of remdesivir. The main outcomes were discharge rate, mortality, and adverse events. This study is registered at INPLASY (INPLASY202060046). RESULTS Data of 1075 subjects showed that remdesivir significantly increased the discharge rate of patients with COVID-19 compared with the placebo (50.4% vs. 45.29%; relative risk [RR] 1.19 [95% confidence interval [CI], 1.05-1.34], I2 = 0.0%, P = 0.754). It also significantly decreased mortality (8.18% vs. 12.70%; RR 0.64 [95% CI, 0.44-0.92], I2 = 45.7%, P = 0.175) compared to the placebo. Data of 1296 subjects showed that remdesivir significantly decreased the occurrence of serious adverse events (RR 0.77 [95% CI, 0.63-0.94], I2 = 0.0%, P = 0.716). CONCLUSION Remdesivir is efficacious and safe for the treatment of COVID-19. TRIAL REGISTRATION NUMBER This study is registered at the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY202060046).", "title": "Efficacy and Safety of Remdesivir for COVID-19 Treatment: An Analysis of Randomized, Double-Blind, Placebo-Controlled Trials", "pid": "qxsr3uii", "bm25_score": 218.80426025390625}, {"text": "Abstract COVID-19 is now pandemic throughout the world. Scientist, doctors are searching for effective therapy of this diseases. The remdesivir, an antiviral drug, is appeared as ‘molecule of hope’ for the treatment of this disease. USFDA approve this drug for the treatment of COVID-19. The molecular mechanism is unknown. In this paper, we tried to describe the probable molecular mechanism of remdesivir to inhibit the RNA synthesis of SARS-CoV-2. However, more detail mechanism is needed to understand mechanism of action of remdesivir.", "title": "Probable Molecular Mechanism of Remdesivir for the Treatment of COVID-19: Need to Know More", "pid": "2lwzhqer", "bm25_score": 218.79161071777344}, {"text": "The rapid progression of corona virus disease in 2019 (COVID-19) pandemic has become an unprecedented global concern. This systemic review aimed at evaluating the available evidence on efficacy, safety to identify any promising role for compassionate use of remdesivir in patient suffered for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) as re-purposeful use. We searched PubMed, EMBASE, Cochrane Library for randomized controlled trials (RCTs), prospective case series studies and case reports that evaluated use of remdesivir in COVID-19. The outcomes were mortality, recovery rate, length of hospital stay and clinical outcome. Though the drug remdesivir (RDV) is not approved by the FDA, still the \"Emergency Use Authorization\" (EUA) for compassionate use in severe cases is endorsed. After vigorous searching, screening and sorting of completed and published scientific evidences in electronic database, there were only 2 randomized control trial (RCT), 2 uncontrolled trials found until April 2020. We also included 3 published case reports to analyze the validity use of RDV because of the scarcity of evidence based reports. Remdesivir was thought to be one of the promising options for treating the patients of COVID-19 based on few laboratory experiments and reports from some compassionate use and case reports. The safety and efficacy of this drug in COVID-19 cases require high-quality evidence from well-designed and adequately-powered clinical trials with proper sample size for precise decision.", "title": "Use of Remdesivir in the Management of COVID-19: A Systematic Review on Current Evidences.", "pid": "x89iy0m2", "bm25_score": 218.78750610351562}, {"text": "Background: Researchers are working hard to find an effective treatment for the new coronavirus 2019. We performed a comprehensive systematic review to investigate the latest clinical evidence on the treatment efficacy and safety of Remdesivir in hospitalized patients with COVID-19. Methods: We performed a systematic search of the Pubmed, Embase, Web of Science, Google scholar, and MedRxiv for relevant observational and interventional studies. Measured outcomes were mortality rates, improvement rates, time to clinical improvement, all adverse event rates and severe adverse event rates. Results: 3 RCTs and 2 cohorts were included in our study. In 2 cohort studies, patients received Remdesivir for 10 days. 2 RCTs evaluated 10-day treatment of Remdesivir efficacy versus placebo group and the other RCT compared its 5-day regimen versus 10-day regimen. Visual inspection of the forest plots revealed that Remdesivir efficacy was not much different in reducing 28-day mortality versus 14-day mortality rates. Besides, 10-day treatment regimen overpowers 5-day treatment and placebo in decreasing time to clinical improvement. All adverse event rates did not have significant difference; however, severe adverse event rate was lower in 5-day Remdesivir group compared to 10-day and placebo groups. Conclusion: 5-day course of Remdesivir therapy in COVID-19 patients is probably efficacious and safe and patients without invasive mechanical ventilation benefit the most. Treatment can be extended to 10 days if satisfactory improvement is not seen by day 5. Most benefits from Remdesivir therapy take place in the first 14 days of the start of the treatment.", "title": "Remdesivir Efficacy in Coronavirus Disease 2019 (COVID-19): A Systematic Review", "pid": "6tcwu832", "bm25_score": 218.75262451171875}, {"text": "", "title": "Covid-19: Selected NHS patients will be treated with remdesivir", "pid": "op4t2mu4", "bm25_score": 218.681640625}, {"text": "[This corrects the article DOI: 10.1021/acscentsci.0c00489.].", "title": "Correction to Remdesivir: A Review of Its Discovery and Development Leading to Human Clinical Trials for Treatment of COVID-19", "pid": "y8ei7xgi", "bm25_score": 218.5974884033203}, {"text": "Human enteroviruses are responsible for diverse diseases, from mild respiratory symptoms to fatal neurological complications. Currently, no registered antivirals have been approved for clinical therapy. Thus, a therapeutic agent for the enterovirus-related disease is urgently needed. Remdesivir (GS-5734) is a novel monophosphoramidate adenosine analog prodrug that exhibits potent antiviral activity against diverse RNA virus families, including positive-sense Coronaviridae and Flaviviridae and negative-sense Filoviridae, Paramyxoviridae, and Pneumoviridae. Currently, remdesivir is under phase 3 clinical development for disease COVID-19 treatment. Here, we found that remdesivir impeded both EV71 viral RNA (vRNA) and complementary (cRNA) synthesis, indicating that EV71 replication is inhibited by the triphosphate (TP) form of remdesivir. Moreover, remdesivir showed potent antiviral activity against diverse enteroviruses. These data extend the remdesivir antiviral activity to enteroviruses and indicate that remdesivir is a promising antiviral treatment for EV71 and other enterovirus infections.", "title": "Remdesivir (GS-5734) Impedes Enterovirus Replication Through Viral RNA Synthesis Inhibition", "pid": "lbnfqv77", "bm25_score": 218.58023071289062}, {"text": "Abstract During outbreak of emerging disease, the most important aim is to discover an effective drug to save life. Consequently, a lot of effort are generally made by the industry to promote clinical trials with new drugs. Here we review evidence of the 8 most recent reports including 3 randomized controlled trials on the clinical efficacy of remdesivir in treating COVID-19 patient. We conclude that it is far too premature to identify remdesivir as a curative or life-saving intervention.", "title": "Remdesivir investigational trials in COVID-19: a critical reappraisal", "pid": "pkklt77i", "bm25_score": 218.5762176513672}, {"text": "Drugs targeting RNA respiratory viruses has resulted in few effective therapies, highlighting challenges for antivirals to treat COVID-19. Several antivirals are being investigated for symptomatic COVID-19 but no definitive data support their clinical use. Remdesivir, with good in vitro activity against SARS-CoV2, appeared to result in favorable outcomes for hospitalized patients in a compassionate use series with shortened time to recovery and a modest decrease in mortality. Currently, remdesivir is available in phase III clinical trials, the compassionate use program, and eventually through the emergency use authorization. A randomized controlled trial of lopinavir/ritonavir demonstrated no apparent clinical or virologic benefit and drug-drug interactions and side effects further limit its utility. Antivirals to treat influenza (oseltamivir) have limited activity against SARS-CoV-2, but favipiravir and umifenovir, influenza antivirals available internationally, have distinct viral targets and require further investigation. Antivirals with evidence of clinical activity must be studied as treatment and prophylaxis for those at high risk for severe COVID-19.", "title": "Antivirals for COVID-19.", "pid": "eaqxifxu", "bm25_score": 218.56275939941406}, {"text": "BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.)", "title": "Compassionate Use of Remdesivir for Patients with Severe Covid-19", "pid": "oyr4klqk", "bm25_score": 218.54934692382812}, {"text": "Background: We evaluated the efficacy and safety of remdesivir for the treatment of COVID-19. Methods: Systematic review in five engines, pre-print webpages and RCT registries until May 22, 2020 for randomized controlled trials (RCTs) and observational studies evaluating remdesivir on confirmed, COVID-19 adults with pneumonia and/or respiratory insufficiency. Primary outcomes were all-cause mortality, clinical improvement or recovery, need for invasive ventilation, and serious adverse events (SAE). Secondary outcomes included length of hospital stay, progression of pneumonia, and adverse events (AE). Inverse variance random effects meta-analyses were performed. Results: Two placebo-controlled RCTs (n=1300) and two case series (n=88) were included. All studies used remdesivir 200mg IV the first day and 100mg IV for 9 more days, and followed up until 28 days. Wang et al. RCT was stopped early due to AEs; ACTT-1 was preliminary reported at 15-day follow up. Time to clinical improvement was not decreased in Wang et al. RCT, but median time to recovery was decreased by 4 days in ACTT-1. Remdesivir did not decrease all-cause mortality (RR 0.71, 95%CI 0.39 to 1.28) and need for invasive ventilation at 14 days (RR 0.57, 95%CI 0.23 to 1.42), but had fewer SAEs (RR 0.77, 95%CI 0.63 to 0.94). AEs were similar between remdesivir and placebo arms. Risk of bias ranged from some concerns to high risk in RCTs. Interpretation: There is paucity of adequately powered and fully reported RCTs evaluating effects of remdesivir in adult, hospitalized COVID-19 patients. Remdesivir should not be recommended for the treatment of severe COVID-19.", "title": "Efficacy and harms of remdesivir for the treatment of COVID-19: a systematic review and meta-analysis", "pid": "4vfk99f5", "bm25_score": 218.53842163085938}, {"text": "We present a case of late initiation of remdesivir antiviral therapy in the successful treatment of a patient with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in a mixed medical intensive care unit of a community teaching hospital. A previously healthy 40‐year‐old man was admitted to the hospital 3 days after the onset of coronavirus disease 2019 (COVID‐19) symptoms including dry cough, fever, and shortness of breath progressing to intubation and increased mechanical ventilator support. A request for compassionate use remdesivir was submitted on the same hospital day as the positive COVID‐19 polymerase chain reaction result. Supportive measures, in addition to a 5‐day course of hydroxychloroquine, were maintained until remdesivir could be supplied on day 9 of hospitalization, 13 days after symptom onset. Sixty hours after initiating remdesivir, the patient was successfully extubated and able to transition to room air within 24 hours of extubation. Late initiation of remdesivir may be effective in treating SARS‐CoV‐2, unlike antivirals utilized for different disease states, such as oseltamivir, that are most effective when started as soon as possible following symptom onset. Urgent action is needed by regulatory agencies to work with drug manufacturers to expedite the study and approval of investigational agents targeting SARS‐CoV‐2 as well as to meet manufacturing demands.", "title": "Delayed Initiation of Remdesivir in a COVID‐19‐Positive Patient", "pid": "ssuao9mb", "bm25_score": 218.53260803222656}, {"text": "BACKGROUND: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2. METHODS: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support. Patients received a 10-day course of remdesivir, consisting of 200 mg administered intravenously on day 1, followed by 100 mg daily for the remaining 9 days of treatment. This report is based on data from patients who received remdesivir during the period from January 25, 2020, through March 7, 2020, and have clinical data for at least 1 subsequent day. RESULTS: Of the 61 patients who received at least one dose of remdesivir, data from 8 could not be analyzed (including 7 patients with no post-treatment data and 1 with a dosing error). Of the 53 patients whose data were analyzed, 22 were in the United States, 22 in Europe or Canada, and 9 in Japan. At baseline, 30 patients (57%) were receiving mechanical ventilation and 4 (8%) were receiving extracorporeal membrane oxygenation. During a median follow-up of 18 days, 36 patients (68%) had an improvement in oxygen-support class, including 17 of 30 patients (57%) receiving mechanical ventilation who were extubated. A total of 25 patients (47%) were discharged, and 7 patients (13%) died; mortality was 18% (6 of 34) among patients receiving invasive ventilation and 5% (1 of 19) among those not receiving invasive ventilation. CONCLUSIONS: In this cohort of patients hospitalized for severe Covid-19 who were treated with compassionate-use remdesivir, clinical improvement was observed in 36 of 53 patients (68%). Measurement of efficacy will require ongoing randomized, placebo-controlled trials of remdesivir therapy. (Funded by Gilead Sciences.).", "title": "Compassionate Use of Remdesivir for Patients with Severe Covid-19", "pid": "kxds6r7t", "bm25_score": 218.5122833251953}, {"text": "", "title": "Synergistic effect of vitamin D and remdesivir can fight COVID-19", "pid": "b18l7je9", "bm25_score": 218.4644317626953}, {"text": "", "title": "Small Study Finds Remdesivir Benefit in COVID-19 But Questions Remain", "pid": "0b8thzom", "bm25_score": 218.44943237304688}, {"text": "On December 31, 2019 a pneumonia outbreak caused by a new coronavirus (SARS-CoV-2) was detected in the city of Wuhan (China) Due to the high capacity of diffusion and human infection it has become a new zoonotic pandemic The absence of a vaccine has determined the search for antiviral drugs with the capacity to inhibit the replication of the new virus Among them, remdesivir, an analogue of adenosine, is what seems to have a more promising future This drug has shown in vitro and in animals a high capacity to block infection and viral replication with attainable concentrations in human plasma Although all studies have been carried out with SARS-CoV and MERS-CoV, it seems that by virological and functional analogy, remdesivir is one of the few antiviral drugs with proven efficacy However, studies and clinical trials in humans are required to know the result of their application in them", "title": "Remdesivir, the antiviral hope against SARS-CoV-2/ Remdesivir, la esperanza antiviral frente al SARS-CoV-2", "pid": "puc13jf1", "bm25_score": 218.4415283203125}, {"text": "", "title": "Synergistic effect of Vitamin D and Remdesivir can fight COVID-19.", "pid": "ke5hxd8o", "bm25_score": 218.43885803222656}, {"text": "SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged &#8805;18 years undergoing mechanical ventilation or with an oxygen saturation level of &#8804;94 % in air or a National Early Warning Score 2 of &#8805;4. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63 %) and discontinued by 13, of whom eight (22.8 %) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3 %) patients from IDW were discharged, two were still hospitalized and one died (5.9 %), whereas in ICU 6 (33.3 %) were discharged, 8 (44.4 %) patients died, three (16.7 %) were still mechanically ventilated and one (5.6 %) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8 % and 22.8 % of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.", "title": "Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post-treatment hospitalisation status", "pid": "pdc3bv33", "bm25_score": 218.416015625}, {"text": "The global pandemic of novel coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has created an urgent need for effective antivirals. Remdesivir (formerly GS‐5734) is a nucleoside analogue pro‐drug currently being evaluated in COVID‐19 clinical trials. Its unique structural features allow high concentrations of the active triphosphate metabolite to be delivered intracellularly and it evades proofreading to successfully inhibit viral RNA synthesis. In pre‐clinical models, remdesivir has demonstrated potent antiviral activity against diverse human and zoonotic β‐coronaviruses, including SARS‐CoV‐2. In this article we critically review available data on remdesivir with an emphasis on biochemistry, pharmacology, pharmacokinetics and in vitro activity against coronaviruses as well as clinical experience and current progress in COVID‐19 clinical trials.", "title": "Remdesivir: Review of pharmacology, pre‐clinical data and emerging clinical experience for COVID‐19", "pid": "uo8k6qic", "bm25_score": 218.37994384765625}, {"text": "SARS-CoV-2 is causing an increasing number of deaths worldwide because no effective treatment is currently available. Remdesivir has shown in vitro activity against coronaviruses and is a possible antiviral treatment for SARS-CoV-2 infection. This prospective (compassionate), open-label study of remdesivir, which was conducted at Luigi Sacco Hospital, Milan, Italy, between February 23 and March 20, 2020, involved patients with SARS-CoV-2 pneumonia aged ≥18 years undergoing mechanical ventilation or with an oxygen saturation level of ≤94% in air or a National Early Warning Score 2 of ≥4. The primary outcome was the change in clinical status based on a 7-category ordinal scale (1 = not hospitalised, resuming normal daily activities; 7 = deceased). The 35 patients enrolled from February 23 to March 20, 2020, included 18 in intensive care unit (ICU), and 17 in our infectious diseases ward (IDW). The 10-day course of remdesivir was completed by 22 patients (63%) and discontinued by 13, of whom eight (22.8%) discontinued because of adverse events. The median follow-up was 39 days (IQR 25-44). At day 28, 14 (82.3%) patients from IDW were discharged, two were still hospitalized and one died (5.9%), whereas in ICU 6 (33.3%) were discharged, 8 (44.4%) patients died, three (16.7%) were still mechanically ventilated and one (5.6%) was improved but still hospitalized. Hypertransaminasemia and acute kidney injury were the most frequent severe adverse events observed (42.8% and 22.8% of the cases, respectively). Our data suggest that remdesivir can benefit patients with SARS-CoV-2 pneumonia hospitalised outside ICU where clinical outcome was better and adverse events are less frequently observed. Ongoing randomised controlled trials will clarify its real efficacy and safety, who to treat, and when.", "title": "Compassionate remdesivir treatment of severe Covid-19 pneumonia in intensive care unit (ICU) and Non-ICU patients: Clinical outcome and differences in post_treatment hospitalisation status", "pid": "nzxbogga", "bm25_score": 218.3135223388672}, {"text": "One of the world’s best hopes for treating COVID-19 — a compound called remdesivir — has been authorized as a therapy against the disease On 1 May, the US Food and Drug Administration (FDA) granted an ‘emergency-use authorization’ for clinicians to use the drug, which is administered intravenously, in hospitals for people with severe COVID-19", "title": "Coronavirus drug, water warning and virus-research funding.", "pid": "5kcl80sj", "bm25_score": 218.2991485595703}, {"text": "", "title": "Remdesivir for COVID-19: challenges of underpowered studies", "pid": "iybj9o93", "bm25_score": 218.29103088378906}, {"text": "[Image: see text] While remdesivir has garnered much hope for its moderate anti-Covid-19 effects, its parent nucleoside, GS-441524, has been overlooked. Pharmacokinetic analysis of remdesivir evidences premature serum hydrolysis to GS-441524; GS-441524 is the predominant metabolite reaching the lungs. With its synthetic simplicity and in vivo efficacy in the veterinary setting, we contend that GS-441524 is superior to remdesivir for Covid-19 treatment.", "title": "Advantages of the Parent Nucleoside GS-441524 over Remdesivir for Covid-19 Treatment", "pid": "kq77whdx", "bm25_score": 218.27761840820312}, {"text": "", "title": "Efficacy of remdesivir in a rhesus macaque model of MERS-CoV infection.", "pid": "vs6rh9i9", "bm25_score": 218.2600860595703}, {"text": "", "title": "Compassionate Use of Remdesivir in Covid-19", "pid": "11wfbtbc", "bm25_score": 218.21934509277344}, {"text": "BACKGROUND: No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. METHODS: We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged &#8805;18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2-10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir-ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. FINDINGS: Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87-1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95-2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. INTERPRETATION: In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. FUNDING: Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.", "title": "Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial", "pid": "c74zdtnn", "bm25_score": 218.21517944335938}, {"text": "", "title": "Compassionate Use of Remdesivir in Covid-19.", "pid": "hgpgeel6", "bm25_score": 218.2066650390625}, {"text": "", "title": "Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro", "pid": "rkwya9l9", "bm25_score": 218.1835174560547}, {"text": "COVID-19 presents a major worldwide public health emergency. Many research efforts are ongoing to find effective antiviral treatments via novel drug design or drug repurposing (Duarte et al., 2020). One drug, remdesivir, has been shown to have activity against the SARS-CoV-2 RNA dependent RNA polymerase (RdRp), and has been used clinically in severe COVID-19 disease, but more accessible and readily available treatments are needed for all stages of infection. This article is protected by copyright. All rights reserved.", "title": "Montelukast drug activity and potential against SARS-CoV-2.", "pid": "ntozf7ba", "bm25_score": 218.14309692382812}, {"text": "COVID-19 presents a major worldwide public health emergency. Many research efforts are ongoing to find effective antiviral treatments via novel drug design or drug repurposing (Duarte et al., 2020). One drug, remdesivir, has been shown to have activity against the SARS-CoV-2 RNA dependent RNA polymerase (RdRp), and has been used clinically in severe COVID-19 disease, but more accessible and readily available treatments are needed for all stages of infection. This article is protected by copyright. All rights reserved.", "title": "Montelukast drug activity and potential against SARS-CoV-2", "pid": "w3ido97l", "bm25_score": 218.1312255859375}, {"text": "", "title": "Efficacy of remdesivir in a rhesus macaque model of MERS-CoV infection", "pid": "qiigfkmg", "bm25_score": 218.11883544921875}, {"text": "The nucleotide analogue remdesivir is an investigational drug for the treatment of human coronavirus infection. Remdesivir is a phosphoramidate prodrug and is known to target viral RNA-dependent RNA polymerases. In this issue, Gordon et al. identify that remdesivir acts as a delayed RNA chain terminator for MERS-CoV polymerase complexes.", "title": "Halting coronavirus polymerase.", "pid": "b8tknq05", "bm25_score": 218.11868286132812}, {"text": "", "title": "Covid-19: Remdesivir is helpful but not a wonder drug, say researchers.", "pid": "ujvei43u", "bm25_score": 218.10011291503906}, {"text": "Summary Background No specific antiviral drug has been proven effective for treatment of patients with severe coronavirus disease 2019 (COVID-19). Remdesivir (GS-5734), a nucleoside analogue prodrug, has inhibitory effects on pathogenic animal and human coronaviruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in vitro, and inhibits Middle East respiratory syndrome coronavirus, SARS-CoV-1, and SARS-CoV-2 replication in animal models. Methods We did a randomised, double-blind, placebo-controlled, multicentre trial at ten hospitals in Hubei, China. Eligible patients were adults (aged ≥18 years) admitted to hospital with laboratory-confirmed SARS-CoV-2 infection, with an interval from symptom onset to enrolment of 12 days or less, oxygen saturation of 94% or less on room air or a ratio of arterial oxygen partial pressure to fractional inspired oxygen of 300 mm Hg or less, and radiologically confirmed pneumonia. Patients were randomly assigned in a 2:1 ratio to intravenous remdesivir (200 mg on day 1 followed by 100 mg on days 2–10 in single daily infusions) or the same volume of placebo infusions for 10 days. Patients were permitted concomitant use of lopinavir–ritonavir, interferons, and corticosteroids. The primary endpoint was time to clinical improvement up to day 28, defined as the time (in days) from randomisation to the point of a decline of two levels on a six-point ordinal scale of clinical status (from 1=discharged to 6=death) or discharged alive from hospital, whichever came first. Primary analysis was done in the intention-to-treat (ITT) population and safety analysis was done in all patients who started their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT04257656. Findings Between Feb 6, 2020, and March 12, 2020, 237 patients were enrolled and randomly assigned to a treatment group (158 to remdesivir and 79 to placebo); one patient in the placebo group who withdrew after randomisation was not included in the ITT population. Remdesivir use was not associated with a difference in time to clinical improvement (hazard ratio 1·23 [95% CI 0·87–1·75]). Although not statistically significant, patients receiving remdesivir had a numerically faster time to clinical improvement than those receiving placebo among patients with symptom duration of 10 days or less (hazard ratio 1·52 [0·95–2·43]). Adverse events were reported in 102 (66%) of 155 remdesivir recipients versus 50 (64%) of 78 placebo recipients. Remdesivir was stopped early because of adverse events in 18 (12%) patients versus four (5%) patients who stopped placebo early. Interpretation In this study of adult patients admitted to hospital for severe COVID-19, remdesivir was not associated with statistically significant clinical benefits. However, the numerical reduction in time to clinical improvement in those treated earlier requires confirmation in larger studies. Funding Chinese Academy of Medical Sciences Emergency Project of COVID-19, National Key Research and Development Program of China, the Beijing Science and Technology Project.", "title": "Remdesivir in adults with severe COVID-19: a randomised, double-blind, placebo-controlled, multicentre trial", "pid": "bzeqs5oh", "bm25_score": 218.09158325195312}, {"text": "", "title": "Compassionate Use of Remdesivir in Covid-19. Reply", "pid": "rz472kcg", "bm25_score": 218.0667266845703}, {"text": "", "title": "Covid-19: Remdesivir is helpful but not a wonder drug, say researchers", "pid": "pi6pezv5", "bm25_score": 218.06219482421875}, {"text": "", "title": "Remdesivir bei Patienten mit schwerer COVID-19./ [Remdesivir for patients with severe COVID-19]", "pid": "2g4d4q8t", "bm25_score": 217.9978790283203}, {"text": "", "title": "Compassionate use remdesivir for treatment of severe COVID-19 in pregnant women at a United States academic center", "pid": "qb9wluxd", "bm25_score": 217.98184204101562}, {"text": "BACKGROUND & AIMS: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. METHODS: We systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as “Remdesivir” or ‘GS-5734″ AND “COVID-19” or “SARS-CoV-2” and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. RESULTS: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. CONCLUSIONS: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.", "title": "Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies", "pid": "gqqdx2r5", "bm25_score": 217.93446350097656}, {"text": "Abstract The novel coronavirus infection that initially found at the end of 2019 has attracted great attention. So far, the number of infectious cases has increased globally to more than 100 thousand and the outbreak has been defined as a pandemic situation, but there are still no “specific drug” available. Relevant reports have pointed out the novel coronavirus has 80% homology with SARS. In the difficulty where new synthesized drug cannot be applied immediately to patients, “conventional drug in new use” becomes a feasible solution. The first medication experience of the recovered patients in the US has led remdesivir to be the “specific drug”. China has also taken immediate action to put remdesivir into clinical trials with the purpose of applying it into clinical therapeutics for Corona Virus Disease 2019 (COVID-19). We started from the structure, immunogenicity, and pathogenesis of coronavirus infections of the novel coronavirus. Further, we analyzed the pharmacological actions and previous trials of remdesivir to identify the feasibility of conducting experiments on COVID-19.", "title": "Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence", "pid": "b518n9dx", "bm25_score": 217.92918395996094}, {"text": "BACKGROUND & AIMS: Remdesivir is a broad spectrum anti-viral drug that has shown to inhibit SARS-CoV-2, in vitro and in vivo. In absence of any effective treatment for SARS-CoV-2 infection (COVID-19), remdesivir has been tried for a compassionate use in severe COVID-19. Newer randomized controlled studies that have recently become available, showed a mixed result. We aimed to systematically search the literature to understand the pharmacology and clinical effects of remdesivir in patients with COVID-19. METHODS: We systematically searched the PubMed, ClinicalTrial.Org and MedRxiv database up till May 5, 2020 using specific key words such as \"Remdesivir\" or 'GS-5734″ AND \"COVID-19\" or \"SARS-CoV-2\" and retrieved all the article published in English language, that have reported the pharmacology and the clinical outcomes of remdesivir in patients with COVID-19. RESULTS: Initial compassionate use of remdesivir has shown a fairly good result, but difficult to quantify, in the absence of control arm. While the very first double-blind, placebo-controlled, randomized trial conducted in Wuhan, did not find any significant benefit compared to the control, the preliminary result of another similar multi-country trial has shown a significant faster time to recovery but without any difference in mortality. CONCLUSIONS: Remdesivir has shown a mixed result in patients with COVID-19 with an acceptable side effect. However, jury is still out while awaiting the results from the forthcoming trials.", "title": "Remdesivir in COVID-19: A critical review of pharmacology, pre-clinical and clinical studies", "pid": "1eiw7bxh", "bm25_score": 217.86517333984375}, {"text": "The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.", "title": "Discovering drugs to treat coronavirus disease 2019 (COVID-19).", "pid": "8ruux4sw", "bm25_score": 217.85919189453125}, {"text": "Background: In spite of the global containment on prevention efforts, the spread of coronavirus disease 2019 (COVID-19) is continuing to rise, with 1.1 million confirmed cases and 60,124 deaths recorded worldwide since 04 April 2020. The outbreak has a significant threat to international health and economy. At present, there is no approved vaccine or treatment for the disease, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomized controlled trials to compare the effectiveness of remdesivir and placebo in patients with COVID-19. Method and analysis: We will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Google scholar databases without restriction in year of publication. We will include randomized controlled trials that assessed the effectiveness of remdesivir versus placebo for patients confirmed with COVID-19. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA 2015) guidelines for the design and reporting of the results. The primary endpoint will be time to clinical recovery. The secondary endpoints will be all cause mortality, discharged date, frequency of respiratory progression, and treatment-emergent adverse events. Two independent authors will perform study selection, data extraction, and methodology quality assessment. RevMan 5.3 software will be used for statistical analysis. Random/fixed effect model will be carried out to calculate mean differences for continuous outcomes and risk ratio for dichotomous outcomes between remdesivir and placebo. Ethics and dissemination: This study does not require ethical approval, because no participants data will be involved in this systematic review and meta-analysis. The findings of this study will be published in reputable and peer-reviewed journal. Registration: This review protocol is submitted in PROSPERO database for registration and we will include the registration number in the revised version of the manuscript. Keywords: 2019 novel coronavirus, 2019-nCoV, Coronavirus diseases 2019, COVID-19, SARS-cov-2, Remdesivir, Randomized Controlled Trials. Systematic review, Meta-analysis, protocol", "title": "Efficacy of remdesivir versus placebo for the treatment of COVID-19: A protocol for systematic review and meta-analysis of randomized controlled trials", "pid": "aosmo568", "bm25_score": 217.8516387939453}, {"text": "The SARS-CoV-2 virus emerged in December 2019 and then spread rapidly worldwide, particularly to China, Japan, and South Korea. Scientists are endeavoring to find antivirals specific to the virus. Several drugs such as chloroquine, arbidol, remdesivir, and favipiravir are currently undergoing clinical studies to test their efficacy and safety in the treatment of coronavirus disease 2019 (COVID-19) in China; some promising results have been achieved thus far. This article summarizes agents with potential efficacy against SARS-CoV-2.", "title": "Discovering drugs to treat coronavirus disease 2019 (COVID-19)", "pid": "ey939w17", "bm25_score": 217.8153076171875}, {"text": "BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACCT-1 ClinicalTrials.gov number, NCT04280705.).", "title": "Remdesivir for the Treatment of Covid-19 - Preliminary Report", "pid": "tn2xfmry", "bm25_score": 217.77703857421875}, {"text": "With society clamoring for something—anything—that can stem the rapidly rising death toll of the COVID-19 pandemic, Gilead Sciences’ antiviral remdesivir has emerged as a closely watched treatment option Laboratory studies of other coronaviruses suggested the drug might be able to take down this new one, which causes COVID-19 As the outbreak took hold in China in January, it was among the first treatments that doctors tried Now, with cases worldwide at more than 3 million, scrutiny of data coming out of clinical trials of the drug has reached fever pitch When the health-focused news site Stat posted a story based on a leaked video of a University of Chicago clinician talking optimistically about remdesivir’s possible effectiveness, it didn’t just prop up Gilead’s stock price;it lifted the entire stock market With each new anecdote, whether about an individual patient or a hunch from a doctor running a trial, the pressure View: PDF ;Full Text HTML", "title": "Scaling up remdesivir amid the coronavirus crisis", "pid": "nez8la3d", "bm25_score": 217.76519775390625}, {"text": "Summary Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the novel viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV) potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 μM). Weaker activity is observed in Vero E6 cells (EC50 = 1.65 μM) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminishes lung viral load and improves pulmonary function compared to vehicle treated animals. These data demonstrate that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.", "title": "Remdesivir inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice.", "pid": "9sjdb7f3", "bm25_score": 217.76092529296875}, {"text": "", "title": "Covid-19: Remdesivir is recommended for authorisation by European Medicines Agency.", "pid": "n0joyhon", "bm25_score": 217.73719787597656}, {"text": "BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%). CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.)", "title": "Remdesivir for the Treatment of Covid-19 — Preliminary Report", "pid": "uohbxoeb", "bm25_score": 217.7166748046875}, {"text": "BACKGROUND: There are limited data regarding treatment options for pregnant women with severe coronavirus disease 2019 (COVID-19). CASE: A 35-year-old primigravid patient at 22 weeks of gestation presented with 7 days of fever, cough, anosmia, and dyspnea. Nasopharyngeal swab was positive for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a chest X-ray demonstrated bilateral patchy infiltrates. Laboratory evaluation was notable for marked elevation of interleukin-6 and C-reactive protein concentrations. On hospital day 3, owing to increased dyspnea and oxygen requirement, the patient was treated with tocilizumab followed by 5 days of remdesivir. She responded well, recovered to room air, and was discharged home after a 9-day hospitalization. CONCLUSION: Tocilizumab and remdesivir may be effective for treatment of severe COVID-19 in pregnancy, but additional data are needed to guide risk-benefit considerations.", "title": "Tocilizumab and Remdesivir in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19)", "pid": "d4tc2xe7", "bm25_score": 217.6990509033203}, {"text": "Countries around the world are currently fighting the coronavirus disease 2019 (COVID-19) pandemic, which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is a betacoronavirus, belonging to the same genus as severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV. Currently, there are no proven antiviral therapies for COVID-19. Numerous clinical trials have been initiated to identify an effective treatment. One leading candidate is remdesivir (GS-5734), a broad-spectrum antiviral that was initially developed for the treatment of Ebola virus (EBOV). Although remdesivir performed well in preclinical studies, it did not meet efficacy endpoints in a randomized trial conducted during an Ebola outbreak. Remdesivir holds promise for treating COVID-19 based on in vitro activity against SARS-CoV-2, uncontrolled clinical reports, and limited data from randomized trials. Overall, current data are insufficient to judge the efficacy of remdesivir for COVID-19, and the results of additional randomized studies are eagerly anticipated. In this narrative review, we provide an overview of Ebola and coronavirus outbreaks. We then summarize preclinical and clinical studies of remdesivir for Ebola and COVID-19.", "title": "The journey of remdesivir: from Ebola to COVID-19", "pid": "aivub6mi", "bm25_score": 217.69261169433594}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections.Communicated by Ramaswamy H. Sarma.", "title": "Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase", "pid": "kjc3j7yz", "bm25_score": 217.67457580566406}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative representative of a severe respiratory illness resulted in widespread human infections and deaths in nearly all of the countries since late 2019. There is no therapeutic FDA-approved drug against SARS-CoV-2 infection, although a combination of anti-viral drugs is directly being practiced in some countries. A broad-spectrum of antiviral agents are being currently evaluated in clinical trials, and in this review, we specifically focus on the application of Remdesivir (RVD) as a potential anti-viral compound against Middle East respiratory syndrome (MERS) -CoV, SARS-CoV and SARS-CoV-2. First, we overview the general information about SARS-CoV-2, followed by application of RDV as a nucleotide analogue which can potentially inhibits RNA-dependent RNA polymerase of COVs. Afterwards, we discussed the kinetics of SARS- or MERS-CoV proliferation in animal models which is significantly different compared to that in humans. Finally, some ongoing challenges and future perspective on the application of RDV either alone or in combination with other anti-viral agents against CoVs infection were surveyed to determine the efficiency of RDV in preclinical trials. As a result, this paper provides crucial evidence of the potency of RDV to prevent SARS-CoV-2 infections. Communicated by Ramaswamy H. Sarma", "title": "Development of remdesivir repositioning as a nucleotide analog against COVID-19 RNA dependent RNA polymerase", "pid": "2ro2p77q", "bm25_score": 217.6508331298828}, {"text": "The novel coronavirus infection that initially found at the end of 2019 has attracted great attention. So far, the number of infectious cases has increased globally to more than 100 thousand and the outbreak has been defined as a pandemic situation, but there are still no \"specific drug\" available. Relevant reports have pointed out the novel coronavirus has 80% homology with SARS. In the difficulty where new synthesized drug cannot be applied immediately to patients, \"conventional drug in new use\" becomes a feasible solution. The first medication experience of the recovered patients in the US has led remdesivir to be the \"specific drug\". China has also taken immediate action to put remdesivir into clinical trials with the purpose of applying it into clinical therapeutics for Corona Virus Disease 2019 (COVID-19). We started from the structure, immunogenicity, and pathogenesis of coronavirus infections of the novel coronavirus. Further, we analyzed the pharmacological actions and previous trials of remdesivir to identify the feasibility of conducting experiments on COVID-19.", "title": "Remdesivir for severe acute respiratory syndrome coronavirus 2 causing COVID-19: An evaluation of the evidence", "pid": "tgtba98u", "bm25_score": 217.6029052734375}, {"text": "In the coming weeks, the world will get a sense of whether Gilead Sciences’ remdesivir, an antiviral developed for Ebola, is useful against the novel coronavirus With the coronavirus pandemic spiraling—during the week of March 30, worldwide infections crossed 900,000 and deaths exceeded 45,000—initial results emerging from several late-stage studies will be under the microscope But infectious disease experts on the front lines warn that the data are unlikely to clearly answer the question of whether remdesivir works in COVID-19, the respiratory illness caused by the SARS-CoV-2 virus Those first tests are in the sickest, hardest-to-treat patients Moreover, antivirals don’t have a great track record at taking down coronaviruses, which can be a little more sophisticated than your average RNA virus Still, some industry watchers hope the studies signal enough success to convince the US Food and Drug Administration to approve Gilead’s experimental drug When a new infectious disease threatens", "title": "What could remdesivir data tell us about tackling COVID-19?", "pid": "svp32re6", "bm25_score": 217.57337951660156}, {"text": "", "title": "Benefit-risk assessment for remdesivir in COVID-19", "pid": "7xci160l", "bm25_score": 217.57252502441406}, {"text": "While the recent study on the compassionate use of remdesivir for COVID-19 patients has shown a 68% clinical improvement7 it is a one-arm study that renders the evaluation of the efficacy in reducing death and the length of stay of hospitalization intractable due to a lacking of the control group. We came up with a two-arm controlled study design to simulate the treated and the untreated (control group) group by applying two respective transition models to the empirical data on dynamics of the disease severity (Figure 2 of the original article7) that are classified into low- (no and low oxygen supplement), medium- (non-invasive ventilator and high oxygen supplement), and high-(ECMO and invasive ventilator) from enrolment until discharge, death or the end of follow-up. By using a simulated two-arm controlled study, the remdesivir treatment group as opposed to the control group led to a statistically significantly 29% (95% CI: 22-35%) reduction of death from COVID-19. The treated group also revealed a 33% (95% CI 28-38%) significantly higher odds of discharge than the control group. The median time to discharge for the treated group (5.5 days, 16.5 days, and 29.5 days for low-, medium-, and high-risk state, respectively) was around half of those of the control arm. Our results with a simulated two-arm controlled study have not only corroborated the efficacy of remdesivir but also made great contribution to designing a further large-scale randomized controlled trial. They have significant implications for reducing transmission probability and infectious time of COVID-19 patients when contacting with susceptible health care workers during hospitalization.", "title": "Efficacy of remdesivir in COVID-19 patients with a simulated two-arm controlled study", "pid": "qpa6tk6v", "bm25_score": 217.54177856445312}, {"text": "Countries such as South Africa have limited intensive care unit (ICU) capacity to handle the expected number of COVID-19 patients requiring ICU care. Remdesivir can prevent deaths in countries such as South Africa by decreasing the number of days people spend in ICU, therefore freeing up ICU bed capacity.", "title": "The role of remdesivir in South Africa: preventing COVID-19 deaths through increasing ICU capacity.", "pid": "7gzem1s5", "bm25_score": 217.5299530029297}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 as the causative agent of the novel pandemic viral disease COVID-19. With no approved therapies, this pandemic illustrates the urgent need for safe, broad-spectrum antiviral countermeasures against SARS-CoV-2 and future emerging CoVs. We report that remdesivir (RDV), a monophosphoramidate prodrug of an adenosine analog, potently inhibits SARS-CoV-2 replication in human lung cells and primary human airway epithelial cultures (EC50 = 0.01 μM). Weaker activity was observed in Vero E6 cells (EC50 = 1.65 μM) due to their low capacity to metabolize RDV. To rapidly evaluate in vivo efficacy, we engineered a chimeric SARS-CoV encoding the viral target of RDV, the RNA-dependent RNA polymerase, of SARS-CoV-2. In mice infected with chimeric virus, therapeutic RDV administration diminished lung viral load and improved pulmonary function as compared to vehicle treated animals. These data provide evidence that RDV is potently active against SARS-CoV-2 in vitro and in vivo, supporting its further clinical testing for treatment of COVID-19.", "title": "Remdesivir potently inhibits SARS-CoV-2 in human lung cells and chimeric SARS-CoV expressing the SARS-CoV-2 RNA polymerase in mice", "pid": "ghrlj6b2", "bm25_score": 217.52606201171875}, {"text": "", "title": "Covid-19: Remdesivir is recommended for authorisation by European Medicines Agency", "pid": "yhgpw0i5", "bm25_score": 217.518798828125}, {"text": "Countries such as South Africa have limited intensive care unit (ICU) capacity to handle the expected number of COVID-19 patients requiring ICU care. Remdesivir can prevent deaths in countries such as South Africa by decreasing the number of days people spend in ICU, therefore freeing up ICU bed capacity.", "title": "The role of remdesivir in South Africa: preventing COVID-19 deaths through increasing ICU capacity", "pid": "sqjaembq", "bm25_score": 217.47528076171875}, {"text": "An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 µM, 26.63 µM, 2.55 µM and 0.46 µM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 µM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 µM in combination with emetine at 0.195 µM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.", "title": "Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro", "pid": "ygygnmgm", "bm25_score": 217.43411254882812}, {"text": "BACKGROUND There are limited data regarding treatment options for pregnant women with severe coronavirus disease 2019 (COVID-19). CASE A 35-year-old primigravid patient at 22 weeks of gestation presented with 7 days of fever, cough, anosmia, and dyspnea. Nasopharyngeal swab was positive for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a chest X-ray demonstrated bilateral patchy infiltrates. Laboratory evaluation was notable for marked elevation of interleukin-6 and C-reactive protein concentrations. On hospital day 3, owing to increased dyspnea and oxygen requirement, the patient was treated with tocilizumab followed by 5 days of remdesivir. She responded well, recovered to room air, and was discharged home after a 9-day hospitalization. CONCLUSION Tocilizumab and remdesivir may be effective for treatment of severe COVID-19 in pregnancy, but additional data are needed to guide risk-benefit considerations.", "title": "Tocilizumab and Remdesivir in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19).", "pid": "tdfqhty8", "bm25_score": 217.4235076904297}, {"text": "BACKGROUND: Despite global containment measures to fight the coronavirus disease 2019 (COVID-19), the pandemic continued to rise, rapidly spread across the world, and resulting in 2.6 million confirmed cases and 185 061 deaths worldwide as of 23 April 2020. Yet, there are no approved vaccines or drugs to make the disease less deadly, while efforts are underway. Remdesivir, a nucleotide-analogue antiviral drug developed for Ebola, is determined to prevent and stop infections with COVID-19, while results are yet controversial. Here, we aim to conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) to evaluate the efficacy of remdesivir in patients with COVID-19. METHOD AND ANALYSIS: We will search MEDLINE-PubMed, Embase, Cochrane Library, ClinicalTrials.gov and Google scholar databases for articles published as of 30 June 2020 and we will complete the study on 30 August 2020. We will follow the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) 2015 guidelines for the design and reporting of the results. We will include RCTs that assessed the efficacy of remdesivir versus placebo or standard of care. The primary endpoint will be time to clinical recovery. The secondary endpoints will be proportion of participants relieved from clinical symptoms defined at the time (in hours) from initiation of the study treatment, all-cause mortality, discharged date, frequency of respiratory progression and treatment-emergent adverse events. RevMan V.5.3 software will be used for statistical analysis. Random effects model will be carried out to calculate mean differences for continuous outcome data and risk ratio for dichotomous outcome data between remdesivir and placebo or standard of care. ETHICS AND DISSEMINATION: There are no ethical considerations associated with this study as we will use publicly available data from previously published studies. We plan to publish results in open-access peer-reviewed journals and present at international and national conferences. PROSPERO REGISTRATION NUMBER: CRD42020177953.", "title": "Efficacy of remdesivir in patients with COVID-19: a protocol for systematic review and meta-analysis of randomised controlled trials", "pid": "kcrmi3x8", "bm25_score": 217.41983032226562}, {"text": "The COVID-19 pandemic potentially makes treatment of acute leukaemia more difficult. Most induction chemotherapy regimens for acute leukaemia lead to extended periods of cytopaenia and immunosuppression rendering patients vulnerable to opportunistic infections. As with many aspects of SARS-CoV-2, there is no universally accepted way of treating patients who present with acute leukaemia and associated infection.", "title": "Remdesivir during induction chemotherapy for newly diagnosed paediatric acute lymphoblastic leukaemia with concomitant SARS-CoV-2 infection.", "pid": "ov308nrl", "bm25_score": 217.41148376464844}, {"text": "SARS-CoV-2 is rapidly evolving with the continuous emergence of new mutations. There is no specific antiviral therapy for COVID-19, and the use of Remdesivir for treating COVID-19 will likely continue before clinical trials are completed. Due to the lengthening pandemic and evolving nature of the virus, predicting potential residues prone to mutations is crucial for the management of Remdesivir resistance. We used a rational ligand-based interface design complemented with mutational mapping to generate a total of 100,000 mutations and provide insight into the functional outcome of mutations in the Remdesivir-binding site in nsp12. After designing 56 residues in the Remdesivir binding site of nsp12, the designs retained 96-98% sequence identity, which suggests that SARS-CoV-2 attains resistance and develops further infectivity with very few mutations in the nsp12. We also identified affinity-attenuating Remdesivir binding designs of nsp12. Several mutants acquired decreased binding affinity with Remdesivir, which suggested drug resistance. These hotspot residues had a higher probability of undergoing selective mutations in the future to develop Remdesivir and related drug-based resistance. A comparison of 21 nsp12 Remdesivir-bound designs to the 13 EIDD-2801-bound nsp12 designs suggested that EIDD-2801 would be more effective in preventing the emergence of resistant mutations and against Remdesivir-resistance strains due to the restricted mutational landscape. Combined with the availability of more genomic data, our information on mutation repertoires is critical to guide scientists to rational structure-based drug discovery. Knowledge of the potential residues prone to mutation improves our understanding and management of drug resistance and disease pathogenesis.", "title": "Rational Design of the Remdesivir Binding Site in the RNA-dependent RNA Polymerase of SARS-CoV-2: Implications for Potential Resistance", "pid": "mu8isrut", "bm25_score": 217.376708984375}, {"text": "An escalating pandemic by the novel SARS-CoV-2 virus is impacting global health and effective therapeutic options are urgently needed. We evaluated the in vitro antiviral effect of compounds that were previously reported to inhibit coronavirus replication and compounds that are currently under evaluation in clinical trials for SARS-CoV-2 patients. We report the antiviral effect of remdesivir, lopinavir, homorringtonine, and emetine against SARS-CoV-2 virus in Vero E6 cells with the estimated 50% effective concentration at 23.15 μM, 26.63 μM, 2.55 μM and 0.46 μM, respectively. Ribavirin or favipiravir that are currently evaluated under clinical trials showed no inhibition at 100 μM. Synergy between remdesivir and emetine was observed, and remdesivir at 6.25 μM in combination with emetine at 0.195 μM may achieve 64.9% inhibition in viral yield. Combinational therapy may help to reduce the effective concentration of compounds below the therapeutic plasma concentrations and provide better clinical benefits.", "title": "Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro", "pid": "7e8zlt3t", "bm25_score": 217.35829162597656}, {"text": "2019 - Novel Coronavirus (2019-nCOV), enclosed large genome positive-sense RNA virus characterized by crown-like spikes that protrude from their surface, and have a distinctive replication strategy. The 2019-nCOV belongs to the Coronaviridae family, principally consists of virulent pathogens showing zoonotic property, has emerged as a pandemic outbreak with high mortality and high morbidity rate around the globe and no therapeutic vaccine or drugs against 2019-nCoV are discovered till now. In this study, in silico methods and algorithms were used for sequence, structure analysis and molecular docking on Mpro of 2019-nCOV. The co-crystal structure of 2019-nCOV protease, 6LU7 have ∼99% identity with SARS-CoV protease. The 6LU7 residues, Cys145 and His164 are playing a significant role in replication and are essential for the survival of 2019-nCOV. Alongside, 2019-nCOV Mpro sequence is non-homologous to human host-pathogen. Complete genome sequence analysis, structural and molecular docking results revealed that Remdesivir is having a better binding affinity with -8.2 kcal/mol than the rest of protease inhibitors, and peptide. Remdesivir is strongly forming h-bonds with crucial Mpro residues, Cys145, and His164. Further, MD simulation analysis also confirmed, that these residues are forming H-bond with Remdesivir during 100 ns simulations run and found stable (∼99%) by RMSD and RMSF. Thus, present in silico study at molecular approaches suggest that, Remdesivir is a potent therapeutic inhibitor against 2019-nCoV.Communicated by Ramaswamy H. Sarma.", "title": "Remdesivir (GS-5734) as a therapeutic option of 2019-nCOV main protease - in silico approach", "pid": "frxsn6sd", "bm25_score": 217.354736328125}, {"text": "The novel coronavirus strain, severe acute respiratory syndrome coronavirus-2, the causative agent of COVID-19 emerged in Wuhan, China, in December 2019 and is skyrocketing throughout the globe and become a global public health emergency. Despite promising preventive measures being taken, there is no vaccine or drug therapy officially approved to prevent or treat the infection. Everybody is waiting the findings of ongoing clinical trials in various chemical and biological products. This review is specifically aimed to summarize the available evidence and ongoing clinical trials of remdesivir as a potential therapeutic option for COVID-19. Remdesivir is an investigational drug having broad spectrum antiviral activity with its target RNA dependent RNA polymerase. It has not yet been officially approved for Ebola and Coronaviruses. Several studies showed that remdesivir had promising in vitro and in vivo antiviral activities against SARS-CoV-1 and MERS-CoV strains. On the top of this, it exhibited a promising in vitro activity against SARS-CoV-2 strains though there are no published studies that substantiate its activity in vivo until the time of this review. There are few phase 3 randomized double-blind placebo controlled trials on the way to investigate the safety and efficacy of remdesivir. Of which, one completed double blind, placebo controlled trial showed that remdesivir showed faster time to clinical improvement in severe COVID-19 patients compared to placebo though not found statistically significant. In addition, two phase 3 randomized open label clinical trials coordinated by Gilead Sciences are being conducted. In addition, WHO Solidarity trial and INSERM DisCoVeRy trials (randomized open labels) were launched recently.", "title": "Available Evidence and Ongoing Clinical Trials of Remdesivir: Could It Be a Promising Therapeutic Option for COVID-19?", "pid": "tasbdhs1", "bm25_score": 217.31613159179688}]}
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In order to comprehensively compare them, their genome sequencing data were examined by principal component analysis. Variations in coronavirus were smaller than those in a subclass of the influenza virus. In addition, differences among coronaviruses in a variety of hosts were small. These characteristics may have facilitated the infection of different hosts. Although many of the coronaviruses were more conservative, those repeatedly found among humans showed annual changes. If SARS-CoV-2 changes its genome like the Influenza H type, it will repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics. One Sentence Summary The genome data of coronavirus were compared to influenza virus, to investigate its spreading mechanism and future status. Coronavirus would repeatedly spread every few years. In addition, the coronavirus family has many other candidates for subsequent pandemics.", "title": "Coronavirus, as a source of pandemic pathogens", "pid": "431ksdno", "bm25_score": 216.59190368652344}, {"text": "We have recently described the discovery of a novel coronavirus, coronavirus HKU1 (CoV-HKU1), associated with community-acquired pneumonia. However, the clinical spectrum of disease and the epidemiology of CoV-HKU1 infections in relation to infections with other respiratory viruses are unknown. In this 12-month prospective study, 4,181 nasopharyngeal aspirates from patients with acute respiratory tract infections were subjected to reverse transcription-PCRs specific for CoV-HKU1 and human coronaviruses NL63 (HCoV-NL63), OC43 (HCoV-OC43), and 229E (HCoV-229E). Coronaviruses were detected in 87 (2.1%) patients, with 13 (0.3%) positive for CoV-HKU1, 17 (0.4%) positive for HCoV-NL63, 53 (1.3%) positive for HCoV-OC43, and 4 (0.1%) positive for HCoV-229E. Of the 13 patients with CoV-HKU1 infections, 11 were children and 8 had underlying diseases. Similar to the case for other coronaviruses, upper respiratory infection was the most common presentation of CoV-HKU1 infections, although pneumonia, acute bronchiolitis, and asthmatic exacerbation also occurred. Despite a shorter duration of fever (mean, 1.7 days) and no difference in maximum temperature in children with CoV-HKU1 infections compared to patients with most other respiratory virus infections, a high incidence of febrile seizures (50%) was noted, which was significantly higher than those for HCoV-OC43 (14%), adenovirus (9%), human parainfluenza virus 1 (0%), and respiratory syncytial virus (8%) infections. CoV-HKU1 and HCoV-OC43 infections peaked in winter, although cases of the former also occurred in spring to early summer. This is in contrast to HCoV-NL63 infections, which mainly occurred in early summer and autumn but were absent in winter. Two genotypes of CoV-HKU1 cocirculated during the study period. Continuous studies over a longer period are warranted to ascertain the seasonal variation and relative importance of the different coronaviruses. Similar studies in other countries are required to better determine the epidemiology and genetic diversity of CoV-HKU1.", "title": "Coronavirus HKU1 and other coronavirus infections in Hong Kong.", "pid": "ccrupdwj", "bm25_score": 216.0381317138672}, {"text": "There is currently debate about human coronavirus (HCoV) seasonality and pathogenicity, as epidemiological data are scarce. Here, we provide epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) examined in primary care general practice. We also describe HCoV seasonality over six influenza surveillance seasons (week 40 to 15 of each season) from the period 2014/2015 to 2019/2020 in Corsica (France). A sample of patients of all ages presenting for consultation for influenza-like illness (ILI) or ARI was included by physicians of the French Sentinelles Network during this period. Nasopharyngeal samples were tested for the presence of 21 respiratory pathogens by real-time RT-PCR. Among the 1389 ILI/ARI patients, 105 were positive for at least one HCoV (7.5%). On an annual basis, HCoVs circulated from week 48 (November) to weeks 14-15 (May) and peaked in week 6 (February). Overall, among the HCoV-positive patients detected in this study, HCoV-OC43 was the most commonly detected virus, followed by HCoV-NL63, HCoV-HKU1, and HCoV-229E. The HCoV detection rates varied significantly with age (p = 0.00005), with the age group 0-14 years accounting for 28.6% (n = 30) of HCoV-positive patients. Fever and malaise were less frequent in HCoV patients than in influenza patients, while sore throat, dyspnoea, rhinorrhoea, and conjunctivitis were more associated with HCoV positivity. In conclusion, this study demonstrates that HCoV subtypes appear in ARI/ILI patients seen in general practice, with characteristic outbreak patterns primarily in winter. This study also identified symptoms associated with HCoVs in patients with ARI/ILI. Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs.", "title": "Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014-2020) in France.", "pid": "1n5ej08f", "bm25_score": 215.93617248535156}, {"text": "There is currently debate about human coronavirus (HCoV) seasonality and pathogenicity, as epidemiological data are scarce. Here, we provide epidemiological and clinical features of HCoV patients with acute respiratory infection (ARI) examined in primary care general practice. We also describe HCoV seasonality over six influenza surveillance seasons (week 40 to 15 of each season) from the period 2014/2015 to 2019/2020 in Corsica (France). A sample of patients of all ages presenting for consultation for influenza-like illness (ILI) or ARI was included by physicians of the French Sentinelles Network during this period. Nasopharyngeal samples were tested for the presence of 21 respiratory pathogens by real-time RT-PCR. Among the 1389 ILI/ARI patients, 105 were positive for at least one HCoV (7.5%). On an annual basis, HCoVs circulated from week 48 (November) to weeks 14-15 (May) and peaked in week 6 (February). Overall, among the HCoV-positive patients detected in this study, HCoV-OC43 was the most commonly detected virus, followed by HCoV-NL63, HCoV-HKU1, and HCoV-229E. The HCoV detection rates varied significantly with age (p = 0.00005), with the age group 0-14 years accounting for 28.6% (n = 30) of HCoV-positive patients. Fever and malaise were less frequent in HCoV patients than in influenza patients, while sore throat, dyspnoea, rhinorrhoea, and conjunctivitis were more associated with HCoV positivity. In conclusion, this study demonstrates that HCoV subtypes appear in ARI/ILI patients seen in general practice, with characteristic outbreak patterns primarily in winter. This study also identified symptoms associated with HCoVs in patients with ARI/ILI. Further studies with representative samples should be conducted to provide additional insights into the epidemiology and clinical features of HCoVs.", "title": "Epidemiology and Clinical Symptoms Related to Seasonal Coronavirus Identified in Patients with Acute Respiratory Infections Consulting in Primary Care over Six Influenza Seasons (2014-2020) in France", "pid": "5qhguue3", "bm25_score": 215.91537475585938}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to sweep the world, causing infection of millions and death of hundreds of thousands. The respiratory disease that it caused, COVID-19 (stands for coronavirus disease in 2019), has similar clinical symptoms with other two CoV diseases, severe acute respiratory syndrome and Middle East respiratory syndrome (SARS and MERS), of which causative viruses are SARS-CoV and MERS-CoV, respectively. These three CoVs resulting diseases also share many clinical symptoms with other respiratory diseases caused by influenza A viruses (IAVs). Since both CoVs and IAVs are general pathogens responsible for seasonal cold, in the next few months, during the changing of seasons, clinicians and public heath may have to distinguish COVID-19 pneumonia from other kinds of viral pneumonia. This is a discussion and comparison of the virus structures, transmission characteristics, clinical symptoms, diagnosis, pathological changes, treatment and prevention of the two kinds of viruses, CoVs and IAVs. It hopes to provide information for practitioners in the medical field during the epidemic season.", "title": "Comparative review of respiratory diseases caused by coronaviruses and influenza A viruses during epidemic season", "pid": "gc3iq0wp", "bm25_score": 215.79342651367188}, {"text": "", "title": "Comparative seasonalities of influenza A, B and ‘common cold’ coronaviruses – setting the scene for SARSCoV-2 infections and possible unexpected host immune interactions", "pid": "thb2pox2", "bm25_score": 215.76991271972656}, {"text": "Four human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63, and HCoV-OC43) are associated with a range of respiratory outcomes, including bronchiolitis and pneumonia. Their epidemiologies and clinical characteristics are poorly described and are often reliant on case reports. To address these problems, we conducted a large-scale comprehensive screening for all four coronaviruses by analysis of 11,661 diagnostic respiratory samples collected in Edinburgh, United Kingdom, over 3 years between July 2006 and June 2009 using a novel four-way multiplex real-time reverse transcription-PCR (RT-PCR) assay. Coronaviruses were detected in 0.3 to 0.85% of samples in all age groups. Generally, coronaviruses displayed marked winter seasonality between the months of December and April and were not detected in summer months, which is comparable to the pattern seen with influenza viruses. HCoV-229E was the exception; detection was confined to the winter of 2008 and was sporadic in the following year. There were additional longer-term differences in detection frequencies between seasons, with HCoV-OC43 predominant in the first and third seasons and HCoV-HKU1 dominating in the second (see Results for definitions of seasons). A total of 11 to 41% of coronaviruses detected were in samples testing positive for other respiratory viruses, although clinical presentations of coronavirus monoinfections were comparable to those of viruses which have an established role in respiratory disease, such as respiratory syncytial virus, influenza virus, and parainfluenza viruses. The novel multiplex assay for real-time pan-coronavirus detection enhances respiratory virus diagnosis, overcomes potential diagnostic problems arising through seasonal variation in coronavirus frequency, and provides novel insights into the epidemiology and clinical implications of coronaviruses.", "title": "Epidemiology and clinical presentations of the four human coronaviruses 229E, HKU1, NL63, and OC43 detected over 3 years using a novel multiplex real-time PCR method.", "pid": "g5shtcs5", "bm25_score": 215.75070190429688}, {"text": "Abstract Background Study of human coronavirus and other virus-associated respiratory illnesses is needed to describe their clinical effects on chronically ill, older adults. Methods A prospective study during 2009 to 2013 clinically assessed acute respiratory illnesses soon after onset and 3 to 4 weeks later in patients aged ≥60 years with chronic lung and heart diseases (group 1, 100 subjects) and healthy adults aged 18 to 40 years (group 2, 101 subjects). Respiratory secretions were tested for nucleic acids of a panel of respiratory viruses. An increase in antibody titer was assessed for 4 coronavirus strains. Results Virus-associated illnesses (29 [39.1%] of 74 illnesses in group 1 and 59 [48.7%] of 121 illnesses in group 2) occurred in all calendar quarters, most commonly in the first and fourth quarters. Coronaviruses (group 1: 14 [18.9%] illnesses; group 2: 26 [21.5%] illnesses) and enteroviruses/rhinoviruses (group 1: 14 [18.9%] illnesses; group 2: 37 [30.6%] illnesses) were most common. Virus co-infections occurred in 10 illnesses. Illnesses with 9 to 11 symptoms were more common in group 1 (17 [23.0%]) than in group 2 (15 [12.4%]) (P < .05). Compared with group 2, more group 1 subjects reported dyspnea, more severe disease of longer duration, and treatment for acute illness with prednisone and antibiotics. Coronavirus-associated illnesses (percent of illnesses, group 1 vs group 2) were characterized by myalgias (21% vs 68%, P < .01), chills (50% vs 52%), dyspnea (71% vs 24%, P < .01), headache (64% vs 72%), malaise (64% vs 84%), cough (86% vs 68%), sputum production (86% vs 60%), sore throat (64% vs 80%), and nasal congestion (93% vs 96%). Conclusions Respiratory illnesses were commonly associated with coronaviruses and enteroviruses/rhinoviruses affecting chronically ill, older patients more than healthy, young adults.", "title": "Coronavirus and Other Respiratory Illnesses Comparing Older with Young Adults", "pid": "bsf8s4mh", "bm25_score": 215.69451904296875}, {"text": "Coronaviruses of humans were first identified more than 60 years ago from individuals with respiratory infections, mainly mild. Two different viruses, 229E and OC43 were initially recognized. Because of difficulty in isolating them using standard techniques, many of the early studies of their occurrence were seroepidemiologic. They were confirmed to be worldwide in distribution, and, in the North Temperate Zone, mainly occurring in the winter season. With the development of the reverse transcriptase polymerase chain reaction (PCR) technique, two additional distinct viruses have been identified, HKU1 and NL63. The four viruses have now been recognized as important in the etiology of common respiratory infections, second only to the rhinoviruses. In 2002, a previously unrecognized betacoronavirus emerged from a zoonotic reservoir in Southern China and spread during the following year to several major cities of the world. The resulting illness was termed Severe Acute Respiratory Syndrome (SARS) because of its potential lethality. More than 8,000 probable cases were reported during 2003, mainly from Hong Kong and mainland China, producing social and economic disruption in those areas affected. A constant feature of the outbreak was the importance of nosocomial spread. In spite of an estimated basic reproductive number higher than influenza, the outbreak was ended, in large part because of control of in-hospital transmission. In 2012, another betacoronavirus has emerged in the Arabian peninsula which is producing a somewhat similar illness, termed Middle East Respiratory Syndrome (MERS), also marked by extensive nosocomial transmission. The outcome of this emergence is currently unknown.", "title": "Coronaviruses", "pid": "jep80bed", "bm25_score": 215.55535888671875}, {"text": "Coronaviruses have recently caused world-wide severe outbreaks: SARS (Severe Acute Respiratory Syndrome) in 2002 and MERS (Middle-East Respiratory Syndrome) in 2012. At the end of 2019, a new coronavirus outbreak appeared in Wuhan (China) seafood market as first focus of infection, becoming a pandemics in 2020, spreading mainly into Europe and Asia. Although the virus family is well-known, this specific virus presents considerable differences, as higher transmission rates, being a challenge for diagnostic methods, treatments and vaccines. Coronavirus.pro is a C++ application which simulates Coronavirus replication cycle. This software has identified virus type in short times and provided FASTA files of virus proteins, a list of mRNA sequences and secondary structures. Furthermore, the software has identified a list of structural, non-structural and accessory proteins in 2019-nCoV virus genome more similar to SARS than to MERS, as several fusion proteins characteristics of this virus type. These results are useful as a first step in order to develop diagnostic methods, new vaccines or antiviral drugs, which could avoid virus replication in any stage: fusion inhibitors, RdRp inhibitors and PL2pro/3CLpro protease inhibitors.", "title": "Coronavirus SARS-CoV-2: Analysis of subgenomic mRNA transcription, 3CLpro and PL2pro protease cleavage sites and protein synthesis", "pid": "ll76vrr3", "bm25_score": 215.4877471923828}, {"text": "Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal human coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.", "title": "Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence", "pid": "snp8o9fw", "bm25_score": 215.46035766601562}, {"text": "In February 2003, a severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in humans in Guangdong Province, China, and caused an epidemic that had severe impact on public health, travel, and economic trade. Coronaviruses are worldwide in distribution, highly infectious, and extremely difficult to control because they have extensive genetic diversity, a short generation time, and a high mutation rate. They can cause respiratory, enteric, and in some cases hepatic and neurological diseases in a wide variety of animals and humans. An enormous, previously unrecognized reservoir of coronaviruses exists among animals. Because coronaviruses have been shown, both experimentally and in nature, to undergo genetic mutations and recombination at a rate similar to that of influenza viruses, it is not surprising that zoonosis and host switching that leads to epidemic diseases have occurred among coronaviruses. Analysis of coronavirus genomic sequence data indicates that SARS-CoV emerged from an animal reservoir. Scientists examining coronavirus isolates from a variety of animals in and around Guangdong Province reported that SARS-CoV has similarities with many different coronaviruses including avian coronaviruses and SARS-CoV-like viruses from a variety of mammals found in live-animal markets. Although a SARS-like coronavirus isolated from a bat is thought to be the progenitor of SARS-CoV, a lack of genomic sequences for the animal coronaviruses has prevented elucidation of the true origin of SARS-CoV. Sequence analysis of SARS-CoV shows that the 5' polymerase gene has a mammalian ancestry; whereas the 3' end structural genes (excluding the spike glycoprotein) have an avian origin. Spike glycoprotein, the host cell attachment viral surface protein, was shown to be a mosaic of feline coronavirus and avian coronavirus sequences resulting from a recombination event. Based on phylogenetic analysis designed to elucidate evolutionary links among viruses, SARS-CoV is believed to have branched from the modern Group 2 coronaviruses, suggesting that it evolved relatively rapidly. This is significant because SARS-CoV is likely still circulating in an animal reservoir (or reservoirs) and has the potential to quickly emerge and cause a new epidemic.", "title": "The relationship of severe acute respiratory syndrome coronavirus with avian and other coronaviruses.", "pid": "8z0ti0dx", "bm25_score": 215.45875549316406}, {"text": "Public health preparedness for coronavirus disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal coronaviruses (sCoVs) and other cocirculating viruses in the West of Scotland, UK. We analyzed routine diagnostic data for >70,000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43 and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.", "title": "Epidemiology of seasonal coronaviruses: Establishing the context for COVID-19 emergence", "pid": "6tzx945b", "bm25_score": 215.4580078125}, {"text": "Four coronaviruses (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1) are endemic in humans and mainly associated with mild respiratory illnesses; whereas the other two coronaviruses [Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) and Middle East Respiratory Syndrome Coronavirus (MERS-CoV)] present as emerging infections causing severe respiratory syndrome. Coronaviruses evolve by accumulation of point mutations and recombination of genomes among different strains or species. Mammalian coronaviruses including those infect humans are evolved from bat coronaviruses. While SARS-CoV and MERS-CoV are genetically closely related to bat coronaviruses, intermediate host(s) is (are) likely to be involved in the emergence and cross-species transmission of these novel human viruses. High prevalence of SARS-like coronaviruses have been found from masked palm civet cats and raccoon dogs collected from markets around the time of outbreaks in humans, but these animals are likely to be a transient accidental host rather than a persisting reservoir. More research is needed to elucidate the ecology of coronaviruses. Vigilance and surveillance should be maintained to promptly identify newly emerged coronaviruses.", "title": "Tracing the SARS-coronavirus.", "pid": "81knkem4", "bm25_score": 215.39930725097656}, {"text": "Coronavirus, which can cause respiratory syndrome, to date has affected over seventeen thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical compounds including histamine and protease; while late activation provokes the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus may be inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.", "title": "Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy.", "pid": "0lsniwyv", "bm25_score": 215.39308166503906}, {"text": "Rhinoviruses are picornaviruses that cause colds. They are naturally temperature sensitive and highly adapted to grow in respiratory epithelium. Coronaviruses are structurally quite different, being enveloped viruses but are also adapted to grow in respiratory epithelium and also cause colds.", "title": "Rhinoviruses and coronaviruses - virological aspects of their role in causing colds in man.", "pid": "8hau76g7", "bm25_score": 215.3861541748047}, {"text": "Public health preparedness for coronavirus (CoV) disease 2019 (COVID-19) is challenging in the absence of setting-specific epidemiological data. Here we describe the epidemiology of seasonal CoVs (sCoVs) and other cocirculating viruses in the West of Scotland, United Kingdom. We analyzed routine diagnostic data for >70 000 episodes of respiratory illness tested molecularly for multiple respiratory viruses between 2005 and 2017. Statistical associations with patient age and sex differed between CoV-229E, CoV-OC43, and CoV-NL63. Furthermore, the timing and magnitude of sCoV outbreaks did not occur concurrently, and coinfections were not reported. With respect to other cocirculating respiratory viruses, we found evidence of positive, rather than negative, interactions with sCoVs. These findings highlight the importance of considering cocirculating viruses in the differential diagnosis of COVID-19. Further work is needed to establish the occurrence/degree of cross-protective immunity conferred across sCoVs and with COVID-19, as well as the role of viral coinfection in COVID-19 disease severity.", "title": "Epidemiology of Seasonal Coronaviruses: Establishing the Context for the Emergence of Coronavirus Disease 2019", "pid": "tdy818j9", "bm25_score": 215.36045837402344}, {"text": "Coronavirus infections have emerged as epidemic and pandemic threats in last two decades. After the H1N1 influenza pandemic in 2009, recently diagnosed novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread across 203 countries and territories in all 5 major continents. World Health Organization (WHO) declared this as a public health emergency of international concern on January 30, 2020. Subsequently on February 11, 2020 a new name was given to this disease i.e. COVID-19 by an expert group from WHO. As of April 12, 2020, 10:00 CET, GMT+2:00, 1,696,588 confirmed cases and 105,952 confirmed deaths have been reported to the WHO. (Coronavirus disease 2019, situation report 83). It possibly originated from a small animal market in Wuhan, China. A cluster of patients were admitted with unusual pneumonia not responding to treatment in various hospitals. Epidemiological, genomic analysis and correlation with other coronaviruses led to the isolation of new coronavirus, closely resembling the bat coronaviruses, from such patients in Wuhan. They were identified as the SARS-CoV-2. This virus infection presents as influenza like illness in the affected people. Fever, cough, respiratory distress with fatigue, diarrhea, nausea and vomiting are common symptoms seen in adults. This may progress on to respiratory distress, hypoxia, need for oxygen supplementation and ventilator support as seen in patients in the SARS-CoV-1 epidemic (2003) in Guangdong, China. The transmissibility of SARS-CoV-1 was less as compared to SARS-CoV-2 infection, and it was well controlled with good public health efforts. The present COVID-19 epidemic is still in the acceleration phase of 3 and 4 in various countries. Without any effective antiviral agents available at present, the need of the hour is early case detection, isolation of cases, use of good preventive care measures by the household contacts and in the hospital set up. The results of ongoing clinical trials on hydroxychloroquine, azithromycin alone or in combination and a new antiviral agent remdesivir may help to treat some of the infections. A need for effective vaccine is being seen an as good preventive strategy in this pandemic. However the results of clinical trials and incorporation of vaccines in public health programs is a long way to go.", "title": "An overview of coronaviruses including the SARS-2 coronavirus - Molecular biology, epidemiology and clinical implications", "pid": "skkng2le", "bm25_score": 215.3594512939453}, {"text": "", "title": "Differences and similarities between Severe Acute Respiratory Syndrome (SARS)-CoronaVirus (CoV) and SARS-CoV-2. Would a rose by another name smell as sweet?", "pid": "j6j3kmqk", "bm25_score": 215.31350708007812}, {"text": "The emergence of 2019 novel coronavirus (2019-nCoV) is of global concern and might have emerged from RNA recombination among existing coronaviruses. CoV spike (S) protein which is crucial for receptor binding, membrane fusion via conformational changes, internalization of the virus, host tissue tropism and comprises crucial targets for vaccine development, remain largely uncharacterized. Therefore, the present study has been planned to determine the sequence variation, structural and antigenic divergence of S glycoprotein which may be helpful for the management of 2019-nCoV infection. The sequences of spike glycoprotein of 2019-nCoV and SARS coronavirus (SARS-CoV) were used for the comparison. The sequence variations were determined using EMBOSS Needle pairwise sequence alignment tools. The variation in glycosylation sites was predicted by NetNGlyc 1.0 and validated by N-GlyDE server. Antigenicity was predicted by NetCTL 1.2 and validated by IEDB Analysis Resource server. The structural divergence was determined by using SuperPose Version 1.0 based on cryo-EM structure of the SARS coronavirus spike glycoprotein. Our data suggests that 2019-nCoV is newly spilled coronavirus into humans in China is closely related to SARS-CoV, which has only 12.8% of difference with SARS-CoV in S protein and has 83.9% similarity in minimal receptor-binding domain with SARS-CoV. Addition of a novel glycosylation sites were observed in 2019-nCoV. In addition, antigenic analysis proposes that great antigenic differences exist between both the viral strains, but some of the epitopes were found to be similar between both the S proteins. In spite of the variation in S protein amino acid composition, we found no significant difference in their structures. Collectively, for the first time our results exhibit the emergence of human 2019-nCoV is closely related to predecessor SARS-CoV and provide the evidence that 2019-nCoV uses various novel glycosylation sites as SARS-CoV and may have a potential to become pandemic owing its antigenic discrepancy. Further, demonstration of novel Cytotoxic T lymphocyte epitopes may impart opportunities for the development of peptide based vaccine for the prevention of 2019-nCoV.", "title": "Structural, glycosylation and antigenic variation between 2019 novel coronavirus (2019-nCoV) and SARS coronavirus (SARS-CoV)", "pid": "b1iyr42n", "bm25_score": 215.30975341796875}, {"text": "The respiratory syndrome caused by a new type of coronavirus has been emerging from China and caused more than 1000 death globally since December 2019. This new virus, called 2019 novel coronavirus (2019-nCoV) uses the same receptor called Angiotensinconverting enzyme 2 (ACE2) to attack humans as the coronavirus that caused the severe acute respiratory syndrome (SARS) seventeen years ago. Both viruses recognize ACE2 through the spike proteins (S-protein) on their surfaces. It was found that the S-protein from the SARS coronavirus (SARS-CoV) bind stronger to ACE2 than 2019-nCoV. However, function of a bio-system is often under kinetic, rather than thermodynamic, control. To address this issue, we constructed a structural model for complex formed between ACE2 and the S-protein from 2019-nCoV, so that the rate of their association can be estimated and compared with the binding of S-protein from SARS-CoV by a multiscale simulation method. Our simulation results suggest that the association of new virus to the receptor is slower than SARS, which is consistent with the experimental data obtained very recently. We further integrated this difference of association rate between virus and receptor into a mathematical model which describes the life cycle of virus in host cells and its interplay with the innate immune system. Interestingly, we found that the slower association between virus and receptor can result in longer incubation period, while still maintaining a relatively higher level of viral concentration in human body. Our computational study therefore provides, from the molecular level, one possible explanation that the new disease by far spread much faster than SARS.", "title": "A Multiscale and Comparative Model for Receptor Binding of 2019 Novel Coronavirus and the Implication of its Life Cycle in Host Cells", "pid": "535lw99y", "bm25_score": 215.30294799804688}, {"text": "PURPOSE: Influenza A viruses, human coronaviruses (hCoV) and human bocavirus (hBoV) are emerging respiratory viruses. This study investigated the association between influenza A viruses co-infection with hBoV and hCoV and severity and the sensitivity of a real-time polymerase chain reaction (RT-PCR) assay for identification of 15 coronaviruses. METHODOLOGY: Published sequences for the 15 human coronaviruses were used to design a consensus PCR targeting the replicase open reading frame 1b. A previously published PCR targeting the NS1 Gene of all known human bocavirus strains was also utilized. A series of 217 samples from patients aged 37.7 (SD ± 30.4)] with seasonal influenza A viruses (SeasFluA) identified between 06/2011 and 06/2012 in NW England were tested for hCoV and hBoV using RT-PCR. Association between co-infection and disease outcome was assessed using logistic regression. RESULTS: The limit of detection of hCoV RT-PCR assay was 2 copies/µl of human coronavirus RNA template, a sensitivity comparable to a previously published SYBR green assay for human coronaviruses. A total of 12 hCoV and 17 hBoV were identified in the 217 influenza A positive samples. A higher proportion (61.5 %; 8/13) of SeasFluA/hBoV co-infections were identified in patients that were admitted either to a general ward or the intensive care unit compared to 44.3 % (66/149) of single SeasFlu A virus infections (OR 2.5 95 % CI 0.67–9.34, p = 0.17). In a stratified analysis, there was a trend towards higher association between FluA, hCoV and hBoV with increasing age (especially in patients aged 24–45 years and >65 year old). CONCLUSION: Our hCoV RT-PCR protocol appeared to be of adequate analytical sensitivity for diagnosis. More and larger studies are needed to confirm the role of hCoV, hBoV in causing severe disease when they co-infect with influenza A viruses.", "title": "Pan-human coronavirus and human bocavirus SYBR Green and TaqMan PCR assays; use in studying influenza A viruses co-infection and risk of hospitalization", "pid": "ph15z424", "bm25_score": 215.30233764648438}, {"text": "Coronavirus can cause respiratory syndrome which to date has affected about twelve thousand individuals, especially in China. Coronavirus is interspecies and can also be transmitted from man to man, with an incubation ranging from 1 to 14 days. Human coronavirus infections can induce not only mild to severe respiratory diseases, but also inflammation, high fever, cough, acute respiratory tract infection and dysfunction of internal organs that may lead to death. Coronavirus infection (regardless of the various types of corona virus) is primarily attacked by immune cells including mast cells (MCs), which are located in the submucosa of the respiratory tract and in the nasal cavity and represent a barrier of protection against microorganisms. Viral activate MCs release early inflammatory chemical copounds including histamine and protease; while late activation provoke the generation of pro-inflammatory IL-1 family members including IL-1, IL-6 and IL-33. Here, we propose for the first time that inflammation by coronavirus maybe inhibited by anti-inflammatory cytokines belonging to the IL-1 family members.", "title": "Mast cells contribute to coronavirus-induced inflammation: new anti-inflammatory strategy", "pid": "tokrvi8i", "bm25_score": 215.29379272460938}, {"text": "After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as \"coronavirus disease 2019\" (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.", "title": "Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV", "pid": "xghn2zy0", "bm25_score": 215.26016235351562}, {"text": "After the outbreak of the severe acute respiratory syndrome (SARS) in the world in 2003, human coronaviruses (HCoVs) have been reported as pathogens that cause severe symptoms in respiratory tract infections. Recently, a new emerged HCoV isolated from the respiratory epithelium of unexplained pneumonia patients in the Wuhan seafood market caused a major disease outbreak and has been named the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This virus causes acute lung symptoms, leading to a condition that has been named as “coronavirus disease 2019” (COVID-19). The emergence of SARS-CoV-2 and of SARS-CoV caused widespread fear and concern and has threatened global health security. There are some similarities and differences in the epidemiology and clinical features between these two viruses and diseases that are caused by these viruses. The goal of this work is to systematically review and compare between SARS-CoV and SARS-CoV-2 in the context of their virus incubation, originations, diagnosis and treatment methods, genomic and proteomic sequences, and pathogenic mechanisms.", "title": "Systematic Comparison of Two Animal-to-Human Transmitted Human Coronaviruses: SARS-CoV-2 and SARS-CoV", "pid": "73a7uvyz", "bm25_score": 215.22549438476562}, {"text": "Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats1-4. Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor-angiotensin converting enzyme II (ACE2)-as SARS-CoV.", "title": "A pneumonia outbreak associated with a new coronavirus of probable bat origin", "pid": "d5yt2fih", "bm25_score": 215.21815490722656}, {"text": "In December 2019, a new pneumonia case emerged in the Wuhan, Hubei province of China which had an association with the novel Corona Virus (2019-nCoV). Most of the diagnosed cases had exposure to the Huanan seafood market. The present case is the successor of three earlier similar cases of Coronavirus known as SARS-Corona (Severe Acute Respiratory Syndrome) Virus and MERS-Corona Virus (Middle Eastern Respiratory Syndrome). The origin of the epidemic is still unknown and a lot of other uncertainties hinders the development of vaccines for the virus. As studies suggest that this virus is an evolution of SARS virus concerns are growing around the world as death toll has already surpassed that of SARS virus. This paper explores about the coronavirus, its relation to the similar SARS and MERS virus, its outreach and global impact according to the current scenario.", "title": "Corona virus: A novel outbreak", "pid": "r6gxdbob", "bm25_score": 215.2040557861328}, {"text": "Summary The novel severe acute respiratory syndrome (SARS) coronavirus caused severe disease and heavy economic losses before apparently coming under complete control. Our understanding of the forces driving seasonal disappearance and recurrence of infectious diseases remains fragmentary, thus limiting any predictions about whether, or when, SARS will recur. It is true that most established respiratory pathogens of human beings recur in wintertime, but a new appreciation for the high burden of disease in tropical areas reinforces questions about explanations resting solely on cold air or low humidity. Seasonal variation in host physiology may also contribute. Newly emergent zoonotic diseases such as ebola or pandemic strains of influenza have recurred in unpredictable patterns. Most established coronaviruses exhibit winter seasonality, with a unique ability to establish persistent infections in a minority of infected animals. Because SARS coronavirus RNA can be detected in the stool of some individuals for at least 9 weeks, recurrence of SARS from persistently shedding human or animal reservoirs is biologically plausible.", "title": "Seasonality of infectious diseases and severe acute respiratory syndrome–what we don't know can hurt us", "pid": "ax87r0bj", "bm25_score": 215.20179748535156}, {"text": "", "title": "Comparative seasonalities of influenza A, B and 'common cold' coronaviruses - setting the scene for SARS-CoV-2 infections and possible unexpected host immune interactions", "pid": "kz0mas3w", "bm25_score": 215.2017822265625}, {"text": "A newly identified betacoronavirus, human coronavirus EMC (HCoV-EMC), has been isolated from several patients with respiratory and renal disease in the Middle East. While only a few infected patients have been identified, the mortality of the infection is greater than 50%. Like its better-known cousin severe acute respiratory syndrome coronavirus (SARS-CoV), HCoV-EMC appears to have originated from bats. In a recent article in mBio, Müller et al. described several important differences between the two viruses [M. A. Müller et al., mBio 3(6):e00515-12, 2012, doi:10.1128/mBio.00515-12]. Unlike SARS-CoV, HCoV-EMC can directly infect bat cells. As important, HCoV-EMC does not enter cells using the SARS-CoV receptor, human angiotensin-converting receptor-2 (hACE2). These results provide a strong incentive for identifying the host cell receptor used by HCoV-EMC. Identification of the receptor will provide insight into the pathogenesis of pulmonary and renal disease and may also suggest novel therapeutic interventions.", "title": "Human Coronavirus EMC Is Not the Same as Severe Acute Respiratory Syndrome Coronavirus", "pid": "nf28saj8", "bm25_score": 215.16455078125}, {"text": "Abstract Strains of human coronavirus (HCoV), namely HCoV-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1, primarily infect the upper respiratory and gastrointestinal tracts and are the most common cause of non-rhinovirus-induced common cold in humans. Although the manifestations of coronavirus infection (i.e., rhinorrhea, sneezing, cough, nasal obstruction, and bronchitis) are generally self-limiting in healthy adults, certain strains such as HCoV-NL63 and HCoV-HKU1 can cause severe lower respiratory tract infection and febrile seizure, especially in infants, people of advanced age, and immunocompromised hosts. In 2003, a novel HCoV strain was identified as the causative agent of the severe acute respiratory syndrome (SARS) epidemic that began in Asia in 2002. The strain has hence been referred to as SARS-CoV. In addition, as recently as September 2012, another novel HCoV, human betacoronavirus 2c EMC2012, was identified as being the cause of fever, renal failure, pneumonia, and severe respiratory distress in two patients in the Middle East. Phylogenetic analysis has revealed highly conserved sequences of ORF1ab, spike, nucleocapsid, and envelope protein genes, but not membrane protein genes, between human betacoronavirus 2c EMC2012 and SARS-CoV. This review focuses on the differences in the genomes of certain HCoV strains, the pathogenesis of said strains, and recent developments in the establishment of therapeutic agents that might aid in the treatment of patients with such infections.", "title": "Human coronaviruses: Clinical features and phylogenetic analysis", "pid": "0zeppske", "bm25_score": 215.15187072753906}, {"text": "1. Coronaviruses accounted for 1.6% (98/6272) of respiratory tract infections based on nasopharyngeal aspirate samples. 2. HCoV-OC43 was the most common coronavirus detected,followed by HCoV-NL63, CoVHKU1,and HCoV-229E. 3. Although CoV-HKU1 infections were most often associated with the upper respiratory tract, more severe illness (pneumonia,acute bronchiolitis, and asthmatic exacerbation) may occur, especially in those with underlying disease. In young children, CoV-HKU1 infection is associated with a high rate of febrile seizures (50%). 4. CoV-HKU1 and HCoV-OC43 infections peaked in winter, in contrast to HCoV-NL63, which mainly occurred in early summer and autumn, but was absent in winter. 5. Reverse transcriptase polymerase chain reaction is useful for the rapid diagnosis of coronavirus infections.", "title": "Epidemiology of coronavirus-associated respiratory tract infections and the role of rapid diagnostic tests: a prospective study.", "pid": "vbq2jyxp", "bm25_score": 215.1412353515625}, {"text": "Abstract Coronavirus infections have emerged as epidemic and pandemic threats in last two decades. After the H1N1 influenza pandemic in 2009, recently diagnosed novel betacoronavirus or severe acute respiratory syndrome coronavirus (SARS-CoV)-2 has spread across 203 countries and territories in all 5 major continents. World Health Organization (WHO) declared this as a public health emergency of international concern on January 30, 2020. Subsequently on February 11, 2020 a new name was given to this disease i.e. COVID-19 by an expert group from WHO. As of April 12, 2020, 10:00 CET, GMT+2:00, 1,696,588 confirmed cases and 105,952 confirmed deaths have been reported to the WHO. (Coronavirus disease 2019, situation report 83). It possibly originated from a small animal market in Wuhan, China. A cluster of patients were admitted with unusual pneumonia not responding to treatment in various hospitals. Epidemiological, genomic analysis and correlation with other coronaviruses led to the isolation of new coronavirus, closely resembling the bat coronaviruses, from such patients in Wuhan. They were identified as the SARS-CoV-2. This virus infection presents as influenza like illness in the affected people. Fever, cough, respiratory distress with fatigue, diarrhea, nausea and vomiting are common symptoms seen in adults. This may progress on to respiratory distress, hypoxia, need for oxygen supplementation and ventilator support as seen in patients in the SARS-CoV-1 epidemic (2003) in Guangdong, China. The transmissibility of SARS-CoV-1 was less as compared to SARS-CoV-2 infection, and it was well controlled with good public health efforts. The present COVID-19 epidemic is still in the acceleration phase of 3 and 4 in various countries. Without any effective antiviral agents available at present, the need of the hour is early case detection, isolation of cases, use of good preventive care measures by the household contacts and in the hospital set up. The results of ongoing clinical trials on hydroxychloroquine, azithromycin alone or in combination and a new antiviral agent remdesivir may help to treat some of the infections. A need for effective vaccine is being seen an as good preventive strategy in this pandemic. However the results of clinical trials and incorporation of vaccines in public health programs is a long way to go.", "title": "An overview of coronaviruses including the SARS-2 coronavirus – Molecular biology, epidemiology and clinical implications", "pid": "izltn367", "bm25_score": 215.13775634765625}, {"text": "The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "title": "Seasonality of Respiratory Viral Infections.", "pid": "1npav6m4", "bm25_score": 215.136962890625}, {"text": "BACKGROUND We have described occurrence and clinical manifestations of human coronaviruses (HCoV) in hospitalized Norwegian children with respiratory tract infection (RTI) and compared them with a group of respiratory syncytial virus (RSV)-infected children. METHODS AND POPULATION We used in-house TaqMan multiplex real-time polymerase chain reaction to test nasopharyngeal samples from 536 RTI episodes in 452 children who were admitted during the 2006-2007 winter. Twenty-one viruses, including HCoV-OC43, HCoV-NL63, HCoV-229E, HCoV-HKU1, and RSV were tested. The amount of viral nucleic acid was recorded semiquantitatively based on the cycle threshold value. RESULTS A total of 665 positive polymerase chain reaction tests were recorded in 536 nasopharyngeal specimens. Coronavirus was found in 68 (12.7%): HCoV-OC43, n = 44 (8.2%), and HCoV-NL63, n = 24 (4.5%). Only RSV and rhinovirus were detected more frequently. Neither HCoV-229E nor HCoV-HKU1 was detected. Among children with HCoV-OC43, 73.0% tested positive for at least one other virus, compared with 41.2% with HCoV-NL63 and 40.3% with RSV (P = 0.03 and P < 0.01, respectively). Children with HCoV-OC43 and HCoV-NL63 were older than children with RSV (median age, 19 vs. 10 months, P = 0.01). Lower respiratory tract infection (LRTI) was half as common in children with HCoV-OC43 (48.6%) and HCoV-NL63 (47.1%) as in children with RSV (82.3%) (both P < 0.01). After adjusting for age, chronic disease, LRTI, and co-detection of other viruses in a multiple logistic regression analysis, HCoV was associated with a shorter fever period and shorter hospitalization time than RSV. CONCLUSIONS HCoV-OC43 and HCoV-NL63 are common among hospitalized Norwegian children with RTI. Children with HCoV-OC43 and HCoV-NL63 have LRTI less frequently and may need a shorter hospital stay than children with RSV.", "title": "Coronavirus causes lower respiratory tract infections less frequently than RSV in hospitalized Norwegian children.", "pid": "gxxv6kmj", "bm25_score": 215.1357879638672}, {"text": "Human coronaviruses (HCoVs) cause mild to severe respiratory diseases. Six types of HCoVs have been discovered, the most recent one termed the Middle East respiratory syndrome coronavirus (MERS-CoV). The aim of this study is to monitor the circulation of HCoV types in the population during 2015–2016 in Israel. HCoVs were detected by real-time PCR analysis in 1910 respiratory samples, collected from influenza-like illness (ILI) patients during the winter sentinel influenza survey across Israel. Moreover, 195 HCoV-positive samples from hospitalized patients were detected during one year at Soroka University Medical Center. While no MERS-CoV infections were detected, 10.36% of patients in the survey were infected with HCoV-OC43 (43.43%), HCoV-NL63 (44.95%), and HCoV-229E (11.62%) viruses. The HCoVs were shown to co-circulate with respiratory syncytial virus (RSV) and to appear prior to influenza virus infections. HCoV clinical symptoms were more severe than those of RSV infections but milder than influenza symptoms. Hospitalized patients had similar HCoV types percentages. However, while it was absent from the public winter survey, 22.6% of the patients were HCoV-HKU1 positives, mainly during the spring-summer period.", "title": "Human Coronavirus Infections in Israel: Epidemiology, Clinical Symptoms and Summer Seasonality of HCoV-HKU1", "pid": "yg8qo13v", "bm25_score": 215.1277313232422}, {"text": "Abstract Human rhinovirus and influenza virus infections of the upper airway lead to colds and the flu and can trigger exacerbations of lower airway diseases including asthma and chronic obstructive pulmonary disease. Novel diagnostic and therapeutic targets are still needed to differentiate between the cold and the flu, since the clinical course of influenza can be severe while that of rhinovirus is usually more mild. In our investigation of influenza and rhinovirus infection of human respiratory epithelial cells, we used a systems approach to identify the temporally changing patterns of host gene expression from these viruses. After infection of human bronchial epithelial cells (BEAS-2B) with rhinovirus, influenza virus or co-infection with both viruses, we studied the time-course of host gene expression changes over three days. We modeled host responses to these viral infections with time and documented the qualitative and quantitative differences in innate immune activation and regulation.", "title": "A systems approach to understanding human rhinovirus and influenza virus infection", "pid": "x0dxxzqw", "bm25_score": 215.10475158691406}, {"text": "Coronaviruses (CoVs) belong to the family of Coronaviridae, the order Nidovirales, and the genus Coronavirus. They are the largest group of viruses causing respiratory and gastrointestinal infections. Morphologically, CoVs are enveloped viruses containing a non-segmented positive-sense, single-stranded ribonucleic acid (RNA) viruses. CoVs are categorized into four important genera that include Alphacoronavirus, Betacoronavirus, Gammacoronavirus, and Deltacoronavirus. A novel member of human CoV that has recently emerged in Wuhan, China, is now formally named as SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2). This is a unique strain of RNA viruses that have not been previously observed in humans. The virus has wide host adaptability and is capable of causing severe diseases in humans, masked palm civets, mice, dogs, cats, camels, pigs, chickens, and bats. The SARS-CoV-2 typically causes respiratory and gastrointestinal sickness in both humans and animals. It can be transmitted through aerosols and direct/indirect contact, as well as during medical cases and laboratory sample handling. Specific structural proteins, which might be found on the surface of the virus, play an important role in the pathogenesis and development of the complications. The disease is characterized by distinct medical signs and symptoms that include high fever, chills, cough, and shortness of breath or difficulty in breathing. The infected people may also present with other symptoms such as diarrhea, myalgia, fatigue, expectoration, and hemoptysis. It is important from the public health and economic point of view as it affects the growth of the country, which is majorly attributed to the restriction in the movement of the people and the cost associated with the control and prevention of the disease. Since there is no specific therapeutic intervention nor a vaccine available against the virus, supportive management and treatment with non-specific therapeutic agents (repurposed drugs) may provide relief to the patients. Some preventive strategies of the disease include blocking the routes of transmission of the infections, disinfection of instruments used during medical case handling, using personal protective equipment, proper and early diagnosis of the disease, avoiding contact with the sick patients, and quarantine of the infected/exposed people.", "title": "Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2): An Update", "pid": "oq16de67", "bm25_score": 215.08831787109375}, {"text": "It: Two Coronaviruses, HCoV-229E and HCoV-OC43, causing generally mild respiratory tract infections in humans, were described in the XX c Pandemic Coronaviruses were first discovered as late as in the XXI c : SARS-HCoV in 2002 – causing severe respiratory tract infections (SARS) in China;MERS-HCoV in 2012 – circulating mostly on the Arabian Peninsula The SARS epidemic ended in 2004 resulting in morbidity of &gt;8000 and &gt;770 deaths, while the MERS epidemic is still ongoing (&gt;2000 ill, &gt;700 deaths) although its intensity decreased Both viruses are zoonotic and require at least two “host jumps” for the transmission of the infection to humans: for HCoV-SARS – from bat to palm civet and then to human;for HCoV-MERS – from bats to camels and subsequently to humans Primary mode of transmission is droplet in close contact (&lt;1 m), but both viruses remain active in aerosol (up to 24 h), so infection can be also spread by air (ventilation) The ability for human-to-human transmission is higher for HCoV-SARS than for HCoV-MERS (8 generations vs 4, respectively) Moreover, there are differences in genome structure and pathogenic mechanisms: different receptor, cell entry mechanism, different way of host response modulation (e g inhibition of IFNβ cascade), etc Probably, these differences influence the overall manifestation of the disease in humans Infection caused by HCoV-MERS might manifest itself as ARDS, a mild-mannered and asymptomatic disease HCoV-SARS infections seem to be associated with severe disease only In this paper, a comparison of the structure of these viruses, the mechanisms underlying their ability to cross the interspecies barrier and to multiply in the human body, including modulation of IFNβ cascade, as well as routes of infection transmission and symptoms caused, were presented", "title": "Pandemic Human Coronavirus – Characterization and Comparison of Selected Properties of Hcov-sars and Hcov-mers", "pid": "9eso10is", "bm25_score": 215.05853271484375}, {"text": "The seasonal cycle of respiratory viral diseases has been widely recognized for thousands of years, as annual epidemics of the common cold and influenza disease hit the human population like clockwork in the winter season in temperate regions. Moreover, epidemics caused by viruses such as severe acute respiratory syndrome coronavirus (SARS-CoV) and the newly emerging SARS-CoV-2 occur during the winter months. The mechanisms underlying the seasonal nature of respiratory viral infections have been examined and debated for many years. The two major contributing factors are the changes in environmental parameters and human behavior. Studies have revealed the effect of temperature and humidity on respiratory virus stability and transmission rates. More recent research highlights the importance of the environmental factors, especially temperature and humidity, in modulating host intrinsic, innate, and adaptive immune responses to viral infections in the respiratory tract. Here we review evidence of how outdoor and indoor climates are linked to the seasonality of viral respiratory infections. We further discuss determinants of host response in the seasonality of respiratory viruses by highlighting recent studies in the field. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "title": "Seasonality of Respiratory Viral Infections", "pid": "5dfg0f5d", "bm25_score": 215.04833984375}, {"text": "Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats(1–4). Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans(5–7). Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.", "title": "A pneumonia outbreak associated with a new coronavirus of probable bat origin", "pid": "o877uul1", "bm25_score": 215.0004425048828}, {"text": "Since the SARS outbreak 18 years ago, a large number of severe acute respiratory syndrome related coronaviruses (SARSr-CoV) have been discovered in their natural reservoir host, bats1-4. Previous studies indicated that some of those bat SARSr-CoVs have the potential to infect humans5-7. Here we report the identification and characterization of a novel coronavirus (nCoV-2019) which caused an epidemic of acute respiratory syndrome in humans, in Wuhan, China. The epidemic, started from December 12th, 2019, has caused 198 laboratory confirmed infections with three fatal cases by January 20th, 2020. Full-length genome sequences were obtained from five patients at the early stage of the outbreak. They are almost identical to each other and share 79.5% sequence identify to SARS-CoV. Furthermore, it was found that nCoV-2019 is 96% identical at the whole genome level to a bat coronavirus. The pairwise protein sequence analysis of seven conserved non-structural proteins show that this virus belongs to the species of SARSr-CoV. The nCoV-2019 virus was then isolated from the bronchoalveolar lavage fluid of a critically ill patient, which can be neutralized by sera from several patients. Importantly, we have confirmed that this novel CoV uses the same cell entry receptor, ACE2, as SARS-CoV.", "title": "Discovery of a novel coronavirus associated with the recent pneumonia outbreak in humans and its potential bat origin", "pid": "o47v5vgw", "bm25_score": 214.99623107910156}, {"text": "Human coronaviruses (HCoV) OC43, 229E, NL63, and HKU1 are common respiratory viruses which cause various respiratory diseases, including pneumonia. There is a paucity of evidence on the epidemiology and clinical manifestations of these four HCoV strains worldwide. We collected 11,399 throat swabs from hospitalized children with acute respiratory tract infection from July 2009 to June 2016 in Guangzhou, China. These were tested for four strains of HCoV infection using real-time polymerase chain reaction (PCR). HCoV-positive patients were then tested for 11 other respiratory pathogens. 4.3% (489/11399) of patients were positive for HCoV, of which 3.0% were positive for OC43 (346/11399), 0.6% for 229E (65/11399), 0.5% for NL63 (60/11399), and 0.3% for HKU1 (38/11399). Patients aged 7–12 months had the highest prevalence of HCoV and OC43 when compared with other age groups (p < 0.001). The peak seasons of infection varied depending on the HCoV strain. Patients infected with a single strain of HCoV infection were less likely to present fever (≥ 38 °C) (p = 0.014) and more likely to present pulmonary rales (p = 0.043) than those co-infected with more than one HCoV strain or other respiratory pathogens. There were also significant differences in the prevalence of certain symptoms, including coughing (p = 0.032), pneumonia (p = 0.026), and abnormal pulmonary rales (p = 0.002) according to the strain of HCoV detected. This retrospective study of the prevalence of four HCoV strains and clinical signs among a large population of pediatric patients in a subtropical region of China provides further insight into the epidemiology and clinical features of HCoV.", "title": "Epidemiology and clinical characteristics of human coronaviruses OC43, 229E, NL63, and HKU1: a study of hospitalized children with acute respiratory tract infection in Guangzhou, China", "pid": "9erqp86r", "bm25_score": 214.995361328125}, {"text": "BACKGROUND Multiplex molecular assays now make it possible for clinical laboratories to detect human coronaviruses (HCoVs). We investigated the clinical characteristics of HCoV-OC43 and HCoV-NL63 in patients <5 years of age during a recent coronavirus season. METHODS Respiratory viruses were detected using a multiplex molecular assay at St. Louis Children`s Hospital starting in November 2012. We analyzed demographic and clinical data from all patients <5 years of age with solo detection of HCoV-OC43 (n = 52) and HCoV-NL63 (n = 44) and for comparison, samples of children with respiratory syncytial virus, parainfluenza virus and picornaviruses. RESULTS During the study period, HCoV-OC43 (4%) was the 5th and HCoV-NL63 the 8th (2%) most common respiratory virus. Coinfections were detected in 35% and 38% of children with HCoV-OC43 and HCoV-NL63, respectively. Croup was more common with HCoV-NL63 (30%) than with HCoV-OC43 (2%). Lower respiratory tract infection occurred in 33% of children with HCoV-OC43 and 25% of children with HCoV-NL63. Severe illness was less common in HCoV-NL63, HCoV-OC43 and parainfluenza virus (14%, each) compared with respiratory syncytial virus (30%) and picornaviruses (26%; P = 0.055 for HCoVs combined compared with the other respiratory viruses) and occurred mainly in those with underlying medical conditions. CONCLUSIONS Infections caused by HCoV-OC43 and HCoV-NL63 are common and include some with lower respiratory tract involvement and severe disease, especially in children with underlying medical conditions. Overall, a substantial burden of disease associated with both HCoV-OC43 and HCoV-NL63 was observed for hospitalized children <5 years of age.", "title": "Characterization of human coronavirus OC43 and human coronavirus NL63 infections among hospitalized children <5 years of age.", "pid": "01x3z3fn", "bm25_score": 214.96029663085938}, {"text": "The pandemic potential of the novel coronavirus (nCoV) that emerged in Wuhan, China, during December 2019 is strongly tied to the number and contagiousness of undocumented human infections. Here we present findings from a proactive longitudinal sampling study of acute viral respiratory infections that documents rates of asymptomatic infection and clinical care seeking for seasonal coronavirus. We find that the majority of infections are asymptomatic by most symptom definitions and that only 4% of individuals experiencing a seasonal coronavirus infection episode sought medical care for their symptoms. These numbers indicate that a very high percentage of seasonal coronavirus infections are undocumented and provide a reference for understanding the spread of the emergent nCoV.", "title": "Direct Measurement of Rates of Asymptomatic Infection and Clinical Care-Seeking for Seasonal Coronavirus", "pid": "90tccg03", "bm25_score": 214.9586944580078}, {"text": "Since December, 2019, an outbreak of pneumonia caused by the new coronavirus (2019-nCoV) has hit the city of Wuhan in the Hubei Province. With the continuous development of the epidemic, it has become a national public health crisis and calls for urgent antiviral treatments or vaccines. The spike protein on the coronavirus envelope is critical for host cell infection and virus vitality. Previous studies showed that 2019-nCoV is highly homologous to human SARS-CoV and attaches host cells though the binding of the spike receptor binding domain (RBD) domain to the angiotensin-converting enzyme II (ACE2). However, the molecular mechanisms of 2019-nCoV binding to human ACE2 and evolution of 2019-nCoV remain unclear. In this study, we have extensively studied the RBD-ACE2 complex, spike protein, and free RBD systems of 2019-nCoV and SARS-CoV using protein-protein docking and molecular dynamics (MD) simulations. It was shown that the RBD-ACE2 binding free energy for 2019-nCoV is significantly lower than that for SARS-CoV, which is consistent with the fact that 2019-nCoV is much more infectious than SARS-CoV. In addition, the spike protein of 2019-nCoV shows a significantly lower free energy than that of SARS-CoV, suggesting that 2019-nCoV is more stable and able to survive a higher temperature than SARS-CoV. This may also provide insights into the evolution of 2019-nCoV because SARS-like coronaviruses are thought to have originated in bats that are known to have a higher body-temperature than humans. It was also revealed that the RBD of 2019-nCoV is much more flexible especially near the binding site and thus will have a higher entropy penalty upon binding ACE2, compared to the RBD of SARS-CoV. That means that 2019-nCoV will be much more temperature-sensitive in terms of human infection than SARS-CoV. With the rising temperature, 2019-nCoV is expected to decrease its infection ability much faster than SARS-CoV, and get controlled more easily. The present findings are expected to be helpful for the disease prevention and control as well as drug and vaccine development of 2019-nCoV.", "title": "Molecular mechanism of evolution and human infection with the novel coronavirus (2019-nCoV)", "pid": "hicqy5sj", "bm25_score": 214.9576873779297}, {"text": "The human coronavirus (HCoV) contains HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV- HKU1, SARS-CoV and MERS-CoV. HCoV-229E, HCoV-NL63, HCoV-OC43 and HCoV-HKU1 are pathogens of common cold. During 2002-2003, a new coronavirus, the SARS-CoV, was found to be the cause of an acute, severe frequently fatal respiratory disease with prominent systemic symptoms (severe acute respiratory syndrome). The outbreak originated in south- ern China, probably following transmission from an animal in animal markets or bats to hu- mans. In 2012, some cases of novel coronavirus infection were reported in Arabian Peninsula with pneumonia and acute kidney injury. This novel coronavirus has been named Middle East respiratory syndrome coronavirus (MERS-CoV). The virus probably has come from camels and bats. I describe here about coronaviruses that have wide disease spectrum.from common colds to severe fatal illness as emerging infectious diseases.", "title": "SARS, MERS and coronavirus infections.", "pid": "66hhozo2", "bm25_score": 214.94161987304688}, {"text": "Severe acute respiratory syndrome (SARS) is caused by the SARS-associated coronavirus (SARS-CoV), which uses angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entry. A group of SARS-like CoVs (SL-CoVs) has been identified in horseshoe bats. SL-CoVs and SARS-CoVs share identical genome organizations and high sequence identities, with the main exception of the N terminus of the spike protein (S), known to be responsible for receptor binding in CoVs. In this study, we investigated the receptor usage of the SL-CoV S by combining a human immunodeficiency virus-based pseudovirus system with cell lines expressing the ACE2 molecules of human, civet, or horseshoe bat. In addition to full-length S of SL-CoV and SARS-CoV, a series of S chimeras was constructed by inserting different sequences of the SARS-CoV S into the SL-CoV S backbone. Several important observations were made from this study. First, the SL-CoV S was unable to use any of the three ACE2 molecules as its receptor. Second, the SARS-CoV S failed to enter cells expressing the bat ACE2. Third, the chimeric S covering the previously defined receptor-binding domain gained its ability to enter cells via human ACE2, albeit with different efficiencies for different constructs. Fourth, a minimal insert region (amino acids 310 to 518) was found to be sufficient to convert the SL-CoV S from non-ACE2 binding to human ACE2 binding, indicating that the SL-CoV S is largely compatible with SARS-CoV S protein both in structure and in function. The significance of these findings in relation to virus origin, virus recombination, and host switching is discussed.", "title": "Difference in receptor usage between severe acute respiratory syndrome (SARS) coronavirus and SARS-like coronavirus of bat origin.", "pid": "zdlbsuys", "bm25_score": 214.92669677734375}, {"text": "were identified beginning with the discovery of SARS-CoV in 2002. With the recent detection of SARS-CoV-2, there are now seven human coronaviruses. Those that cause mild diseases are the 229E, OC43, NL63 and HKU1, and the pathogenic species are SARS-CoV, MERS-CoV and SARS-CoV-2 Coronaviruses (order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae) are spherical (125nm diameter), and enveloped with club-shaped spikes on the surface giving the appearance of a solar corona. Within the helically symmetrical nucleocapsid is the large positive sense, single stranded RNA. Of the four coronavirus genera (&#945;,ß,γ,δ), human coronaviruses (HCoVs) are classified under &#945;-CoV (HCoV-229E and NL63) and ß-CoV (MERS-CoV, SARS-CoV, HCoVOC43 and HCoV-HKU1). SARS-CoV-2 is a ß-CoV and shows fairly close relatedness with two bat-derived CoV-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Even so, its genome is similar to that of the typical CoVs. SARS-CoV and MERS-CoV originated in bats, and it appears to be so for SARS-CoV-2 as well. The possibility of an intermediate host facilitating the emergence of the virus in humans has already been shown with civet cats acting as intermediate hosts for SARS-CoVs, and dromedary camels for MERS-CoV. Human-to-human transmission is primarily achieved through close contact of respiratory droplets, direct contact with the infected individuals, or by contact with contaminated objects and surfaces. The coronaviral genome contains four major structural proteins: the spike (S), membrane (M), envelope (E) and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. The S protein mediates attachment of the virus to the host cell surface receptors resulting in fusion and subsequent viral entry. The M protein is the most abundant protein and defines the shape of the viral envelope. The E protein is the smallest of the major structural proteins and participates in viral assembly and budding. The N protein is the only one that binds to the RNA genome and is also involved in viral assembly and budding. Replication of coronaviruses begin with attachment and entry. Attachment of the virus to the host cell is initiated by interactions between the S protein and its specific receptor. Following receptor binding, the virus enters host cell cytosol via cleavage of S protein by a protease enzyme, followed by fusion of the viral and cellular membranes. The next step is the translation of the replicase gene from the virion genomic RNA and then translation and assembly of the viral replicase complexes. Following replication and subgenomic RNA synthesis, encapsidation occurs resulting in the formation of the mature virus. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.", "title": "Properties of Coronavirus and SARS-CoV-2", "pid": "bm0ldeue", "bm25_score": 214.92514038085938}, {"text": "OBJECTIVE Human infections with zoonotic coronavirus contain emerging and reemerging pathogenic characteristics which have raised great public health concern. This study aimed at investigating the global prevalence, biological and clinical characteristics of novel coronavirus, Wuhan China (2019-nCoV), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection outbreaks. MATERIALS AND METHODS The data on the global outbreak of \"2019-nCoV, SARS-CoV, and MERS-CoV\" were obtained from World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), concerned ministries and research institutes. We also recorded the information from research documents published in global scientific journals indexed in ISI Web of Science and research centers on the prevalence, biological and clinical characteristics of 2019-nCoV, SARS-CoV, and MERS-CoV. RESULTS Worldwide, SARS-CoV involved 32 countries, with 8422 confirmed cases and 916 (10.87%) casualties from November 2002 to August 2003. MERS-CoV spread over 27 states, causing 2496 cases and 868 (34.77%) fatalities during the period April 2012 to December 2019. However, the novel coronavirus 2019-nCoV spread swiftly the global borders of 27 countries. It infected 34799 people and resulted in 724 (2.08%) casualties during the period December 29, 2019 to February 7, 2020. The fatality rate of coronavirus MERS-CoV was (34.77%) higher than SARS-CoV (10.87%) and 2019-nCoV (2.08%); however, the 2019-nCoV transmitted rapidly in comparison to SARS-CoV and MERS-CoV. CONCLUSIONS The novel coronavirus 2019-nCoV has diverse epidemiological and biological characteristics, making it more contagious than SARS-CoV and MERS-CoV. It has affected more people in a short time period compared to SARS-CoV and MERS-CoV, although the fatality rate of MERS-CoV was higher than SARS-CoV and 2019-nCoV. The major clinical manifestations in coronavirus infections 2019-nCoV, MERS-CoV, and SARS CoV are fever, chills, cough, shortness of breath, generalized myalgia, malaise, drowsy, diarrhea, confusion, dyspnea, and pneumonia. Global health authorities should take immediate measures to prevent the outbreaks of such emerging and reemerging pathogens across the globe to minimize the disease burden locally and globally.", "title": "Novel coronavirus 2019-nCoV: prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV.", "pid": "zppc6p20", "bm25_score": 214.9042205810547}, {"text": "", "title": "Seasonal Influenza Vaccination and the Heightened Risk of Coronavirus and Other Pandemic Virus Infections: Fact or Fiction?", "pid": "sslt85h9", "bm25_score": 214.90357971191406}, {"text": "Detailed genomic and structure-based analysis of a new coronavirus, namely 2019-nCoV, showed that the new virus is a new type of bat coronavirus and is genetically fairly distant from the human SARS coronavirus. Structure analysis of the spike (S) protein of this new virus showed that its S protein only binds weakly to the ACE2 receptor on human cells whereas the human SARS coronavirus exhibits strongly affinity to the ACE receptor. These findings suggest that the new virus does not readily transmit between humans and should theoretically not able to cause very serious human infection. These data are important to guide design of infection control policy and inform the public on the nature of threat imposed by 2019-nCov when results of direct laboratory tests on this virus are not expected to be available in the near future.", "title": "Genomic and protein structure modelling analysis depicts the origin and infectivity of 2019-nCoV, a new coronavirus which caused a pneumonia outbreak in Wuhan, China", "pid": "3qds5j1p", "bm25_score": 214.90158081054688}, {"text": "The positive-strand RNA viruses, severe acute respiratory syndrome coronavirus (SARS-CoV) and recently emerged COVID-19 epidemics, demonstrated the transmission capability of the coronaviruses by crossing the species barrier and emergence in humans. The source of coronavirus disease 2019 (COVID-19) is severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), firstly reported in December 2019 at Wuhan, China. COVID-19 is a kind of viral pneumonia. The outbreak of SARS-CoV-2 (COVID-19) has been reported as the introduction of the third highly pathogenic coronavirus which crossed the species barrier and spread into the human population. Severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) were the first two epidemic viruses, respectively, in the twenty-first century. Introduction of the 2019 novel coronaviruses (2019-nCoV) in human population is a worldwide concern, and this might have generated via RNA recombination among the previous reported coronaviruses. The COVID-19 is spreading in an alarming rate, and till date no vaccine or specific medicines are available in the market. The newly emerged coronavirus COVID-19 is strongly related to SARS-CoV except little dissimilarity. In this chapter, we will discuss about the alterations and variations in antigenicity, structural changes, and RNA recombination which might be responsible for the COVID-19 emergence.", "title": "Emergence and Reemergence of Severe Acute Respiratory Syndrome (SARS) Coronaviruses", "pid": "jqexwnq2", "bm25_score": 214.8960723876953}, {"text": "HCoV-NL63 and HCoV-229E are two of the four human coronaviruses that circulate worldwide. These two viruses are unique in their relationship towards each other. Phylogenetically, the viruses are more closely related to each other than to any other human coronavirus, yet they only share 65% sequence identity. Moreover, the viruses use different receptors to enter their target cell. HCoV-NL63 is associated with croup in children, whereas all signs suggest that the virus probably causes the common cold in healthy adults. HCoV-229E is a proven common cold virus in healthy adults, so it is probable that both viruses induce comparable symptoms in adults, even though their mode of infection differs. Here, we present an overview of the current knowledge on both human coronaviruses, focusing on similarities and differences.", "title": "Human Coronaviruses 229E and NL63: Close Yet Still So Far", "pid": "3zq8l5z0", "bm25_score": 214.8948211669922}, {"text": "Background. Human coronavirus NL63 (HCoV-NL63) is a recently discovered human coronavirus found to cause respiratory illness in children and adults that is distinct from the severe acute respiratory syndrome (SARS) coronavirus and human coronaviruses 229E (HCoV-229E) and OC43 (HCoV-OC43). Methods. We investigated the role that HCoV-NL63, HCoV-OC43, and HCoV-229E played in children hospitalized with fever and acute respiratory symptoms in Hong Kong during the period from August 2001 through August 2002. Results. Coronavirus infections were detected in 26 (4.4%) of 587 children studied; 15 (2.6%) were positive for HCoV-NL63, 9 (1.5%) were positive for HCoV-OC43, and 2 (0.3%) were positive for HCoV-229E. In addition to causing upper respiratory disease, we found that HCoV-NL63 can present as croup, asthma exacerbation, febrile seizures, and high fever. The mean age (± standard deviation [SD]) of the infected children was 30.7 ± 19.8 months (range, 6–57 months). The mean maximum temperature (±SD) for the 12 children who were febrile was 39.3°C ± 0.9°C, and the mean total duration of fever (±SD) for all children was 2.6 ± 1.2 days (range, 1–5 days). HCoV-NL63 infections were noted in the spring and summer months of 2002, whereas HCoV-OC43 infection mainly occurred in the fall and winter months of 2001. HCoV-NL63 viruses appeared to cluster into 2 evolutionary lineages, and viruses from both lineages cocirculated in the same season. Conclusions. HCoV-NL63 is a significant pathogen that contributes to the hospitalization of children, and it was estimated to have caused 224 hospital admissions per 100,000 population aged ⩽6 years each year in Hong Kong.", "title": "Human Coronavirus NL63 Infection and Other Coronavirus Infections in Children Hospitalized with Acute Respiratory Disease in Hong Kong, China", "pid": "62qe4fb0", "bm25_score": 214.890380859375}, {"text": "Coronaviruses (CoVs) are positive-strand RNA viruses with the largest genome among all RNA viruses. They are able to infect many host, such as mammals or birds. Whereas CoVs were identified 1930s, they became known again in 2003 as the agents of the Severe Acute Respiratory Syndrome (SARS). The spike protein is thought to be essential in the process of CoVs entry, because it is associated with the binding to the receptor on the host cell. It is also involved in cell tropism and pathogenesis. Receptor recognition is the crucial step in the infection. CoVs are able to bind a variety of receptors, although the selection of receptor remains unclear. Coronaviruses were initially believed to enter cells by fusion with the plasma membrane. Further studies demonstrated that many of them involve endocytosis through clathrin-dependent, caveolae-dependent, clathrin-independent, as well as caveolae-independent mechanisms. The aim of this review is to summarise current knowledge about coronaviruses, focussing especially on CoVs entry into the host cell. Advances in understanding coronaviruses replication strategy and the functioning of the replicative structures are also highlighted. The development of host-directed antiviral therapy seems to be a promising way to treat infections with SARS-CoV or other pathogenic coronaviruses. There is still much to be discovered in the inventory of pro- and anti-viral host factors relevant for CoVs replication. The latest pandemic danger, originating from China, has given our previously prepared work even more of topicality.", "title": "Coronaviruses fusion with the membrane and entry to the host cell.", "pid": "16ofs0pu", "bm25_score": 214.87753295898438}, {"text": "After the outbreak of the middle east respiratory syndrome (MERS) worldwide in 2012. Currently, a novel human coronavirus has caused a major disease outbreak, and named corona virus disease 2019 (COVID-19). The emergency of MRES-COV and COVID-19 has caused global panic and threatened health security. Unfortunately, the similarities and differences between the two coronavirus diseases remain to be unknown. The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. We searched PubMed, EMBASE and Cochrane Register of Controlled Trials database to identify potential studies reported COVID-19 or MERS-COV. Epidemiological, clinical and laboratory outcomes, the admission rate of intensive cure unit (ICU), discharge rate and fatality rate were evaluated using GraphPad Prism software. Thirty-two studies involving 3770 patients (COVID-19 = 1062, MERS-COV = 2708) were included in this study. The present study revealed that compared with COVID-19 population, MERS-COV population had a higher rate of ICU admission, discharge and fatality and longer incubation time. It pointed out that fever, cough and generalised weakness and myalgia were main clinical manifestations of both COVID-19 and MERS-COV, whereas ARDS was main complication. The most effective drug for MERS-COV is ribavirin and interferon.", "title": "Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus.", "pid": "2u6ki9dv", "bm25_score": 214.87631225585938}, {"text": "OBJECTIVE: Human infections with zoonotic coronavirus contain emerging and reemerging pathogenic characteristics which have raised great public health concern. This study aimed at investigating the global prevalence, biological and clinical characteristics of novel coronavirus, Wuhan China (2019-nCoV), Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection outbreaks. MATERIALS AND METHODS: The data on the global outbreak of \"2019-nCoV, SARS-CoV, and MERS-CoV\" were obtained from World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), concerned ministries and research institutes. We also recorded the information from research documents published in global scientific journals indexed in ISI Web of Science and research centers on the prevalence, biological and clinical characteristics of 2019-nCoV, SARS-CoV, and MERS-CoV. RESULTS: Worldwide, SARS-CoV involved 32 countries, with 8422 confirmed cases and 916 (10.87%) casualties from November 2002 to August 2003. MERS-CoV spread over 27 states, causing 2496 cases and 868 (34.77%) fatalities during the period April 2012 to December 2019. However, the novel coronavirus 2019-nCoV spread swiftly the global borders of 27 countries. It infected 34799 people and resulted in 724 (2.08%) casualties during the period December 29, 2019 to February 7, 2020. The fatality rate of coronavirus MERS-CoV was (34.77%) higher than SARS-CoV (10.87%) and 2019-nCoV (2.08%); however, the 2019-nCoV transmitted rapidly in comparison to SARS-CoV and MERS-CoV. CONCLUSIONS: The novel coronavirus 2019-nCoV has diverse epidemiological and biological characteristics, making it more contagious than SARS-CoV and MERS-CoV. It has affected more people in a short time period compared to SARS-CoV and MERS-CoV, although the fatality rate of MERS-CoV was higher than SARS-CoV and 2019-nCoV. The major clinical manifestations in coronavirus infections 2019-nCoV, MERS-CoV, and SARS CoV are fever, chills, cough, shortness of breath, generalized myalgia, malaise, drowsy, diarrhea, confusion, dyspnea, and pneumonia. Global health authorities should take immediate measures to prevent the outbreaks of such emerging and reemerging pathogens across the globe to minimize the disease burden locally and globally.", "title": "Novel coronavirus 2019-nCoV: prevalence, biological and clinical characteristics comparison with SARS-CoV and MERS-CoV", "pid": "ovmso3qu", "bm25_score": 214.86570739746094}, {"text": "PURPOSE: To compare the frequency and the severity of influenza and respiratory syncytial viruses (RSV) infections among children < 24 months hospitalized with respiratory symptoms. METHODS: Data from a prospective study conducted during the peak of five influenza seasons in the Province of Quebec, Canada were used. RESULTS: We detected higher frequency of RSV compared to influenza viruses (55.3% vs. 16.3%). Radiologically confirmed pneumonia was significantly more frequent in children with RSV (39%) than those with influenza (18%) and the clinical course was more severe in RSV than influenza-infected children, especially among infants < 3 months. CONCLUSION: Even during peak weeks of influenza season, we found a higher burden and severity of RSV compared with influenza virus disease in hospitalized children < 24 months.", "title": "Respiratory syncytial virus contributes to more severe respiratory morbidity than influenza in children < 2 years during seasonal influenza peaks", "pid": "lpxmmbpy", "bm25_score": 214.848388671875}, {"text": "Emerging of infectious diseases such as severe acute respiratory syndrome (SARS) which is a present major menace to public health, although intense research efforts, how, when, and where new diseases are appearing which still a source of considerable uncertainty is A serious respiratory disease was recently reported in Wuhan, Hubei province, china At least 1,975cases had been reported till 25 January 2020, since the patient was hospitalized on 12 December 2019 Epidemiology research has suggested that the beginning of the virus was associated with seafood contact in Wuhan Here we considered a single patient who was one of the workers in the market and was admitted to Central Hospital of Wuhan on 26 December of 2019 He was experiencing severe respiratory syndrome which is included with dizziness and cough After analysis, it was identified as a new RNA virus strain, from the family Coronaviridae, which is generally designated as WH-Human 1’ Corona virus is also referred to 2019 –nCoV The phylogenetic analysis started that this virus was mostly closely selected to a group of SARS and MERS like corona virus these are previously been found in bats in China", "title": "Corona virus-An upadated review", "pid": "03eod3df", "bm25_score": 214.8466339111328}, {"text": "The novel coronavirus pneumonia (NCP) continues to spread throughout the country, and the prevention and control of the epidemic has entered a critical period. However, southern cities with severe outbreaks are about to enter the seasonal influenza season. We should strengthen the epidemiological investigation, optimize the laboratory testing strategy, take effective measures, strengthen the prevention and control of influenza epidemic, and minimize the interference to the new coronavirus epidemic.", "title": "[Be alert to superposed effect of seasonal influenza while fighting against novel coronavirus pneumonia].", "pid": "4d979wj4", "bm25_score": 214.84446716308594}, {"text": "Lower respiratory tract symptoms during seasonal coronavirus infections in children are associated with RSV co-detection and increased levels of Haemophilus and Fusobacterium species.", "title": "Symptomatology during seasonal coronavirus infections in children is associated with viral and bacterial co-detection", "pid": "9objjgsj", "bm25_score": 214.8444366455078}, {"text": "SUMMARYIn recent decades, several new diseases have emerged in different geographical areas, with pathogens including Ebola virus, Zika virus, Nipah virus, and coronaviruses (CoVs). Recently, a new type of viral infection emerged in Wuhan City, China, and initial genomic sequencing data of this virus do not match with previously sequenced CoVs, suggesting a novel CoV strain (2019-nCoV), which has now been termed severe acute respiratory syndrome CoV-2 (SARS-CoV-2). Although coronavirus disease 2019 (COVID-19) is suspected to originate from an animal host (zoonotic origin) followed by human-to-human transmission, the possibility of other routes should not be ruled out. Compared to diseases caused by previously known human CoVs, COVID-19 shows less severe pathogenesis but higher transmission competence, as is evident from the continuously increasing number of confirmed cases globally. Compared to other emerging viruses, such as Ebola virus, avian H7N9, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has shown relatively low pathogenicity and moderate transmissibility. Codon usage studies suggest that this novel virus has been transferred from an animal source, such as bats. Early diagnosis by real-time PCR and next-generation sequencing has facilitated the identification of the pathogen at an early stage. Since no antiviral drug or vaccine exists to treat or prevent SARS-CoV-2, potential therapeutic strategies that are currently being evaluated predominantly stem from previous experience with treating SARS-CoV, MERS-CoV, and other emerging viral diseases. In this review, we address epidemiological, diagnostic, clinical, and therapeutic aspects, including perspectives of vaccines and preventive measures that have already been globally recommended to counter this pandemic virus.", "title": "Coronavirus Disease 2019-COVID-19.", "pid": "v861kk0i", "bm25_score": 214.827880859375}, {"text": "Coronavirus is a large family of viruses that infect mammals and birds. Coronaviruses are known to cross barrier species and infect new ones. In the past twenty years, we witnessed the emergence of three different coronaviruses, the latest one being the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for the COVID-19 (covid disease 19) pandemic. Coronaviruses are enveloped virus with a long positive sense RNA genome. Like all viruses, they hijack the cellular machinery to replicate and produce new virions. There is no approved vaccine or specific antiviral molecule against coronaviruses but with the urgency to treat COVID-19, several candidate therapies are currently investigated.", "title": "[Coronavirus, emerging viruses].", "pid": "xkzvzonj", "bm25_score": 214.82688903808594}, {"text": "Those downplaying the coronavirus ignore our lack of immunity and vaccines", "title": "This really is nothing like flu", "pid": "t9u7d029", "bm25_score": 214.82467651367188}, {"text": "Human coronaviruses (HCoVs) are responsible for respiratory tract infections ranging from common colds to severe acute respiratory syndrome. HCoV-NL63 and HCoV-229E are two of the four HCoVs that circulate worldwide and are close phylogenetic relatives. HCoV infections can lead to hospitalization of children, elderly individuals, and immunocompromised patients. Globally, approximately 5% of all upper and lower respiratory tract infections in hospitalized children are caused by HCoV-229E and HCoV-NL63. The latter virus has recently been associated with the childhood disease croup. Thus, differentiation between the two viruses is relevant for epidemiology studies. The aim of this study was to develop a double-antibody sandwich enzyme-linked immunosorbent assay (DAS-ELISA) as a potential tool for identification and differentiation between HCoV-NL63 and HCoV-229E. The nucleocapsid (N) proteins of HCoV-NL63 and HCoV-229E were expressed in an Escherichia coli system and used to immunize mice in order to obtain monoclonal antibodies (MAbs) specific for each virus. Three specific MAbs to HCoV-NL63, one MAb specific to HCoV-229E, and four MAbs that recognized both viruses were obtained. After their characterization, three MAbs were selected in order to develop a differential DAS-ELISA. The described assay could detect up to 3 ng/ml of N protein and 50 50% tissue culture infective doses/ml of virus stock. No cross-reactivity with other human coronaviruses or closely related animal coronaviruses was found. The newly developed DAS-ELISA was species specific, and therefore, it could be considered a potential tool for detection and differentiation of HCoV-NL63 and HCoV-229E infections.", "title": "Differentiation between human coronaviruses NL63 and 229E using a novel double-antibody sandwich enzyme-linked immunosorbent assay based on specific monoclonal antibodies.", "pid": "xia53pf6", "bm25_score": 214.80136108398438}, {"text": "Coronaviruses (CoVs) are a large family of enveloped, positive-strand RNA viruses Four human CoVs (HCoVs), the non-severe acute respiratory syndrome (SARS)-like HCoVs (namely HCoV 229E, NL63, OC43, and HKU1), are globally endemic and account for a substantial fraction of upper respiratory tract infections Non-SARS-like CoV can occasionally produce severe diseases in frail subjects but do not cause any major (fatal) epidemics In contrast, SARS like CoVs (namely SARS-CoV and Middle-East respiratory syndrome coronavirus, MERS-CoV) can cause intense short-lived fatal outbreaks The current epidemic caused by the highly contagious SARS-CoV-2 and its rapid spread globally is of major concern There is scanty knowledge on the actual pandemic potential of this new SARS-like virus It might be speculated that SARS-CoV-2 epidemic is grossly underdiagnosed and that the infection is silently spreading across the globe with two consequences: (i) clusters of severe infections among frail subjects could haphazardly occur linked to unrecognized index cases;(ii) the current epidemic could naturally fall into a low-level endemic phase when a significant number of subjects will have developed immunity Understanding the role of paucisymptomatic subjects and stratifying patients according to the risk of developing severe clinical presentations is pivotal for implementing reasonable measures to contain the infection and to reduce its mortality Whilst the future evolution of this epidemic remains unpredictable, classic public health strategies must follow rational patterns The emergence of yet another global epidemic underscores the permanent challenges that infectious diseases pose and underscores the need for global cooperation and preparedness, even during inter-epidemic periods", "title": "Coronavirus infections: Epidemiological, clinical and immunological features and hypotheses", "pid": "syt4r964", "bm25_score": 214.7836456298828}, {"text": "BACKGROUND: The prevalence, symptom course, and shedding in persons infected with the 4 most common human coronaviruses (HCoV)‐229E, HKU1, NL63, and OC43 are poorly described. OBJECTIVES: We estimate their prevalence and associated symptoms among college students identified via a social network study design. PATIENTS/METHODS: We collected 1‐3 samples (n = 250 specimens) from 176 participants between October 2012 and January 17, 2013: participants with acute respiratory infection (ARI; cough and body aches or chills or fever/feverishness) and their social contacts. Virus was detected using RT‐PCR. RESULTS: 30.4% (76/250) of specimens tested positive for any virus tested, and 4.8% (12/250) were positive for 2 or more viruses. Human coronaviruses (HCoVs [22.0%; 55/250]), rhinovirus (7.6%; 19/250), and influenza A (6.4%; 16/250) were most prevalent. Symptoms changed significantly over time among ARI participants with HCoV: the prevalence of cough and chills decreased over 6 days (P = .04, and P = .01, respectively), while runny nose increased over the same period (P = .02). HCoV‐NL63 was the most frequent virus detected 6 days following symptom onset (8.9%), followed by rhinovirus (6.7%). CONCLUSIONS: During a 3‐month period covering a single season, HCoVs were common, even among social contacts without respiratory symptoms; specific symptoms may change over the course of HCoV‐associated illness and were similar to symptoms from influenza and rhinovirus.", "title": "Human coronaviruses and other respiratory infections in young adults on a university campus: Prevalence, symptoms, and shedding", "pid": "t33cp9li", "bm25_score": 214.77957153320312}, {"text": "Coronavirus (CoV) infection of humans is usually not associated with severe disease. However, discovery of the severe acute respiratory syndrome (SARS) CoV revealed that highly pathogenic human CoVs (HCoVs) can evolve. The identification and characterization of new HCoVs is, therefore, an important task. Recently, a HCoV termed NL63 was discovered in patients with respiratory tract illness. Here, cell tropism and receptor usage of HCoV-NL63 were analyzed. The NL63 spike (S) protein mediated infection of different target cells compared with the closely related 229E-S protein but facilitated entry into cells known to be permissive to SARS-CoV-S-driven infection. An analysis of receptor engagement revealed that NL63-S binds angiotensin-converting enzyme (ACE) 2, the receptor for SARS-CoV, and HCoV-NL63 uses ACE2 as a receptor for infection of target cells. Potent neutralizing activity directed against NL63- but not 229E-S protein was detected in virtually all sera from patients 8 years of age or older, suggesting that HCoV-NL63 infection of humans is common and usually acquired during childhood. Here, we show that SARS-CoV shares its receptor ACE2 with HCoV-NL63. Because the two viruses differ dramatically in their ability to induce disease, analysis of HCoV-NL63 might unravel pathogenicity factors in SARS-CoV. The frequent HCoV-NL63 infection of humans suggests that highly pathogenic variants have ample opportunity to evolve, underlining the need for vaccines against HCoVs.", "title": "Human coronavirus NL63 employs the severe acute respiratory syndrome coronavirus receptor for cellular entry.", "pid": "esg72lpv", "bm25_score": 214.77207946777344}, {"text": "Recently, Coronavirus has been given considerable attention from the biomedical community based on the emergence and isolation of a deadly coronavirus infecting human. To understand the behavior of the newly emerging MERS-CoV requires knowledge at different levels (epidemiologic, antigenic, and pathogenic), and this knowledge can be generated from the most related viruses. In this study, we aimed to compare between 3 species of Coronavirus, namely Middle East Respiratory Syndrome (MERS-CoV), Severe Acute Respiratory Syndrome (SARS-CoV), and NeoCoV regarding whole genomes and 6 similar proteins (E, M, N, S, ORF1a, and ORF1ab) using different bioinformatics tools to provide a better understanding of the relationship between the 3 viruses at the nucleotide and amino acids levels. All sequences have been retrieved from National Center for Biotechnology Information (NCBI). Regards to target genomes’ phylogenetic analysis showed that MERS and SARS-CoVs were closer to each other compared with NeoCoV, and the last has the longest relative time. We found that all phylogenetic methods in addition to all parameters (physical and chemical properties of amino acids such as the number of amino acid, molecular weight, atomic composition, theoretical pI, and structural formula) indicated that NeoCoV proteins were the most related to MERS-CoV one. All phylogenetic trees (by both maximum-likelihood and neighbor-joining methods) indicated that NeoCoV proteins have less evolutionary changes except for ORF1a by just maximum-likelihood method. Our results indicated high similarity between viral structural proteins which are responsible for viral infectivity; therefore, we expect that NeoCoV sooner may appear in human-related infection.", "title": "NeoCoV Is Closer to MERS-CoV than SARS-CoV", "pid": "k325yctx", "bm25_score": 214.7711639404297}, {"text": "BACKGROUND: More than a decade after the outbreak of human coronaviruses (HCoVs) SARS in Guangdong province and Hong Kong SAR of China in 2002, there is still no reoccurrence, but the evolution and recombination of the coronaviruses in this region are still unknown. Therefore, surveillance on the prevalence and the virus variation of HCoVs circulation in this region is conducted. METHODS: A total of 3298 nasopharyngeal swabs samples were collected from cross-border children (<6 years, crossing border between Southern China and Hong Kong SAR) showing symptoms of respiratory tract infection, such as fever (body temperature > 37.5 °C), from 2014 May to 2015 Dec. Viral nucleic acids were analyzed and sequenced to study the prevalence and genetic diversity of the four human coronaviruses. The statistical significance of the data was evaluated with Fisher chi-square test. RESULTS: 78 (2.37%; 95%CI 1.8-2.8%) out of 3298 nasopharyngeal swabs specimens were found to be positive for OC43 (36;1.09%), HKU1 (34; 1.03%), NL63 (6; 0.18%) and 229E (2;0.01%). None of SARS or MERS was detected. The HCoVs predominant circulating season was in transition of winter to spring, especially January and February and NL63 detected only in summer and fall. Complex population with an abundant genetic diversity of coronaviruses was circulating and they shared homology with the published strains (99-100%). Besides, phylogenetic evolutionary analysis indicated that OC43 coronaviruses were clustered into three clades (B,D,E), HKU1 clustered into two clades(A,B) and NL63 clustered into two clades(A,B). Moreover, several novel mutations including nucleotides substitution and the insertion of spike of the glycoprotein on the viral surface were discovered. CONCLUSIONS: The detection rate and epidemic trend of coronaviruses were stable and no obvious fluctuations were found. The detected coronaviruses shared a conserved gene sequences in S and RdRp. However, mutants of the epidemic strains were detected, suggesting continuous monitoring of the human coronaviruses is in need among cross-border children, who are more likely to get infected and transmit the viruses across the border easily, in addition to the general public.", "title": "Prevalence and genetic diversity analysis of human coronaviruses among cross-border children", "pid": "000tfenb", "bm25_score": 214.7644805908203}, {"text": "Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19's first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.", "title": "Coronaviruses and SARS-COV-2", "pid": "lm9urlat", "bm25_score": 214.7632293701172}, {"text": "Human coronavirus (HCoV) infection causes respiratory diseases with mild to severe outcomes. In the last 15 years, we have witnessed the emergence of two zoonotic, highly pathogenic HCoVs: severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Replication of HCoV is regulated by a diversity of host factors and induces drastic alterations in cellular structure and physiology. Activation of critical signaling pathways during HCoV infection modulates the induction of antiviral immune response and contributes to the pathogenesis of HCoV. Recent studies have begun to reveal some fundamental aspects of the intricate HCoV-host interaction in mechanistic detail. In this review, we summarize the current knowledge of host factors co-opted and signaling pathways activated during HCoV infection, with an emphasis on HCoV-infection-induced stress response, autophagy, apoptosis, and innate immunity. The cross talk among these pathways, as well as the modulatory strategies utilized by HCoV are also discussed. Expected final online publication date for the Annual Review of Microbiology Volume 73 is September 9, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.", "title": "Human Coronavirus: Host-Pathogen Interaction.", "pid": "sgiuqs6z", "bm25_score": 214.76129150390625}, {"text": "Summary Background An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. Methods We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. Findings Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. Interpretation A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.", "title": "Coronavirus as a possible cause of severe acute respiratory syndrome", "pid": "3t0jhzji", "bm25_score": 214.760009765625}, {"text": "PURPOSE: During the late autumn to winter season (October to December) in the Republic of Korea, respiratory syncytial virus (RSV) is the most common pathogen causing lower respiratory tract infections (LRTIs). Interestingly, in 2014, human coronavirus (HCoV) caused not only upper respiratory infections but also LRTIs more commonly than in other years. Therefore, we sought to determine the epidemiology, clinical characteristics, outcomes, and severity of illnesses associated with HCoV infections at a single center in Korea. MATERIALS AND METHODS: We retrospectively identified patients with positive HCoV respiratory specimens between October 2014 and December 2014 who were admitted to Severance Children’s Hospital at Yonsei University Medical Center for LRTI. Charts of the patients with HCoV infection were reviewed and compared with RSV infection. RESULTS: During the study period, HCoV was the third most common respiratory virus and accounted for 13.7% of infections. Coinfection was detected in 43.8% of children with HCoV. Interestingly, one patient had both HCoV-OC43 and HCoV-NL63. Mild pneumonia was most common (60.4%) with HCoV, and when combined with RSV, resulted in bronchiolitis. Two patients required care in the intensive care unit. However, compared with that of RSV infection, the disease course HCoV was short. CONCLUSION: Infections caused by HCoVs are common, and can cause LRTIs. During an epidemic season, clinicians should be given special consideration thereto. When combined with other medical conditions, such as neurologic or cardiologic diseases, intensive care unit (ICU) care may be necessary.", "title": "Human Coronavirus in the 2014 Winter Season as a Cause of Lower Respiratory Tract Infection", "pid": "k7g7ybyp", "bm25_score": 214.75230407714844}, {"text": "BACKGROUND: Human coronaviruses (HCoVs) have been recognized as causative agents of respiratory tract infections.Our aim was to describe HCoV infections in hospitalized children in a prospective surveillance study for 14 years and compare them with other respiratory viruses. METHODS: As a part of an ongoing prospective study to identify the etiology of viral respiratory infections in Spain, we performed the analysis of HCoV infections in children hospitalized in a secondary hospital in Madrid, between October 2005 and June 2018. Clinical data of HCoV patients were compared with those infected by rhinovirus, respiratory syncytial virus and influenza. RESULTS: The study population consisted of 5131 hospitalizations for respiratory causes in children. A total of 3901 cases (75.9%) had a positive viral identification and 205 cases (4.1%) were positive for HCoV. Only 41 cases (20%) of HCoV infection were detected as single infections. Episodes of recurrent wheezing were the most common diagnosis, and 112 children (54%) had hypoxia. Clinical data in HCoV cases were similar to those associated with rhinovirus; however, patients with HCoV were younger. Other viruses were associated with hypoxia more frequently than cases with HCoV; high fever was more common in influenza infections and bronchiolitis in respiratory syncytial virus group. Although a slight peak of circulation appears mostly in winter, HCoV has been detected throughout the year as well. CONCLUSIONS: HCoV infections represent a small fraction of respiratory infections that require hospitalization in children and their characteristics do not differ greatly from other respiratory viral infections.", "title": "A 14-year Prospective Study of Human Coronavirus Infections in Hospitalized Children: Comparison With Other Respiratory Viruses", "pid": "fe2dy4r9", "bm25_score": 214.75160217285156}, {"text": "Acute respiratory viruses often result in significant morbidity and mortality. The potential impact of human respiratory coronavirus (CoV) infections was underestimated until the severe acute respiratory syndrome (SARS-CoV) outbreak in 2003, which showed that new, highly pathogenic coronaviruses could be introduced to humans, highlighting the importance of monitoring the circulating coronaviruses. The use of sensitive molecular methods has contributed to the differential diagnosis of viruses circulating in humans. Our study aim was to investigate the molecular epidemiology of human CoV strains circulating in Arkansas, their genetic variability and their association with reported influenza-like symptoms. We analyzed 200 nasal swab samples, collected by the Arkansas Department of Health in 2010, for influenza diagnosis. All samples were from patients showing acute respiratory symptoms while testing negative for influenza. Samples were pre-screened, using a quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) multiprobe for coronavirus, and subjected to confirmatory pancoronavirus and/or strain-specific reverse transcriptase (RT)-PCR followed by sequence analysis. Seventy-nine samples (39.5%) were positive by qRT-PCR and 35 samples (17.5%) were confirmed by conventional RT-PCR. Twenty-three of the confirmed samples (59%) were sequenced. The most frequent strain detected was HCoV-OC43-like followed by NL63-like; only one sample was positive for HCoV-229E and one for HCoV-HKU1. Feline-like CoV strains were detected in three samples, representing possible evidence of interspecies transmission or a new human strain. Seventeen percent of the coronavirus positive samples were also positive for other respiratory viruses, such as Respiratory Syncytial Virus (RSV), Parainfluenza 2 and 3, and Rhinovirus. Thus, HCoV-OC43, NL63, HKU1 and new feline-like strains were circulating in Arkansas in 2010. HCoV was the sole respiratory virus detected in 16% of the patients who showed acute respiratory symptoms with negative diagnoses for influenza virus.", "title": "Human Respiratory Coronaviruses Detected In Patients with Influenza-Like Illness in Arkansas, USA", "pid": "g4jlg9pw", "bm25_score": 214.75100708007812}, {"text": "were identified beginning with the discovery of SARS-CoV in 2002. With the recent detection of SARS-CoV-2, there are now seven human coronaviruses. Those that cause mild diseases are the 229E, OC43, NL63 and HKU1, and the pathogenic species are SARS-CoV, MERS-CoV and SARS-CoV-2 Coronaviruses (order Nidovirales, family Coronaviridae, and subfamily Orthocoronavirinae) are spherical (125nm diameter), and enveloped with club-shaped spikes on the surface giving the appearance of a solar corona. Within the helically symmetrical nucleocapsid is the large positive sense, single stranded RNA. Of the four coronavirus genera (α,β,γ,δ), human coronaviruses (HCoVs) are classified under α-CoV (HCoV-229E and NL63) and β-CoV (MERS-CoV, SARS-CoV, HCoVOC43 and HCoV-HKU1). SARS-CoV-2 is a β-CoV and shows fairly close relatedness with two bat-derived CoV-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. Even so, its genome is similar to that of the typical CoVs. SARS-CoV and MERS-CoV originated in bats, and it appears to be so for SARS-CoV-2 as well. The possibility of an intermediate host facilitating the emergence of the virus in humans has already been shown with civet cats acting as intermediate hosts for SARS-CoVs, and dromedary camels for MERS-CoV. Human-to-human transmission is primarily achieved through close contact of respiratory droplets, direct contact with the infected individuals, or by contact with contaminated objects and surfaces. The coronaviral genome contains four major structural proteins: the spike (S), membrane (M), envelope (E) and the nucleocapsid (N) protein, all of which are encoded within the 3' end of the genome. The S protein mediates attachment of the virus to the host cell surface receptors resulting in fusion and subsequent viral entry. The M protein is the most abundant protein and defines the shape of the viral envelope. The E protein is the smallest of the major structural proteins and participates in viral assembly and budding. The N protein is the only one that binds to the RNA genome and is also involved in viral assembly and budding. Replication of coronaviruses begin with attachment and entry. Attachment of the virus to the host cell is initiated by interactions between the S protein and its specific receptor. Following receptor binding, the virus enters host cell cytosol via cleavage of S protein by a protease enzyme, followed by fusion of the viral and cellular membranes. The next step is the translation of the replicase gene from the virion genomic RNA and then translation and assembly of the viral replicase complexes. Following replication and subgenomic RNA synthesis, encapsidation occurs resulting in the formation of the mature virus. Following assembly, virions are transported to the cell surface in vesicles and released by exocytosis.", "title": "Properties of Coronavirus and SARS-CoV-2.", "pid": "713ey27b", "bm25_score": 214.75059509277344}, {"text": "As the result of prolonged (17 years) observations of patients with acute respiratory infections hospitalized in basic departments of clinics of the Research Institute of Influenza, coronavirus infection was found to be the cause of respiratory diseases, on the average, in 12% of cases (in some years in 6.8% to 28.6% of cases). The analysis of extensive morbidity rates among different age groups of the population showed that children were affected by coronavirus infection 5-7 times more often than adults. Three year cycles of this infection were established. The periods of coronaviruses activation were accompanied by their detection in patient material by electron-microscopy, a sharp increase of immune response of patients as well as in the number of nosocomial infections and the proportion of the monoinfection of the coronavirus nature. Coronaviruses played the leading role among other viruses in the etiology of hospital respiratory infections. Mucosal antibodies to coronaviruses in the secretions of the nasal cavity proved to be more important than serum antibodies not only in protection from infection, but also in the pattern of clinical manifestations of the disease.", "title": "[Seroepidemiological study of coronavirus infection in children and adults in St. Petersburg].", "pid": "9yg2ikfm", "bm25_score": 214.74911499023438}, {"text": "AIM Study the circulation of respiratory viruses in children with community-acquired pneumonia (CAP) during the period from October 2012 to May 2013. MATERIALS AND METHODS 136 children with CAP aged from 3 months to 16 years with ARI symptoms at the disease debut were studied. RNA/DNA of influenza A, B, parainfluenza (PI); adeno-, rhino-, RS-viruses, corona-, metapneumo- (MPV) and bocaviruses were detected in nasopharynx smears by PCR with hybridization-fluorescent detection in real time. Antibodies against influenza viruses A/H1N1/pdm09 California/07/09, epidemic reference strains of influenza viruses A/H1N1/Brisbane/59/07, A/ H3N2/Victoria/361/201 1, B/Wisconsin/1/10, against PI viruses type 1, 2, 3 were determined in paired sera by HAI. RESULTS In February-March 2013 the number of children protected by antibodies against influenza decreased, and circulation of influenza viruses A/H3N2 and A/H1N1/ pdm09 was detected. Rhinoviruses and PI viruses were determined throughout the epidemic season, bocavirus and adenoviruses--during the autumn-winter period, RS-virus and MPV--during winter-spring. Coronaviruses were not detected. The peak of virus detection was established in February when the threshold of influenza and ARI morbidity was exceeded. The main pathogens of children of the first 3 years of life are rhinoviruses, RS-virus, PI viruses and bocavirus. RS-virus infection at the debut of CAP in children younger than 3 years in 55.5% of cases is associated with the development of broncho-obstructive syndrome. Bocavirus infection in 50% of cases progresses with laryngo-tracheitis and bronchiolitis. CONCLUSION The fraction of viruses in etiologic structure ofARI in children varies depending on immune layer, season and age of children. Etiology of viral infection at the debut of CAP could only be proven using specialized laboratory studies.", "title": "[Monitoring of influenza and other respiratory diseases causative agents in children, hospitalized with community-acquired pneumonia in 2012-2013 epidemic season].", "pid": "unv8ss65", "bm25_score": 214.74789428710938}, {"text": "Coronaviruses (CoVs) cause a broad spectrum of diseases in domestic and wild animals, poultry, and rodents, ranging from mild to severe enteric, respiratory, and systemic disease, and also cause the common cold or pneumonia in humans. Seven coronavirus species are known to cause human infection, 4 of which, HCoV 229E, HCoV NL63, HCoV HKU1 and HCoV OC43, typically cause cold symptoms in immunocompetent individuals. The others namely SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome coronavirus) were zoonotic in origin and cause severe respiratory illness and fatalities. On 31 December 2019, the existence of patients with pneumonia of an unknown aetiology was reported to WHO by the national authorities in China. This virus was officially identified by the coronavirus study group as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the present outbreak of a coronavirus-associated acute respiratory disease was labelled coronavirus disease 19 (COVID-19). COVID-19’s first cases were seen in Turkey on March 10, 2020 and was number 47,029 cases and 1006 deaths after 1 month. Infections with SARS-CoV-2 are now widespread, and as of 10 April 2020, 1,727,602 cases have been confirmed in more than 210 countries, with 105,728 deaths.", "title": "Coronaviruses and SARS-COV-2", "pid": "gjdlp10q", "bm25_score": 214.7474822998047}, {"text": "Coronaviridae is a family of single-stranded positive enveloped RNA viruses. This article aimed to review the history of these viruses in the last 60 years since their discovery to understand what lessons can be learned from the past. A review of the PubMed database was carried out, describing taxonomy, classification, virology, genetic recombination, host adaptation, and main symptoms related to each type of virus. SARS-CoV-2 is responsible for the ongoing global pandemic, and SARS-CoV and MERS-CoV were responsible for causing severe respiratory illness and regional epidemics in the past while the four other strains of CoVs (229-E OC43, NL63, and HKU1) circulate worldwide and normally only cause mild upper respiratory tract infections. Given the enormous diversity of coronavirus viruses in wildlife and their continuous evolution and adaptation to humans, future outbreaks would undoubtedly occur. Restricting or banning all trade in wild animals in wet markets would be a necessary measure to reduce future zoonotic infections.", "title": "Coronaviridae-Old friends, new enemy!", "pid": "dplg8kdw", "bm25_score": 214.7322998046875}, {"text": "A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 100,000 confirmed infections and 4000 fatalities (as of 10 March 2020). The outbreak has been declared a pandemic by the WHO on Mar 11, 2020. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterise our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures, and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.", "title": "Potential impact of seasonal forcing on a SARS-CoV-2 pandemic", "pid": "ac0whd9v", "bm25_score": 214.73153686523438}, {"text": "Coronaviruses (CoVs) are positive-strand RNA viruses with the largest genome among all RNA viruses. They are able to infect many host, such as mammals or birds. Whereas CoVs were identified 1930s, they became known again in 2003 as the agents of the Severe Acute Respiratory Syndrome (SARS). The spike protein is thought to be essential in the process of CoVs entry, because it is associated with the binding to the receptor on the host cell. It is also involved in cell tropism and pathogenesis. Receptor recognition is the crucial step in the infection. CoVs are able to bind a variety of receptors, although the selection of receptor remains unclear. Coronaviruses were initially believed to enter cells by fusion with the plasma membrane. Further studies demonstrated that many of them involve endocytosis through clathrin-dependent, caveolae-dependent, clathrin-independent, as well as caveolae-independent mechanisms. The aim of this review is to summarise current knowledge about coronaviruses, focussing especially on CoVs entry into the host cell. Advances in understanding coronaviruses replication strategy and the functioning of the replicative structures are also highlighted. The development of host-directed antiviral therapy seems to be a promising way to treat infections with SARS-CoV or other pathogenic coronaviruses. There is still much to be discovered in the inventory of pro- and anti-viral host factors relevant for CoVs replication. The latest pandemic danger, originating from China, has given our previously prepared work even more of topicality.", "title": "Coronaviruses fusion with the membrane and entry to the host cell", "pid": "e2agtvvu", "bm25_score": 214.72732543945312}, {"text": "Corona viruses belong to a group of not yet well known viruses isolated in patients with infections of the upper respiratory organs, especially in winter months. It is presumed that they provoke about 15% - 20% of all infections. However, in the last years more attention has been paid to the role of human corona viruses in the provocation of sickness in man and they are becoming a special field of interest in scientific studies.", "title": "[Coronaviruses].", "pid": "pkmkgppp", "bm25_score": 214.72723388671875}, {"text": "Abstract Influenza A and B, and many unrelated viruses including rhinovirus, RSV, adenovirus, metapneumovirus and coronavirus share the same seasonality, since these viral acute respiratory tract infections (vARIs) are much more common in winter than summer. Unfortunately, early investigations that used recycled “pedigree” virus strains seem to have led microbiologists to dismiss the common folk belief that vARIs often follow chilling. Today, incontrovertible evidence shows that ambient temperature dips and host chilling increase the incidence and severity of vARIs. This review considers four possible mechanisms, M1 - 4, that can explain this link: (M1) increased crowding in winter may enhance viral transmission; (M2) lower temperatures may increase the stability of virions outside the body; (M3) chilling may increase host susceptibility; (M4) lower temperatures or host chilling may activate dormant virions. There is little evidence for M1 or M2, which are incompatible with tropical observations. Epidemiological anomalies such as the repeated simultaneous arrival of vARIs over wide geographical areas, the rapid cessation of influenza epidemics, and the low attack rate of influenza within families are compatible with M4, but not M3 (in its simple form). M4 seems to be the main driver of seasonality, but M3 may also play an important role.", "title": "Seasonality and selective trends in viral acute respiratory tract infections", "pid": "zg17f7bd", "bm25_score": 214.71719360351562}, {"text": "The novel coronavirus pneumonia (NCP) continues to spread throughout the country, and the prevention and control of the epidemic has entered a critical period. However, southern cities with severe outbreaks are about to enter the seasonal influenza season. We should strengthen the epidemiological investigation, optimize the laboratory testing strategy, take effective measures, strengthen the prevention and control of influenza epidemic, and minimize the interference to the new coronavirus epidemic.", "title": "[Be alert to superposed effect of seasonal influenza while fighting against novel coronavirus pneumonia]", "pid": "euecd8bd", "bm25_score": 214.7134246826172}, {"text": "A novel coronavirus (SARS-CoV-2) first detected in Wuhan, China, has spread rapidly since December 2019, causing more than 100,000 confirmed infections and 4000 fatalities (as of 10 March 2020). The outbreak has been declared a pandemic by the WHO on Mar 11, 2020. Here, we explore how seasonal variation in transmissibility could modulate a SARS-CoV-2 pandemic. Data from routine diagnostics show a strong and consistent seasonal variation of the four endemic coronaviruses (229E, HKU1, NL63, OC43) and we parameterise our model for SARS-CoV-2 using these data. The model allows for many subpopulations of different size with variable parameters. Simulations of different scenarios show that plausible parameters result in a small peak in early 2020 in temperate regions of the Northern Hemisphere and a larger peak in winter 2020/2021. Variation in transmission and migration rates can result in substantial variation in prevalence between regions. While the uncertainty in parameters is large, the scenarios we explore show that transient reductions in the incidence rate might be due to a combination of seasonal variation and infection control efforts but do not necessarily mean the epidemic is contained. Seasonal forcing on SARS-CoV-2 should thus be taken into account in the further monitoring of the global transmission. The likely aggregated effect of seasonal variation, infection control measures, and transmission rate variation is a prolonged pandemic wave with lower prevalence at any given time, thereby providing a window of opportunity for better preparation of health care systems.", "title": "Potential impact of seasonal forcing on a SARS-CoV-2 pandemic.", "pid": "28sgnyh1", "bm25_score": 214.7067413330078}, {"text": "A serologic surveillance of lower respiratory tract disease in 417 hospitalized children under 18 months of age revealed infection with coronaviruses (strains OC43 and/or 229E) in 34 (8.2%). During the same interval, one of 13 control infants was infected. There were two distinct periods lasting six and 14 weeks, respectively, during which the incidence rose to as high as 18.9% of patients with lower respiratory tract disease. The incidence of coronavirus infection in patients with pneumonia and bronchiolitis was higher than the incidences of adenoviruses, influenza, parainfluenza viruses types 1 and 2, and rhinoviruses, and lower only than the incidences of parainfluenza virus type 3 and respiratory syncytial virus. Coronaviruses serologically similar or identical to strain 229E were recovered from frozen nasal washes obtained during the acute phase of pneumonia in two children.", "title": "Coronavirus Infection in Acute Lower Respiratory Tract Disease of Infants", "pid": "va27t39c", "bm25_score": 214.7051239013672}, {"text": "Many respiratory viral infections such as influenza and measles result in severe acute respiratory symptoms and epidemics. In the spring of 2003, an epidemic of coronavirus pneumonia spread from Guangzhou to Hong Kong and subsequently to the rest of the world. The WHO coined the acronym SARS (severe acute respiratory syndrome) and subsequently the causative virus as SARS-CoV. In the summer of 2012, epidemic of pneumonia occurred again in Saudi Arabia which was subsequently found to be caused by another novel coronavirus. WHO coined the term MERS (Middle East respiratory syndrome) to denote the Middle East origin of the novel virus (MERS-CoV). In the winter of 2019, another outbreak of pneumonia occurred in Wuhan, China which rapidly spread globally. Yet another novel coronavirus was identified as the culprit and has been named SARS-CoV-2 due to its similarities with SARS-CoV, and the disease as coronavirus disease-2019. This overview aims to compare and contrast the similarities and differences of these three major episodes of coronavirus outbreak, and conclude that they are essentially the same viral respiratory syndromes caused by similar strains of coronavirus with different names. Coronaviruses have caused major epidemics and outbreaks worldwide in the last two decades. From an epidemiological perspective, they are remarkably similar in the mode of spread by droplets. Special focus is placed on the pediatric aspects, which carry less morbidity and mortality in all three entities.", "title": "Overview: The history and pediatric perspectives of severe acute respiratory syndromes: Novel or just like SARS", "pid": "49ybh6fj", "bm25_score": 214.7032012939453}, {"text": "Acute respiratory tract infection is a leading cause of hospital admission of children. This study used a broad capture, rapid and sensitive method (multiplex PCR assay) to detect 20 different respiratory pathogens including influenza A subtypes H1, H3, and H5; influenza B; parainfluenza types 1, 2, 3, and 4; respiratory syncytial virus (RSV) groups A and B; adenoviruses; human rhinoviruses; enteroviruses; human metapneumoviruses; human coronaviruses OC43, 229E, and SARS‐CoV; Chlamydophila pneumoniae; Legionella pneumophila; and Mycoplasma pneumoniae; from respiratory specimens of 475 children hospitalized over a 12‐month period for acute respiratory tract infections. The overall positive rate (47%) was about twice higher than previous reports based on conventional methods. Influenza A, parainfluenza and RSV accounted for 51%, and non‐cultivable viruses accounted for 30% of positive cases. Influenza A peaked at March and June. Influenza B was detected in January, February, and April. Parainfluenza was prevalent throughout the year except from April to June. Most RSV infections were found between February and September. Adenovirus had multiple peaks, whereas rhinovirus and coronavirus OC43 were detected mainly in winter and early spring. RSV infection was associated with bronchiolitis, and parainfluenza was associated with croup; otherwise the clinical manifestations were largely nonspecific. In general, children infected with influenza A, adenovirus and mixed viruses had higher temperatures. In view of the increasing concern about unexpected outbreaks of severe viral infections, a rapid multiplex PCR assay is a valuable tool to enhance the management of hospitalized patients, and for the surveillance for viral infections circulating in the community. J. Med. Virol. 81:153–159, 2009. © 2008 Wiley‐Liss, Inc.", "title": "Identification of viral and atypical bacterial pathogens in children hospitalized with acute respiratory infections in Hong Kong by multiplex PCR assays", "pid": "p6ukvcy9", "bm25_score": 214.70184326171875}, {"text": "In the winter–spring seasons 2003–2004 and 2004–2005, 47 (5.7%) patients with acute respiratory infection associated with human coronavirus (hCoV) 229E‐, NL63‐, and OC43‐like strains were identified among 823 (597 immunocompetent and 226 immunocompromised) patients admitted to hospital with acute respiratory syndromes. Viral infections were diagnosed by either immunological (monoclonal antibodies) or molecular (RT‐PCR) methods. Each of two sets of primer pairs developed for detection of all CoVs (panCoV) failed to detect 15 of the 53 (28.3%) hCoV strains identified. On the other hand, all hCoV strains could be detected by using type‐specific primers targeting genes 1ab and N. The HuH‐7 cell line was found to be susceptible to isolation and identification of OC43‐ and 229E‐like strains. Overall, hCoV infection was caused by OC43‐like, 229E‐like, and NL63‐like strains in 25 (53.2%), 10 (21.3%), and 9 (19.1%) patients, respectively. In addition, three patients (6.4%) were infected by untypeable hCoV strains. NL63‐like strains were not found to circulate in 2003–2004, and 229E‐like strains did not circulate in 2004–2005, while OC43‐like strains were detected in both seasons. The monthly distribution reached a peak during January through March. Lower predominated over upper respiratory tract infections in each age group. In addition, hCoV infections interested only immunocompetent infants and young children during the first year of life, while all adults were immunocompromised patients. Coinfections of hCoVs and other respiratory viruses (mostly interesting the first year of life) were observed in 14 of the 47 (29.8%) patients and were associated with severe respiratory syndromes more frequently than hCoV single infections (P = 0.002). In conclusion, the use of multiple primer sets targeting different genes is recommended for diagnosis of all types of hCoV infection. In addition, the detection of still untypeable hCoV strains suggests that the number of hCoVs involved in human pathology might further increase. Finally, hCoVs should be screened routinely for in both infants and immunocompromised patients with acute respiratory infection. J. Med. Virol. 78:938–949, 2006. © 2006 Wiley‐Liss, Inc.", "title": "Genetic variability of human coronavirus OC43‐, 229E‐, and NL63‐like strains and their association with lower respiratory tract infections of hospitalized infants and immunocompromised patients", "pid": "cmjnb0al", "bm25_score": 214.70118713378906}, {"text": "The pathogenesis of severe acute respiratory syndrome (SARS) is poorly understood and cytokine dysregulation has been suggested as one relevant mechanism to be explored. We compared the cytokine profile in Caco2 cells after infection of SARS coronavirus (SARS‐CoV) with other respiratory viruses including respiratory syncytial virus (RSV), influenza A virus (FluAV), and human parainfluenza virus type 2 (hPIV2). Interferon (IFN) system (production and response) was not suppressed by SARS‐CoV infection. Therefore, SARS‐CoV replication was suppressed by pretreatment with IFN. SARS‐CoV and RSV induced high levels of IL‐6 and RANTES compared with FluAV and hPIV2. Induction level of suppressor of cytokine signaling‐3 (SOCS3) by SARS‐CoV was significantly lower than that by RSV in spite of the significant production of IL‐6. Toll‐like receptors 4 and 9, which correlate with the induction of inflammatory response, were upregulated by SARS‐CoV infection. Collectively, overinduction of inflammatory cytokine and dysregulation of cytokine signaling may contribute to the immunopathology associated with “severe” inflammation in SARS. J. Med. Virol. 78:417–424, 2006. © 2006 Wiley‐Liss, Inc.", "title": "Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infections", "pid": "76hg33n8", "bm25_score": 214.69998168945312}, {"text": "BACKGROUND Human coronaviruses (HCoVs) have been recognized as causative agents of respiratory tract infections.Our aim was to describe HCoV infections in hospitalized children in a prospective surveillance study for 14 years and compare them with other respiratory viruses. METHODS As a part of an ongoing prospective study to identify the etiology of viral respiratory infections in Spain, we performed the analysis of HCoV infections in children hospitalized in a secondary hospital in Madrid, between October 2005 and June 2018. Clinical data of HCoV patients were compared with those infected by rhinovirus, respiratory syncytial virus and influenza. RESULTS The study population consisted of 5131 hospitalizations for respiratory causes in children. A total of 3901 cases (75.9%) had a positive viral identification and 205 cases (4.1%) were positive for HCoV. Only 41 cases (20%) of HCoV infection were detected as single infections. Episodes of recurrent wheezing were the most common diagnosis, and 112 children (54%) had hypoxia. Clinical data in HCoV cases were similar to those associated with rhinovirus; however, patients with HCoV were younger. Other viruses were associated with hypoxia more frequently than cases with HCoV; high fever was more common in influenza infections and bronchiolitis in respiratory syncytial virus group. Although a slight peak of circulation appears mostly in winter, HCoV has been detected throughout the year as well. CONCLUSIONS HCoV infections represent a small fraction of respiratory infections that require hospitalization in children and their characteristics do not differ greatly from other respiratory viral infections.", "title": "A 14-year Prospective Study of Human Coronavirus Infections in Hospitalized Children: Comparison With Other Respiratory Viruses.", "pid": "igjknls2", "bm25_score": 214.68728637695312}, {"text": "BACKGROUND: Viral interaction in which outbreaks of influenza and other common respiratory viruses might affect each other has been postulated by several short studies. Regarding longer time periods, influenza epidemics occasionally occur very early in the season, as during the 2009 pandemic. Whether early occurrence of influenza epidemics impacts outbreaks of other common seasonal viruses is not clear. OBJECTIVES: We investigated whether early occurrence of influenza outbreaks coincides with shifts in the occurrence of other common viruses, including both respiratory and non‐respiratory viruses. METHODS: We investigated time trends of and the correlation between positive laboratory diagnoses of eight common viruses in the Netherlands over a 10‐year time period (2003–2012): influenza viruses types A and B, respiratory syncytial virus (RSV), rhinovirus, coronavirus, norovirus, enterovirus, and rotavirus. We compared trends in viruses between early and late influenza seasons. RESULTS: Between 2003 and 2012, influenza B, RSV, and coronavirus showed shifts in their occurrence when influenza A epidemics occurred earlier than usual (before week 1). Although shifts were not always consistently of the same type, when influenza type A hit early, RSV outbreaks tended to be delayed, coronavirus outbreaks tended to be intensified, and influenza virus type B tended not to occur at all. Occurrence of rhinovirus, norovirus, rotavirus, and enterovirus did not change. CONCLUSION: When influenza A epidemics occured early, timing of the epidemics of several respiratory winter viruses usually occurring close in time to influenza A was affected, while trends in rhinoviruses (occurring in autumn) and trends in enteral viruses were not.", "title": "Early occurrence of influenza A epidemics coincided with changes in occurrence of other respiratory virus infections", "pid": "psog34u3", "bm25_score": 214.68597412109375}, {"text": "BACKGROUND: Influenza virus (IV) is a leading cause of morbidity and mortality worldwide; however, understanding the contribution of non-influenza viruses (NIV) to the annual burden of respiratory illnesses (RI) is evolving. Improvements in diagnostic techniques, including the increasing clinical use of respiratory viral PCR panels (vPCR), have markedly advanced our understanding of the contributions of NIV to the “influenza season.” METHODS: A retrospective analysis of all vPCR results from one hospital system, collected between October 1, 2016 and March 7, 2017, including inpatient and outpatient samples was performed. 2,047 vPCR tests were reviewed; after removing those with undetermined results and internal control samples, 1,924 were analyzed. Data points abstracted included detection and identification of virus, and date of detection. We compared the total and monthly rates of NIV with IV, throughout the study period. RESULTS: Of 1,924 vPCR results, 985 (51%) were positive for a respiratory virus. Of these, 302 (31%) were IV, and 683 (69%) were NIV. For every month studied, the ratio of NIV to IV exceeded 50%, including the height of the season. The most commonly detected viruses were Influenza A (30%), Rhino/Enterovirus (24%), RSV (19%), Coronavirus OC43 (7%) and Metapneumovirus (5%). The peak influenza incidence temporally coincided with the national peak months of January and February. The NIV incidence paralleled the trend in IV incidence, dominated by Rhino/Enterovirus and RSV, but without a specific virus driving the trend. CONCLUSION: Non-influenza respiratory viruses cause substantial viral RI during the winter months. Many viral syndromes during the height of influenza season have traditionally been attributed to IV, including influenza-like-illness (ILI); however, these can now be better characterized using patient-specific vPCR panels, leading to improved understanding of NIV epidemiology. Even during the period of highest IV incidence, NIV infections were more common than IV. Understanding the high prevalence of NIV infections may improve the judicious use of both antibiotics and antivirals. There may also be a role for refinement of ILI, including best practices for diagnosis and treatment. DISCLOSURES: All Authors: No reported disclosures.", "title": "2518. The Role of Non-Influenza Viruses in the Seasonal Viral Respiratory Illness: A Epidemiologic Study From October 2016–March 2017", "pid": "p57tsbyw", "bm25_score": 214.68368530273438}, {"text": "Rhinoviruses and coronaviruses cause the majority of common colds and play a part in more serious respiratory illnesses that lead to increased morbidity and mortality. Patients who are infants or elderly, have asthma or chronic obstructive pulmonary disease (COPD), or are immunosuppressed have increased frequency of rhinovirus-related respiratory complications. Newer diagnostic tests such as reverse transcriptase polymerase chain reaction (RT-PCR) have greatly expanded our understanding of the importance of these respiratory viruses. Although there are no currently approved antiviral agents for clinical use, our increased understanding of the virus-host interaction should lead to new intervention strategies.", "title": "Rhinovirus and coronavirus infections.", "pid": "hx10tc7v", "bm25_score": 214.6802978515625}, {"text": "This manuscript explores the question of the seasonality of severe acute respiratory syndrome coronavirus 2 by reviewing 4 lines of evidence related to viral viability, transmission, ecological patterns, and observed epidemiology of coronavirus disease 2019 in the Southern Hemispheres' summer and early fall.", "title": "Will Coronavirus Disease 2019 Become Seasonal?", "pid": "kvh60zd5", "bm25_score": 214.67811584472656}, {"text": "Coronaviridae is a family of single‐stranded positive enveloped RNA viruses. This article aimed to review the history of these viruses in the last 60 years since their discovery to understand what lessons can be learned from the past. A review of the PubMed database was carried out, describing taxonomy, classification, virology, genetic recombination, host adaptation, and main symptoms related to each type of virus. SARS‐CoV‐2 is responsible for the ongoing global pandemic, SARS‐CoV and MERS‐CoV were responsible for causing severe respiratory illness and regional epidemics in the past while the four other strains of CoVs (229‐E OC43, NL63, and HKU1) circulate worldwide and normally only cause mild upper respiratory tract infections. Given the enormous diversity of coronavirus viruses in wildlife and their continuous evolution and adaptation to humans, future outbreaks would undoubtedly occur. Restricting or banning all trade in wild animals in wet markets would be a necessary measure to reduce future zoonotic infections.", "title": "Coronaviridae ‐ old friends, new enemy!", "pid": "36j840wm", "bm25_score": 214.6617889404297}, {"text": "Viruses require specific cellular receptors to infect their target cells. Angiotensin-converting enzyme 2 (ACE2) is a cellular receptor for two divergent coronaviruses, SARS coronavirus (SARS-CoV) and human coronavirus NL63 (HCoV-NL63). In addition to hostcell receptors, lysosomal cysteine proteases are required for productive infection by some viruses. Here we show that SARS-CoV, but not HCoV-NL63, utilizes the enzymatic activity of the cysteine protease cathepsin L to infect ACE2-expressing cells. Inhibitors of cathepsin L blocked infection by SARS-CoV and by a retrovirus pseudotyped with the SARS-CoV spike (S) protein but not infection by HCoV-NL63 or a retrovirus pseudotyped with the HCoV-NL63 S protein. Expression of exogenous cathepsin L substantially enhanced infection mediated by the SARS-CoV S protein and by filovirus GP proteins but not by the HCoV-NL63 S protein or the vesicular stomatitis virus G protein. Finally, an inhibitor of endosomal acidification had substantially less effect on infection mediated by the HCoV-NL63 S protein than on that mediated by the SARS-CoV S protein. Our data indicate that two coronaviruses that utilize a common receptor nonetheless enter cells through distinct mechanisms.", "title": "SARS coronavirus, but not human coronavirus NL63, utilizes cathepsin L to infect ACE2-expressing cells.", "pid": "ryt4ggp0", "bm25_score": 214.65911865234375}]}
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Therefore, we analyzed the S gene sequences of SARS-CoV-2 to better understand the antigenicity and immunogenicity of this virus in this study. In phylogenetic analysis, two subtypes (SARS-CoV-2a and -b) were confirmed within SARS-CoV-2 strains. These two subtypes were divided by a novel synonymous mutation of D614G. This may play a crucial role in the evolution of SARS-CoV-2 to evade the host immune system. The region containing this mutation point was confirmed as a B-cell epitope located in the S1 domain, and SARS-CoV-2b strains exhibited severe reduced antigenic indexes compared to SARS-CoV-2a in this area. This may allow these two subtypes to have different antigenicity. If the two subtypes have different serological characteristics, a vaccine for both subtypes will be more effective to prevent COVID-19. Thus, further study is urgently required to confirm the antigenicity of these two subtypes.", "title": "A Novel Synonymous Mutation of SARS-CoV-2: Is This Possible to Affect Their Antigenicity and Immunogenicity?", "pid": "1sbnewog", "bm25_score": 217.23545837402344}, {"text": "Since its emergence in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected &#8776;6 million persons worldwide. As SARS-CoV-2 spreads across the planet, we explored the range of human cells that can be infected by this virus. We isolated SARS-CoV-2 from 2 infected patients in Toronto, Canada; determined the genomic sequences; and identified single-nucleotide changes in representative populations of our virus stocks. We also tested a wide range of human immune cells for productive infection with SARS-CoV-2. We confirm that human primary peripheral blood mononuclear cells are not permissive for SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor single-nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine viral genotype and phenotype by using in vitro and in vivo infection models.", "title": "Isolation, Sequence, Infectivity, and Replication Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2", "pid": "hrgb0e03", "bm25_score": 217.01947021484375}, {"text": "A recent study by Tang et al. (2020) claimed that two major types of SARS-CoV-2 had evolved in the ongoing COVID-19 pandemic and that one of these types was more “aggressive” than the other. Given the repercussions of these claims and the intense media coverage of these types of articles, we have examined in detail the data presented by Tang et al, and show that the major conclusions of that paper cannot be substantiated. Using examples from other viral outbreaks we discuss the difficulty in demonstrating the existence or nature of a functional effect of a viral mutation, and we advise against overinterpretation of genomic data during the pandemic.", "title": "No evidence for distinct types in the evolution of SARS-CoV-2", "pid": "m61qihyq", "bm25_score": 216.99151611328125}, {"text": "The World Health Organization characterized the COVID-19 as a pandemic in March 2020, the second pandemic of the 21st century. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-stranded RNA betacoronavirus of the family Coronaviridae. Expanding virus populations, as that of SARS-CoV-2, accumulate a number of narrowly shared polymorphisms imposing a confounding effect on traditional clustering methods. In this context, approaches that reduce the complexity of the sequence space occupied by the SARS-CoV-2 population are necessary for a robust clustering. Here, we proposed the subdivision of the global SARS-CoV-2 population into sixteen well-defined subtypes by focusing on the widely shared polymorphisms in nonstructural (nsp3, nsp4, nsp6, nsp12, nsp13 and nsp14) cistrons, structural (spike and nucleocapsid) and accessory (ORF8) genes. Six virus subtypes were predominant in the population, but all sixteen showed amino acid replacements which might have phenotypic implications. We hypothesize that the virus subtypes detected in this study are records of the early stages of the SARS-CoV-2 diversification that were randomly sampled to compose the virus populations around the world, a typical founder effect. The genetic structure determined for the SARS-CoV-2 population provides substantial guidelines for maximizing the effectiveness of trials for testing the candidate vaccines or drugs.", "title": "The global population of SARS-CoV-2 is composed of six major subtypes", "pid": "h0q93in1", "bm25_score": 216.84051513671875}, {"text": "We examined 169 genomes of SARS-CoV-2 and found that they can be classified into two major genotypes, Type I and Type II. Type I can be further divided into Type IA and IB. Our phylogenetic analysis showed that the Type IA resembles the ancestral SARS-CoV-2 most. Type II was likely evolved from Type I and predominant in the infections. Our results suggest that Type II SARS-CoV-2 was the source of the outbreak in the Wuhan Huanan market and it was likely originated from a super-spreader. The outbreak caused by the Type I virus should have occurred somewhere else, because the patients had no direct link to the market. Furthermore, by analyzing three genomic sites that distinguish Type I and Type II strains, we found that synonymous changes at two of the three sites confer higher protein translational efficiencies in Type II strains than in Type I strains, which might explain why Type II strains are predominant, implying that Type II is more contagious (transmissible) than Type I. These findings could be valuable for the current epidemic prevention and control.", "title": "Genomic variations of SARS-CoV-2 suggest multiple outbreak sources of transmission", "pid": "a12708qd", "bm25_score": 216.70762634277344}, {"text": "Abstract There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.", "title": "The SARS-CoV-2 outbreak: What we know", "pid": "5fg87lvu", "bm25_score": 216.5752716064453}, {"text": "COVID-19 pandemic is a major human tragedy. Worldwide, SARS-CoV-2 has already infected over 3 million and has killed about 230,000 people. SARS-CoV-2 originated in China and, within three months, has evolved to an additional 10 subtypes. One particular subtype with a non-silent (Aspartate to Glycine) mutation at 614th position of the Spike protein (D614G) rapidly outcompeted other pre-existing subtypes, including the ancestral. We assessed that D614G mutation generates an additional serine protease (Elastase) cleavage site near the S1-S2 junction of the Spike protein. We also identified that a single nucleotide deletion (delC) at a known variant site (rs35074065) in a cis-eQTL of TMPRSS2, is extremely rare in East Asians but is common in Europeans and North Americans. The delC allele facilitates entry of the 614G subtype into host cells, thus accelerating the spread of 614G subtype in Europe and North America where the delC allele is common. The delC allele at the cis-eQTL locus rs35074065 of TMPRSS2 leads to overexpression of both TMPRSS2 and a nearby gene MX1. The cis-eQTL site, rs35074065 overlaps with a transcription factor binding site of an activator (IRF1) and a repressor (IRF2). IRF1 activator can bind to variant delC allele, but IRF2 repressor fails to bind. Thus, in an individual carrying the delC allele, there is only activation, but no repression. On viral entry, IRF1 mediated upregulation of MX1 leads to neutrophil infiltration and processing of 614G mutated Spike protein by neutrophil Elastase. The simultaneous processing of 614G spike protein by TMPRSS2 and Elastase serine proteases facilitates the entry of the 614G subtype into host cells. Thus, SARS-CoV-2, particularly the 614G subtype, has spread more easily and with higher frequency to Europe and North America where the delC allele regulating expression of TMPRSS2 and MX1 host proteins is common, but not to East Asia where this allele is rare.", "title": "Global Spread of SARS-CoV-2 Subtype with Spike Protein Mutation D614G is Shaped by Human Genomic Variations that Regulate Expression of TMPRSS2 and MX1 Genes", "pid": "bbhf4qus", "bm25_score": 216.56617736816406}, {"text": "Coronaviruses have recently caused world-wide severe outbreaks: SARS (Severe Acute Respiratory Syndrome) in 2002 and MERS (Middle-East Respiratory Syndrome) in 2012. At the end of 2019, a new coronavirus outbreak appeared in Wuhan (China) seafood market as first focus of infection, becoming a pandemics in 2020, spreading mainly into Europe and Asia. Although the virus family is well-known, this specific virus presents considerable differences, as higher transmission rates, being a challenge for diagnostic methods, treatments and vaccines. Coronavirus.pro is a C++ application which simulates Coronavirus replication cycle. This software has identified virus type in short times and provided FASTA files of virus proteins, a list of mRNA sequences and secondary structures. Furthermore, the software has identified a list of structural, non-structural and accessory proteins in 2019-nCoV virus genome more similar to SARS than to MERS, as several fusion proteins characteristics of this virus type. These results are useful as a first step in order to develop diagnostic methods, new vaccines or antiviral drugs, which could avoid virus replication in any stage: fusion inhibitors, RdRp inhibitors and PL2pro/3CLpro protease inhibitors.", "title": "Coronavirus SARS-CoV-2: Analysis of subgenomic mRNA transcription, 3CLpro and PL2pro protease cleavage sites and protein synthesis", "pid": "ll76vrr3", "bm25_score": 216.54954528808594}, {"text": "There is a current worldwide outbreak of the novel coronavirus Covid-19 (coronavirus disease 2019; the pathogen called SARS-CoV-2; previously 2019-nCoV), which originated from Wuhan in China and has now spread to 6 continents including 66 countries, as of 24:00 on March 2, 2020. Governments are under increased pressure to stop the outbreak from spiraling into a global health emergency. At this stage, preparedness, transparency, and sharing of information are crucial to risk assessments and beginning outbreak control activities. This information should include reports from outbreak site and from laboratories supporting the investigation. This paper aggregates and consolidates the epidemiology, clinical manifestations, diagnosis, treatments and preventions of this new type of coronavirus.", "title": "The SARS-CoV-2 outbreak: What we know", "pid": "950x4b9a", "bm25_score": 216.54298400878906}, {"text": "A recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected more than 1100000 (April 5, 2020) individuals worldwide and is spreading rapidly. The virus is reported to be derived from bats and the infection was first reported in China. Similar to the severe acute respiratory syndrome and the Middle East respiratory syndrome coronaviruses, it is responsible for respiratory tract infection. Real time polymerase chain reaction and radiography are the two main diagnostic methods. Guidelines from the Center for Disease Control and Prevention and the World Health Organization (WHO) should be followed for diagnostic and precautionary measures. Treatment of the infection is still not available; however, antivirals are under clinical trials.", "title": "SARS-CoV-2; What We Know so far.", "pid": "tp5q8bbp", "bm25_score": 216.54188537597656}, {"text": "Taiwan experienced two waves of imported cases of coronavirus disease 2019 (COVID-19), first from China in January to late February, followed by those from other countries starting in early March. Additionally, several cases could not be traced to any imported cases and were suspected as sporadic local transmission. Twelve full viral genomes were determined in this study by Illumina sequencing either from virus isolates or directly from specimens, among which 5 originated from clustered infections. Phylogenetic tree analysis revealed that these sequences were in different clades, indicating that no major strain has been circulating in Taiwan. A deletion in open reading frame 8 was found in one isolate. Only a 4-nucleotide difference was observed among the 5 genomes from clustered infections.", "title": "Sequence variation among SARS-CoV-2 isolates in Taiwan", "pid": "6phwc7s7", "bm25_score": 216.532958984375}, {"text": "Coronaviruses (CoVs) are one of the largest groups of positive-sense RNA virus families within the Nidovirales order, which are further classified into four genera: alpha, beta, gamma, and delta. Coronaviruses have an extensive range of natural hosts and are known to be responsible for a broad spectrum of diseases in multiple species. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing coronavirus disease 2019 (COVID-19) that has unleashed a global threat to public health and the economy. Coronaviruses are extensively present in birds and mammals, with horseshoe bats (Rhinolophus affinis), being the reservoir for the ongoing SARS-CoV-2 that seems to have resulted from a zoonotic spillover to the human host, causing respiratory infections, lung injury and Acute Respiratory Distress Syndrome(ARDS). About six coronavirus serotypes are linked with the disease in humans, namely HCoV-229E, HCoV-NL63, HCoV-OC43, HCoV-HKU1, SARS-CoV, SARS-CoV-2, and MERS-CoV. SARS-CoV-2 is the seventh CoV to infect humans. We analyzed the genome sequence of CoV-2 from isolates derived from China as well from India and encountered minute variations in their sequence. A cladogram analysis revealed the predominant strain circulating in India belongs to the A2a clad. We took one such strain (MT012098) and performed a rigorous in-silico genotypic and antigenic analysis to identify its relatedness to other strains. Further, we also performed a detailed prediction for B and T cell epitopes using BepiPred 2.0 server and NetCTL 1.2 server (DTU Bioinformatics), respectively. We hope this information may assist in an effective vaccine designing program against SARS-CoV-2.", "title": "Genotypic and antigenic study of SARS-CoV-2 from an Indian isolate", "pid": "12540n1s", "bm25_score": 216.5128936767578}, {"text": "Abstract On December 31, 2019, an outbreak of pneumonia of unknown etiology was detected in the city of Wuhan (China). A week later, a new coronavirus was isolated in these patients, initially designated as 2019-nCoV and subsequently SARS-CoV-2. This is a new virus that is much closer genetically to the coronavirus of bats than to human SARS. The new virus infects and replicates in the lung parenchyma pneumocytes and macrophages in which the ACE-2 cell receptor resides. He has now infected many more people than his predecessors (>85,000). From the clinical point of view, those infected have an average age of 55 years; the main symptoms are fever, dry cough, lymphopenia, dyspnea, and pneumonia in its severe form. The overall lethality rate is 2-3% in China and 0.1% in cases detected outside of this country. The incubation period has been set at about 3 days (0-24 days). There are no specific antivirals or vaccines.", "title": "The SARS-CoV-2, a new pandemic zoonosis that threatens the world", "pid": "inlv102z", "bm25_score": 216.48672485351562}, {"text": "In January 2020, we identified two severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients in a familial cluster with one person coming from Wuhan, China. The complete genome sequences of two SARS-CoV-2 strains isolated from these patients were identical and 99.98% similar to strains isolated in Wuhan. This is genetically suggestive of human-to-human transmission of SARS-CoV-2 and indicates Wuhan as the most plausible origin of the early outbreak in Vietnam. The younger patient had a mild upper respiratory illness and a brief viral shedding, whereas the elderly with multi-morbidity had pneumonia, prolonged viral shedding, and residual lung damage. The evidence of nonsynonymous substitutions in the ORF1ab region of the viral sequence warrants further studies.", "title": "Clinical features, isolation, and complete genome sequence of severe acute respiratory syndrome coronavirus 2 from the first two patients in Vietnam", "pid": "cr4yp5b7", "bm25_score": 216.4567413330078}, {"text": "Four signature groups of single-nucleotide variants (SNVs) were identified using two-way clustering method in about twenty thousand high quality and high coverage SARS-CoV-2 complete genome sequences. Some frequently occurred SNVs predominate but are mutually exclusively presented in patients from different countries and areas. These major SNV signatures exhibited distinguished evolution patterns overtime. Although it was rare, our data indicated possible cross-infections with multiple groups of SNVs existed simultaneously in some patients, suggesting infections from different SARS-CoV-2 clades or potential re-combination of SARS-CoV-2 sequences. Interestingly nucleotide substitutions among SARS-CoV-2 genomes tend to occur at the sites where one bat RaTG13 coronavirus sequences differ from Wuhan-Hu-1 genome, indicating the tolerance of mutations on those sites or suggesting that major viral strains might exist between Wuhan-Hu-1 and RaTG13 coronavirus.", "title": "Distinct genetic spectrums and evolution patterns of SARS-CoV-2", "pid": "xly61tfw", "bm25_score": 216.44247436523438}, {"text": "Since its emergence in Wuhan, China, in December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected ≈6 million persons worldwide. As SARS-CoV-2 spreads across the planet, we explored the range of human cells that can be infected by this virus. We isolated SARS-CoV-2 from 2 infected patients in Toronto, Canada; determined the genomic sequences; and identified single-nucleotide changes in representative populations of our virus stocks. We also tested a wide range of human immune cells for productive infection with SARS-CoV-2. We confirm that human primary peripheral blood mononuclear cells are not permissive for SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor single-nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine viral genotype and phenotype by using in vitro and in vivo infection models.", "title": "Isolation, Sequence, Infectivity, and Replication Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2.", "pid": "a9h25l7j", "bm25_score": 216.44183349609375}, {"text": "Taiwan experienced two waves of imported infections with Coronavirus Disease 2019 (COVID-19). This study aimed at investigating the genomic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Taiwan and compared their evolutionary trajectories with the global strains. We performed culture and full-genome sequencing of SARS-CoV-2 strains followed by phylogenetic analysis. A 382-nucleotides deletion in open reading frame 8 (ORF8) was found in a Taiwanese strain isolated from a patient on February 4, 2020 who had a travel history to Wuhan. Patients in the first wave also included several sporadic, local transmission cases. Genomes of 5 strains sequenced from clustered infections were classified into a new clade with ORF1ab-V378I mutation, in addition to 3 dominant clades ORF8-L84S, ORF3a-G251V and S-D614G. This highlighted clade also included some strains isolated from patients who had a travel history to Turkey and Iran. The second wave mostly resulted from patients who had a travel history to Europe and Americas. All Taiwanese viruses were classified into various clades. Genomic surveillance of SARS-CoV-2 in Taiwan revealed a new ORF8-deletion mutant and a virus clade that may be associated with infections in the Middle East, which contributed to a better understanding of the global SARS-CoV-2 transmission dynamics.", "title": "SARS-CoV-2 genomic surveillance in Taiwan revealed novel ORF8-deletion mutant and clade possibly associated with infections in Middle East", "pid": "b15befg1", "bm25_score": 216.42938232421875}, {"text": "Taiwan experienced two waves of imported infections with Coronavirus Disease 2019 (COVID-19). This study aimed at investigating the genomic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Taiwan and compared their evolutionary trajectories with the global strains. We performed culture and full-genome sequencing of SARS-CoV-2 strains followed by phylogenetic analysis. A 382-nucleotides deletion in open reading frame 8 (ORF8) was found in a Taiwanese strain isolated from a patient on February 4, 2020 who had a travel history to Wuhan. Patients in the first wave also included several sporadic, local transmission cases. Genomes of 5 strains sequenced from clustered infections were classified into a new clade with ORF1ab-V378I mutation, in addition to 3 dominant clades ORF8-L84S, ORF3a-G251V and S-D614G. This highlighted clade also included some strains isolated from patients who had a travel history to Turkey and Iran. The second wave mostly resulted from patients who had a travel history to Europe and Americas. All Taiwanese viruses were classified into various clades. Genomic surveillance of SARS-CoV-2 in Taiwan revealed a new ORF8-deletion mutant and a virus clade that may be associated with infections in the Middle East, which contributed to a better understanding of the global SARS-CoV-2 transmission dynamics.", "title": "SARS-CoV-2 genomic surveillance in Taiwan revealed novel ORF8-deletion mutant and clade possibly associated with infections in Middle East.", "pid": "p47lhd25", "bm25_score": 216.37060546875}, {"text": "Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in China in late December 2019 and has spread worldwide. Coronaviruses are enveloped, positive sense, single-stranded RNA viruses and employ a complicated pattern of virus genome length RNA replication as well as transcription of genome length and leader containing subgenomic RNAs. Although not fully understood, both replication and transcription are thought to take place in so-called double-membrane vesicles in the cytoplasm of infected cells. We here describe detection of SARS-CoV-2 subgenomic RNAs in diagnostic samples up to 17 days after initial detection of infection, and provide a likely explanation not only for extended PCR positivity of such samples, but also for discrepancies in results of different PCR methods described by others. Overall, we present evidence that subgenomic RNAs may not be an indicator of active coronavirus replication/infection, but that these RNAs, similar to the virus genome RNA, may be rather stable, and thus detectable for an extended period, most likely due to their close association with cellular membranes.", "title": "SARS-CoV-2 genomic and subgenomic RNAs in diagnostic samples are not an indicator of active replication", "pid": "1qnwi5s7", "bm25_score": 216.3004150390625}, {"text": "The SARS-CoV-2 epidemic started in late December 2019 in Wuhan, China, and has since impacted a large portion of China and raised major global concern. Herein, we investigated the extent of molecular divergence between SARS-CoV-2 and other related coronaviruses. Although we found only 4% variability in genomic nucleotides between SARS-CoV-2 and a bat SARS-related coronavirus (SARSr-CoV; RaTG13), the difference at neutral sites was 17%, suggesting the divergence between the two viruses is much larger than previously estimated. Our results suggest that the development of new variations in functional sites in the receptor-binding domain (RBD) of the spike seen in SARS-CoV-2 and viruses from pangolin SARSr-CoVs are likely caused by mutations and natural selection besides recombination. Population genetic analyses of 103 SARS-CoV-2 genomes indicated that these viruses evolved into two major types (designated L and S), that are well defined by two different SNPs that show nearly complete linkage across the viral strains sequenced to date. Although the L type (∼70%) is more prevalent than the S type (∼30%), the S type was found to be the ancestral version. Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020. Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure. These findings strongly support an urgent need for further immediate, comprehensive studies that combine genomic data, epidemiological data, and chart records of the clinical symptoms of patients with coronavirus disease 2019 (COVID-19).", "title": "On the origin and continuing evolution of SARS-CoV-2", "pid": "j99cgsjt", "bm25_score": 216.29269409179688}, {"text": "The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu(TM) database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau (τ) using the formula t=τ/2u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.", "title": "Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data", "pid": "127c5bve", "bm25_score": 216.28172302246094}, {"text": "A novel pathogen, named SARS-CoV-2, has caused an unprecedented worldwide pandemic in the first half of 2020. As the SARS-CoV-2 genome sequences have become available, one of the important focus of scientists has become tracking variations in the viral genome. In this study, 30366 SARS-CoV-2 isolate genomes were aligned using the software developed by our group (ODOTool) and 11 variations in SARS-CoV-2 genome over 10% of whole isolates were discussed. Results indicated that, frequency rates of these 11 variations change between 3.56%–88.44 % and these rates differ greatly depending on the continents they have been reported. Despite some variations being in low frequency rate in some continents, C14408T and A23403G variations on Nsp12 and S protein, respectively, observed to be the most prominent variations all over the world, in general, and both cause missense mutations. It is also notable that most of isolates carry C14408T and A23403 variations simultaneously and also nearly all isolates carrying the G25563T variation on ORF3a, also carry C14408T and A23403 variations, although their location distributions are not similar. All these data should be considered towards development of vaccine and antiviral treatment strategies as well as tracing diversity of virus in all over the world.", "title": "An updated analysis of variations in SARS-CoV-2 genome", "pid": "od3c25qg", "bm25_score": 216.27703857421875}, {"text": "To determine prevalence of, seroprevalence of, and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a cohort of evacuees returning to the United States from Wuhan, China, in January 2020, we conducted a cross-sectional study of quarantined evacuees from 1 repatriation flight. Overall, 193 of 195 evacuees completed exposure surveys and submitted upper respiratory or serum specimens or both at arrival in the United States. Nearly all evacuees had taken preventive measures to limit potential exposure while in Wuhan, and none had detectable SARS-CoV-2 in upper respiratory tract specimens, suggesting the absence of asymptomatic respiratory shedding among this group at the time of testing. Evidence of antibodies to SARS-CoV-2 was detected in 1 evacuee, who reported experiencing no symptoms or high-risk exposures in the previous 2 months. These findings demonstrated that this group of evacuees posed a low risk of introducing SARS-CoV-2 to the United States.", "title": "Severe Acute Respiratory Syndrome Coronavirus 2 Prevalence, Seroprevalence, and Exposure Among Evacuees from Wuhan, China, 2020.", "pid": "c58nf9vb", "bm25_score": 216.26266479492188}, {"text": "SARS-CoV-2 emerged in December 2019 in Wuhan, China and has since infected over 1.5 million people, of which over 107,000 have died. As SARS-CoV-2 spreads across the planet, speculations remain about the range of human cells that can be infected by SARS-CoV-2. In this study, we report the isolation of SARS-CoV-2 from two cases of COVID-19 in Toronto, Canada. We determined the genomic sequences of the two isolates and identified single nucleotide changes in representative populations of our virus stocks. More importantly, we tested a wide range of human immune cells for productive infection with SARS-CoV-2. Here we confirm that human primary peripheral blood mononuclear cells (PBMCs) are not permissive for SARS-CoV-2. As SARS-CoV-2 continues to spread globally, it is essential to monitor single nucleotide polymorphisms in the virus and to continue to isolate circulating viruses to determine viral genotype and phenotype using in vitro and in vivo infection models.", "title": "Isolation, sequence, infectivity and replication kinetics of SARS-CoV-2", "pid": "p5ejn9op", "bm25_score": 216.25494384765625}, {"text": "To determine prevalence of, seroprevalence of, and potential exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among a cohort of evacuees returning to the United States from Wuhan, China, in January 2020, we conducted a cross-sectional study of quarantined evacuees from 1 repatriation flight. Overall, 193 of 195 evacuees completed exposure surveys and submitted upper respiratory or serum specimens or both at arrival in the United States. Nearly all evacuees had taken preventive measures to limit potential exposure while in Wuhan, and none had detectable SARS-CoV-2 in upper respiratory tract specimens, suggesting the absence of asymptomatic respiratory shedding among this group at the time of testing. Evidence of antibodies to SARS-CoV-2 was detected in 1 evacuee, who reported experiencing no symptoms or high-risk exposures in the previous 2 months. These findings demonstrated that this group of evacuees posed a low risk of introducing SARS-CoV-2 to the United States.", "title": "Severe Acute Respiratory Syndrome Coronavirus 2 Prevalence, Seroprevalence, and Exposure Among Evacuees from Wuhan, China, 2020", "pid": "plyao9wn", "bm25_score": 216.2480926513672}, {"text": "Since December 2019, the emergence of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection has been reported unexpectedly in Wuhan, China, with staggering infection speed across China and around the world. To date, seven known strains of HCoVs belonging to four genera (i.e., α?, β?, γ, and δ-CoV) have been recognized; the latest one has been identified as the SARS-CoV-2. Although the common transmission routes of SARS-CoV-2 is the respiratory tract, it seems that other routes such as the gastrointestinal tract may be effective for the entry of the virus in the body. Although there are no biological markers to predict the susceptibility of humans to COVID-19, several risk factors have been identified to predict the susceptibility of patients to COVID-19. Initial data revealed that males, pregnant women, elderly, and underlying conditions predispose patients to higher morbidity or mortality and also might be at risk for a severe infection of COVID-19. There is a greater need to better understand the mechanisms and risk factors of transmission routes. To date, despite the whole world effort to review various aspects of SARS-CoV-2, including epidemiology, clinical manifestations, diagnosis, and treatment options, there are still gaps in the knowledge of this disease and many issues remain unclear. Therefore, there is an urgent need for update data on SARS-CoV-2. Here, this study provide the current epidemiological status (transmission routes and risk of transmission, possible origins and source, mortality and morbidity risk, and geographical distribution) of the SARS-CoV-2 in the world in 2020.", "title": "Emerging coronaviruses: first SARS, second MERS and third SARS-CoV-2: epidemiological updates of COVID-19.", "pid": "kkknzw2i", "bm25_score": 216.2474822998047}, {"text": "Clinical laboratory testing routinely provides actionable results, which help direct patient care in the inpatient and outpatient settings. Since December 2019, a novel coronavirus (SARS-CoV-2) has been causing disease (COVID-19 [coronavirus disease 2019]) in patients, beginning in China and now extending worldwide. In this context of a novel viral pandemic, clinical laboratories have developed multiple novel assays for SARS-CoV-2 diagnosis and for managing patients afflicted with this illness. These include molecular and serologic-based tests, some with point-of-care testing capabilities. Herein, we present an overview of the types of testing available for managing patients with COVID-19, as well as for screening of potential plasma donors who have recovered from COVID-19.", "title": "Types of Assays for SARS-CoV-2 Testing: A Review.", "pid": "zyrzfm40", "bm25_score": 216.24526977539062}, {"text": "Coronavirus disease 2019 (COVID-19) is newly emerging human infectious diseases, which is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2, also previously known as 2019-nCoV). Within two months of the outbreak, more than 80,000 cases of COVID-19 have been confirmed worldwide. Since the human to human transmission occurred easily and the human infection is rapidly increasing, the sensitive and early diagnosis is essential to prevent the global outbreak. Recently, World Health Organization (WHO) announced various primer and probe sets for SARS-CoV-2 previously developed in China, Germany, Hong Kong, Japan, Thailand, and USA. In this study, we compared the ability to detect SARS-CoV-2 RNA among the seven primer-probe sets for N gene and the three primer-probe sets for Orf1 gene. The result of the comparative analysis represented that the ‘2019-nCoV_N2, N3’ of USA and the ‘ORF1ab’ of China are the most sensitive primer-probe sets for N and Orf1 genes, respectively. Therefore, the appropriate combination from ORF1ab (China), 2019-nCoV_N2, N3 (USA), and NIID_2019-nCOV_N (Japan) sets should be selected for the sensitive and reliable laboratory confirmation of SARS-CoV-2.", "title": "Comparative analysis of primer-probe sets for the laboratory confirmation of SARS-CoV-2", "pid": "2hyiped2", "bm25_score": 216.23159790039062}, {"text": "Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 6156 genome samples collected up to April 24, 2020, we report that SARS-CoV-2 has had 4459 alarmingly mutations which can be clustered into five subtypes. We introduce mutation ratio and mutation $h$-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively non-conservative. In particular, the nucleocapsid protein has more than half its genes changed in the past few months, signaling devastating impacts on the ongoing development of COVID-19 diagnosis, vaccines, and drugs.", "title": "Decoding SARS-CoV-2 transmission, evolution and ramification on COVID-19 diagnosis, vaccine, and medicine", "pid": "u6ewlh16", "bm25_score": 216.22862243652344}, {"text": "The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu TM database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau ( &#964;) using the formula t= &#964;/2 u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.", "title": "Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data", "pid": "gy78e87y", "bm25_score": 216.22506713867188}, {"text": "An ongoing outbreak of pneumonia caused by a novel coronavirus, currently designated as the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), was reported recently. However, as SARS-CoV-2 is an emerging virus, we know little about it. In this review, we summarize the key events occurred during the early stage of SARS-CoV-2 outbreak, the basic characteristics of the pathogen, the signs and symptoms of the infected patients as well as the possible transmission pathways of the virus. Furthermore, we also review the current knowledge on the origin and evolution of the SARS-CoV-2. We highlight bats as the potential natural reservoir and pangolins as the possible intermediate host of the virus, but their roles are waiting for further investigation. Finally, the advances in the development of chemotherapeutic options are also briefly summarized.", "title": "SARS-CoV-2: an Emerging Coronavirus that Causes a Global Threat", "pid": "0jzr5anm", "bm25_score": 216.21881103515625}, {"text": "To investigate the evolutionary history of the current pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a total of 137 genomes of coronavirus strains with release dates between January 2019 and 25 March 2020, were analyzed. To investigate the potential intermediate host of the SARS-CoV-2, we analyzed spike glycoprotein sequences from different animals, with particular emphasis on bats. We performed phylogenetic analysis and structural reconstruction of the spike glycoproteins with subsequent alignment and comparison. Our phylogenetic results revealed that SARS-CoV-2 was more similar to the bats' betacoronavirus isolates: HKU5-related from Pipistrellus abramus and HKU4-related from Tylonycteris pachypus. We also identified a yak betacoronavirus strain, YAK/HY24/CH/2017, as the closest match in the comparison of the structural models of spike glycoproteins. Interestingly, a set of unique features has been described for this particular strain of the yak betacoronavirus. Therefore, our results suggest that the human SARS-CoV-2, responsible for the current outbreak of COVID-19, could also come from yak as an intermediate host.", "title": "SARS-CoV-2: Structural diversity, phylogeny, and potential animal host identification of spike glycoprotein", "pid": "d9qtn37b", "bm25_score": 216.1728515625}, {"text": "The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused thousands of deaths worldwide, including >18,000 in New York City (NYC) alone. The sudden emergence of this pandemic has highlighted a pressing clinical need for rapid, scalable diagnostics that can detect infection, interrogate strain evolution, and identify novel patient biomarkers. To address these challenges, we designed a fast (30-minute) colorimetric test (LAMP) for SARS-CoV-2 infection from naso/oropharyngeal swabs, plus a large-scale shotgun metatranscriptomics platform (total-RNA-seq) for host, bacterial, and viral profiling. We applied both technologies across 857 SARS-CoV-2 clinical specimens and 86 NYC subway samples, providing a broad molecular portrait of the COVID-19 NYC outbreak. Our results define new features of SARS-CoV-2 evolution, nominate a novel, NYC-enriched viral subclade, reveal specific host responses in interferon, ACE, hematological, and olfaction pathways, and examine risks associated with use of ACE inhibitors and angiotensin receptor blockers. Together, these findings have immediate applications to SARS-CoV-2 diagnostics, public health, and new therapeutic targets.", "title": "Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions", "pid": "kyoa5gsf", "bm25_score": 216.15737915039062}, {"text": "On December 31, 2019, an outbreak of pneumonia of unknown etiology was detected in the city of Wuhan (China). A week later, a new coronavirus was isolated in these patients, initially designated as 2019-nCoV and subsequently SARS-CoV-2. This is a new virus that is much closer genetically to the coronavirus of bats than to human SARS. The new virus infects and replicates in the lung parenchyma pneumocytes and macrophages in which the ACE-2 cell receptor resides. He has now infected many more people than his predecessors (> 85,000). From the clinical point of view, those infected have an average age of 55 years; the main symptoms are fever, dry cough, lymphopenia, dyspnea, and pneumonia in its severe form. The overall lethality rate is 2-3% in China and 0.1% in cases detected outside of this country. The incubation period has been set at about 3 days (0-24 days). There are no specific antivirals or vaccines.", "title": "El SARS-CoV-2, una nueva zoonosis pandémica que amenaza al mundo", "pid": "kp2ewbn1", "bm25_score": 216.15194702148438}, {"text": "Clinical laboratory testing routinely provides actionable results, which help direct patient care in the inpatient and outpatient settings. Since December 2019, a novel coronavirus (SARS-CoV-2) has been causing disease (COVID-19 [coronavirus disease 2019]) in patients, beginning in China and now extending worldwide. In this context of a novel viral pandemic, clinical laboratories have developed multiple novel assays for SARS-CoV-2 diagnosis and for managing patients afflicted with this illness. These include molecular and serologic-based tests, some with point-of-care testing capabilities. Herein, we present an overview of the types of testing available for managing patients with COVID-19, as well as for screening of potential plasma donors who have recovered from COVID-19.", "title": "Types of Assays for SARS-CoV-2 Testing: A Review", "pid": "qexn0nuy", "bm25_score": 216.14797973632812}, {"text": "Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the virus strain that causes coronavirus disease 2019 (COVID-19), was first identified in Wuhan, China in December 2019. It spread to several countries across continents and infected more than one million people within three months. While there is no consensus on the treatment of the disease yet, understanding the virus and its transmission is a cardinal priority. SARS-CoV-2 can be transmitted through bodily fluid. Upon inoculation, the surface enzyme angiotensin-converting enzyme 2 (ACE2) acts as a receptor protein for viral entry. The mean incubation period is 5.1 days, and infected individuals can exhibit a variety of symptoms from fever, cough, dyspnea, and respiratory failure to even multiorgan failure. Given the current situation, it is of paramount importance to understand the virus as thoroughly as possible. In this review, we discuss the background, epidemiology, possible pathophysiology, clinical presentation, and diagnostic studies related to SARS-CoV-2 infection. We also elaborate on the current research and evidence on treatment options and vaccine development based on the literature.", "title": "A Comprehensive Review of Severe Acute Respiratory Syndrome Coronavirus 2", "pid": "9usyb1nn", "bm25_score": 216.14620971679688}, {"text": "Although primary genomic analysis has revealed that severe acute respiratory syndrome coronavirus (SARS CoV) is a new type of coronavirus, the different protein trees published in previous reports have provided no conclusive evidence indicating the phylogenetic position of SARS CoV. To clarify the phylogenetic relationship between SARS CoV and other coronaviruses, we compiled a large data set composed of 7 concatenated protein sequences and performed comprehensive analyses, using the maximum-likelihood, Bayesian-inference, and maximum-parsimony methods. All resulting phylogenetic trees displayed an identical topology and supported the hypothesis that the relationship between SARS CoV and group 2 CoVs is monophyletic. Relationships among all major groups were well resolved and were supported by all statistical analyses.", "title": "Monophyletic Relationship between Severe Acute Respiratory Syndrome Coronavirus and Group 2 Coronaviruses", "pid": "005b2j4b", "bm25_score": 216.14230346679688}, {"text": "Starting around December 2019, an epidemic of pneumonia, which was named COVID-19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full-length genomic sequences of SARAS-CoV-2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS-CoV-2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%-100%) at the nucleotide level and 99.99% (99.79%-100%) at the amino acid level. Although overall variation in open-reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS-COV-2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS-CoV-2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS-CoV-2 infection in the future.", "title": "The establishment of reference sequence for SARS-CoV-2 and variation analysis", "pid": "g1zxlaer", "bm25_score": 216.14047241210938}, {"text": "The SARS-CoV­2 causes a disease spectrum that includes asymptomatic and mildly symptomatic infections with subclinical manifestations but which can nevertheless still be potentially contagious. Evidence from SARS-CoV­2 infected macaque monkeys and from studies with seasonal coronaviruses suggests that the infection is likely to produce an immunity that is protective for a certain period of time. Available test methods enable a high degree of reliability, e.g. if high-quality serological methods are combined. Although individual test results have to be interpreted with caution, serosurveillance in a tertiary eye care center and large eye research institute can reduce anxiety and provide clarity regarding the actual number of (unreported) SARS-CoV­2 infections.", "title": "Seroprävalenz und SARS-CoV-2-Testung in Gesundheitsberufen./ [Seroprevalence and SARS-CoV-2 testing in healthcare occupations]", "pid": "rlpe6tpm", "bm25_score": 216.13148498535156}, {"text": "[This corrects the article DOI: 10.1016/j.cmrp.2020.04.001.].", "title": "Corrigendum to 'An Overview of Coronaviruses including the SARS-2 Coronavirus - Molecular Biology, Epidemiology and Clinical Implications' [Cur Med Res Pract. (2019) Vol. 10, pages 54-64]", "pid": "bcrqld0q", "bm25_score": 216.13052368164062}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is a major concern in coronavirus disease 2019 (COVID-19) prevention and economic reopening. However, rigorous determination of SARS-COV-2 infectivity is essentially impossible owing to its continuous evolution with over 13752 single nucleotide polymorphisms (SNP) variants in six different subtypes. We develop an advanced machine learning algorithm based on the algebraic topology to quantitatively evaluate the binding affinity changes of SARS-CoV-2 spike glycoprotein (S protein) and host angiotensin-converting enzyme 2 (ACE2) receptor following the mutations. Based on mutation-induced binding affinity changes, we reveal that five out of six SARS-CoV-2 subtypes have become either moderately or slightly more infectious, while one subtype has weakened its infectivity. We find that SARS-CoV-2 is slightly more infectious than SARS-CoV according to computed S protein-ACE2 binding affinity changes. Based on a systematic evaluation of all possible 3686 future mutations on the S protein receptor-binding domain (RBD), we show that most likely future mutations will make SARS-CoV-2 more infectious. Combining sequence alignment, probability analysis, and binding affinity calculation, we predict that a few residues on the receptor-binding motif (RBM), i.e., 452, 489, 500, 501, and 505, have very high chances to mutate into significantly more infectious COVID-19 strains.", "title": "Mutations strengthened SARS-CoV-2 infectivity", "pid": "8s8gezpz", "bm25_score": 216.11500549316406}, {"text": "The initial cases of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) occurred in Wuhan, China, in December 2019 and swept the world by 23 June 2020 with 8,993,659 active cases, 469,587 deaths across 216 countries, areas or territories. This strongly implies global transmission occurred before the lockdown of China. However, the initial source's transmission routes of SARS-CoV-2 remain obscure and controversial. Research data suggest bat (RaTG13) and pangolin carried CoV were the proximal source of SARS-CoV-2. In this study, we used systematic phylogenetic analysis of Coronavirinae subfamily along with wild type human SARS-CoV, MERS-CoV, and SARS-CoV-2 strains. The key residues of the receptor-binding domain (RBD) and O-linked glycan were compared. SARS-CoV-2 strains were clustered with RaTG13 (97.41% identity), Pangolin-CoV (92.22% identity) and Bat-SL-CoV (80.36% identity), forms a new clade-2 in lineage B of beta-CoV. The alignments of RBD contact residues to ACE2 justified? Those SARS-CoV-2 strains sequences were 100% identical by each other, significantly varied in RaTG13 and pangolin-CoV. SARS-CoV-2 has a polybasic cleavage site with an inserted sequence of PRRA compared to RaTG13 and only PRR to pangolin. Only serine (Ser) in pangolin and both threonine (Thr) and serine (Ser) O-linked glycans were seen in RaTG13, suggesting that a detailed study needed in Pangolin (Manis javanica) and bat (Rhinolophus affinis) related CoV. This article is protected by copyright. All rights reserved.", "title": "An update on origin of SARS-CoV-2: Despite closest identity, bat (RaTG13) and Pangolin derived Coronaviruses varied in the critical binding site and O-linked glycan residues", "pid": "r25aqii5", "bm25_score": 216.1134490966797}, {"text": "Background & objectives SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the pandemic over time and to identify similarities and differences of viral diversity and evolution across geographical regions (countries). Methods Publicly available data on type definitions based on whole-genome sequences of the SARS-CoV-2 sampled during December and March 2020 from 3636 infected patients spread over 55 countries were collected. Phylodynamic analyses were performed and the temporal and spatial evolution of the virus was examined. Results It was found that (i) temporal variation in frequencies of types of the coronavirus was significant; ancestral viruses of type O were replaced by evolved viruses belonging to type A2a; (ii) spatial variation was not significant; with the spread of SARS-CoV-2, the dominant virus was the A2a type virus in every geographical region; (iii) within a geographical region, there was significant micro-level variation in the frequencies of the different viral types, and (iv) the evolved coronavirus of type A2a swept rapidly across all continents. Interpretation & conclusions SARS-CoV-2 belonging to the A2a type possesses a non-synomymous variant (D614G) that possibly eases the entry of the virus into the lung cells of the host. This may be the reason why the A2a type has an advantage to infect and survive and as a result has rapidly swept all geographical regions. Therefore, large-scale sequencing of coronavirus genomes and, as required, of host genomes should be undertaken in India to identify regional and ethnic variation in viral composition and its interaction with host genomes. Further, careful collection of clinical and immunological data of the host can provide deep learning in relation to infection and transmission of the types of coronavirus genomes.", "title": "Analysis of RNA sequences of 3636 SARS-CoV-2 collected from 55 countries reveals selective sweep of one virus type.", "pid": "b61alj5x", "bm25_score": 216.10708618164062}, {"text": "In a phylogenetic network analysis of 160 complete human severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) genomes, we find three central variants distinguished by amino acid changes, which we have named A, B, and C, with A being the ancestral type according to the bat outgroup coronavirus. The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia. The network faithfully traces routes of infections for documented coronavirus disease 2019 (COVID-19) cases, indicating that phylogenetic networks can likewise be successfully used to help trace undocumented COVID-19 infection sources, which can then be quarantined to prevent recurrent spread of the disease worldwide.", "title": "Phylogenetic network analysis of SARS-CoV-2 genomes", "pid": "d5qzzvy3", "bm25_score": 216.08154296875}, {"text": "On 31 December, 2019, a cluster of 27 pneumonia cases of unknown etiology was reported by Chinese health authorities in Wuhan City (China) [ ]", "title": "Outbreak of Novel Coronavirus (SARS-CoV-2): First Evidences From International Scientific Literature and Pending Questions", "pid": "99doz9m6", "bm25_score": 216.06100463867188}, {"text": "Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.", "title": "Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV", "pid": "dtwstwbe", "bm25_score": 216.06004333496094}, {"text": "Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has been declared a global pandemic. Our goal was to determine whether coinfections with other respiratory pathogens occur in a significant subset of SARS-CoV-2 infected patients in the greater New York City metropolitan area. During the period from March 16, 2020 through April 20, 2020, our laboratory detected SARS-CoV-2 infection in 8,990 patients of a total 18,704 tested by real-time reverse-transcription-polymerase-chain-reaction amplification (SARS-CoV-2 Test, cobas® 6800 system, RocheDiagnostics). Amongst the patients who tested positive for SARS-CoV-2, 1,204 were also tested for other respiratory viruses, and concurrent infection was found in only 36 (< 3%). In comparison, coinfection with at least one non-SARS-CoV-2 respiratory viral pathogen was found in 13.1% of patients who tested negative for SARS-CoV-2. Additionally, in patients who tested negative for SARS-CoV-2, the most common respiratory virus co-infections were those commonly seen circulating in the community including rhinovirus/enterovirus, influenza viruses and coronavirus NL63, whereas non-SARS-CoV-2 coronaviridae were the most common concurrent respiratory viruses found in SARS-CoV-2 -positive patients. Additional studies are needed to establish whether simultaneous viral infection in SARS-CoV-2 patients could potential drive viral interference or influence disease outcomes. This article is protected by copyright. All rights reserved.", "title": "Co-infection in SARS-CoV-2 infected Patients: Where Are Influenza Virus and Rhinovirus/Enterovirus?", "pid": "zeq8b776", "bm25_score": 216.03274536132812}, {"text": "Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a new infectious disease that first emerged in Hubei province, China, in December 2019, which was found to be associated with a large seafood and animal market in Wuhan. Airway epithelial cells from infected patients were used to isolate a novel coronavirus, named the SARS-CoV-2, on January 12, 2020, which is the seventh member of the coronavirus family to infect humans. Phylogenetic analysis of full-length genome sequences obtained from infected patients showed that SARS-CoV-2 is similar to severe acute respiratory syndrome coronavirus (SARS-CoV) and uses the same cell entry receptor, angiotensin-converting enzyme 2 (ACE2), as SARS-CoV. The possible person-to-person disease rapidly spread to many provinces in China as well as other countries. Without a therapeutic vaccine or specific antiviral drugs, early detection and isolation become essential against novel Coronavirus. In this review, we introduced current diagnostic methods and criteria for the SARS-CoV-2 in China and discuss the advantages and limitations of the current diagnostic methods, including chest imaging and laboratory detection.", "title": "The genetic sequence, origin, and diagnosis of SARS-CoV-2", "pid": "eyitkr3s", "bm25_score": 216.03018188476562}, {"text": "Summary SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Although the SARS-CoV-2 genome was reported recently, its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous discontinuous transcription events. In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif, AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the modification and the 3′ tail. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.", "title": "The Architecture of SARS-CoV-2 Transcriptome", "pid": "ypsh3rjv", "bm25_score": 216.02975463867188}, {"text": "Background & objectives: SARS-CoV-2 (Severe acute respiratory syndrome coronavirus-2) is evolving with the progression of the pandemic. This study was aimed to investigate the diversity and evolution of the coronavirus SARS-CoV-2 with progression of the pandemic over time and to identify similarities and differences of viral diversity and evolution across geographical regions (countries). Methods: Publicly available data on type definitions based on whole-genome sequences of the SARS-CoV-2 sampled during December and March 2020 from 3636 infected patients spread over 55 countries were collected. Phylodynamic analyses were performed and the temporal and spatial evolution of the virus was examined. Results: It was found that (i) temporal variation in frequencies of types of the coronavirus was significant; ancestral viruses of type O were replaced by evolved viruses belonging to type A2a; (ii) spatial variation was not significant; with the spread of SARS-CoV-2, the dominant virus was the A2a type virus in every geographical region; (iii) within a geographical region, there was significant micro-level variation in the frequencies of the different viral types, and (iv) the evolved coronavirus of type A2a swept rapidly across all continents. Interpretation & conclusions: SARS-CoV-2 belonging to the A2a type possesses a non-synomymous variant (D614G) that possibly eases the entry of the virus into the lung cells of the host. This may be the reason why the A2a type has an advantage to infect and survive and as a result has rapidly swept all geographical regions. Therefore, large-scale sequencing of coronavirus genomes and, as required, of host genomes should be undertaken in India to identify regional and ethnic variation in viral composition and its interaction with host genomes. Further, careful collection of clinical and immunological data of the host can provide deep learning in relation to infection and transmission of the types of coronavirus genomes.", "title": "Analysis of RNA sequences of 3636 SARS-CoV-2 collected from 55 countries reveals selective sweep of one virus type", "pid": "04bi0d50", "bm25_score": 216.0120086669922}, {"text": "The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak and is a major public health issue. As of 11 February 2020, data from the World Health Organization (WHO) have shown that more than 43 000 confirmed cases have been identified in 28 countries/regions, with >99% of cases being detected in China. On 30 January 2020, the WHO declared COVID-19 as the sixth public health emergency of international concern. SARS-CoV-2 is closely related to two bat-derived severe acute respiratory syndrome-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. It is spread by human-to-human transmission via droplets or direct contact, and infection has been estimated to have mean incubation period of 6.4 days and a basic reproduction number of 2.24-3.58. Among patients with pneumonia caused by SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough. Bilateral lung involvement with ground-glass opacity was the most common finding from computed tomography images of the chest. The one case of SARS-CoV-2 pneumonia in the USA is responding well to remdesivir, which is now undergoing a clinical trial in China. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary intervention being used. However, public health authorities should keep monitoring the situation closely, as the more we can learn about this novel virus and its associated outbreak, the better we can respond.", "title": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges", "pid": "u9lp0rtz", "bm25_score": 215.99964904785156}, {"text": "SARS-CoV-2 is a novel strain of coronavirus that has not been previously identified in humans. It has been declared a pandemic and has infected at least 1,844,683 individuals and caused 117,021 deaths as of 14th April 2020. Transmission among humans occurs via close contact with an infected individual that produces respiratory droplets. Patients have been shown to undergo acute respiratory distress syndrome, which is defined as cytokine storm. The diagnosis relies on detection of nucleic acid, IgG/IgM antibodies, and a chest radiograph of the suspected individuals. The genome of SARS-CoV-2 is similar to other coronaviruses that comprise of ten open reading frames (ORFs). SARS-CoV-2 spike protein exhibits higher affinity to ACE2 receptor as compared with SARS-CoV. Repurposing drugs like favipiravir, remdesivir, chloroquine, and TMPRSS2 protease inhibitors have been shown to be effective for the treatment of COVID-19. Personal protective measures should be followed to prevent SARS-CoV-2 infection. In addition, a clinical trial of SARS-CoV-2 vaccine, mRNA-1273, has been started. This chapter provides a glimpse of advancements made in the area of SARS-CoV-2 infection by proving recent clinical and research trials in the field.", "title": "Current Insight into the Novel Coronavirus Disease 2019 (COVID-19)", "pid": "zv0ysi8m", "bm25_score": 215.98095703125}, {"text": "Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002–2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients’ sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.", "title": "Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV", "pid": "dqour5jr", "bm25_score": 215.9671630859375}, {"text": "Tremendous effort has been given to the development of diagnostic tests, preventive vaccines, and therapeutic medicines for coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Much of this development has been based on the reference genome collected on January 5, 2020. Based on the genotyping of 15 140 genome samples collected up to June 1, 2020, we report that SARS-CoV-2 has undergone 8309 single mutations which can be clustered into six subtypes. We introduce mutation ratio and mutation h-index to characterize the protein conservativeness and unveil that SARS-CoV-2 envelope protein, main protease, and endoribonuclease protein are relatively conservative, while SARS-CoV-2 nucleocapsid protein, spike protein, and papain-like protease are relatively nonconservative. In particular, we have identified mutations on 40% of nucleotides in the nucleocapsid gene in the population level, signaling potential impacts on the ongoing development of COVID-19 diagnosis, vaccines, and antibody and small-molecular drugs.", "title": "Decoding SARS-CoV-2 Transmission and Evolution and Ramifications for COVID-19 Diagnosis, Vaccine, and Medicine", "pid": "lzrxdi6a", "bm25_score": 215.9625244140625}, {"text": "In late December 2019, several cases of pneumonia of unknown origin were reported from China, which in early January 2020 were announced to be caused by a novel coronavirus. The virus was later denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and defined as the causal agent of coronavirus disease 2019 (COVID-19). Despite massive attempts to contain the disease in China, the virus has spread globally, and COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. Here we provide a short background on coronaviruses, and describe in more detail the novel SARS-CoV-2 and attempts to identify effective therapies against COVID-19.", "title": "Coronaviruses and SARS-CoV-2: A Brief Overview", "pid": "yzizn5ig", "bm25_score": 215.95712280273438}, {"text": "In late December 2019, several cases of pneumonia of unknown origin were reported from China, which in early January 2020 were announced to be caused by a novel coronavirus. The virus was later denominated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and defined as the causal agent of Coronavirus Disease 2019 (COVID-19). Despite massive attempts to contain the disease in China, the virus has spread globally, and COVID-19 was declared a pandemic by the World Health Organization (WHO) in March 2020. Here we provide a short background on coronaviruses, and describe in more detail the novel SARS-CoV-2 and attempts to identify effective therapies against COVID-19.", "title": "Coronaviruses and SARS-CoV-2: A Brief Overview", "pid": "kx5hihnr", "bm25_score": 215.95712280273438}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been confirmed as the etiological pathogen of the coronavirus disease 2019 (COVID-19) SARS-CoV-2 is the seventh member of coronavirus family that can infect humans after the emergence of the severe acute respiratory syndrome coronavirus (SARS-CoV) and the Middle East respiratory syndrome coronavirus (MERS-CoV) SARS-CoV-2 is a single-stranded, positive-sense RNA virus Due to its strong infectiousness and the lack of immunity in humans, the epidemic of the COVID-19 is still spreading On January 30, 2020 (local time), the World Health Organization (WHO) defined the epidemics of SARS-CoV-2-infected pneumonia as a Public Health Emergency of International Concern (PHEIC) This paper reviews the etiology and pathogenicity of SARS-CoV-2, and the detection and diagnosis, prevention and control, as well as the treatment of COVID-19", "title": "Severe acute respiratory syndrome coronavirus 2 and coronavirus disease 2019", "pid": "2mh0cuan", "bm25_score": 215.94432067871094}, {"text": "Bats were recently identified as natural reservoirs of SARS-like coronavirus (SL-CoV) or SARS coronavirus-like virus. These viruses, together with SARS coronaviruses (SARS-CoV) isolated from human and palm civet, form a distinctive cluster within the group 2 coronaviruses of the genus Coronavirus, tentatively named group 2b (G2b). In this study, complete genome sequences of two additional group 2b coronaviruses (G2b-CoVs) were determined from horseshoe bat Rhinolophus ferrumequinum (G2b-CoV Rf1) and Rhinolophus macrotis (G2b-CoV Rm1). The bat G2b-CoV isolates have an identical genome organization and share an overall genome sequence identity of 88-92 % among themselves and between them and the human/civet isolates. The most variable regions are located in the genes encoding nsp3, ORF3a, spike protein and ORF8 when bat and human/civet G2b-CoV isolates are compared. Genetic analysis demonstrated that a diverse G2b-CoV population exists in the bat habitat and has evolved from a common ancestor of SARS-CoV.", "title": "Full-length genome sequences of two SARS-like coronaviruses in horseshoe bats and genetic variation analysis.", "pid": "4h6hp97j", "bm25_score": 215.9370880126953}, {"text": "Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9-17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.", "title": "Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2", "pid": "buwz6lu3", "bm25_score": 215.92947387695312}, {"text": "SARS-CoV-2 is a betacoronavirus responsible for the COVID-19 pandemic. Although the SARS-CoV-2 genome was reported recently, its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous discontinuous transcription events. In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif, AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the modification and the 3' tail. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2.", "title": "The Architecture of SARS-CoV-2 Transcriptome", "pid": "6quqydr6", "bm25_score": 215.927490234375}, {"text": "More than 100,000 people worldwide are known to have been infected with SARS-CoV-2 beginning in December 2019. The virus has now spread to over 93 countries including the United States, with the largest cluster of US cases to date in the Seattle metropolitan area in Washington. Given the rapid increase in the number of local cases, the availability of accurate, high-throughput SARS-CoV-2 testing is vital to efforts to manage the current public health crisis. In the course of optimizing SARS-CoV-2 testing performed by the University of Washington Clinical Virology Lab (UW Virology Lab), we tested assays using seven different primer/probe sets and one assay kit. We found that the most sensitive assays were those the used the E-gene primer/probe set described by Corman et al. (Eurosurveillance 25(3), 2020, https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000045) and the N2 set described by the CDC (Division of Viral Diseases, Centers for Disease Control and Prevention, 2020, https://www.cdc.gov/coronavirus/2019-ncov/downloads/rt-pcr-panel-primer-probes.pdf). All assays tested were found to be highly specific for SARS-CoV-2, with no cross-reactivity with other respiratory viruses observed in our analyses regardless of the primer/probe set or kit used. These results will provide invaluable information to other clinical laboratories who are actively developing SARS-CoV-2 testing protocols at a time when increased testing capacity is urgently needed worldwide.", "title": "Comparative Performance of SARS-CoV-2 Detection Assays using Seven Different Primer/Probe Sets and One Assay Kit.", "pid": "tvbi15yq", "bm25_score": 215.92022705078125}, {"text": "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) emerged in late 2019 and since evolved into a global threat with nearly 4.4 million infected people and over 290,000 confirmed deaths worldwide.1 SARS-CoV-2 is an enveloped virus presenting spike (S) glycoproteins on its outer surface. Binding of S to host cell angiotensin converting enzyme 2 (ACE2) is thought to be critical for cellular entry. The host range of the virus extends far beyond humans and non-human primates. Natural and experimental infections have confirmed high susceptibility of cats, ferrets, and hamsters, whereas dogs, mice, rats, pigs, and chickens seem refractory to SARS-CoV-2 infection. To investigate the reason for the variable susceptibility observed in different species, we have developed molecular descriptors to efficiently analyze our dynamic simulation models of complexes between SARS-CoV-2 S and ACE2. Based on our analyses we predict that: (i) the red squirrel is likely susceptible to SARS-CoV-2 infection and (ii) specific mutations in ACE2 of dogs, rats, and mice render them susceptible to SARS-CoV-2 infection.", "title": "ACE2-Variants Indicate Potential SARS-CoV-2-Susceptibility in Animals: An Extensive Molecular Dynamics Study", "pid": "q814d6l7", "bm25_score": 215.90829467773438}, {"text": "The recent global outbreak of viral pneumonia designated as Coronavirus Disease 2019 (COVID-19) by coronavirus (SARS-CoV-2) has threatened global public health and urged to investigate its source. Whole genome analysis of SARS-CoV-2 revealed ~96% genomic similarity with bat CoV (RaTG13) and clustered together in phylogenetic tree. Furthermore, RaTGl3 also showed 97.43% spike protein similarity with SARS-CoV-2 suggesting that RaTGl3 is the closest strain. However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. In short, our findings propose that homologous recombination has been occurred between bat and pangolin CoVs that triggered cross-species transmission and emergence of SARS-CoV-2, and, during the ongoing outbreak, SARS-CoV-2 is still evolving for its adaptability.", "title": "Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)", "pid": "fw4pmaoc", "bm25_score": 215.9075927734375}, {"text": "Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.", "title": "New understanding of the damage of SARS-CoV-2 infection outside the respiratory system", "pid": "xxo2hip9", "bm25_score": 215.903564453125}, {"text": "Abstract Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3,000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.", "title": "New understanding of the damage of SARS-CoV-2 infection outside the respiratory system", "pid": "tv13furv", "bm25_score": 215.89630126953125}, {"text": "Since December 2019, the outbreak of Coronavirus Disease 2019 (COVID-19) spread from Wuhan, China to the world, it has caused more than 87,000 diagnosed cases and more than 3,000 deaths globally. To fight against COVID-19, we carried out research for the near native SARS-CoV-2 and report here our preliminary results obtained. The pathogen of the COVID-19, the native SARS-CoV-2, was isolated, amplified and purified in a BSL-3 laboratory. The whole viral architecture of SARS-CoV-2 was examined by transmission electron microscopy (both negative staining and cryo-EM). We observed that the virion particles are roughly spherical or moderately pleiomorphic. Spikes have nail-like shape towards outside with a long body embedded in the envelope. The morphology of virion observed in our result indicates that the S protein of SARS-CoV-2 is in post-fusion state, with S1 disassociated. This state revealed by cryo-EM first time could provide an important information for the identification and relevant clinical research of this new coronavirus.", "title": "Viral Architecture of SARS-CoV-2 with Post-Fusion Spike Revealed by Cryo-EM", "pid": "cr22vp8b", "bm25_score": 215.88475036621094}, {"text": "In December 2019, a pneumonia outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and presented a major threat to public health. Nationwide, there were more than 70 000 confirmed cases and 2500 deaths. Most patients were elderly, with severe disease. For acute respiratory infection, reverse-transcription polymerase chain reaction (RT-PCR) is routinely used to detect causative viruses in respiratory secretions. Coronavirus RNA can be detected from nose and throat swabs, sputum and other lower respiratory tract secretions, blood, and feces. Such specimens were examined by RT-PCR. Three targets, RdRP, E, and N genes were detected, indicating samples were positive for SARS-CoV-2. After patient recovery, a chest computed tomography examination, combined with SARS-CoV-2 RNA detection, confirmed diagnosis. However, some recovery patients with negative RNA tests turned RNA positive. The preliminary data is about 14% of discharged patients in Guangdong reported by the Guangdong Center for Disease Control (CDC). This is an important scientific issue. If samples are positive for SARS-CoV-2 RNA, patients should be managed according to infection source. Fortunately, there were no close contacts of second-generation cases. We herein report six SARS-CoV-2 cases confirmed in our hospital, for the changes of results of SARS-CoV-2 RNA should attract attention. Most patients were elderly, with a low Geriatric Nutritional Risk Index (GNRI). However, the association of the phenomenon with aging and GNRI has not yet been reported in detail. Further investigations are necessary to confirm and improve these findings. Similarly, discharged patient follow-up should be strengthened.", "title": "Caution should be exercised for the detection of SARS-CoV-2, especially in the elderly", "pid": "ptkgyje8", "bm25_score": 215.87936401367188}, {"text": "In recent years, the prevalence and spread of coronavirus has had a huge impact on global public health. Due to the incomplete understanding of the pathogenic mechanism of the virus, it is difficult for humans to fight against the virus quickly and effectively once the outbreak occurs. In early 2020, a novel coronavirus was discovered in Wuhan, China. Soon after, similar cases were found in other countries around the world, and the number of infected people increased rapidly. So far, the global cumulative number of infected people has exceeded 3 million, and more than 200,000 people have died, which has had a huge impact on global human health and economic development. Every outbreak of disease makes a deep impression on mankind. Herein, we summarize the virology, epidemiology, clinical manifestations, diagnosis, treatment and prevention of SARS-CoV-2, and hope that countries can control the outbreak as soon as possible to minimize the loss.", "title": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2): a review", "pid": "5l1bknw2", "bm25_score": 215.87351989746094}, {"text": "BACKGROUND Shortly after its emergence in December 2019, the coronavirus disease 2019 (COVID-19) was declared as a pandemic by the World Health Organization. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the seventh member of the Coronaviridae family of viruses that causes disease in humans. THE PROBLEM Despite the established role of molecular diagnostics, COVID-19 serodiagnosis remains a poorly discovered and enigmatic area. Although there are numerous commercial serological products available globally, there is a severe paucity of high-quality peer-reviewed literature on their true performance characteristics. That being said, publications including in-house developed serological tests started to shed light on the kinetics of the humoral response. SUMMARY In spite of intense focus of assessing the performance characteristics of the commercially-available kits, the main issue remains rather invisible, that is, lack of solid science behind COVID-19 serology its clinical usefulness thereof. This short review summarizes the key points as to why COVID-19 is not jest ready to fly. PURPOSE OF REVIEW Despite having been mentioned as a testing option, COVID-19 serology has significant shortcomings that needs discussing. This short review is meant to shed light on one of those aspects.", "title": "Severe acute respiratory syndrome coronavirus 2, original antigenic sin, and antibody-dependent enhancement: ménage à trois.", "pid": "ugx8unte", "bm25_score": 215.86402893066406}, {"text": "The new coronavirus outbreak is an ongoing pandemic that is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The new coronavirus SARS-Cov-2 belongs to the subfamily of ß-coronaviruses and shares 79.5% of the genetic sequence of SARS-CoV, the causative agent of the epidemic that started in 2002 and ended in 2004. Considering the clinical impact of the new outbreak, it is highly important to study the potential responses of the human immune system during the SARS-CoV-2 infection as well as the role of virus-specific T cells and by B-lymphocytes. Moreover, specific data on the production of IgG and IgM is crucial to allow the rapid identification of the infection. In this paper we also described the importance of sensitive and specific rapid test for SARS-CoV-2. Indeed, this test represents an important immunological tool aimed at identifying the precise phase of the infection in order to undertake a more appropriate pharmacological treatment. Lastly, we provided an overview of pharmacological treatments aimed to reduce inflammatory processes underlying the infection and the need for the discovery of a new vaccine against SARS-CoV-2.", "title": "SARS-Cov-2 infection: Response of human immune system and possible implications for the rapid test and treatment", "pid": "w3bq48hk", "bm25_score": 215.86231994628906}, {"text": "The severe respiratory disease COVID-19 was initially reported in Wuhan, China, in December 2019, and spread into many provinces from Wuhan. The corresponding pathogen was soon identified as a novel coronavirus named SARS-CoV-2 (formerly, 2019-nCoV). As of 2 May, 2020, over 3 million COVID-19 cases had been confirmed, and 235,290 deaths had been reported globally, and the numbers are still increasing. It is important to understand the phylogenetic relationship between SARS-CoV-2 and known coronaviruses, and to identify its hosts for preventing the next round of emergency outbreak. In this study, we employ an effective alignment-free approach, the Natural Vector method, to analyze the phylogeny and classify the coronaviruses based on genomic and protein data. Our results show that SARS-CoV-2 is closely related to, but distinct from the SARS-CoV branch. By analyzing the genetic distances from the SARS-CoV-2 strain to the coronaviruses residing in animal hosts, we establish that the most possible transmission path originates from bats to pangolins to humans.", "title": "Analysis of the Hosts and Transmission Paths of SARS-CoV-2 in the COVID-19 Outbreak", "pid": "i14gkdw0", "bm25_score": 215.8553466796875}, {"text": "The rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has been accompanied by the emergence of distinct viral clades, though their clinical significance remains unclear. Here, we examined the genome sequences of 88 SARS-CoV-2 viruses from COVID-19 patients in Chicago, USA and identified three distinct phylogenetic clades. Clade 1 was most closely related to clades centered in New York, and showed evidence of rapid expansion across the USA, while Clade 3 was most closely related to those in Washington. Clade 2 was localized primarily to the Chicago area with limited evidence of expansion elsewhere. Average viral loads in the airways of patients infected with the rapidly spreading Clade 1 viruses were significantly higher than those of the poorly spreading Clade 2. These results show that multiple variants of SARS-CoV-2 are circulating in the USA that differ in their relative airway viral loads and potential for expansion.", "title": "A Unique Clade of SARS-CoV-2 Viruses is Associated with Lower Viral Loads in Patient Upper Airways", "pid": "24viekl7", "bm25_score": 215.84640502929688}, {"text": "PURPOSE: The purpose of this study was to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA) in urine and blood specimens, and anal and oropharyngeal swabs from patients with confirmed SARS-CoV-2 infection, and correlated positive results with clinical findings. METHODS: Patients with confirmed SARS-CoV-2 infections were included in this study. Patients' demographic and clinical data were recorded. Quantitative real-time polymerase chain reaction was used to detect SARS-CoV-2 RNA in urine and blood specimens, and anal and oropharyngeal swabs. The study is registered at ClinicalTrials.gov (No. NCT04279782, 19 February, 2020). RESULTS: SARS-CoV-2 RNA was present in all four specimen types, though not all specimen types were positive simultaneously. The presence of viral RNA was not necessarily predictive of clinical symptoms, for example, the presence of viral RNA in the urine did not necessarily predict urinary tract symptoms. CONCLUSIONS: SARS-CoV-2 can infect multiple systems, including the urinary tract. Testing different specimen types may be useful for monitoring disease changes and progression, and for establishing a prognosis.", "title": "SARS-CoV-2 can be detected in urine, blood, anal swabs, and oropharyngeal swabs specimens", "pid": "fgms7mar", "bm25_score": 215.84307861328125}, {"text": "Nearly 400,000 people worldwide are known to have been infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) beginning in December 2019. The virus has now spread to over 168 countries including the United States, where the first cluster of cases was observed in the Seattle metropolitan area in Washington. Given the rapid increase in the number of cases in many localities, the availability of accurate, high-throughput SARS-CoV-2 testing is vital to efforts to manage the current public health crisis. In the course of optimizing SARS-CoV-2 testing performed by the University of Washington Clinical Virology Lab (UW Virology Lab), we evaluated assays using seven different primer-probe sets and one assay kit. We found that the most sensitive assays were those that used the E-gene primer-probe set described by Corman et al. (V. M. Corman, O. Landt, M. Kaiser, R. Molenkamp, et al., Euro Surveill 25:2000045, 2020, https://doi.org/10.2807/1560-7917.ES.2020.25.3.2000045) and the N2 set developed by the CDC (Division of Viral Diseases, Centers for Disease Control and Prevention, 2020, https://www.cdc.gov/coronavirus/2019-ncov/downloads/rt-pcr-panel-primer-probes.pdf). All assays tested were found to be highly specific for SARS-CoV-2, with no cross-reactivity with other respiratory viruses observed in our analyses regardless of the primer-probe set or kit used. These results will provide valuable information to other clinical laboratories who are actively developing SARS-CoV-2 testing protocols at a time when increased testing capacity is urgently needed worldwide.", "title": "Comparative Performance of SARS-CoV-2 Detection Assays Using Seven Different Primer-Probe Sets and One Assay Kit", "pid": "2a1onlj1", "bm25_score": 215.83946228027344}, {"text": "Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is the agent responsible for the coronavirus disease 2019 (COVID-19) global pandemic. SARS-CoV-2 is closely related to SARS-CoV, which caused the 2003 SARS outbreak but disappeared rapidly. Although numerous reagents were developed to study SARS-CoV infections, few have been applicable to evaluating SARS-CoV-2 infection and immunity. Current limitations in studying SARS-CoV-2 include few validated assays with fully replication-competent wild-type virus. We have developed protocols to propagate, quantify, and work with infectious SARS-CoV-2. Here, we describe: (1) virus stock generation, (2) RT-qPCR quantification of SARS-CoV-2 RNA; (3) detection of SARS-CoV-2 antigen by flow cytometry, (4) quantification of infectious SARS-CoV-2 by focus-forming and plaque assays; and 5) validated protocols for virus inactivation. Collectively, these methods can be adapted to a variety of experimental designs, which should accelerate our understanding of SARS-CoV-2 biology and the development of effective countermeasures against COVID-19.", "title": "Growth, detection, quantification, and inactivation of SARS-CoV-2", "pid": "ahu7lda5", "bm25_score": 215.8372039794922}, {"text": "In December 2019, a pneumonia outbreak, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first identified in Wuhan, China and presented a major threat to public health. Nationwide, there were more than 70,000 confirmed cases, and 2500 deaths. Most patients were elderly, with severe disease. For acute respiratory infection, RT-PCR is routinely used to detect causative viruses in respiratory secretions. Coronavirus RNA can be detected from nose and throat swabs, sputum and other lower respiratory tract secretions, blood and feces. Such specimens were examined by RT-PCR. Three targets, RdRP, E and N genes were detected, indicating samples were positive for SARS-CoV-2]. After patient recovery, a chest CT examination, combined with SARS-CoV-2 RNA detection, confirmed diagnosis. However, some recovery patients with negative RNA tests turned RNA positive. The preliminary data is about 14% of discharged patients in Guangdong reported by the Guangdong Center for Disease Control (CDC). This is an important scientific issue. If samples are positive for SARS-CoV-2 RNA, patients should be managed according to infection source. Fortunately, there were no close contacts of second-generation cases. We herein report six SARS-CoV-2 cases confirmed in our hospital, for the changes of results of SARS-CoV-2 RNA should attract attention. Most patients were elderly, with a low Geriatric Nutritional Risk Index (GNRI). However, the association of the phenomenon with aging and GNRI has not yet been reported in detail. Further investigations are necessary to confirm and improve these findings. Similarly, discharged patient follow-up should be strengthened. This article is protected by copyright. All rights reserved.", "title": "Caution should be exercised for the detection of SARS-CoV-2, especially in the elderly.", "pid": "m09q1c58", "bm25_score": 215.8269805908203}, {"text": "The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Hubei province in China in late 2019 demonstrates the epidemic potential of coronaviruses. The rapid spread of this virus across the world in only 2 months highlights the transmissibility of this family of viruses and the significant morbidity and mortality that they can cause. We highlight the current state of knowledge of coronavirus biology while answering questions concerning the current outbreak of SARS-CoV-2.", "title": "COVID-19: Knowns, Unknowns, and Questions", "pid": "ft15w83r", "bm25_score": 215.822265625}, {"text": "BACKGROUND: The pneumonia caused by the 2019 novel coronavirus (SARS-CoV-2, also called 2019-nCoV) recently break out in Wuhan, China, and was named as COVID-19. With the spread of the disease, similar cases have also been confirmed in other regions of China. We aimed to report the imaging and clinical characteristics of these patients infected with SARS-CoV-2 in Guangzhou, China. METHODS: All patients with laboratory-identified SARS-CoV-2 infection by real-time polymerase chain reaction (PCR) were collected between January 23, 2020, and February 4, 2020, in a designated hospital (Guangzhou Eighth People's Hospital). This analysis included 90 patients (39 men and 51 women; median age, 50 years (age range, 18-86 years). All the included SARS-CoV-2-infected patients underwent non-contrast enhanced chest computed tomography (CT). We analyzed the clinical characteristics of the patients, as well as the distribution characteristics, pattern, morphology, and accompanying manifestations of lung lesions. In addition, after 1-6 days (mean 3.5 days), follow-up chest CT images were evaluated to assess radiological evolution. FINDINGS: The majority of infected patients had a history of exposure in Wuhan or to infected patients and mostly presented with fever and cough. More than half of the patients presented bilateral, multifocal lung lesions, with peripheral distribution, and 53 (59%) patients had more than two lobes involved. Of all included patients, COVID-19 pneumonia presented with ground glass opacities in 65 (72%), consolidation in 12 (13%), crazy paving pattern in 11 (12%), interlobular thickening in 33 (37%), adjacent pleura thickening in 50 (56%), and linear opacities combined in 55 (61%). Pleural effusion, pericardial effusion, and lymphadenopathy were uncommon findings. In addition, baseline chest CT did not show any abnormalities in 21 patients (23%), but 3 patients presented bilateral ground glass opacities on the second CT after 3-4 days. CONCLUSION: SARS-CoV-2 infection can be confirmed based on the patient's history, clinical manifestations, imaging characteristics, and laboratory tests. Chest CT examination plays an important role in the initial diagnosis of the novel coronavirus pneumonia. Multiple patchy ground glass opacities in bilateral multiple lobular with periphery distribution are typical chest CT imaging features of the COVID-19 pneumonia.", "title": "Imaging and clinical features of patients with 2019 novel coronavirus SARS-CoV-2", "pid": "zpmlb143", "bm25_score": 215.82196044921875}, {"text": "BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused considerable disruption across the world, resulting in more than 235,000 deaths since December 2019. SARS-CoV-2 has a wide tropism and detection of the virus has been described in multiple specimen types, including various respiratory secretions, cerebrospinal fluid, and stool. OBJECTIVE: To evaluate the accuracy and sensitivity of a laboratory modified CDCbased SARS-CoV-2 N1 and N2 assay across a range of sample types. Study Design We compared the matrix effect on the analytical sensitivity of SARS-CoV-2 detection by qRT-PCR in nasal swabs collected in viral transport medium (VTM), bronchoalveolar lavage (BAL), sputum, plasma, cerebral spinal fluid (CSF), stool, VTM, phosphate buffered saline (PBS), and Hanks' Balanced Salt Solution (HBSS). Initial limits of detection (LoD) were subsequently narrowed to confirm an LoD for each specimen type and target gene. RESULTS: LoDs were established using a modified CDC-based laboratory developed test and ranged from a mean CT cut-off of 33.8-35.7 (10-20 copies/reaction) for the N1 gene target, and 34.0-36.2 (1-10 copies/reaction) for N2. Alternatives to VTM such as PBS and HBSS had comparable LoDs. The N2 gene target was found to be most sensitive in CSF. CONCLUSION: A modified CDC-based laboratory developed test is able to detect SARSCoV- 2 accurately with similar sensitivity across all sample types tested.", "title": "Validation of SARS-CoV-2 detection across multiple specimen types", "pid": "kad7x2ai", "bm25_score": 215.8169403076172}, {"text": "A cluster of severe pneumonia of unknown etiology in Wuhan City, Hubei province in China emerged in December 2019. A novel coronavirus named severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was isolated from lower respiratory tract sample as the causative agent. The current outbreak of infections with SARS-CoV-2 is termed Coronavirus Disease 2019 (COVID-19) by the World Health Organization (WHO). COVID-19 rapidly spread into at least 114 countries and killed more than 4,000 people by March 11 2020. WHO officially declared COVID-19 a pandemic on March 11, 2020. There have been two novel coronavirus outbreaks in the past two decades. The 2002-2003 outbreak of severe acute respiratory syndrome (SARS) in 2002-2003 caused by SARS-CoV had a case fatality rate of around 10% (8,098 confirmed cases and 774 death), while Middle East respiratory syndrome (MERS) caused by MERS-CoV killed 861 people out of a total 2,502 confirmed cases between 2012 and 2019. The purpose of this review is to summarize known-to-date information about SARS-CoV-2, transmission of SARS-CoV-2, and clinical features.", "title": "Epidemiology, virology, and clinical features of severe acute respiratory syndrome -coronavirus-2 (SARS-CoV-2; Coronavirus Disease-19)", "pid": "qjwqmeyo", "bm25_score": 215.8156280517578}, {"text": "The SARS-CoV-2 is a new human coronavirus candidate recently detected in China that is now reported in people on inhabited continents. The virus shares a high level of identity with some bat coronaviruses and is recognised as a potentially zoonotic virus. We are utilizing the One Health concept to understand the emergence of the virus, as well as to point to some possible control strategies that might reduce the spread of the virus across the globe; thus, containment of such virus would be possible.", "title": "The SARS-CoV-2 outbreak from a one health perspective", "pid": "dljpcwl8", "bm25_score": 215.8121337890625}, {"text": "A novel coronavirus SARS-CoV-2 was identified in Wuhan, Hubei Province, China in December of 2019. According to WHO report, this new coronavirus has resulted in 76,392 confirmed infections and 2,348 deaths in China by 22 February, 2020, with additional patients being identified in a rapidly growing number internationally. SARS-CoV-2 was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. Here based on the public database and the state-of-the-art single-cell RNA-Seq technique, we analyzed the ACE2 RNA expression profile in the normal human lungs. The result indicates that the ACE2 virus receptor expression is concentrated in a small population of type II alveolar cells (AT2). Surprisingly, we found that this population of ACE2-expressing AT2 also highly expressed many other genes that positively regulating viral entry, reproduction and transmission. This study provides a biological background for the epidemic investigation of the COVID-19, and could be informative for future anti-ACE2 therapeutic strategy development.", "title": "Single-cell RNA expression profiling of ACE2,thereceptor of SARS-CoV-2", "pid": "4pgish5x", "bm25_score": 215.807861328125}, {"text": "The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; previously provisionally named 2019 novel coronavirus or 2019-nCoV) disease (COVID-19) in China at the end of 2019 has caused a large global outbreak and is a major public health issue. As of 11 February 2020, data from the World Health Organization (WHO) have shown that more than 43 000 confirmed cases have been identified in 28 countries/regions, with >99% of cases being detected in China. On 30 January 2020, the WHO declared COVID-19 as the sixth public health emergency of international concern. SARS-CoV-2 is closely related to two bat-derived severe acute respiratory syndrome-like coronaviruses, bat-SL-CoVZC45 and bat-SL-CoVZXC21. It is spread by human-to-human transmission via droplets or direct contact, and infection has been estimated to have mean incubation period of 6.4 days and a basic reproduction number of 2.24–3.58. Among patients with pneumonia caused by SARS-CoV-2 (novel coronavirus pneumonia or Wuhan pneumonia), fever was the most common symptom, followed by cough. Bilateral lung involvement with ground-glass opacity was the most common finding from computed tomography images of the chest. The one case of SARS-CoV-2 pneumonia in the USA is responding well to remdesivir, which is now undergoing a clinical trial in China. Currently, controlling infection to prevent the spread of SARS-CoV-2 is the primary intervention being used. However, public health authorities should keep monitoring the situation closely, as the more we can learn about this novel virus and its associated outbreak, the better we can respond.", "title": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): The epidemic and the challenges", "pid": "0xhho1sh", "bm25_score": 215.80279541015625}, {"text": "COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.", "title": "Genetic diversity and evolution of SARS-CoV-2", "pid": "can1e8ro", "bm25_score": 215.80245971679688}, {"text": "SARS-CoV-2 is a betacoronavirus that is responsible for the COVID-19 pandemic. The genome of SARS-CoV-2 was reported recently, but its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we here present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical. In addition to the genomic RNA and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces a large number of transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif being AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the internal modification and the 3′ tail. Functional investigation of the unknown ORFs and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2. Highlights We provide a high-resolution map of SARS-CoV-2 transcriptome and epitranscriptome using nanopore direct RNA sequencing and DNA nanoball sequencing. The transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical. In addition to the genomic and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces transcripts encoding unknown ORFs. We discover at least 41 potential RNA modification sites with an AAGAA motif.", "title": "The architecture of SARS-CoV-2 transcriptome", "pid": "wt4pxu08", "bm25_score": 215.80047607421875}, {"text": "SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7,426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.", "title": "The biological characteristics of SARS-CoV-2 Spike protein Pro330-Leu650", "pid": "vhl5adaw", "bm25_score": 215.7924041748047}, {"text": "SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.", "title": "The biological characteristics of SARS-CoV-2 spike protein Pro330-Leu650", "pid": "ufmzv9f4", "bm25_score": 215.7903594970703}, {"text": "In late 2019, a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, the capital of the Chinese province Hubei. Since then, SARS-CoV-2 has been responsible for a worldwide pandemic resulting in over 4 million infections and over 250,000 deaths. The pandemic has instigated widespread research related to SARS-CoV-2 and the disease that it causes, COVID-19. Research into this new virus will be facilitated by the availability of clearly described and effective procedures that enable the propagation and quantification of infectious virus. As work with the virus is recommended to be performed at biosafety level 3, validated methods to effectively inactivate the virus to enable the safe study of RNA, DNA, and protein from infected cells are also needed. Here, we report methods used to grow SARS-CoV-2 in multiple cell lines and to measure virus infectivity by plaque assay using either agarose or microcrystalline cellulose as an overlay as well as a SARS-CoV-2 specific focus forming assay. We also demonstrate effective inactivation by TRIzol, 10% neutral buffered formalin, beta propiolactone, and heat.", "title": "Propagation, Inactivation, and Safety Testing of SARS-CoV-2.", "pid": "eayisepd", "bm25_score": 215.78834533691406}, {"text": "SARS-CoV-2, the novel coronavirus from China, is spreading around the world, causing a huge reaction despite its current low incidence outside China and the Far East. Four common coronaviruses are in current circulation and cause millions of cases worldwide. This article compares the incidence and mortality rates of these four common coronaviruses with those of SARS-CoV-2 in Organisation for Economic Co-operation and Development countries. It is concluded that the problem of SARS-CoV-2 is probably being overestimated, as 2.6 million people die of respiratory infections each year compared with less than 4000 deaths for SARS-CoV-2 at the time of writing.", "title": "SARS-CoV-2: fear versus data", "pid": "zuxos7fi", "bm25_score": 215.7799072265625}, {"text": "Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has caused considerable disruption across the world, resulting in more than 235,000 deaths since December 2019. SARS-CoV-2 has a wide tropism and detection of the virus has been described in multiple specimen types, including various respiratory secretions, cerebrospinal fluid, and stool. Objective To evaluate the accuracy and sensitivity of a laboratory modified CDCbased SARS-CoV-2 N1 and N2 assay across a range of sample types. Study Design We compared the matrix effect on the analytical sensitivity of SARS-CoV-2 detection by qRT-PCR in nasal swabs collected in viral transport medium (VTM), bronchoalveolar lavage (BAL), sputum, plasma, cerebral spinal fluid (CSF), stool, VTM, phosphate buffered saline (PBS), and Hanks' Balanced Salt Solution (HBSS). Initial limits of detection (LoD) were subsequently narrowed to confirm an LoD for each specimen type and target gene. Results LoDs were established using a modified CDC-based laboratory developed test and ranged from a mean CT cut-off of 33.8-35.7 (10-20 copies/reaction) for the N1 gene target, and 34.0-36.2 (1-10 copies/reaction) for N2. Alternatives to VTM such as PBS and HBSS had comparable LoDs. The N2 gene target was found to be most sensitive in CSF. Conclusion A modified CDC-based laboratory developed test is able to detect SARSCoV- 2 accurately with similar sensitivity across all sample types tested.", "title": "Validation of SARS-CoV-2 detection across multiple specimen types.", "pid": "lhj7cd8t", "bm25_score": 215.77877807617188}, {"text": "Coronaviruses are a well-known cause of upper and lower respiratory disease, and since 2002 have been a recognized source of potential pandemic spread. Over the past two decades, since the Severe Acute Respiratory Syndrome (SARS) outbreak, a large body of research has accumulated on the virology, clinical symptoms and signs, and experimental treatments of Coronaviruses. In 2020, a new form of Coronaviruses (SARS-CoV-2) emerged and spread rapidly throughout the globe. Given the wide-ranging clinical presentations of those infected with SARS-CoV-2, other viruses might be overlooked when evaluating at-risk patients. Furthermore, due to suboptimal testing capabilities, an early clinical diagnosis is not always possible. Here, we present a case of a patient with pneumonia thought to be caused by SARS-CoV-2 only to be found to have another Coronavirus. This emphasizes the need to be vigilant when evaluating patients with viral-like respiratory infections.", "title": "Endemic and emerging coronavirus pulmonary infections.", "pid": "74ze1825", "bm25_score": 215.77706909179688}, {"text": "Despite initial findings indicating that SARS-CoV and SARS-CoV-2 are genetically related belonging to the same virus species and that the two viruses used the same entry receptor, angiotensin-converting enzyme 2 (ACE2), our data demonstrated that there is no detectable cross-neutralization by SARS patient sera against SARS-CoV-2. We also found that there are significant levels of neutralizing antibodies in recovered SARS patients 9–17 years after initial infection. These findings will be of significant use in guiding the development of serologic tests, formulating convalescent plasma therapy strategies, and assessing the longevity of protective immunity for SARS-related coronaviruses in general as well as vaccine efficacy.", "title": "Lack of cross-neutralization by SARS patient sera towards SARS-CoV-2", "pid": "8i1u1a9t", "bm25_score": 215.7716827392578}, {"text": "We sequenced four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Malaysia during the second wave of infection and found unique mutations which suggest local evolution. Circulating Malaysian strains represent introductions from different countries, particularly during the first wave of infection. Genome sequencing is important for understanding local epidemiology.", "title": "Complete Genome Sequences of SARS-CoV-2 Strains Detected in Malaysia", "pid": "8r6u3e3i", "bm25_score": 215.767822265625}, {"text": "A newly emerged coronavirus, SARS-CoV-2, caused severe pneumonia outbreaks in China in December 2019 and has since spread to various countries around the world. To trace the evolution route and probe the transmission dynamics of this virus, we performed phylodynamic analysis of 247 high quality genomic sequences available in the GISAID platform as of 5 March 2020. Among them, four genetic clusters, defined as super-spreaders (SSs), could be identified and were found to be responsible for the major outbreaks that subsequently occurred in various countries. SS1 was widely disseminated in Asia and the US, and mainly responsible for outbreaks in the states of Washington and California as well as South Korea, whereas SS4 contributed to the pandemic in Europe. Using the signature mutations of each SS as markers, we further analysed 1539 genome sequences reported after 29 February 2020 and found that 90% of these genomes belonged to SSs, with SS4 being the most dominant. The relative degree of contribution of each SS to the pandemic in different continents was also depicted. Identification of these super-spreaders greatly facilitates development of new strategies to control the transmission of SARS-CoV-2.", "title": "Genetic cluster analysis of SARS-CoV-2 and the identification of those responsible for the major outbreaks in various countries.", "pid": "4zyfc0y4", "bm25_score": 215.76382446289062}, {"text": "Coronavirus disease-19 (COVID-19) pandemic has emerged as one of the major outbreaks to be mentioned in history in coming times. Like Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS), Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a respiratory virus infecting the lungs with fever, dry cough and acute pneumonia being the major symptoms. It infects the epithelial cells expressing Angiotensin converting enzyme 2 (ACE2) receptor, which is crucial for the viral entry. Based on evolving clinical evidence, it is now unfitting to label SARS-CoV-2 as just a respiratory virus, as lately there are various reports that substantiate its pathogenicity in other organs of the body, including brain. In this review, we discuss the epidemiology of SARS-CoV-2 in comparison to SARS and MERS along with possibilities of viral entry into central nervous system (CNS) tissues. The review provides detailed information about the virulence, epidemiology and insights into molecular pathways involved in the infectivity of the SARS-CoV-2 virus, along with in-depth view of current concepts about the neurological significance of the SARS-CoV-2 virus and its neuropathological competence. The review also touches upon our current understanding of placental transmission of SARS-CoV-2, an important aspect of vertical transmission. Furthermore, the review provides the current update on strategies that have been used, being used or under trial for treating the disease.", "title": "SARS-CoV-2 more than a respiratory virus: Its potential role in neuropathogenesis.", "pid": "3buo7now", "bm25_score": 215.7543182373047}, {"text": "Since December 2019, the emergence of the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV-2) infection has been reported unexpectedly in Wuhan, China, with staggering infection speed across China and around the world To date, seven known strains of HCoVs belonging to four genera (i e , alpha?, beta?, gamma, and delta-CoV) have been recognized;the latest one has been identified as the SARS-CoV-2 Although the common transmission routes of SARS-CoV-2 is the respiratory tract, it seems that other routes such as the gastrointestinal tract may be effective for the entry of the virus in the body Although there are no biological markers to predict the susceptibility of humans to COVID-19, several risk factors have been identified to predict the susceptibility of patients to COVID-19 Initial data revealed that males, pregnant women, elderly, and underlying conditions predispose patients to higher morbidity or mortality and also might be at risk for a severe infection of COVID-19 There is a greater need to better understand the mechanisms and risk factors of transmission routes To date, despite the whole world effort to review various aspects of SARS-CoV-2, including epidemiology, clinical manifestations, diagnosis, and treatment options, there are still gaps in the knowledge of this disease and many issues remain unclear Therefore, there is an urgent need for update data on SARS-CoV-2 Here, this study provide the current epidemiological status (transmission routes and risk of transmission, possible origins and source, mortality and morbidity risk, and geographical distribution) of the SARS-CoV-2 in the world in 2020", "title": "Emerging coronaviruses: first SARS, second MERS and third SARS-CoV-2: epidemiological updates of COVID-19", "pid": "o908k448", "bm25_score": 215.75096130371094}, {"text": "COVID-19 has effectively spread worldwide. As of May 2020, Turkey is among the top ten countries with the most cases. A comprehensive genomic characterization of the virus isolates in Turkey is yet to be carried out. Here, we built a phylogenetic tree with globally obtained 15,277 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes. We identified the subtypes based on the phylogenetic clustering in comparison with the previously annotated classifications. We performed a phylogenetic analysis of the first thirty SARS-CoV-2 genomes isolated and sequenced in Turkey. We suggest that the first introduction of the virus to the country is earlier than the first reported case of infection. Virus genomes isolated from Turkey are dispersed among most types in the phylogenetic tree. We find two of the seventeen sub-clusters enriched with the isolates of Turkey, which likely have spread expansively in the country. Finally, we traced virus genomes based on their phylogenetic placements. This analysis suggested multiple independent international introductions of the virus and revealed a hub for the inland transmission. We released a web application to track the global and interprovincial virus spread of the isolates from Turkey in comparison to thousands of genomes worldwide.", "title": "Phylogenetic Analysis of SARS-CoV-2 Genomes in Turkey", "pid": "7u97in7o", "bm25_score": 215.75042724609375}, {"text": "Coronavirus disease-19 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is now a pandemic threat. This virus is supposed to be spread by human to human transmission. Cellular angiotensin-converting enzyme 2 (ACE2) is the receptor of SARS-CoV-2 which is identical or similar in different species of animals such as pigs, ferrets, cats, orangutans, monkeys, and humans. Moreover, a recent study predicted that dogs might be secondary hosts during the evolution of SARS-CoV-2 from bat to human. Therefore, there is a possibility of spreading SARS-CoV-2 through domestic pets. There are now many reports of SARS-CoV-2 positive cases in dogs, cats, tigers, lion, and minks. Experimental data showed ferrets and cats are highly susceptible to SARS-CoV-2 as infected by virus inoculation and can transmit the virus directly or indirectly by droplets or airborne routes. Based on these natural infection reports and experimental data, whether the pets are responsible for SARS-CoV-2 spread to humans; needs to be deeply investigated. Humans showing clinical symptoms of respiratory infections have been undergoing for the COVID-19 diagnostic test but many infected people and few pets confirmed with SARS-CoV-2 remained asymptomatic. In this review, we summarize the natural cases of SARS-CoV-2 in animals with the latest researches conducted in this field. This review will be helpful to think insights of SARS-CoV-2 transmissions, spread, and demand for seroprevalence studies, especially in companion animals.", "title": "SARS-CoV-2 host diversity: An update of natural infections and experimental evidence", "pid": "8dmkchqe", "bm25_score": 215.74803161621094}, {"text": "We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)-associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.", "title": "The Genome sequence of the SARS-associated coronavirus.", "pid": "flu3lrif", "bm25_score": 215.74594116210938}, {"text": "In December 2019, some cases of viral pneumonia were epidemiologically related to a new coronavirus in the province of Hubei, China. Subsequently, there has been an increase in infections attributable to this virus throughout China and worldwide. The World Health Organization (WHO) has officially named the infection coronavirus disease 2019 (COVID-19), and the virus has been classified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This appears to be a virus from Rhinolophus bats, but the intermediate host has not yet been identified. The mechanism of infection of SARS-CoV-2 is not yet known; it appears to have affinity for cells located in the lower airways, where it replicates. The interhuman transmission of coronaviruses mainly occurs through saliva droplets and direct and indirect contact via surfaces. As of March 10, 2020, the number of cases worldwide was 113,702. Along with severe acute respiratory syndrome (SARS) and Middle Eastern respiratory syndrome (MERS), COVID-19 appears to cause a severe clinical picture in humans, ranging from mild malaise to death by sepsis/acute respiratory distress syndrome. The prognosis is worse in elderly patients with comorbidities. To date, there is no specific therapy for COVID-19. Prevention of SARS-CoV-2 infection implies strategies that limit the spread of the virus. WHO and other international and national bodies have developed continuously updated strategic objectives and provisions to contain the spread of the virus and infection.", "title": "Coronavirus: Update Related to the Current Outbreak of COVID-19.", "pid": "g1k3zlax", "bm25_score": 215.74375915527344}]}
{"idx": 32, "qid": "33", "q_text": "What vaccine candidates are being tested for Covid-19?", "qrels": {"01a8er2v": 0, "01lrhbja": 0, "01plpnzu": 0, "01qch6c8": 0, "023h20vk": 2, "qcgc2bo3": 2, "04czoarc": 0, "06jjqmh3": 2, "06xf01wf": 0, "08n9d0au": 0, "yzr7ifbj": 2, "0dbuo39v": 0, "0dxl6t4p": 0, "0f0guyea": 1, "0faqel02": 0, "0fgquau3": 0, "0fx1b7ph": 0, "0g7a9s5z": 1, "0ge95s7r": 2, "0hlj6r10": 0, "0iq9s94n": 1, "0j5bg59c": 1, "0kxo3a4q": 2, "0nplh22v": 0, "0nqz5y20": 0, "0o05oskr": 2, "0oxozbpf": 0, "0pmsfrcx": 0, "0pt6dxb3": 1, "0qtzcda0": 1, "0razl9qf": 0, "0rbgbsj8": 0, "0rq0wdpq": 0, "0sm0r4v8": 0, "0t4uxmj2": 0, "0tdfvlqd": 0, "0tk38fs4": 0, "0u4ar3b5": 0, "0ve0yqfm": 0, "bgbin0y0": 0, "0yqyclxk": 2, "10b7de22": 0, "10ucu0lt": 2, "13jupb26": 2, "14yfs4pa": 0, "15ev0b9d": 0, "18fbtlfg": 2, "19sejitq": 0, "1awz5712": 0, "1c0i5q74": 0, "1c15qxb8": 2, "1cnmpew9": 0, "1ewhqpwb": 0, "1fgnfh62": 0, "1ghjd0c7": 0, "1ir19s25": 2, "fzbu506l": 0, "1kmfxc1e": 0, "1ksz6nmx": 1, "1le537yd": 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An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 – the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.", "title": "Vaccines for COVID-19: the current state of play", "pid": "ievuxa6k", "bm25_score": 216.32479858398438}, {"text": "There is a strong consensus globally that a COVID-19 vaccine is likely the most effective approach to sustainably controlling the COVID-19 pandemic. An unprecedented research effort and global coordination has resulted in a rapid development of vaccine candidates and initiation of trials. Here, we review vaccine types, and progress with 10 vaccine candidates against SARS-CoV-2 - the virus that causes COVID-19 - currently undergoing early phase human trials. We also consider the many challenges of developing and deploying a new vaccine on a global scale, and recommend caution with respect to our expectations of the timeline that may be ahead.", "title": "Vaccines for COVID-19: The current state of play", "pid": "o8bkorjn", "bm25_score": 216.2977752685547}, {"text": "The development of vaccines against SARS-CoV-2 is progressing at an unparalleled speed. As of the 29th of March, there were at least 68 vaccine candidates comprising several different vaccine designs, including whole killed virus, subunit, attenuated, viral vector, DNA and mRNA vaccines. Whilst it usually takes 10-15 years to develop a vaccine, it has only taken just over 9 weeks from the publication of the viral genetic sequence for the first vaccine candidate to reach clinical testing. Development has been expediated by using existing technological platforms and by performing preclinical and clinical testing simultaneously.", "title": "[At least 68 vaccine candidates under development].", "pid": "l9l6z1o0", "bm25_score": 216.26219177246094}, {"text": "", "title": "Trials of BCG vaccine will test for covid-19 protection", "pid": "esqq01qy", "bm25_score": 216.17718505859375}, {"text": "", "title": "COVID-19 vaccines start moving into advanced trials.", "pid": "d0xablub", "bm25_score": 215.97288513183594}, {"text": "", "title": "COVID-19 vaccines start moving into advanced trials", "pid": "3se9jbq4", "bm25_score": 215.7837677001953}, {"text": "SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this, outbreak specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS- CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. UISS is then potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2.", "title": "In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform", "pid": "71n1tgrw", "bm25_score": 215.72886657714844}, {"text": "SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this outbreak, specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS-CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. Universal Immune System Simulator (UISS) in silico platform is potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2.", "title": "In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform", "pid": "48knj0tm", "bm25_score": 215.71932983398438}, {"text": "Drug developers are moving their experimental vaccines for COVID-19 into clinical trials at a frenetic pace Trials for five such vaccines have begun in China Two are being tested in the US, with a third slated to start this month And trials of two more are due to begin in the UK and Australia in the coming weeks “Everything from basic science to clinical science is progressing at a pace faster than ever before—and very appropriately, given the grave nature of the current global crisis,” says Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center The World Health Organization says at least 70 COVID-19 vaccines are in development, while scientists at the Coalition for Epidemic Preparedness Innovations (CEPI) have counted 115 Moderna was the first to begin clinical testing of a COVID-19 vaccine, just 66 days after downloading the genome of SARS-CoV-2,", "title": "COVID-19 vaccines move toward clinic", "pid": "y2bylnte", "bm25_score": 215.51296997070312}, {"text": "The whole globe is reeling under the COVID-19 pandemic now. With the scale and severity of infection, number of deaths and lack of any definite therapeutic armamentarium, the vaccine development has been accelerated at a never-before pace. A wide variety of vaccine technologies and platforms are being attempted. Out of the over 108 efforts, 100 are in preclinical and eight in Phase 1 or 2 trial stage. While the availability of newer technologies has facilitated development, there are several challenges on the way including limited understanding of the pathophysiology, targeting humoral or mucosal immunity, lack of suitable animal model, poor success of human severe acute respiratory syndrome/Middle East Respiratory Syndrome vaccines, limited efficacy of influenza vaccines, and immune exaggeration with animal coronavirus vaccines. With the current scenario with political, funding, research, and regulatory supports, if everything sails through smoothly, the successful vaccine is expected in 12-18 months. Modestly efficacious vaccine may be also a good achievement.", "title": "COVID-19 vaccine development and the way forward.", "pid": "d51wognj", "bm25_score": 215.4732208251953}, {"text": "", "title": "Development of potential COVID-19 vaccines continues to accelerate", "pid": "2oukbdmx", "bm25_score": 215.34860229492188}, {"text": "Rapid diagnostics, vaccines and therapeutics are important interventions for the management of the 2019 novel coronavirus (2019-nCoV) outbreak. It is timely to systematically review the potential of these interventions, including those for Middle East respiratory syndrome-Coronavirus (MERS-CoV) and severe acute respiratory syndrome (SARS)-CoV, to guide policymakers globally on their prioritization of resources for research and development. A systematic search was carried out in three major electronic databases (PubMed, Embase and Cochrane Library) to identify published studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Supplementary strategies through Google Search and personal communications were used. A total of 27 studies fulfilled the criteria for review. Several laboratory protocols for confirmation of suspected 2019-nCoV cases using real-time reverse transcription polymerase chain reaction (RT-PCR) have been published. A commercial RT-PCR kit developed by the Beijing Genomic Institute is currently widely used in China and likely in Asia. However, serological assays as well as point-of-care testing kits have not been developed but are likely in the near future. Several vaccine candidates are in the pipeline. The likely earliest Phase 1 vaccine trial is a synthetic DNA-based candidate. A number of novel compounds as well as therapeutics licensed for other conditions appear to have in vitro efficacy against the 2019-nCoV. Some are being tested in clinical trials against MERS-CoV and SARS-CoV, while others have been listed for clinical trials against 2019-nCoV. However, there are currently no effective specific antivirals or drug combinations supported by high-level evidence.", "title": "Potential Rapid Diagnostics, Vaccine and Therapeutics for 2019 Novel Coronavirus (2019-nCoV): A Systematic Review", "pid": "m95bmi9t", "bm25_score": 215.31393432617188}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.", "title": "Development of an inactivated vaccine candidate for SARS-CoV-2", "pid": "5bftuzw5", "bm25_score": 215.30157470703125}, {"text": "The whole globe is reeling under the COVID-19 pandemic now. With the scale and severity of infection, number of deaths and lack of any definite therapeutic armamentarium, the vaccine development has been accelerated at a never-before pace. A wide variety of vaccine technologies and platforms are being attempted. Out of the over 108 efforts, 100 are in preclinical and eight in Phase 1 or 2 trial stage. While the availability of newer technologies has facilitated development, there are several challenges on the way including limited understanding of the pathophysiology, targeting humoral or mucosal immunity, lack of suitable animal model, poor success of human severe acute respiratory syndrome/Middle East Respiratory Syndrome vaccines, limited efficacy of influenza vaccines, and immune exaggeration with animal coronavirus vaccines. With the current scenario with political, funding, research, and regulatory supports, if everything sails through smoothly, the successful vaccine is expected in 12-18 months. Modestly efficacious vaccine may be also a good achievement.", "title": "COVID-19 vaccine development and the way forward", "pid": "8boyzwxf", "bm25_score": 215.25167846679688}, {"text": "", "title": "The COVID-19 vaccine development landscape.", "pid": "o9fke21q", "bm25_score": 215.1945037841797}, {"text": "Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres.", "title": "Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19", "pid": "jgbjxgh1", "bm25_score": 215.06166076660156}, {"text": "As the COVID-19 pandemic is intensifying globally, more and more people are pinning their hopes on the development of vaccines. At present, there are many research teams who have adopted different vaccine technology routes to develop 2019-nCoV vaccines. This article reviews and analyzes the current development and research status of 2019-nCoV vaccines in different routes, and explores their possible development in the future.", "title": "[Progress and analysis on the development of 2019-nCoV vaccine].", "pid": "tfa4lixq", "bm25_score": 215.0012664794922}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are currently no SARS-CoV-2-specific treatments or vaccines available due to the novelty of the virus. Hence, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans.", "title": "Development of an inactivated vaccine candidate for SARS-CoV-2", "pid": "f5s0ntps", "bm25_score": 215.00119018554688}, {"text": "Vaccine development against SARS-CoV-2 has drawn attention around the globe due to the exploding pandemic. Although COVID-19 is caused by a new coronavirus, SARS-CoV-2, previous research on other coronavirus vaccines, such as FIPV, SARS, and MERS, has provided valuable information for the rapid development of COVID-19 vaccine. However, important knowledge gaps remain - some are specific to SARS-CoV-2, others are fundamental to immunology and vaccinology. Here, we discuss areas that need to be addressed for COVID-19 vaccine development, and what can be learned from examples of vaccine development in the past. Since the beginning of the outbreak, the research progress on COVID-19 has been remarkable. We are therefore optimistic about the rapid development of COVID-19 vaccine.", "title": "COVID-19 vaccines: Knowing the unknown", "pid": "hotn7qha", "bm25_score": 214.97499084472656}, {"text": "The recent outbreak of SARS-CoV-2 (2019-nCoV) virus has highlighted the need for fast and efficacious vaccine development. Stimulation of a proper immune response that leads to protection is highly dependent on presentation of epitopes to circulating T-cells via the HLA complex. SARS-CoV-2 is a large RNA virus and testing of all overlapping peptides in vitro to deconvolute an immune response is not feasible. Therefore HLA-binding prediction tools are often used to narrow down the number of peptides to test. We tested 19 epitope-HLA-binding prediction tools, and using an in vitro peptide MHC stability assay, we assessed 777 peptides that were predicted to be good binders across 11 MHC allotypes. In this investigation of potential SARS-CoV-2 epitopes we found that current prediction tools vary in performance when assessing binding stability, and they are highly dependent on the MHC allotype in question. Designing a COVID-19 vaccine where only a few epitope targets are included is therefore a very challenging task. Here, we present 174 SARS-CoV-2 epitopes with high prediction binding scores, validated to bind stably to 11 HLA allotypes. Our findings may contribute to the design of an efficacious vaccine against COVID-19.", "title": "COVID-19 Vaccine Candidates: Prediction and Validation of 174 SARS-CoV-2 Epitopes", "pid": "wxagjqbt", "bm25_score": 214.918212890625}, {"text": "", "title": "The COVID-19 vaccine development landscape", "pid": "diq2x0nx", "bm25_score": 214.91116333007812}, {"text": "To counter the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), some have proposed accelerating SARS-CoV-2 vaccine development through controlled human infection (or 'challenge') trials. These trials would involve the deliberate exposure of relatively few young, healthy volunteers to SARS-CoV-2. We defend this proposal against the charge that there is still too much uncertainty surrounding the risks of COVID-19 to responsibly run such a trial.", "title": "Why continuing uncertainties are no reason to postpone challenge trials for coronavirus vaccines.", "pid": "6dwyv4qo", "bm25_score": 214.9080047607422}, {"text": "SARS-CoV-2 is spreading globally at a rapid pace. To contain its spread and prevent further fatalities, the development of a vaccine against SARS-CoV-2 is an urgent prerequisite. Thus, in this article, by utilizing the in silico approach, a vaccine candidate for SARS-CoV-2 has been proposed. Moreover, the effectiveness and safety measures of our proposed epitopic vaccine candidate have been evaluated by in silico tools and servers (AllerTOP and AllergenFP servers). We observed that the vaccine candidate has no allergenicity and successfully combined with Toll-like receptor (TLR) protein to elicit an inflammatory immune response. Stable, functional mobility of the vaccine-TLR protein binding interface was confirmed by the Normal Mode Analysis. The in silico cloning model demonstrated the efficacy of the construct vaccine along with the identified epitopes against SARS-CoV-2. Taken together, our proposed in silico vaccine candidate has potent efficacy against COVID-19 infection, and successive research work might validate its effectiveness in in vitro and in vivo models.", "title": "A SARS-CoV-2 vaccine candidate: In silico cloning and validation", "pid": "du2zxq96", "bm25_score": 214.90109252929688}, {"text": "", "title": "Challenges in evaluating SARS-CoV-2 vaccines during the COVID-19 pandemic.", "pid": "5lgo81qm", "bm25_score": 214.87997436523438}, {"text": "", "title": "COVID-19 vaccine development pipeline gears up", "pid": "3vjj5m3s", "bm25_score": 214.87538146972656}, {"text": "", "title": "Challenges in evaluating SARS-CoV-2 vaccines during the COVID-19 pandemic", "pid": "8z81pcnb", "bm25_score": 214.79818725585938}, {"text": "In December 2019, the outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a serious pandemic in China and other countries worldwide. So far, more than 460,000 confirmed cases were diagnosed in nearly 190 countries, causing globally over 20,000 deaths. Currently, the epidemic is still spreading and there is no effective means to prevent the infection. Vaccines are proved to be the most effective and economical means to prevent and control infectious diseases. Several countries, companies, and institutions announced their programs and progress on vaccine development against the virus. While most of the vaccines are under design and preparation, there are some that have entered efficacy evaluation in animals and initial clinical trials. This review mainly focused on the progress and our prospects on field of vaccine development against SARS-CoV-2.", "title": "Progress and Prospects on Vaccine Development against SARS-CoV-2", "pid": "gl0wiyt2", "bm25_score": 214.77801513671875}, {"text": "", "title": "Questions remain following first COVID-19 vaccine results.", "pid": "uyvbn3u9", "bm25_score": 214.770263671875}, {"text": "Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) emerged in December 20191,2 and is responsible for the COVID-19 pandemic3. Vaccines are an essential countermeasure urgently needed to control the pandemic4. Here, we show that the adenovirus-vectored vaccine ChAdOx1 nCoV-19, encoding the spike protein of SARS-CoV-2, is immunogenic in mice, eliciting a robust humoral and cell-mediated response. This response was not Th2 dominated, as demonstrated by IgG subclass and cytokine expression profiling. A single vaccination with ChAdOx1 nCoV-19 induced a humoral and cellular immune response in rhesus macaques. We observed a significantly reduced viral load in bronchoalveolar lavage fluid and respiratory tract tissue of vaccinated animals challenged with SARS-CoV-2 compared with control animals, and no pneumonia was observed in vaccinated rhesus macaques. Importantly, no evidence of immune-enhanced disease following viral challenge in vaccinated animals was observed. ChAdOx1 nCoV-19 is currently under investigation in a phase I clinical trial. Safety, immunogenicity and efficacy against symptomatic PCR-positive COVID-19 disease will now be assessed in randomised controlled human clinical trials.", "title": "ChAdOx1 nCoV-19 vaccination prevents SARS-CoV-2 pneumonia in rhesus macaques", "pid": "uexahhdr", "bm25_score": 214.75997924804688}, {"text": "", "title": "Developing a vaccine for covid-19.", "pid": "aoxsl823", "bm25_score": 214.7550811767578}, {"text": "The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.", "title": "Immunogenicity of a DNA vaccine candidate for COVID-19", "pid": "f5xs0tv2", "bm25_score": 214.73907470703125}, {"text": "The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern. However, no specific antiviral treatments or vaccines are available yet. This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2.", "title": "The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines", "pid": "zn182czp", "bm25_score": 214.73046875}, {"text": "COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.", "title": "Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials.", "pid": "oa8vzf02", "bm25_score": 214.710693359375}, {"text": "", "title": "COVID-19 vaccination clinical trials should consider multiple doses of BCG.", "pid": "751esa3a", "bm25_score": 214.6771240234375}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has reached global epidemic status claiming more than 319K lives and affecting more than 4 81M people and counting worldwide Considering the severity of the situation and low recovery rate many research institutions and pharmaceutical industries are rushing to learn more about this new virus and the morbid physiology of this disease with effective diagnostic methods, therapeutic agents and vaccines Various approaches are highlighted for comparing the possible treatment methods available for COVID-19 some of which are BCG vaccination on COVID-19 and Non-pharmaceutical interventions, drug based clinical trials of Hydroxychloroquine-Azithromycin, chloroquine, lopinavir/ritonavir, ChAdOx1 nCoV-19, Remdesivir, Stem Cell therapy and mesenchymal stromal cell therapy, etc", "title": "Current Clinical Trials and Vaccine Development Strategies for Corona Virus Disease (COVID-19)", "pid": "ev8n2n52", "bm25_score": 214.67391967773438}, {"text": "Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for which a vaccine is urgently needed to control its spreading. To facilitate the representation of a native-like immunogen without being infectious, here, we reported a SARS-CoV-2 vaccine candidate (designated ShaCoVacc) by incorporating spike-encoding mRNA inside and decorating spike protein on the surface of the virus simulating particles (VSPs) derived from lentiviral particles. We characterized the mRNA copy number, glycosylation status, transduction efficiency, and innate immune property of the new vaccine platform. Importantly, we showed the ShaCoVacc induced strong spike-specific humoral immune responses and potent neutralizing activities by a single injection. Additionally, we disclosed the epitopes of spike-specific antibodies using peptide microarray and revealed epitopes susceptible to specific neutralizing antibodies. These results support further development of ShaCoVacc as a candidate vaccine for COVID-19 and VSP may serve as a new vaccine platform for emerging infectious diseases.", "title": "A single dose SARS-CoV-2 simulating particle vaccine induces potent neutralizing activities", "pid": "ptvsie6m", "bm25_score": 214.66114807128906}, {"text": "", "title": "COVID-19: The race for a vaccine", "pid": "rgi28k3d", "bm25_score": 214.64952087402344}, {"text": "The ongoing novel coronavirus disease 2019 (COVID-19) pandemic has been responsible for millions of infections and hundreds of thousands of deaths. To date, there is no approved targeted treatment, and many investigational therapeutic agents and vaccine candidates are being considered for the treatment of COVID-19. To extract and summarize information on potential vaccines and therapeutic agents against COVID-19 at different stages of clinical trials from January to March 2020, we reviewed major clinical trial databases such as ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP), and other primary registries between January and March 15, 2020. Interventional studies at different phases under the COVID-19 pipeline were included. A total of 249 clinical trials were identified between January to March 15, 2020. After filtering observational studies (194 studies), a total of 56 interventional trials were considered. The majority of clinical trials have been conducted on chloroquine (n=10) and traditional Chinese medications (TCMs; n=10), followed by antivirals (n=8), anti-inflammatory/immunosuppressants (n=9), cellular therapies (n=4), combinations of different antivirals therapies (n=3), antibacterial (n=1), and other therapies (n=5). Five vaccines are under phase I, and there are a couple of phase III trials on the Bacillus Calmette-Guérin (BCG) vaccine under investigation among healthcare workers. Many novel compounds and vaccines against COVID-19 are currently under investigation. Some candidates have been tested for other viral infections and are listed for clinical trials against the COVID-19 pipeline. Currently, there are no effective specific antivirals or drug combinations available for the treatment of COVID-19.", "title": "Vaccines and Drug Therapeutics to Lock Down Novel Coronavirus Disease 2019 (COVID-19): A Systematic Review of Clinical Trials", "pid": "p36zubnf", "bm25_score": 214.63345336914062}, {"text": "", "title": "Coronavirus vaccine trials have delivered their first results - but their promise is still unclear", "pid": "np7for7b", "bm25_score": 214.63319396972656}, {"text": "PURPOSE OF REVIEW: The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19). RECENT FINDINGS: Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS-CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID-19 epidemic in China. Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS-CoV vaccines, it is expected that all COVID-19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID-19 vaccine target product profile must address vaccinating at-risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. SUMMARY: Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time.", "title": "The SARS-CoV-2 Vaccine Pipeline: an Overview", "pid": "rl2qxd03", "bm25_score": 214.6298065185547}, {"text": "Purpose of Review: The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19). Recent Findings: Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS-CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID-19 epidemic in China. Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS-CoV vaccines, it is expected that all COVID-19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID-19 vaccine target product profile must address vaccinating at-risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. Summary: Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time.", "title": "The SARS-CoV-2 Vaccine Pipeline: an Overview", "pid": "7jsponjx", "bm25_score": 214.6298065185547}, {"text": "COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.", "title": "Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials", "pid": "3sepefqa", "bm25_score": 214.61392211914062}, {"text": "", "title": "The Development of COVID-19 Vaccines: Safeguards Needed.", "pid": "7q0v7ezd", "bm25_score": 214.5976104736328}, {"text": "The continued explosive spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) despite aggressive public health measures has triggered an unprecedented international vaccine effort. However, correlates of protection, which can help guide intelligent vaccine design, are not known for SARS-CoV-2. Research on influenza immunity and vaccine development may provide valuable lessons for coronavirus efforts, especially considering similarities in rapid evolutionary potential. The apparent inevitability of future novel coronavirus outbreaks must prompt work on a universal coronavirus vaccine.", "title": "Universal coronavirus vaccines: the time to start is now", "pid": "yrrz7oef", "bm25_score": 214.577392578125}, {"text": "", "title": "COVID-19: An update on vaccine development", "pid": "zo7xfgds", "bm25_score": 214.56900024414062}, {"text": "", "title": "Developing Covid-19 Vaccines at Pandemic Speed.", "pid": "0qd7bn53", "bm25_score": 214.5491180419922}, {"text": "", "title": "Four vaccine manufacturers have been asked by the US HHS to test their vaccines against coronavirus,", "pid": "zz8wvos9", "bm25_score": 214.54603576660156}, {"text": "", "title": "Can existing live vaccines prevent COVID-19?", "pid": "1on7j9w3", "bm25_score": 214.54196166992188}, {"text": "", "title": "Covid-19: What do we know so far about a vaccine?", "pid": "j6lbxlm3", "bm25_score": 214.53094482421875}, {"text": "", "title": "Progress and Concept for COVID-19 Vaccine Development", "pid": "9j63ilwo", "bm25_score": 214.51614379882812}, {"text": "", "title": "The Development of COVID-19 Vaccines: Safeguards Needed", "pid": "m0v0nzxl", "bm25_score": 214.4846649169922}, {"text": "", "title": "Questions remain following first COVID-19 vaccine results", "pid": "ocqsg8e4", "bm25_score": 214.48306274414062}, {"text": "", "title": "Coronavirus vaccine trials have delivered their first results - but their promise is still unclear.", "pid": "eanrbr0a", "bm25_score": 214.4810791015625}, {"text": "", "title": "Developing a vaccine for covid-19", "pid": "gf44xeb6", "bm25_score": 214.47305297851562}, {"text": "The COVID-19 has turned in to a global human tragedy and economic devastation. Governments have implemented lockdown measures, blocked international travel, and enforced other public containment measures to mitigate the virus morbidity and mortality. As of today, no drug has the power to fight the infection and bring normalcy to the utter chaos. This leaves us with only one choice namely an effective and safe vaccine that shall be manufactured as soon as possible and available to all countries and populations affected by the pandemic at an affordable price. There has been an unprecedented fast track path taken in Research & Development (R&D) by the World community for developing an effective and safe vaccine. Platform technology has been exploited to develop candidate vaccines in a matter of days to weeks and as of now, 108 such vaccines are available. Six of these vaccines have entered clinical trials. As clinical trials are ‘rate-limiting’ and ‘time-consuming’, many innovative methods are in practice for a fast track. These include parallel phase I-II trials and obtaining efficacy data from phase IIb trials. Human ‘challenge experiments’ to confirm efficacy in humans is under serious consideration. The availability of the COVID-19 vaccine has become a race against time in the middle of death and devastation. There is an atmosphere of tremendous hype around the COVID-19 vaccine and developers are using every moment to make claims, which remain unverified. However, concerns are raised about a rush to deploy a COVID-19 vaccine. Applying ‘Quick fix’ and ‘short cuts’ can lead to errors with disastrous consequences.", "title": "COVID-19 vaccines: A race against time in the middle of death and devastation!", "pid": "u3ek83tn", "bm25_score": 214.47048950195312}, {"text": "In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS-COV-2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID-19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.", "title": "Towards effective COVID-19 vaccines: Updates, perspectives and challenges (Review)", "pid": "0o05oskr", "bm25_score": 214.44869995117188}, {"text": "The recent Coronavirus Disease 2019 (COVID-19) causes an immense health crisis to global public health. The World Health Organization (WHO) declared the COVID-19 as a pandemic. The COVID-19 is the etiologic agent of a recently arose disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Presently, there is no vaccine available against this emerged viral disease. Therefore, it is indeed a need of the hour to develop an effectual and safe vaccine against this decidedly pandemic disease. In the current study, we collected SARS-CoV-2 genome from Indian geographical origin against human host, further more using reverse vaccinology and immunoinformatics tools here we claim effective vaccine candidates that can be mile stone in battle against COVID19. This novel study divulged two promising antigenic peptide GVYFASTEK and NFRVQPTESIV from surface glycoproteins (protein accession no. – QIA98583.1 and QHS34546.1) of SARS-CoV-2, which were predicated to be interacted with class I and class II MHC alleles and showed up to 90% conservancy and high value of antigenicity. Subsequently, the molecular docking studies were verified molecular interaction of these prime antigenic peptides with the residues of HLA-A*11-01 allele for MHC Class I and HLA DRB1*04-01 allele for MHC class II. After vigorous analysis, these peptides were predicted to be suitable epitopes which are capable to elicit the strong cell-mediated immune response against the SARS-CoV-2. Consequences from the present study could facilitate selecting SARS-CoV-2 epitopes for vaccine production pipelines in the immediate future. This novel research will certainly pave the way for a fast, reliable and virtuous platform to provide timely countermeasure of this dangerous pandemic disease, COVID-19.", "title": "Identification of potential vaccine candidates against SARS-CoV-2, A step forward to fight novel coronavirus 2019-nCoV: A Reverse Vaccinology Approach", "pid": "sdiwnhs0", "bm25_score": 214.4462890625}, {"text": "", "title": "The starting line for COVID-19 vaccine development", "pid": "3qkjq6a3", "bm25_score": 214.4437713623047}, {"text": "Conventional wisdom is that a vaccine for COVID-19 is at least 1 year away, but the organizers of a U S government push called Operation Warp Speed have little use for conventional wisdom The project, vaguely described to date but likely to be formally announced by the White House in the coming days, will pick a diverse set of vaccine candidates and pour essentially limitless resources into unprecedented comparative studies in animals, fast-tracked human trials, and manufacturing Eschewing international cooperation—and any vaccine candidates from China—it hopes to have 300 million doses by January 2021 of a proven product, reserved for Americans", "title": "Unveiling ‘Warp Speed,’ the White House’s America-first push for a coronavirus vaccine", "pid": "29jafdti", "bm25_score": 214.4290771484375}, {"text": "The explosively expanding COVID-19 pandemic urges the development of safe, efficacious and fast-acting vaccines to quench the unrestrained spread of SARS-CoV-2. Several promising vaccine platforms, developed in recent years, are leveraged for a rapid emergency response to COVID-191. We employed the live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express the prefusion form of the SARS-CoV-2 Spike antigen. In mice, the vaccine candidate, tentatively named YF-S0, induces high levels of SARS-CoV-2 neutralizing antibodies and a favorable Th1 cell-mediated immune response. In a stringent hamster SARS-CoV-2 challenge model2, vaccine candidate YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose confers protection from lung disease in most vaccinated animals even within 10 days. These results warrant further development of YF-S0 as a potent SARS-CoV-2 vaccine candidate.", "title": "A single-dose live-attenuated YF17D-vectored SARS-CoV2 vaccine candidate", "pid": "zwsvlnwe", "bm25_score": 214.4213104248047}, {"text": "More than 100 coronavirus vaccines are in development, but will any of them work?", "title": "Countdown to a vaccine", "pid": "wrgyeng3", "bm25_score": 214.41783142089844}, {"text": "In response to provocative comments by 2 European clinicians and scientists, the World Health Organization Director General has declared that Africa will not host COVID-19 vaccine trials. Such a stance risks stigmatizing COVID-19 vaccine trials in Africa and depriving Africa of critical research. To the contrary, there is a critical need for Africa to host COVID-19 vaccine trials on public health, scientific, and ethics grounds.", "title": "The Case for Why Africa Should Host COVID-19 Candidate Vaccine Trials", "pid": "dv1g8jz7", "bm25_score": 214.40615844726562}, {"text": "", "title": "Covid-19: Oxford team begins vaccine trials in Brazil and South Africa to determine efficacy.", "pid": "xrfm8i3j", "bm25_score": 214.40432739257812}, {"text": "Abstract While a human challenge study holds the prospect of accelerating the development of a vaccine for the coronavirus SARS-CoV-2, it may be opposed due to risks of harm to participants and researchers. Given the increasing number of human deaths and severe disruption to lives worldwide, we argue that a SARS-CoV-2 challenge study is ethically justifiable as its social value substantially outweighs the risks. Such a study should therefore be seriously considered as part of the global research response towards the COVID-19 pandemic. In this paper, we contribute to the debate by addressing the misperception that a challenge study for the coronavirus would lower scientific and ethical standards for vaccine research and development, and examine how it could be ethically conducted. We also set out information that needs to be disclosed to prospective participants to obtain their consent.", "title": "COVID-19 vaccine development: Time to consider SARS-CoV-2 challenge studies?", "pid": "v2559gaz", "bm25_score": 214.37034606933594}, {"text": "In the current context of the pandemic triggered by SARS-COV-2, the immunization of the population through vaccination is recognized as a public health priority. In the case of SARS­COV­2, the genetic sequencing was done quickly, in one month. Since then, worldwide research has focused on obtaining a vaccine. This has a major economic impact because new technological platforms and advanced genetic engineering procedures are required to obtain a COVID­19 vaccine. The most difficult scientific challenge for this future vaccine obtained in the laboratory is the proof of clinical safety and efficacy. The biggest challenge of manufacturing is the construction and validation of production platforms capable of making the vaccine on a large scale.", "title": "Towards effective COVID­19 vaccines: Updates, perspectives and challenges (Review)", "pid": "fdprd9c4", "bm25_score": 214.3646240234375}, {"text": "", "title": "COVID-19 vaccination clinical trials should consider multiple doses of BCG", "pid": "y56doh22", "bm25_score": 214.34970092773438}, {"text": "", "title": "Covid-19 pandemic: Will a vaccine be available soon?", "pid": "0ge95s7r", "bm25_score": 214.3413543701172}, {"text": "", "title": "Developing Covid-19 Vaccines at Pandemic Speed", "pid": "tfwyuhmx", "bm25_score": 214.33876037597656}, {"text": "Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. A possibility of a resurgence of COVID-19 in places where lockdowns have already worked is also developing. Thus, for controlling COVID-19, vaccines may be a better option than drugs. An mRNA-based anti-COVID-19 candidate vaccine has entered a phase 1 clinical trial. However, its efficacy and potency have to be evaluated and validated. Since vaccines have high failure rates, as an alternative, we are presenting a new, designed multi-peptide subunit-based epitope vaccine against COVID-19. The recombinant vaccine construct comprises an adjuvant, cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes joined by linkers. The computational data suggest that the vaccine is non-toxic, non-allergenic, thermostable, with the capability to elicit a humoral and cell-mediated immune response. The stabilization of the vaccine construct is validated with molecular dynamics simulation studies. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host-receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as a public health priority.", "title": "Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2", "pid": "8lktpcda", "bm25_score": 214.3379669189453}, {"text": "", "title": "Coronavirus vaccines: five key questions as trials begin.", "pid": "laww0spk", "bm25_score": 214.33639526367188}, {"text": "Recently, there are several routes for COVID-19 vaccine research, yet their weaknesses lie in low efficiency, tolerability, immune adaptability and safety. We describe a new approach to COVID-19 based on engineered human mesenchymal stem cells(hu-MSC), which is like a small protein antigen response device, but will be gradually cleared and degraded by body’s immune system among recognization process. The antibody response results show that this is effective and fast. Furthermore, after several antibody response tests, we obtained an injection of a set of cocktail-like modified human mesenchymal stem cell line. This strategy opened a new avenue for vaccine design against COVID-19.", "title": "Engineered human mesenchymal stem cells as new vaccine platform for COVID-19", "pid": "4oy6cf2k", "bm25_score": 214.33367919921875}, {"text": "In this review, we address issues that relate to the rapid \"Warp Speed\" development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of \"Warp Speed\" immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the \"Warp Speed\" vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.", "title": "SARS-CoV-2 vaccines: 'Warp Speed' needs mind melds not warped minds", "pid": "khfiy0m2", "bm25_score": 214.33323669433594}, {"text": "In this review, we address issues that relate to the rapid \"Warp Speed\" development of vaccines to counter the COVID-19 pandemic. We review the antibody response that is triggered by SARS-CoV-2 infection of humans, and how it may inform vaccine research. The isolation and properties of neutralizing monoclonal antibodies from COVID-19 patients provide additional information on what vaccines should try to elicit. The nature and longevity of the antibody response to coronaviruses are relevant to the potency and duration of vaccine-induced immunity. We summarize the immunogenicity of leading vaccine candidates tested to date in animals and humans, and discuss the outcome and interpretation of virus-challenge experiments in animals. By far the most immunogenic vaccine candidates for antibody responses are recombinant proteins, which are not included in the initial wave of \"Warp Speed\" immunogens. A substantial concern for SARS-CoV-2 vaccines is adverse events, which we review by considering what was seen in studies of SARS-CoV-1 and MERS-CoV vaccines. We conclude by outlining the possible outcomes of the \"Warp Speed\" vaccine program, which range from the hoped-for rapid success to a catastrophic adverse influence on vaccine uptake generally.", "title": "SARS-CoV-2 vaccines: 'Warp Speed' needs mind melds not warped minds.", "pid": "y883anmp", "bm25_score": 214.32936096191406}, {"text": "While a human challenge study holds the prospect of accelerating the development of a vaccine for the coronavirus SARS-CoV-2, it may be opposed due to risks of harm to participants and researchers. Given the increasing number of human deaths and severe disruption to lives worldwide, we argue that a SARS-CoV-2 challenge study is ethically justifiable as its social value substantially outweighs the risks. Such a study should therefore be seriously considered as part of the global research response towards the COVID-19 pandemic. In this paper, we contribute to the debate by addressing the misperception that a challenge study for the coronavirus would lower scientific and ethical standards for vaccine research and development, and examine how it could be ethically conducted. We also set out information that needs to be disclosed to prospective participants to obtain their consent.", "title": "COVID-19 vaccine development: Time to consider SARS-CoV-2 challenge studies?", "pid": "f92w4dld", "bm25_score": 214.32901000976562}, {"text": "At present, novel Coronavirus (2019-nCoV, the causative agent of COVID-19) has caused worldwide social and economic disruption. The disturbing statistics of this infection promoted us to develop an effective vaccine candidate against the COVID-19. In this study, bioinformatics approaches were employed to design and introduce a novel multi-epitope vaccine against 2019-nCoV that can potentially trigger both CD4+ and CD8+ T-cell immune responses and investigated its biological activities by computational tools. Three known antigenic proteins (Nucleocapsid, ORF3a, and Membrane protein, hereafter called NOM) from the virus were selected and analyzed for prediction of the potential immunogenic B and T-cell epitopes and then validated using bioinformatics tools. Based on in silico analysis, we have constructed a multi-epitope vaccine candidate (NOM) with five rich-epitopes domain including highly scored T and B-cell epitopes. After predicting and evaluating of the third structure of the protein candidate, the best 3 D predicted model was applied for docking studies with Toll-like receptor 4 (TLR4) and HLA-A*11:01. In the next step, molecular dynamics (MD) simulation was used to evaluate the stability of the designed fusion protein with TLR4 and HLA-A*11:01 receptors. MD studies demonstrated that the NOM-TLR4 and NOM-HLA-A*11:01 docked models were stable during simulation time. In silico evaluation showed that the designed chimeric protein could simultaneously elicit humoral and cell-mediated immune responses. Communicated by Ramaswamy H. Sarma.", "title": "Reverse vaccinology approach to design a novel multi-epitope vaccine candidate against COVID-19: an in silico study", "pid": "rwtv6yys", "bm25_score": 214.3255615234375}, {"text": "At present, novel Coronavirus (2019-nCoV, the causative agent of COVID-19) has caused worldwide social and economic disruption. The disturbing statistics of this infection promoted us to develop an effective vaccine candidate against the COVID-19. In this study, bioinformatics approaches were employed to design and introduce a novel multi-epitope vaccine against 2019-nCoV that can potentially trigger both CD(4+) and CD(8+) T-cell immune responses and investigated its biological activities by computational tools. Three known antigenic proteins (Nucleocapsid, ORF3a, and Membrane protein, hereafter called NOM) from the virus were selected and analyzed for prediction of the potential immunogenic B and T-cell epitopes and then validated using bioinformatics tools. Based on in silico analysis, we have constructed a multi-epitope vaccine candidate (NOM) with five rich-epitopes domain including highly scored T and B-cell epitopes. After predicting and evaluating of the third structure of the protein candidate, the best 3 D predicted model was applied for docking studies with Toll-like receptor 4 (TLR4) and HLA-A*11:01. In the next step, molecular dynamics (MD) simulation was used to evaluate the stability of the designed fusion protein with TLR4 and HLA-A*11:01 receptors. MD studies demonstrated that the NOM-TLR4 and NOM-HLA-A*11:01 docked models were stable during simulation time. In silico evaluation showed that the designed chimeric protein could simultaneously elicit humoral and cell-mediated immune responses. Communicated by Ramaswamy H. Sarma", "title": "Reverse vaccinology approach to design a novel multi-epitope vaccine candidate against COVID-19: an in silico study", "pid": "c5uesg6p", "bm25_score": 214.31558227539062}, {"text": "The global coronavirus pandemic is unlike any other since 1918. A century of dramatic medical advances has produced a public expectation that the medical field will rapidly provide solutions to restore normalcy. In under 6 months, since SARS-CoV-2 was identified, the massive international effort to develop a SARS-CoV-2 vaccine has generated more than 140 vaccines in different stages of development with 9 already recruiting into clinical trials posted on clinicaltrials.gov. The long-term strategy to handle COVID-19 will almost certainly rely on vaccines. But, what type of protection can we realistically expect to achieve from vaccines and when?", "title": "On setting expectations for a SARS-CoV-2 Vaccine", "pid": "7lk8h93q", "bm25_score": 214.2977294921875}, {"text": "Wuhan Novel Coronavirus disease (COVID-19) outbreak has become a global outbreak which has raised the concern of scientific community to design and discover a definitive cure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no antiviral therapy or vaccine is available which can effectively combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Later, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. Hopefully, this study will contribute to uphold the present efforts of the researches to secure a definitive treatment against this lethal virus.", "title": "The Essential Facts of Wuhan Novel Coronavirus Outbreak in China and Epitope-based Vaccine Designing against COVID-19", "pid": "7vrm081c", "bm25_score": 214.29579162597656}, {"text": "A public-private partnership and platform for harmonized clinical trials aims to accelerate licensure and distribution.", "title": "A strategic approach to COVID-19 vaccine R&D.", "pid": "dd4avd5w", "bm25_score": 214.283447265625}, {"text": "", "title": "Anticipating SARS-CoV-2 Vaccine Testing, Licensure, and Recommendations for Use", "pid": "udlz5mjm", "bm25_score": 214.28111267089844}, {"text": "", "title": "Logistical challenges for potential SARS-CoV-2 vaccine and a call to research institutions, developers and manufacturers", "pid": "ttoysaxz", "bm25_score": 214.27883911132812}, {"text": "Controlled human challenge trials of SARS-CoV-2 vaccine candidates could accelerate the testing and potential rollout of efficacious vaccines. By replacing conventional phase 3 testing of vaccine candidates, such trials may subtract many months from the licensure process, making efficacious vaccines available more quickly. Obviously, challenging volunteers with this live virus risks inducing severe disease and possibly even death. However, we argue that such studies, by accelerating vaccine evaluation, could reduce the global burden of coronavirus-related mortality and morbidity. Volunteers in such studies could autonomously authorize the risks to themselves, and their net risk could be acceptable if participants comprise healthy young adults, who are at relatively low risk of serious disease following natural infection, if they have a high baseline risk of natural infection, and if during the trial they receive frequent monitoring and, following any infection, the best available care.", "title": "Human Challenge Studies to Accelerate Coronavirus Vaccine Licensure", "pid": "vqxrjtgb", "bm25_score": 214.2740478515625}, {"text": "The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading globally, and the WHO has declared this outbreak a pandemic. Vaccines are an effective way to prevent the rapid spread of COVID-19. Furthermore, the immune response against SARS-CoV-2 infection needs to be understood for the development of an efficient and safe vaccine. Here, we review the current understanding of vaccine targets and the status of vaccine development for COVID-19. We also describe host immune responses to highly pathogenic human coronaviruses in terms of innate and adaptive immunities.", "title": "Progress and Challenges in the Development of COVID-19 Vaccines and Current Understanding of SARS-CoV-2- Specific Immune Responses.", "pid": "m7yii8el", "bm25_score": 214.2655487060547}, {"text": "PURPOSE: COVID-19 as a pandemic calls for rapid development of vaccines. METHODS: Here a proposal of a seamless, adaptive, phase 1–3 trial for accelerated vaccine development is described. RESULTS: Starting at 10, the number of vaccinated volunteers would exponentially increase by tenfold at an interval of 2 weeks; close surveillance of antibody responses, safety and efficacy is necessary. After only 16 weeks, general vaccination would be feasible if supply meets the demand. CONCLUSION: A COVID-19 vaccine would be rapidly available at a slightly increased risk for undetected late side effects or insufficient efficacy if compared with standard vaccine development schemes.", "title": "Calling for an exponential escalation scheme in vaccine development for COVID-19", "pid": "f2iuy9e1", "bm25_score": 214.26119995117188}, {"text": "Novel corona virus disease 2019 (COVID-19) is emerging as a pandemic situation and declared as a global health emergency by WHO. Due to lack of specific medicine and vaccine, viral infection has gained a frightening rate and created a devastating state across the globe. Here the authors have attempted to design epitope based potential peptide as a vaccine candidate using immunoinformatics approach. As of evidence from literatures, SARS-CoV-2 Spike protein is a key protein to initiate the viral infection within a host cell thus used here as a reasonable vaccine target. We have predicted a 9-mer peptide as representative of both B-cell and T-cell epitopic region along with suitable properties such as antigenic and non-allergenic. To its support, strong molecular interaction of the predicted peptide was also observed with MHC molecules and Toll Like receptors. The present study may helpful to step forward in the development of vaccine candidates against COVID-19.", "title": "Identification of peptide candidate against COVID-19 through reverse vaccinology: An immunoinformatics approach", "pid": "1ir19s25", "bm25_score": 214.25733947753906}, {"text": "Abstract In March 2020, the WHO declared a pandemic of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). With >8.8 million cases and >450,000 deaths reported globally, a vaccine is urgently needed. We report the available safety, tolerability, and immunogenicity data from an ongoing placebo-controlled, observer-blinded dose escalation study among healthy adults, 18-55 years of age, randomized to receive 2 doses, separated by 21 days, of 10 g, 30 g, or 100 g of BNT162b1, a lipid nanoparticle-formulated, nucleoside-modified, mRNA vaccine that encodes trimerized SARS-CoV-2 spike glycoprotein RBD. Local reactions and systemic events were dose-dependent, generally mild to moderate, and transient. RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titers in sera increased with dose level and after a second dose. Geometric mean neutralizing titers reached 1.8- to 2.8-fold that of a panel of COVID-19 convalescent human sera. These results support further evaluation of this mRNA vaccine candidate.", "title": "Phase 1/2 Study to Describe the Safety and Immunogenicity of a COVID-19 RNA Vaccine Candidate (BNT162b1) in Adults 18 to 55 Years of Age: Interim Report", "pid": "akbq0ogs", "bm25_score": 214.24708557128906}, {"text": "Abstract Zika virus outbreaks have been explosive and unpredictable and have led to significant adverse health effects—as well as considerable public anxiety. Significant scientific work has resulted in multiple candidate vaccines that are now undergoing further clinical development, with several vaccines now in phase 2 clinical trials. In this review, we survey current vaccine efforts, preclinical and clinical results, and ethical and other concerns that directly bear on vaccine development. It is clear that the world needs safe and effective vaccines to protect against Zika virus infection. Whether such vaccines can be developed through to licensure and public availability absent significant financial investment by countries, and other barriers discussed within this article, remains uncertain.", "title": "Zika Vaccine Development: Current Status", "pid": "0pmsfrcx", "bm25_score": 214.24020385742188}, {"text": "Efforts towards developing a vaccine for Middle East respiratory syndrome coronavirus (MERS-CoV) have yielded promising results. Utilizing a variety of platforms, several vaccine approaches have shown efficacy in animal models and begun to enter clinical trials. In this review, we summarize the current progress towards a MERS-CoV vaccine and highlight potential roadblocks identified from previous attempts to generate coronavirus vaccines.", "title": "Middle East Respiratory Syndrome Vaccine Candidates: Cautious Optimism", "pid": "cy45w8vq", "bm25_score": 214.23959350585938}, {"text": "The twenty-first century has come with a new era in vaccinology, in which recombinant genetic technology has contributed to setting an unprecedented fast pace in vaccine development, clearly demonstrated during the recent COVID-19 pandemic.", "title": "COVID-19 vaccines: breaking record times to first-in-human trials", "pid": "6r9cgkgw", "bm25_score": 214.23834228515625}, {"text": "", "title": "Covid-19: Oxford team begins vaccine trials in Brazil and South Africa to determine efficacy", "pid": "b1elwvwt", "bm25_score": 214.23699951171875}, {"text": "PURPOSE: COVID-19 as a pandemic calls for rapid development of vaccines. METHODS: Here a proposal of a seamless, adaptive, phase 1-3 trial for accelerated vaccine development is described. RESULTS: Starting at 10, the number of vaccinated volunteers would exponentially increase by tenfold at an interval of 2 weeks; close surveillance of antibody responses, safety and efficacy is necessary. After only 16 weeks, general vaccination would be feasible if supply meets the demand. CONCLUSION: A COVID-19 vaccine would be rapidly available at a slightly increased risk for undetected late side effects or insufficient efficacy if compared with standard vaccine development schemes.", "title": "Calling for an exponential escalation scheme in vaccine development for COVID-19", "pid": "u7xfq6zo", "bm25_score": 214.23548889160156}, {"text": "", "title": "Scores of coronavirus vaccines are in competition - how will scientists choose the best?", "pid": "p6mmt2am", "bm25_score": 214.22962951660156}, {"text": "The ongoing outbreak of the recently emerged 2019 novel coronavirus (nCoV), which has seriously threatened global health security, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with high morbidity and mortality. Despite the burden of the disease worldwide, still, no licensed vaccine or any specific drug against 2019-nCoV is available. Data from several countries show that few repurposed drugs using existing antiviral drugs have not (so far) been satisfactory and more recently were proven to be even highly toxic. These findings underline an urgent need for preventative and therapeutic interventions designed to target specific aspects of 2019-nCoV. Again the major factor in this urgency is that the process of data acquisition by physical experiment is time-consuming and expensive to obtain. Scientific simulations and more in-depth data analysis permit to validate or refute drug repurposing opportunities predicted via target similarity profiling to speed up the development of a new more effective anti-2019-nCoV therapy especially where in vitro and/or in vivo data are not yet available. In addition, several research programs are being developed, aiming at the exploration of vaccines to prevent and treat the 2019-nCoV. Computational-based technology has given us the tools to explore and identify potentially effective drug and/or vaccine candidates which can effectively shorten the time and reduce the operating cost. The aim of the present review is to address the available information on molecular determinants in disease pathobiology modules and define the computational approaches employed in systematic drug repositioning and vaccine development settings for SARS-CoV-2.", "title": "Vaccine development and therapeutic design for 2019-nCoV/SARS-CoV-2: Challenges and chances", "pid": "y5tts376", "bm25_score": 214.2248992919922}, {"text": "Azithromycin has been shown to have a clinical efficacy against severe acute respiratory syndrome coronavirus 2; ivermectin has also demonstrated a remarkable experimental efficacy with a potential to be used for Coronavirus disease 2019. Further, BCG vaccination is being considered for clinical trials aiming to test its potential for lowering COVID-19 morbidity and mortality. This article illustrates some structural and functional relationships that may gather these drugs and the author, basing on a combined pathophysiological and pharmacological approach, recommends the FDA-approved antidiarrhea drug; nitazoxanide, which has been previously suggested but unfortunately widely ignored, to be tested in combination with azithromycin for their potential activity against SARS CoV-2, soonest. The author also recommends testing their combined administration as early during the clinical course of COVID-19 as possible. Further, basing on the same represented concept, the author suggests more trials for interferons to be tested against SARS CoV-2, especially in severe and critical COVID-19 cases.", "title": "Nitazoxanide/azithromycin combination for COVID-19: A suggested new protocol for early management", "pid": "xiwi5149", "bm25_score": 214.19671630859375}, {"text": "", "title": "Biovacc-19: A Candidate Vaccine for Covid-19 (SARS-CoV-2) Developed from Analysis of its General Method of Action for Infectivity", "pid": "3byzr4qe", "bm25_score": 214.1954345703125}, {"text": "The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).", "title": "SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice", "pid": "2nruf2g7", "bm25_score": 214.19464111328125}, {"text": "Many drugs and vaccines are now being developed and tested", "title": "The hunt for covid-19 drugs", "pid": "cdctlduc", "bm25_score": 214.19427490234375}, {"text": "Researchers in four countries will soon start a clinical trial of an unorthodox approach to the new coronavirus They will test whether a century-old vaccine against tuberculosis (TB), a bacterial disease, can rev up the human immune system in a broad way, allowing it to better fight the virus that causes coronavirus disease 2019 and, perhaps, prevent infection with it altogether The studies will be done in physicians and nurses, who are at higher risk of becoming infected with the respiratory disease than the general population, and in the elderly, who are at higher risk of serious illness if they become infected", "title": "Can a century-old TB vaccine steel the immune system against the new coronavirus?", "pid": "9xome3no", "bm25_score": 214.1875}, {"text": "", "title": "Vaccines, convalescent plasma, and monoclonal antibodies for covid-19.", "pid": "t9wz4t6e", "bm25_score": 214.1775360107422}, {"text": "Abstract Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. A possibility of a resurgence of COVID-19 in places where lockdowns have already worked is also developing. Thus, for controlling COVID-19, vaccines may be a better option than drugs. An mRNA-based anti-COVID-19 candidate vaccine has entered a phase 1 clinical trial. However, its efficacy and potency have to be evaluated and validated. Since vaccines have high failure rates, as an alternative, we are presenting a new, designed multi-peptide subunit-based epitope vaccine against COVID-19. The recombinant vaccine construct comprises an adjuvant, cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes joined by linkers. The computational data suggest that the vaccine is non-toxic, non-allergenic, thermostable, with the capability to elicit a humoral and cell-mediated immune response. The stabilization of the vaccine construct is validated with molecular dynamics simulation studies. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host-receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as a public health priority.", "title": "Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2", "pid": "d2j9wpqk", "bm25_score": 214.171142578125}]}
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"ysbopqqq": 0, "ysiuvdc8": 2, "ysyqai97": 0, "yth3t2cf": 0, "kcimahsa": 0, "ytk3jcb4": 0, "yv5q8pyr": 1, "yvtsgqco": 0, "ywhwjso6": 0, "yxmqmetv": 0, "yxnq17cd": 0, "s91sz7c0": 0, "yy96yeu9": 0, "yzffm05r": 0, "z0jp7dt7": 0, "z0vup2lr": 0, "z1fj5n5l": 0, "z1ueptnf": 0, "vqxi8zqf": 0, "z3oqccqn": 0, "f6szlsxr": 0, "z6my1d83": 0, "za3qypgg": 0, "zaaj1jw2": 0, "zblitbo0": 0, "ze2hnddp": 0, "7kidc16v": 0, "6dqepr39": 0, "zfn440oj": 0, "zg51e060": 0, "zgapjjjw": 0, "zgr2xkzk": 0, "ktug3nk1": 0, "zhcamsqa": 0, "zhrpiknd": 0, "zi98dq1v": 0, "zifccdqm": 0, "zio8yhuy": 0, "zju2cscs": 0, "zkaau32d": 0, "eecj4uud": 0, "zlp6v2e3": 0, "zm19i41q": 0, "zmaw9lbz": 0, "zndtddty": 0, "zo3bh4se": 0, "zp4uy1v7": 0, "zpb9jicw": 0, "zpqgz95r": 0, "zqbw7uc9": 0, "52vh3ohw": 0, "j48ajsfx": 1, "zs86lyxq": 0, "zszexapf": 0, "v0v0ahjh": 0, "hlbjrkqp": 0, "zwgqnhhc": 0, "zwz0z35n": 0, "zxg4e064": 0, "j6p9fepp": 0}, "bm25_results": [{"text": "With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.", "title": "Long term complications and rehabilitation of COVID-19 patients.", "pid": "7s04ygm2", "bm25_score": 217.27159118652344}, {"text": "With the ongoing pandemic of COVID-19 having caught the world almost unaware millions of people across the globe are presently grappling to deal with its acute effects . Our previous experience with members of the same corona virus family (SARS and MERS) which have caused two major epidemics in the past albeit of much lower magnitude , has taught us that the harmful effect of such outbreaks are not limited to acute complications alone .Long term cardiopulmonary, glucometabolic and neuropsychiatric complications have been documented following these infections .In the given circumstance it is therefore imperative to keep in mind the possible complications that may occur after the acute phase of the disease subsides and to prepare the healthcare system for such challenges.", "title": "Long term complications and rehabilitation of COVID-19 patients", "pid": "yudrouue", "bm25_score": 217.22225952148438}, {"text": "Objective: To determine the long-term clinical problems in adult survivors of coronavirus (CoV) infection [Coronavirus disease 2019 (COVID-19), Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS)] after hospitalisation or Intensive Care Unit (ICU) admission. Design: Systematic review and meta-analysis of the literature. Data sources: Ovid MEDLINE, EMBASE, CINAHL Plus and PsycINFO were searched using the strategy: (Coronavirus OR Coronavirus Infections OR COVID OR SARS virus OR Severe acute respiratory syndrome OR MERS OR Middle east respiratory syndrome) AND (Follow-up OR Follow-up studies OR Prevalence). Original studies reporting the clinical outcomes of adult survivors of coronavirus outbreaks two months after discharge or three months after admission were included. The quality of the studies was assessed using the Oxford Centre for Evidence-Based Medicine (OCEBM) 2009 Level of Evidence Tool. Meta-analysis was conducted to derive pooled estimates of prevalence and severity for different outcomes at time points up to 6 months follow-up and beyond 6 months follow-up. Results: The search yielded 1169 studies of which 28 were included in this review. There were 15 Level 1b, 8 Level 2b, 2 Level 3b and 3 Level 4 studies by OCEBM grading. Pooled analysis of studies revealed that complications commonly observed were impaired diffusing capacity for carbon monoxide (DLCO) [prevalence of 27.26%, 95% CI 14.87 to 44.57] and reduced exercise capacity [(6-minute walking distance (6MWD) mean 461m, 95% CI 449.66 to 472.71] at 6 months with limited improvement beyond 6 months. Coronavirus survivors had considerable prevalence of psychological disorders such as post-traumatic stress disorder (PTSD) [38.80%, CI 30.93 to 47.31], depression [33.20%, CI 19.80 to 50.02] and anxiety [30.04%, CI 10.44 to 61.26) beyond 6 months. These complications were accompanied by low Short Form 36 (SF-36) scores at 6 months and beyond indicating reduced quality of life which is present long-term. Conclusions: The long term clinical problems in survivors of CoV infections (SARS and MERS) after hospitalisation or Intensive Care Unit (ICU) admission include respiratory dysfunction, reduced exercise capacity, psychological problems such as PTSD, depression and anxiety, and reduced quality of life. Critical care, rehabilitation and mental health services should anticipate a high prevalence of these problems following COVID-19 and ensure their adequate and timely management with the aim of restoring premorbid quality of life.", "title": "LONG-TERM CLINICAL OUTCOMES IN SURVIVORS OF CORONAVIRUS OUTBREAKS AFTER HOSPITALISATION OR ICU ADMISSION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF FOLLOW-UP STUDIES", "pid": "bzc7luwj", "bm25_score": 216.0171356201172}, {"text": "Patients who survive influenza A (H7N9) virus infection are at risk of physical and psychological complications of lung injury and multi-organ dysfunction. However, there were no prospectively individualized assessments of physiological, functional and quality-of-life measures after hospital discharge. The current study aims to assess the main determinants of functional disability of these patients during the follow-up. Fifty-six influenza A (H7N9) survivors were investigated during the 2-year after discharge from the hospital. Results show interstitial change and fibrosis on pulmonary imaging remained 6 months after hospital discharge. Both ventilation and diffusion dysfunction improved, but restrictive and obstructive patterns on ventilation function test persisted throughout the follow-up period. For patients with acute respiratory distress syndrome lung functions improved faster during the first six months. Role-physical and Role-emotional domains in the 36-Item Short-Form Health Survey were worse than those of a sex- and age-matched general population group. The quality of life of survivors with ARDS was lower than those with no ARDS. Our findings suggest that pulmonary function and imaging findings improved during the first 6 months especially for those with ARDS, however long-term lung disability and psychological impairment in H7N9 survivors persisted at 2 years after discharge from the hospital.", "title": "Long term outcomes in survivors of epidemic Influenza A (H7N9) virus infection", "pid": "mena480g", "bm25_score": 215.6993865966797}, {"text": "OBJECTIVE To determine long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infections after hospitalization or intensive care unit admission. DATA SOURCES Ovid MEDLINE, EMBASE, CINAHL Plus, and PsycINFO were searched. STUDY SELECTION Original studies reporting clinical outcomes of adult SARS and MERS survivors 3 months after admission or 2 months after discharge were included. DATA EXTRACTION Studies were graded using the Oxford Centre for Evidence-Based Medicine 2009 Level of Evidence Tool. Meta-analysis was used to derive pooled estimates for prevalence/severity of outcomes up to 6 months, and beyond. DATA SYNTHESIS Of 1,169 identified studies, 28 were included in the analysis. Pooled analysis revealed that common complications up to 6 months were: impaired diffusing capacity for carbon monoxide (prevalence 27%, 95% confidence interval (CI) 15-45%); and reduced exercise capacity ((mean 6-min walking distance 461 m, CI 450-473 m). The prevalences of post-traumatic stress disorder (39%, 95% CI 31-47%), depression (33%, 95% CI 20-50%) and anxiety (30%, 95% CI 10-61) beyond 6 months were considerable. Low scores on Short-Form 36 were identified at 6 months and beyond. CONCLUSION Lung function abnormalities, psychological impairment and reduced exercise capacity were common in SARS and MERS survivors. Clinicians should anticipate and investigate similar long-term outcomes in COVID-19 survivors.", "title": "Long-term clinical outcomes in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: A systematic review and meta-analysis.", "pid": "bpiiddi7", "bm25_score": 215.48109436035156}, {"text": "OBJECTIVE: To determine long-term clinical outcomes in survivors of severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus infections after hospitalization or intensive care unit admission. DATA SOURCES: Ovid MEDLINE, EMBASE, CINAHL Plus, and PsycINFO were searched. STUDY SELECTION: Original studies reporting clinical outcomes of adult SARS and MERS survivors 3 months after admission or 2 months after discharge were included. DATA EXTRACTION: Studies were graded using the Oxford Centre for Evidence-Based Medicine 2009 Level of Evidence Tool. Meta-analysis was used to derive pooled estimates for prevalence/severity of outcomes up to 6 months after hospital discharge, and beyond 6 months after discharge. DATA SYNTHESIS: Of 1,169 identified studies, 28 were included in the analysis. Pooled analysis revealed that common complications up to 6 months after discharge were: impaired diffusing capacity for carbon monoxide (prevalence 27%, 95% confidence interval (CI) 15­45%); and reduced exercise capacity (mean 6-min walking distance 461 m, CI 450­473 m). The prevalences of post-traumatic stress disorder (39%, 95% CI 31­47%), depression (33%, 95% CI 20­50%) and anxiety (30%, 95% CI 10­61) beyond 6 months after discharge were considerable. Low scores on Short-Form 36 were identified beyond 6 months after discharge. CONCLUSION: Lung function abnormalities, psychological impairment and reduced exercise capacity were common in SARS and MERS survivors. Clinicians should anticipate and investigate similar long-term outcomes in COVID-19 survivors.", "title": "Long-term clinical outcomes in survivors of severe acute respiratory syndrome and Middle East respiratory syndrome coronavirus outbreaks after hospitalisation or ICU admission: A systematic review and meta-analysis", "pid": "0sd7rv5v", "bm25_score": 215.43946838378906}, {"text": "COVID-19 survivors can have serious complications from this viral infection, particularly respiratory and cardiovascular with severe asthenia and fatigue. Several studies have already demonstrated the benefit of early rehabilitation after the acute phase, especially in patients who have been in intensive care. The authors present a rehabilitation program including interdisciplinary care with simple and reproducible clinical criteria.", "title": "[Rehabilitation is crucial for severe COVID-19 survivors].", "pid": "jud53dmv", "bm25_score": 215.40074157714844}, {"text": "", "title": "Long-term Pulmonary Consequences of Coronavirus Disease 2019 (COVID-19): What We Know and What to Expect.", "pid": "1ebmmjve", "bm25_score": 215.2244110107422}, {"text": "", "title": "Long-term Pulmonary Consequences of Coronavirus Disease 2019 (COVID-19): What We Know and What to Expect", "pid": "x84qatio", "bm25_score": 215.1875}, {"text": "Up to 20-30% of patients hospitalized with coronavirus disease (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment for COVID-19 may affect convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk for cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19 associated cardiac injury is needed. The type of testing, and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of \"post-COVID-19 Cardiac Syndrome\".", "title": "COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors", "pid": "bsqpkjcj", "bm25_score": 215.13348388671875}, {"text": "Up to 20-30% of patients hospitalized with coronavirus disease (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment for COVID-19 may affect convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk for cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19 associated cardiac injury is needed. The type of testing, and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of “post-COVID-19 Cardiac Syndrome”", "title": "COVID-19 Cardiac Injury: Implications for Long-Term Surveillance and Outcomes in Survivors", "pid": "3tna1y5o", "bm25_score": 215.11605834960938}, {"text": "Corona virus disease 2019 (COVID-19) is a new disease characterized by lung damage and involvement in multiple tissues and organs in the whole body. Some of the patients may have long-term impairment and dysfunctions, including pulmonary fibrosis, heart, liver, kidney, nerve and immune system. Rehabilitation has certain beneficial effect in the acute stage, and especially in the recovery stage, including improving respiratory function, exercise endurance, self-care in daily living activities, as well as psychological support, etc. Rehabilitation is not offside or absent. A reasonable rehabilitation program needs scientific research to avoid arbitrary conclusions.", "title": "Rehabilitation management of patients with COVID-19. Lessons learned from the first experiences in China", "pid": "i1i8ab07", "bm25_score": 214.97850036621094}, {"text": "The scale of the COVID-19 pandemic is entirely unprecedented. However, as depicted in Fig. 1, evidence from previous large-scale disasters indicates that following a first wave of admissions and deaths from COVID-19, there are likely to be subsequent waves of people with acute care needs worsened by delayed hospital treatment, and people with long-term conditions whose routine care has been disrupted [1]. People with diabetes are likely to constitute a large proportion of those with acute second- and third-wave care needs, and in many cases, management of their condition may also have been negatively affected by lockdown.", "title": "How do we recover from COVID-19? Helping diabetes teams foresee and prepare for the psychological harms", "pid": "q79r4dbl", "bm25_score": 214.92750549316406}, {"text": "The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been recently declared a pandemic by the World Health Organization. In addition to its acute respiratory manifestations, SARS-CoV-2 may also adversely affect other organ systems. To date, however, there is very limited understanding of the extent and management of COVID-19-related conditions outside of the pulmonary system. This narrative review provides an overview of the current literature about the extra-pulmonary manifestations of COVID-19 that may affect the urinary, cardiovascular, gastrointestinal, hematological, hematopoietic, neurological, or reproductive systems. This review also describes current understanding of the extra-pulmonary complications caused by COVID-19 in order to improve the management and prognosis of patients with COVID-19. This article is protected by copyright. All rights reserved.", "title": "Extra-pulmonary complications of COVID-19: a multi-system disease?", "pid": "t9dpmh0h", "bm25_score": 214.91201782226562}, {"text": "Increasing evidence suggests that infection with Sars-CoV-2 causes neurological deficits in a substantial proportion of affected patients. While these symptoms arise acutely during the course of infection, less is known about the possible long-term consequences for the brain. Severely affected COVID-19 cases experience high levels of proinflammatory cytokines and acute respiratory dysfunction and often require assisted ventilation. All these factors have been suggested to cause cognitive decline. Pathogenetically, this may result from direct negative effects of the immune reaction, acceleration or aggravation of pre-existing cognitive deficits, or de novo induction of a neurodegenerative disease. This article summarizes the current understanding of neurological symptoms of COVID-19 and hypothesizes that affected patients may be at higher risk of developing cognitive decline after overcoming the primary COVID-19 infection. A structured prospective evaluation should analyze the likelihood, time course, and severity of cognitive impairment following the COVID-19 pandemic.", "title": "Immediate and long-term consequences of COVID-19 infections for the development of neurological disease", "pid": "ds12pmp1", "bm25_score": 214.91058349609375}, {"text": "Corona virus disease 2019 (COVID-19) is a new disease characterized by lung damage and involvement in multiple tissues and organs in the whole body. Some of the patients may have long-term impairment and dysfunctions, including pulmonary fibrosis, heart, liver, kidney, nerve and immune system. Rehabilitation has certain beneficial effect in the acute stage, and especially in the recovery stage, including improving respiratory function, exercise endurance, self-care in daily living activities, as well as psychological support, etc. Rehabilitation is not offside or absent. A reasonable rehabilitation program needs scientific research to avoid arbitrary conclusions.", "title": "Effect and enlightenment of rehabilitation medicine in COVID-19 management.", "pid": "0354z6wh", "bm25_score": 214.87164306640625}, {"text": "The pandemic of swine flu (H1N1) influenza spread to involve the whole world rapidly. Many patients manifested a mild clinical illness but some developed pneumonia and respiratory failure. High mortality was observed in patients with severe disease. Among survivors, studies are limited. Ground-glass opacities on a high-resolution computerized tomography scan and reduced diffusion capacity were noted after 3 months in a study. But long-term complications in patients with swine flu pneumonia have not been studied well. We are presenting an unusual case of swine flu pneumonia who developed interstitial lung disease after recovery.", "title": "Pulmonary sequelae in a patient recovered from swine flu", "pid": "aclzp3iy", "bm25_score": 214.83421325683594}, {"text": "Recovery from coronavirus disease 2019 (COVID-19) will be principally defined in terms of remission from respiratory symptoms, however both clinical and animal studies have shown that coronaviruses may spread to the nervous system. A systematic search on previous viral epidemics revealed that while there has been relatively little research in this area, clinical studies have commonly reported neurological disorders and cognitive difficulties. Little is known with regard to their incidence, duration or underlying neural basis. The hippocampus appears to be particularly vulnerable to coronavirus infections, thus increasing the probability of post-infection memory impairment, and acceleration of neurodegenerative disorders such as Alzheimer’s disease. Future knowledge of the impact of COVID-19, from epidemiological studies and clinical practice, will be needed to develop future screening and treatment programmes to minimize the long-term cognitive consequences of COVID-19.", "title": "The cognitive consequences of the COVID-19 epidemic: collateral damage?", "pid": "cb7k2zbe", "bm25_score": 214.81942749023438}, {"text": "Coronavirus disease 2019 (COVID-19) represents a significant global medical issue, with a growing number of cumulative confirmed cases. However, a large number of COVID-19 patients have overcome the disease, meeting hospital discharge criteria, and are gradually returning to work and social life. Nonetheless, COVID-19 may cause further downstream issues in these patients, such as due to possible reactivation of the virus, long-term pulmonary defects, and post-traumatic stress disorder. In this study, we therefore queried relevant literature concerning SARS, MERS, and COVID-19 for reference to come to a consensus on follow-up strategies. We found that strategies such as implementation of PCR testing, imaging surveillance, and psychological assessments, starting at the time of discharge, were necessary for long-term follow-up. If close care is given to every aspect of coronavirus management, we expect that the pandemic outbreak will soon be overcome. This article is protected by copyright. All rights reserved.", "title": "Patient Follow-up after Discharge after COVID-19 Pneumonia: Considerations for Infectious Control", "pid": "x7rzvmcr", "bm25_score": 214.7559356689453}, {"text": "Prior studies of patient survivorship after an intensive care unit (ICU) stay suggest that many critically ill patients with COVID-19 will face long-lasting physical, cognitive and/or mental health impairments. This anticipated survivorship experience highlights the importance of collaboration between the fields of critical care and rehabilitation to optimize post-COVID-19 recovery.", "title": "Survivorship after COVID-19 ICU stay", "pid": "lcqxnrge", "bm25_score": 214.75582885742188}, {"text": "BACKGROUND: The long-term pulmonary function and related physiological characteristics of COVID-19 survivors have not been studied in depth, thus many aspects are not understood. METHODS: COVID-19 survivors were recruited for high resolution computed tomography (HRCT) of the thorax, lung function and serum levels of SARS-CoV-2 IgG antibody tests 3 months after discharge. The relationship between the clinical characteristics and the pulmonary function or CT scores were investigated. FINDINGS: Fifty-five recovered patients participated in this study. SARS-CoV-2 infection related symptoms were detected in 35 of them and different degrees of radiological abnormalities were detected in 39 patients. Urea nitrogen concentration at admission was associated with the presence of CT abnormalities (P = 0.046, OR 7.149, 95% CI 1.038 to 49.216). Lung function abnormalities were detected in 14 patients and the measurement of D-dimer levels at admission may be useful for prediction of impaired diffusion defect (P = 0.031, OR 1.066, 95% CI 1.006 to 1.129). Of all the subjects, 47 of 55 patients tested positive for SARS-CoV-2 IgG in serum, among which the generation of Immunoglobulin G (IgG) antibody in female patients was stronger than male patients in infection rehabilitation phase. INTERPRETATION: Radiological and physiological abnormalities were still found in a considerable proportion of COVID-19 survivors without critical cases 3 months after discharge. Higher level of D-dimer on admission could effectively predict impaired DLCO after 3 months discharge. It is necessary to follow up the COVID-19 patients to appropriately manage any persistent or emerging long-term sequelae. FUNDING: Key Scientific Research Projects of Henan Higher Education Institutions", "title": "Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery", "pid": "9cnuxusj", "bm25_score": 214.71762084960938}, {"text": "", "title": "Long-Term Neurological Threats of COVID-19: A Call to Update the Thinking About the Outcomes of the Coronavirus Pandemic", "pid": "x8lxfwvt", "bm25_score": 214.68331909179688}, {"text": "Observation of infection trends through the course of the ongoing COVID-19 pandemic has indicated that those with certain pre-existing chronic conditions, such as hypertension, chronic obstructive pulmonary disease and obesity, are particularly likely to develop severe infection and experience disastrous sequelae, including near-fatal pneumonia. This article aims to outline how SARS-CoV-2 affects people and to consider why individuals living with long-term conditions are at increased risk from infection caused by this virus. A summary of available clinical guidelines with recommendations is presented, to provide community nurses with the up-to-date information required for protecting individuals living with a number of long-term conditions. Additionally, special measures required are outlined, so that community nurses may reflect on how to best provide nursing care for individuals living with long-term conditions and understand protection measures for individuals at increased risk from severe COVID-19.", "title": "Long-term conditions and severe acute respiratory syndrome SARS-CoV-2 (COVID-19).", "pid": "4n2xmx2w", "bm25_score": 214.6219482421875}, {"text": "Coronavirus disease (COVID-19), the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 31, 2019. Because it has only been studied for just over three months, our understanding of this disease is still incomplete, particularly regarding its sequelae and long-term outcomes. Moreover, very little has been written about the rehabilitation needs of patients with COVID-19 after discharge from acute care. The objective of this report is to answer the question “What rehabilitation services do survivors of COVID-19 require?” The question was asked within the context of a subacute hospital delivering geriatric inpatient and outpatient rehabilitation services. Three areas relevant to rehabilitation after COVID-19 were identified. First, details of how patients may present have been summarized, including comorbidities, complications from an intensive care unit stay with or without intubation, and the effects of the virus on multiple body systems, including those pertaining to cardiac, neurological, cognitive, and mental health. Second, I have suggested procedures regarding the design of inpatient rehabilitation units for COVID-19 survivors, staffing issues, and considerations for outpatient rehabilitation. Third, guidelines for rehabilitation (physiotherapy, occupational therapy, speech-language pathology) following COVID-19 have been proposed with respect to recovery of the respiratory system as well as recovery of mobility and function. A thorough assessment and an individualized, progressive treatment plan which focuses on function, disability, and return to participation in society will help each patient to maximize their function and quality of life. Careful consideration of the rehabilitation environment will ensure that all patients recover as completely as possible.", "title": "Considerations for Postacute Rehabilitation for Survivors of COVID-19", "pid": "gfzobzrg", "bm25_score": 214.60873413085938}, {"text": "This review intends to provide an overview of the current knowledge on neurologic sequelae of COVID-19 and their possible etiology, and, based on available data, proposes possible improvements in current medical care procedures. We conducted a thorough review of the scientific literature on neurologic manifestations of COVID-19, the neuroinvasive propensity of known coronaviruses (CoV) and their possible effects on brain structural and functional integrity. It appears that around one third of COVID-19 patients admitted to intensive care units (ICU) for respiratory difficulties exhibit neurologic symptoms. This may be due to progressive brain damage and dysfunction triggered by severe hypoxia and hypoxemia, heightened inflammation and SARS-CoV-2 dissemination into brain parenchyma, as suggested by current reports and analyses of previous CoV outbreaks. Viral invasion of the brain may particularly target and alter brainstem and thalamic functions and, consequently, result in sensorimotor dysfunctions and psychiatric disorders. Moreover, data collected from other structurally homologous CoV suggest that SARS-CoV-2 infection may lead to brain cell degeneration and demyelination similar to multiple sclerosis (MS). Hence, current evidence warrants further evaluation and long-term follow-up of possible neurologic sequelae in COVID-19 patients. It may be particularly relevant to evaluate brainstem integrity in recovered patients, as it is suspected that this cerebral area may particularly be dysfunctional following SARS-CoV-2 infection. Because CoV infection can potentially lead to chronic neuroinflammation and progressive demyelination, neuroimaging features and signs of MS may also be evaluated in the long term in recovered COVID-19 patients.", "title": "HOW TO DETECT AND TRACK CHRONIC NEUROLOGIC SEQUELAE OF COVID-19? USE OF AUDITORY BRAINSTEM RESPONSES AND NEUROIMAGING FOR LONG-TERM PATIENT FOLLOW-UP.", "pid": "e1t3qcw7", "bm25_score": 214.59967041015625}, {"text": "The outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is centralizing the interest of the scientific world. In the next months, long-term consequences on the endocrine system may arise following COVID-19. In this article, we hypothesized the effects of SARS-CoV-2 taking into account what learned from the severe acute respiratory syndrome coronavirus (SARS-CoV) that caused SARS in 2003.", "title": "Possible long-term endocrine-metabolic complications in COVID-19: lesson from the SARS model", "pid": "hcla915y", "bm25_score": 214.59030151367188}, {"text": "Observation of infection trends through the course of the ongoing COVID-19 pandemic has indicated that those with certain pre-existing chronic conditions, such as hypertension, chronic obstructive pulmonary disease and obesity, are particularly likely to develop severe infection and experience disastrous sequelae, including near-fatal pneumonia. This article aims to outline how SARS-CoV-2 affects people and to consider why individuals living with long-term conditions are at increased risk from infection caused by this virus. A summary of available clinical guidelines with recommendations is presented, to provide community nurses with the up-to-date information required for protecting individuals living with a number of long-term conditions. Additionally, special measures required are outlined, so that community nurses may reflect on how to best provide nursing care for individuals living with long-term conditions and understand protection measures for individuals at increased risk from severe COVID-19.", "title": "Long-term conditions and severe acute respiratory syndrome SARS-CoV-2 (COVID-19)", "pid": "s6oi477q", "bm25_score": 214.5885009765625}, {"text": "This review intends to provide an overview of the current knowledge on neurologic sequelae of COVID-19 and their possible etiology, and, based on available data, proposes possible improvements in current medical care procedures. We conducted a thorough review of the scientific literature on neurologic manifestations of COVID-19, the neuroinvasive propensity of known coronaviruses (CoV) and their possible effects on brain structural and functional integrity. It appears that around one third of COVID-19 patients admitted to intensive care units (ICU) for respiratory difficulties exhibit neurologic symptoms. This may be due to progressive brain damage and dysfunction triggered by severe hypoxia and hypoxemia, heightened inflammation and SARS-CoV-2 dissemination into brain parenchyma, as suggested by current reports and analyses of previous CoV outbreaks. Viral invasion of the brain may particularly target and alter brainstem and thalamic functions and, consequently, result in sensorimotor dysfunctions and psychiatric disorders. Moreover, data collected from other structurally homologous CoV suggest that SARS-CoV-2 infection may lead to brain cell degeneration and demyelination similar to multiple sclerosis (MS). Hence, current evidence warrants further evaluation and long-term follow-up of possible neurologic sequelae in COVID-19 patients. It may be particularly relevant to evaluate brainstem integrity in recovered patients, as it is suspected that this cerebral area may particularly be dysfunctional following SARS-CoV-2 infection. Because CoV infection can potentially lead to chronic neuroinflammation and progressive demyelination, neuroimaging features and signs of MS may also be evaluated in the long term in recovered COVID-19 patients.", "title": "How to Detect and Track Chronic Neurologic Sequelae of Covid-19? Use of Auditory Brainstem Responses and Neuroimaging for Long-term Patient Follow-up", "pid": "4ud6awrw", "bm25_score": 214.55633544921875}, {"text": "The scale of the COVID‐19 pandemic is entirely unprecedented. However, as depicted in Fig. 1, evidence from previous large‐scale disasters indicates that following a first wave of admissions and deaths from COVID‐19, there are likely to be subsequent waves of people with acute care needs worsened by delayed hospital treatment, and people with long‐term conditions whose routine care has been disrupted [1]. People with diabetes are likely to constitute a large proportion of those with acute second‐ and third‐wave care needs, and in many cases, management of their condition may also have been negatively affected by lockdown.", "title": "How do we recover from COVID‐19? Helping diabetes teams foresee and prepare for the psychological harms", "pid": "lo58re8s", "bm25_score": 214.54812622070312}, {"text": "Coronavirus disease (COVID-19), the infection caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first reported on December 31, 2019. Because it has only been studied for just over three months, our understanding of this disease is still incomplete, particularly regarding its sequelae and long-term outcomes. Moreover, very little has been written about the rehabilitation needs of patients with COVID-19 after discharge from acute care. The objective of this report is to answer the question \"What rehabilitation services do survivors of COVID-19 require?\" The question was asked within the context of a subacute hospital delivering geriatric inpatient and outpatient rehabilitation services. Three areas relevant to rehabilitation after COVID-19 were identified. First, details of how patients may present have been summarized, including comorbidities, complications from an intensive care unit stay with or without intubation, and the effects of the virus on multiple body systems, including those pertaining to cardiac, neurological, cognitive, and mental health. Second, I have suggested procedures regarding the design of inpatient rehabilitation units for COVID-19 survivors, staffing issues, and considerations for outpatient rehabilitation. Third, guidelines for rehabilitation (physiotherapy, occupational therapy, speech-language pathology) following COVID-19 have been proposed with respect to recovery of the respiratory system as well as recovery of mobility and function. A thorough assessment and an individualized, progressive treatment plan which focuses on function, disability, and return to participation in society will help each patient to maximize their function and quality of life. Careful consideration of the rehabilitation environment will ensure that all patients recover as completely as possible.", "title": "Considerations for Postacute Rehabilitation for Survivors of COVID-19", "pid": "7l17lern", "bm25_score": 214.5063934326172}, {"text": "After long term hospitalization or ICU treatment, COVID-19 patients are severe functionally impaired. They experience not only physical weakness but may also suffer from problems on the pulmonary, physical, psychosocial and cognitive domain. These domains interact and the impact on participation varies between patients. Therefore aftercare should be costumized to the patients individual needs. In this article we present a patient centered model to tailor treatment in the view of the Dutch health care system. This model can be helpful to determine the appropriate treatment for each patient at the right time in the right setting.", "title": "Personalized recovery of severe COVID19: Rehabilitation from the perspective of patient needs", "pid": "oedadxeg", "bm25_score": 214.4803466796875}, {"text": "Coronavirus disease 2019 (COVID‐19) represents a significant global medical issue, with a growing number of cumulative confirmed cases. However, a large number of COVID‐19 patients have overcome the disease, meeting hospital discharge criteria, and are gradually returning to work and social life. Nonetheless, COVID‐19 may cause further downstream issues in these patients, such as due to possible reactivation of the virus, long‐term pulmonary defects, and post‐traumatic stress disorder. In this study, we therefore queried relevant literature concerning SARS, MERS, and COVID‐19 for reference to come to a consensus on follow‐up strategies. We found that strategies such as implementation of PCR testing, imaging surveillance, and psychological assessments, starting at the time of discharge, were necessary for long‐term follow‐up. If close care is given to every aspect of coronavirus management, we expect that the pandemic outbreak will soon be overcome. This article is protected by copyright. All rights reserved.", "title": "Patient Follow‐up after Discharge after COVID‐19 Pneumonia: Considerations for Infectious Control", "pid": "3cr5x88g", "bm25_score": 214.4606475830078}, {"text": "Background: The coronavirus disease 19 (COVID-19) pandemic has become a global threat. Few studies have explored the risk factors for the recovery time of patients with COVID-19. This study aimed to explore risk factors associated with long-term hospitalization in patients with COVID-19. Methods: In this retrospective study, patients with laboratory-confirmed COVID-19 hospitalized in a hospital in Wuhan by March 30, 2020, were included. Demographic, clinical, laboratory, and radiological data from COVID-19 patients on hospital admission were extracted and were compared between the two groups, defined as short- and long-term hospitalization, respectively according to the median hospitalization time. Univariable and multivariable logistic regression methods were performed to identify risk factors associated with long-term hospitalization in patients with COVID-19. Results: A total of 125 discharged patients with COVID-19 were reviewed, including 123 general patients and two severe patients. The median hospitalization time was 13.0 days (IQR 10.0–17.0). Among them, 66 patients were discharged <14 days (short-term group) and 59 patients were discharged ≥14 days (long-term group). Compared with the short-term group, patients in the long-term group had significantly higher levels of C-reactive protein (P = 0.000), troponin I (P = 0.002), myoglobin (P = 0.037), aspartate aminotransferase (P = 0.005), lactic dehydrogenase (P = 0.000), prothrombin time (P = 0.030), fibrinogen (P = 0.000), and D-dimer (P = 0.006), but had significantly lower levels of lymphocyte count (P = 0.001), platelet count (P = 0.017), albumin (P = 0.001), and calcium (P = 0.000). Additionally, the incidences of hypocalcemia (P = 0.001), hyponatremia (P = 0.021), hypochloremia (P = 0.019), and bilateral pneumonia (P = 0.000) in the long-term group were significantly higher than those in the short-term group. Multivariable regression showed that hypocalcemia (P = 0.007, OR 3.313, 95% CI 1.392–7.886), hypochloremia (P = 0.029, OR 2.663, 95% CI 1.104–6.621), and bilateral pneumonia (P = 0.009, OR 5.907, 95% CI 1.073–32.521) were independent risk factors associated with long-term hospitalization in patients with COVID-19. Furthermore, a ROC curve where the area under the ROC was 0.766 for retained variables is presented. Conclusions: Hypocalcemia, hypochloremia, and bilateral pneumonia on hospital admission were independent risk factors associated with long-term hospitalization in patients with COVID-19. To the best of our knowledge, this is the first study to highlight the importance of electrolyte imbalance in predicting the hospitalization time of patients with COVID-19.", "title": "Risk Factors Associated With Long-Term Hospitalization in Patients With COVID-19: A Single-Centered, Retrospective Study", "pid": "xzpqxwr2", "bm25_score": 214.45220947265625}, {"text": "After long term hospitalization or ICU treatment, COVID‐19 patients are severe functionally impaired. They experience not only physical weakness but may also suffer from problems on the pulmonary, physical, psychosocial and cognitive domain. These domains interact and the impact on participation varies between patients. Therefore aftercare should be costumized to the patients individual needs. In this article we present a patient centered model to tailor treatment in the view of the Dutch health care system. This model can be helpful to determine the appropriate treatment for each patient at the right time in the right setting", "title": "Personalized recovery of severe COVID19: Rehabilitation from the perspective of patient needs", "pid": "efss2mib", "bm25_score": 214.4176025390625}, {"text": "This manuscript provides support for physical therapists to focus on the long-term, as well as the short-term, consequences of acute respiratory distress syndrome (ARDS) associated with COVID-19. Since late November 2019, COVID-19 has become a global health pandemic and threat. Although most people have no or mild symptoms, COVID-19 spreads aggressively and can lead to ARDS rapidly in a proportion of individuals. The evidence supports that gas exchange and countering the negative effects of bed rest and immobility are priorities in severely affected patients admitted to the intensive care unit (ICU). However, in recent years, research has focused on poor long-term functional outcomes in patients with ARDS, often associated with ICU-acquired weakness, deconditioning, and myopathies and neuropathies. In addition to physical therapists providing respiratory support in the ICU, the literature unequivocally supports the view that early intervention for ICU management of patients with ARDS secondary to COVID-19 needs to focus on reducing contributors to impaired long-term function, with direct attention paid to preventing or managing ICU-acquired weakness, deconditioning, and myopathies and neuropathies, in conjunction with respiratory care.", "title": "Consideration of prevention and management of long-term consequences of post-acute respiratory distress syndrome in patients with COVID-19", "pid": "ygosfou2", "bm25_score": 214.4039764404297}, {"text": "BACKGROUND: Pulmonary complications and infections frequently affect patients with head and neck squamous cell carcinoma (HNSCC). Common characteristics can predispose these patients to the development of severe respiratory illness, which may be particularly relevant during the 2019 coronavirus disease (COVID-19) pandemic. METHODS: A scoping review was performed to assess the impact of pulmonary comorbidities and adverse respiratory outcomes in HNSCC patients. RESULTS: Advanced age, history of tobacco and alcohol abuse, and cardiopulmonary comorbidities are significant risk factors for the development of adverse respiratory outcomes. Treatment toxicities from radiation or chemoradiation therapy significantly increase these risks. CONCLUSION: Respiratory complications are a frequent cause of morbidity and mortality among HNSCC patients, and the COVID-19 pandemic may disproportionately affect this population. Interventions designed to decrease smoking and alcohol use, improve oral hygiene, and aggressively manage medical comorbidities are important to the long-term management and health of these patients.", "title": "Respiratory and pulmonary complications in head and neck cancer patients: Evidence-based review for the COVID-19 era", "pid": "j3zp1a72", "bm25_score": 214.38600158691406}, {"text": "Although we are currently overwhelmed by the astonishing speed of infection of the Covid-19 pandemic, and the daily onslaught of new, and ever-worsening predictions, it is vital that we begin to prepare for the aftershocks of the pandemic. Prominent among this will be the cohort of post-intensive case survivors who have been mechanically ventilated and will like experience short- and medium-term consequences. The notion that patients surviving intensive care and mechanical ventilation for several weeks can be discharged home without further medical attention is a dangerous illusion. Post Intensive Care Syndrome and other severe conditions will require not only adequate screening but early rehabilitation and other interventions. Action must be taken now to prepare for this inevitable aftershock to the healthcare system.", "title": "Covid-19 and Post Intensive Care Syndrome: A Call for Action", "pid": "8njjxg8s", "bm25_score": 214.3836669921875}, {"text": "BACKGROUND: Acute respiratory distress syndrome (ARDS) due to severe influenza A H1N1 pneumonitis would result in impaired pulmonary functions and health‐related quality of life (HRQoL) after hospital discharge. OBJECTIVES: The recovery of pulmonary functions, exercise capacity, and HRQoL in the survivors of ARDS due to 2009 pandemic influenza A H1N1 pneumonitis (H1N1‐ARDS) was evaluated in a tertiary teaching hospital in northern Taiwan between May 2010 and June 2011. PATIENTS AND METHODS: Data of spirometry, total lung capacity (TLC), diffusing capacity of carbon monoxide (DL(CO)), and 6‐minute walk distance (6MWD) in the patients survived from H1N1‐ARDS were collected 1, 3, and 6 months post‐hospital discharge. HRQoL was evaluated with St. George respiratory questionnaire (SGRQ). RESULTS: Nine survivors of H1N1‐ARDS in the study period were included. All these patients received 2 months’ pulmonary rehabilitation program. Pulmonary functions and exercise capacity included TLC, forced vital capacity (FVC), forced expiratory volume in the first second (FEV (1)), DL(CO), and 6MWD improved from 1 to 3 months post‐hospital discharge. Only TLC had further significant improvement from 3 to 6 months. HRQoL represented as the total score of SGRQ had no significant improvement in the first 3 months but improved significantly from 3 to 6 months post‐discharge. CONCLUSION: The impaired pulmonary functions and exercise capacity in the survivors of H1N1‐ARDS improved soon at 3 months after hospital discharge. Their quality of life had keeping improved at 6 months even though there was no further improvement of their pulmonary functions and exercise capacity.", "title": "Recovery of pulmonary functions, exercise capacity, and quality of life after pulmonary rehabilitation in survivors of ARDS due to severe influenza A (H1N1) pneumonitis", "pid": "2hwirj2e", "bm25_score": 214.3695068359375}, {"text": "This manuscript provides support for physical therapists to focus on the long-term, as well as the short-term, consequences of acute respiratory distress syndrome (ARDS) associated with COVID-19. Since late November 2019, COVID-19 has become a global health pandemic and threat. Although most people have no or mild symptoms, COVID-19 spreads aggressively and can lead to ARDS rapidly in a proportion of individuals. The evidence supports that gas exchange and countering the negative effects of bed rest and immobility are priorities in severely affected patients admitted to the intensive care unit (ICU). However, in recent years, research has focused on poor long-term functional outcomes in patients with ARDS, often associated with ICU-acquired weakness, deconditioning, and myopathies and neuropathies. In addition to physical therapists providing respiratory support in the ICU, the literature unequivocally supports the view that early intervention for ICU management of patients with ARDS secondary to COVID-19 needs to focus on reducing contributors to impaired long-term function, with direct attention paid to preventing or managing ICU-acquired weakness, deconditioning, and myopathies and neuropathies, in conjunction with respiratory care.", "title": "Consideration of prevention and management of long-term consequences of post-acute respiratory distress syndrome in patients with COVID-19.", "pid": "3xfhjddg", "bm25_score": 214.3532257080078}, {"text": "The present outbreak caused by SARS-CoV-2, an influenza virus with neurotropic potential, presents with neurological manifestations in a large proportion of the affected individuals. Disorders of the central and peripheral nervous system are all present, while stroke, ataxia, seizures, and depressed level of consciousness are more common in severely affected patients. People with these severe complications are most likely elderly with medical comorbidities, especially hypertension and other vascular risk factors. However, postinfectious complications are also expected. Neurological disorders as sequelae of influenza viruses have been repeatedly documented in the past and include symptoms, signs, and diseases occurring during the acute phase and, not rarely, during follow-up. Postinfectious neurological complications are the result of the activation of immune mechanisms and can explain the insurgence of immune-mediated diseases, including the Guillain-Barré syndrome and other diseases of the central and peripheral nervous system that in the past occurred as complications of viral infections and occasionally with vaccines. For these reasons, the present outbreak calls for the introduction of surveillance systems to monitor changes in the frequency of several immune-mediated neurological diseases. These changes will determine a reorganization of the measures apt to describe the interaction between the virus, the environment, and the host in areas of different dimensions, from local communities to regions with several millions of inhabitants. The public health system, mainly primary care, needs to be strengthened to ensure that research and development efforts are directed toward right needs and directions. To cope with the present pandemic, better collaboration is required between international organizations along with more research funding, and tools in order to detect, treat, and prevent future epidemics.", "title": "COVID-19 Infection and Neurological Complications: Present Findings and Future Predictions.", "pid": "i43xer43", "bm25_score": 214.3136749267578}, {"text": "OBJECTIVE: This retrospective study aimed to analysis the clinical characteristics and complications in death cases with novel coronavirus disease-19 (COVID-19). METHOD: We collected the medical records of 92 patients with COVID-19 in Renmin Hospital of Wuhan University who died during January 6th to February 25th, 2020, summarized the clinical characteristics of complications. RESULTS: There were 91 death cases who developed different complications including acute respiratory distress syndrome (ARDS) (73/91), myocardial injury (31/91), liver injury (15/91), renal insufficiency (14/91), multiple organ dysfunction syndrome (MODS) (14/91) and pneumothorax (1/91). Among these patients, 83 patients had at least one complication. While 1 patient who died of recurrent gastrointestinal bleeding was not directly linked to COVID-19. CONCLUSION: The main complications of deceased patients with COVID-19 were ARDS, myocardial injury, liver injury, renal insufficiency and MODS. This article is protected by copyright. All rights reserved.", "title": "Analysis of 92 deceased patients with COVID-19", "pid": "dumf55yg", "bm25_score": 214.28369140625}, {"text": "COVID-19 survivors can have serious complications from this viral infection, particularly respiratory and cardiovascular with severe asthenia and fatigue. Several studies have already demonstrated the benefit of early rehabilitation after the acute phase, especially in patients who have been in intensive care. The authors present a rehabilitation program including interdisciplinary care with simple and reproducible clinical criteria.", "title": "La réhabilitation: indispensable pour les survivants d'un COVID-19 sévère./ [Rehabilitation is crucial for severe COVID-19 survivors]", "pid": "6ztf2n5w", "bm25_score": 214.27088928222656}, {"text": "BACKGROUND: There are few data about long-term respiratory complications following Middle East Respiratory Syndrome coronavirus (MERS-CoV) infection. This study aimed to evaluate respiratory functions and radiologic sequelae according to the severity of infection one year after the patients experienced MERS-CoV infection. METHODS: A total of 73 patients undergoing MERS-CoV infection during the 2015 MERS outbreak in South Korea were enrolled in this prospective multicenter study. Pulmonary function tests and 6-minute walking tests were performed 1 year after infection. Radiologic sequelae was defined as fibrosis or atelectasis on chest computer tomography and severe pneumonia was defined as that requiring oxygen therapy. Multivariate linear regression tests were used to evaluate the effect of infection severity on respiratory function. RESULTS: At the time of MERS-CoV infection, 18 patients had no pneumonia, 35 experienced mild pneumonia, and 20 did severe pneumonia. The median age was not different between groups (P = 0.942). Forced vital capacity (FVC) was 102.6%, 94.9%, and 88.7% in the no, mild, and severe pneumonia group, respectively (P = 0.010) and forced expiratory volume in 1 second was 105.3%, 95.7%, and 91.7% (P = 0.057). Diffusing capacity (DLCO) was significantly lower in the severe pneumonia group than in the no or mild pneumonia group (78.3% vs. 89.4% or 88.6%, P = 0.035). In multivariate analyses, FVC and DLCO were significantly correlated with infection severity after adjustment with age, sex, underlying lung disease, and smoking. There was no difference in the walking distance of 6 minute tests between groups. Radiologic sequelae were shown in 18.8%, 65.6%, and 100% in the no, mild, and severe pneumonia group, respectively (P < 0.001). CONCLUSION: The patients with more severe pneumonia by MERS-CoV had more impaired respiratory function in one year follow-up, which was compatible with radiologic sequelae. DISCLOSURES: All authors: No reported disclosures.", "title": "Long-term Respiratory Complication in Patients with Middle East Respiratory Syndrome: 1-year Follow-up After the 2015 Outbreak in South Korea", "pid": "15dcbib0", "bm25_score": 214.25997924804688}, {"text": "The global outbreak of coronavirus disease 2019 has created an unprecedented challenge to the society. Currently, the United States stands as the most affected country, and the entire healthcare system is affected, from emergency department, intensive care unit, postacute care, outpatient, to home care. Considering the debility, neurological, pulmonary, neuromuscular, and cognitive complications, rehabilitation professionals can play an important role in the recovery process for individuals with coronavirus disease 2019. Clinicians across the nation's rehabilitation system have already begun working to initiate intensive care unit-based rehabilitation care and develop programs, settings, and specialized care to meet the short- and long-term needs of these individuals. We describe the anticipated rehabilitation demands and the strategies to meet the needs of this population. The complications from coronavirus disease 2019 can be reduced by (1) delivering interdisciplinary rehabilitation that is initiated early and continued throughout the acute hospital stay, (2) providing patient/family education for self-care after discharge from inpatient rehabilitation at either acute or subacute settings, and (3) continuing rehabilitation care in the outpatient setting and at home through ongoing therapy either in-person or via telehealth.", "title": "The War on COVID-19 Pandemic: Role of Rehabilitation Professionals and Hospitals", "pid": "hc7dndxt", "bm25_score": 214.25894165039062}, {"text": "The present outbreak caused by SARS-CoV-2, an influenza virus with neurotropic potential, presents with neurological manifestations in a large proportion of the affected individuals. Disorders of the central and peripheral nervous system are all present, while stroke, ataxia, seizures, and depressed level of consciousness are more common in severely affected patients. People with these severe complications are most likely elderly with medical comorbidities, especially hypertension and other vascular risk factors. However, postinfectious complications are also expected. Neurological disorders as sequelae of influenza viruses have been repeatedly documented in the past and include symptoms, signs, and diseases occurring during the acute phase and, not rarely, during follow-up. Postinfectious neurological complications are the result of the activation of immune mechanisms and can explain the insurgence of immune-mediated diseases, including the Guillain-Barré syndrome and other diseases of the central and peripheral nervous system that in the past occurred as complications of viral infections and occasionally with vaccines. For these reasons, the present outbreak calls for the introduction of surveillance systems to monitor changes in the frequency of several immune-mediated neurological diseases. These changes will determine a reorganization of the measures apt to describe the interaction between the virus, the environment, and the host in areas of different dimensions, from local communities to regions with several millions of inhabitants. The public health system, mainly primary care, needs to be strengthened to ensure that research and development efforts are directed toward right needs and directions. To cope with the present pandemic, better collaboration is required between international organizations along with more research funding, and tools in order to detect, treat, and prevent future epidemics.", "title": "COVID-19 Infection and Neurological Complications: Present Findings and Future Predictions", "pid": "60uyco7t", "bm25_score": 214.24403381347656}, {"text": "Some people with covid-19 need ventilation. Those who survive this will need a lot of physical and mental rehabilitation, finds Clare Wilson.", "title": "What comes after the ICU?", "pid": "p8g6t7gv", "bm25_score": 214.21542358398438}, {"text": "By April 2020, COVID-19 lockdowns had restricted the movements of over half the world's population. As health authorities advise people living with chronic conditions to self-isolate because they are at particular risk of serious complications and death, the epidemiological split between communicable and noncommunicable disease is tenuous. We argue that much more is at stake for people living with (multiple) medical conditions than being \"at risk\" of infection of coronavirus. We emphasize the need to attend to the long-term effects of COVID-19, but also the importance of the continued care of people living with other lifelong medical conditions.", "title": "Chronic Living in a Communicable World.", "pid": "xui949ap", "bm25_score": 214.207763671875}, {"text": "As coronavirus disease 2019 (COVID-19) pandemic continues, an increasing number of countries and territories are adopting restrictive measures based on physical (\"social\") distancing, aimed at preventing human-to-human transmission and thereby limiting virus propagation. Nationwide lockdowns, encompassing mass quarantine under stay-at-home ordinances, have already been proven effective to contain the COVID-19 outbreak in some countries. Nevertheless, a prolonged homestay may also be associated with potential side effects, which may jeopardize people's health and thus must be recognized and mitigated in a way without violating local ordinances. Some of the most important undesirable consequences of prolonged homestay such as physical inactivity, weight gain, behavioral addiction disorders, insufficient sunlight exposure and social isolation will be critically addressed in this article, which also aims to provide some tentative recommendations for the alleviation of side effects.", "title": "Health risks and potential remedies during prolonged lockdowns for coronavirus disease 2019 (COVID-19)", "pid": "c5fi434e", "bm25_score": 214.20509338378906}, {"text": "First identified in November 2019 in Hubei Province, the coronavirus disease of 2019 (COVID-19) caused by SARS-CoV-2 soon spread worldwide to become a global health pandemic. The COVID-19 preferentially damages the respiratory system that produces symptoms such as fever, cough, and shortness of breath. However, the infection often tends to disseminate to involve various organ systems. Recent evidence indicates that SARS-CoV-2 can cause significant neurological damage and resultant neurological symptoms and complications. Here, we provide a comprehensive and thorough review of original articles, case reports, and case series to delineate the possible mechanisms of nervous system invasion and damage by SARS-CoV-2 and subsequent consequences. We divided the neurological manifestations into three categories: (1) Central Nervous System involvement, (2) Peripheral Nervous System manifestations, and (3) Skeletal Muscle Injury. Headache and dizziness were found to be the most prevalent symptoms followed by impaired consciousness. Among the symptoms indicating peripheral nervous system invasion, anosmia and dysgeusia were commonly reported. Skeletal muscle injury predominantly presents as myalgia. In addition, encephalitis, myelitis, cerebrovascular disease, Guillain-Barre syndrome, and Miller Fischer syndrome were among the commonly noted complications. We also emphasized the association of pre-existing comorbidities with neurological manifestations. The aim of this review is to provide a deeper understanding of the potential neurological implications to help neurologists have a high index of clinical suspicion allowing them to manage the patient appropriately.", "title": "Neurological Consequences of 2019-nCoV Infection: A Comprehensive Literature Review", "pid": "lptyk6n4", "bm25_score": 214.19276428222656}, {"text": "Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now a global pandemic with the highest number of affected individuals in the modern era. Not only is the infection inflicting significant morbidity and mortality, but there has also been a significant strain to the health care system and the economy. COVID-19 typically presents as viral pneumonia, occasionally leading to acute respiratory distress syndrome (ARDS) and death. However, emerging evidence suggests that it has a significant impact on the cardiovascular (CV) system by direct myocardial damage, severe systemic inflammatory response, hypoxia, right heart strain secondary to ARDS and lung injury, and plaque rupture secondary to inflammation. Primary cardiac manifestations include acute myocarditis, myocardial infarction, arrhythmia, and abnormal clotting. Several consensus documents have been released to help manage CV disease during this pandemic. In this review, we summarize key cardiac manifestations, their management, and future implications.", "title": "COVID-19 Pandemic: Cardiovascular Complications and Future Implications", "pid": "1vcpq06y", "bm25_score": 214.1883087158203}, {"text": "Severe acute respiratory syndrome (SARS) is associated with considerable morbidity and mortality in the acute phase. Worldwide case fatality rate is 11% (range 7 to 27%) for the most severely affected regions. Several adverse prognostic factors have been identified, including advanced age, presence of comorbidity, higher lactose dehydrogenase levels and initial neutrophil count, but the impact of viral and other host factors on outcome is unknown. Published data on sequelae of SARS are limited. Clinical follow‐up of patients who recovered from SARS has demonstrated radiological, functional and psychological abnormalities of varying degrees. In the early rehabilitation phase, many complained of limitations in physical function from general weakness and/or shortness of breath. In a small series of subjects who underwent CT scan of the chest, over half showed some patchy changes consistent with pulmonary fibrosis. Lung function testing at 6–8 weeks after hospital discharge showed mild or moderate restrictive pattern consistent with muscle weakness in 6–20% of subjects. Mild decrease in carbon monoxide diffusing capacity was detected in a minority of subjects. Preliminary evidence suggests that these lung function abnormalities will improve over time. Psychobehavioural problems of anxiety and/or depression were not uncommon in the early recovery phase, and improved over time in the majority of patients. Avascular necrosis of the hip has been reported as another complication. The long‐term sequelae of SARS are still largely unknown. It is important to follow up these patients to detect and appropriately manage any persistent or emerging long‐term sequelae in the physical, psychological and social domains.", "title": "SARS: prognosis, outcome and sequelae", "pid": "kqgzk3yn", "bm25_score": 214.18496704101562}, {"text": "Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), emerged at the end of 2019 and caused an infection named COVID-19 (Guan, Ni et al. 2020). Patients with compromised immune systems are at increased risk of complications but this risk is not precisely defined (Liang, Guan et al. 2020). Although age, gender, comorbidities and ethnicity are risk factors for adverse outcomes (Huang, Wang et al. 2020), various pre-existing conditions, including haematological cancers, have also been reported to correlate with poor outcomes (Aries, Davies et al. 2020, He, Chen et al. 2020, Malard, Genthon et al. 2020, Martin-Moro, Marquet et al. 2020, medRxiv 2020).", "title": "Poor outcome and prolonged persistence of SARS-CoV-2 RNA in COVID-19 patients with haematological malignancies; King's College Hospital experience", "pid": "l1odoy1l", "bm25_score": 214.1798553466797}, {"text": "As coronavirus disease 2019 (COVID-19) pandemic continues, an increasing number of countries and territories are adopting restrictive measures based on physical (\"social\") distancing, aimed at preventing human-to-human transmission and thereby limiting virus propagation. Nationwide lockdowns, encompassing mass quarantine under stay-at-home ordinances, have already been proven effective to contain the COVID-19 outbreak in some countries. Nevertheless, a prolonged homestay may also be associated with potential side effects, which may jeopardize people's health and thus must be recognized and mitigated in a way without violating local ordinances. Some of the most important undesirable consequences of prolonged homestay such as physical inactivity, weight gain, behavioral addiction disorders, insufficient sunlight exposure and social isolation will be critically addressed in this article, which also aims to provide some tentative recommendations for the alleviation of side effects.", "title": "Health risks and potential remedies during prolonged lockdowns for coronavirus disease 2019 (COVID-19).", "pid": "45d9tj2l", "bm25_score": 214.17904663085938}, {"text": "Here we report the clinical features of 25 discharged patients with COVID-19 recovery. Our analysis indicated that there was a significant inverse correlation existed between serum D-Dimer level and the duration of antiviral treatment, while lymphocyte concentration significantly positively correlated with the duration of virus reversal.", "title": "Clinical Characteristics on 25 Discharged Patients with COVID-19 Virus Returning", "pid": "jarnavwl", "bm25_score": 214.17637634277344}, {"text": "Covid-19 is a respiratory infectious disease that can cause respiratory, physical and psychological long-term dysfunctions in patients. First recommendations on respiratory management were published, but they were not based on the specific needs due to Covid-19. In this paper we share the early experiences from the clinical field in Northern Italy, where the epidemic started in February. This paper summarizes the second webinar on Covid-19 (230 live attendees, 11,600 viewers of the recorded version) organized by the Italian Society of Physical and Rehabilitation Medicine about rehabilitation and in particular respiratory management in the acute (Intensive Care Unit - ICU) and immediate post-acute phases. There is the need to prepare for the post-acute phase. ICU length of stay is relatively long, with immobilisation in prone position. Some specific problems are described, including severe muscle weakness and fatigue, joint stiffness, dysphagia, (neuro)psychological problems, impaired functioning concerning mobility, activities of daily life and work. A lot is yet unknown and patients can experience long-term consequences as we know from the literature on the post-intensive care syndrome, but Covid-19 has unique features to be investigated and understood. As one colleague stated during the Covinar: this is a marathon, not a sprint….", "title": "Rehabilitation and respiratory management in the acute and early post-acute phase. \"Instant paper from the field\" on rehabilitation answers to the Covid-19 emergency.", "pid": "2exi7j6u", "bm25_score": 214.1695556640625}, {"text": "Some people with covid-19 need ventilation. Those who survive this will need a lot of physical and mental rehabilitation, finds Clare Wilson", "title": "What comes after the ICU?", "pid": "sgouesvq", "bm25_score": 214.15609741210938}, {"text": "OBJECTIVE: This retrospective study aimed to analysis the clinical characteristics and complications in death cases with novel coronavirus disease‐19 (COVID‐19). METHOD: We collected the medical records of 92 patients with COVID‐19 in Renmin Hospital of Wuhan University who died during January 6th to February 25th, 2020, summarized the clinical characteristics of complications. RESULTS: There were 91 death cases who developed different complications including acute respiratory distress syndrome (ARDS) (73/91), myocardial injury (31/91), liver injury (15/91), renal insufficiency (14/91), multiple organ dysfunction syndrome (MODS) (14/91) and pneumothorax (1/91). Among these patients, 83 patients had at least one complication. While 1 patient who died of recurrent gastrointestinal bleeding was not directly linked to COVID‐19. CONCLUSION: The main complications of deceased patients with COVID‐19 were ARDS, myocardial injury, liver injury, renal insufficiency and MODS. This article is protected by copyright. All rights reserved.", "title": "Analysis of 92 deceased patients with COVID‐19", "pid": "i8kwhhwt", "bm25_score": 214.13970947265625}, {"text": "", "title": "Persisting olfactory dysfunction in patients after recovering from COVID-19", "pid": "9mdoy31d", "bm25_score": 214.1356658935547}, {"text": "Covid-19 infections and related illness and death are rightly at the forefront of our minds. It is critical that we consider how to reduce infections, treat those who are ill and protect health systems. We must, however, also consider how the pandemic is affecting the families of those infected, and how interventions to prevent the spread of the virus come with large negative economic and social consequences. We must begin to identify the ways in which we can soften these blows and recover from the negative consequences over the medium and long-term. We highlight here the importance of moving away the tendency to search for interventions to improve one outcome at a time. It will be essential, particularly in highly resource constrained settings, to look for accelerators, interventions which improve multiple outcomes simultaneously. We discuss how this will be especially important for groups who are at particular risk at this time, including of long-term negative outcomes. These include very young children, adolescents and those who have limited capacity to benefit from narrow interventions given critical needs in multiple domains. Searching for accelerators requires that we take a step back and look to identify common causes of negative outcomes and consider how we might address them. For many countries, recovery from this epidemic will be highly constrained by the limited availability of financial resources. Wise investments will be especially important at this time.", "title": "Covid-19: accelerating recovery", "pid": "bhlp1acq", "bm25_score": 214.1110076904297}, {"text": "BACKGROUND: Pulmonary complications and infections frequently affect patients with head and neck squamous cell carcinoma (HNSCC). Common characteristics can predispose these patients to the development of severe respiratory illness, which may be particularly relevant during the 2019 coronavirus disease (COVID‐19) pandemic. METHODS: A scoping review was performed to assess the impact of pulmonary comorbidities and adverse respiratory outcomes in HNSCC patients. RESULTS: Advanced age, history of tobacco and alcohol abuse, and cardiopulmonary comorbidities are significant risk factors for the development of adverse respiratory outcomes. Treatment toxicities from radiation or chemoradiation therapy significantly increase these risks. CONCLUSION: Respiratory complications are a frequent cause of morbidity and mortality among HNSCC patients, and the COVID‐19 pandemic may disproportionately affect this population. Interventions designed to decrease smoking and alcohol use, improve oral hygiene, and aggressively manage medical comorbidities are important to the long‐term management and health of these patients.", "title": "Respiratory and pulmonary complications in head and neck cancer patients: Evidence‐based review for the COVID‐19 era", "pid": "g9hk1iq5", "bm25_score": 214.10800170898438}, {"text": "Abstract Background The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. Objective This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. Discussion The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. Conclusions Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "title": "Cardiovascular complications in COVID-19", "pid": "mbbnk3la", "bm25_score": 214.10496520996094}, {"text": "BACKGROUND: The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur. OBJECTIVE: This brief report evaluates cardiovascular complications in the setting of COVID-19 infection. DISCUSSION: The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death. The virus binds and enters through angiotensin-converting enzyme 2 (ACE2). COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness. The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events. Current therapies for COVID-19 may interact with cardiovascular medications. CONCLUSIONS: Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.", "title": "Cardiovascular complications in COVID-19", "pid": "hl225efn", "bm25_score": 214.1041259765625}, {"text": "", "title": "Opinion: An Increase in Severe, Late Dental Complications Might Result From Reliance on Home Dental Remedies During the COVID-19 Pandemic", "pid": "d93yfc7d", "bm25_score": 214.1031951904297}, {"text": "In this commentary, I argue that the mental health impact of COVID-19 will show substantial variation across individuals, contexts, and time. Further, one key contributor to this variation will be the proximal and long-term impact of COVID-19 on the social environment. In addition to the mental health costs of the pandemic, it is likely that a subset of people will experience improved social and mental health functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Heterogeneous mental health consequences of COVID-19: Costs and benefits.", "pid": "u02vjcjs", "bm25_score": 214.09298706054688}, {"text": "Although we are currently overwhelmed by the astonishing speed of infection of the Covid-19 pandemic, and the daily onslaught of new, and ever-worsening predictions, it is vital that we begin to prepare for the aftershocks of the pandemic. Prominent among this will be the cohort of post-intensive case survivors who have been mechanically ventilated and will like experience short- and medium-term consequences of the experience. The notion that patients surviving intensive care and mechanical ventilation for several weeks can be discharged home without further medical attention is a dangerous illusion. Post Intensive Care Syndrome and other severe conditions will require not only adequate screening but early rehabilitation and other interventions. Action must be taken now to prepare for this inevitable shock to the healthcare system.", "title": "Covid-19 and Post Intensive Care Syndrome: A Call for Action.", "pid": "2v43ymp7", "bm25_score": 214.0770263671875}, {"text": "", "title": "COVID-19: long-term effects on the community response to cardiac arrest?", "pid": "jbnx2l85", "bm25_score": 214.07211303710938}, {"text": "In this commentary, I argue that the mental health impact of COVID-19 will show substantial variation across individuals, contexts, and time. Further, one key contributor to this variation will be the proximal and long-term impact of COVID-19 on the social environment. In addition to the mental health costs of the pandemic, it is likely that a subset of people will experience improved social and mental health functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Heterogeneous mental health consequences of COVID-19: Costs and benefits", "pid": "ingq7m2m", "bm25_score": 214.06324768066406}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) – also known as COVID-19 – is primarily known for respiratory illness. While it is clear that patients with moderate to severe cases of COVID-19 will require pulmonary rehabilitation, physiatrists will need to consider effective management plans for COVID-19 survivors with extra-pulmonary involvement. This report will summarize key non-pulmonary considerations to guide rehabilitation clinicians who may be involved in the care of COVID-19 survivors with the best available early evidence.", "title": "COVID-19 Guide for the Rehabilitation Clinician: A Review of Non-Pulmonary Manifestations and Complications", "pid": "7y9bdzpd", "bm25_score": 214.05494689941406}, {"text": "Coronavirus disease 19 (COVID-19) is now an epidemic of global proportion with major adverse impacts on older adults, persons with chronic diseases, and especially residents of long-term care facilities. This health catastrophe has challenged healthcare facilities' capacity to deliver care to not only COVID-19 patients but all patients who need hospital care. We report on a novel approach of utilizing long-term care beds at a Department of Veterans Affairs healthcare facility for managing recovering COVID-19 patients.", "title": "Establishment of a COVID-19 Recovery Unit in a Veteran Affairs (VA) Post-Acute Facility", "pid": "3thnu3kk", "bm25_score": 214.05223083496094}, {"text": "Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), can cause neurological complications. We provide a brief overview of these recent observations and discuss some of their possible implications. In particular, given the global dimension of the current pandemic, we highlight the need to consider the possible long-term impact of COVID-19, potentially including neurological and neurodegenerative disorders.", "title": "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Central Nervous System", "pid": "f5khmuc4", "bm25_score": 214.0335693359375}, {"text": "Anosmia, stroke, paralysis, cranial nerve deficits, encephalopathy, delirium, meningitis, and seizures are some of the neurological complications in patients with coronavirus disease-19 (COVID-19) which is caused by acute respiratory syndrome coronavirus 2 (SARS-Cov2). There remains a challenge to determine the extent to which neurological abnormalities in COVID-19 are caused by SARS-Cov2 itself, the exaggerated cytokine response it triggers, and/or the resulting hypercoagulapathy and formation of blood clots in blood vessels throughout the body and the brain. In this article, we review the reports that address neurological manifestations in patients with COVID-19, who may present with acute neurological symptoms (e.g., stroke), even without typical respiratory symptoms such as fever, cough, or shortness of breath. Next, we discuss the different neurobiological processes and mechanisms that may underlie the link between SARS-Cov2 and COVID-19 in the brain, cranial nerves, peripheral nerves, and muscles. Finally, we propose a basic \"NeuroCovid\" classification scheme that integrates these concepts and highlights some of the short-term challenges for the practice of neurology today and the long-term sequalae of COVID-19 such as depression, OCD, insomnia, cognitive decline, accelerated aging, Parkinson's disease, or Alzheimer's disease in the future. In doing so, we intend to provide a basis from which to build on future hypotheses and investigations regarding SARS-Cov2 and the nervous system.", "title": "Neurobiology of COVID-19.", "pid": "5sc1hdcn", "bm25_score": 214.0278778076172}, {"text": "The coronavirus pandemic that started in December 2019 is mainly related to clinical pictures consistent with respiratory symptoms; nevertheless, reports about neurological complications have recently appeared in the medical literature. We describe a case of a 36-year-old coronavirus-positive patient that was admitted on emergency basis; his clinical presentation included neurological symptoms such as drowsiness and mild confusion. Imaging revealed findings consistent with meningoencephalitis complicated by intracerebral hematoma and subdural hematoma. The latter was surgically evacuated after it became chronic and evidence of coronavirus was found in the fluid. Our experience confirms that neurological complications might be a likely event in COVID-19. Although uncommon, the possible occurrence of meningoencephalitis should be kept in mind by physicians involved in the management of COVID-19 patients. Early recognition of brain involvement may provide better prognosis, preventing evolution into intracerebral hemorrhagic events.", "title": "COVID-19-associated meningoencephalitis complicated with intracranial hemorrhage: a case report", "pid": "4hnltxbm", "bm25_score": 214.0128173828125}, {"text": "The novel Coronavirus disease 2019 (COVID-19) is an illness caused due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) has declared this outbreak a global health emergency and as on April 24, 2020, it has spread to 213 countries, with 25,91,015 confirmed cases and 742,855 cases have been recovered from COVID-19. In this dreadful situation our team has already published an article in the Science of the Total Environment, which elaborates the various aspects of the SARS-CoV-2 infection. In this situation, it is imperative to understand the possible outcome of COVID-19 recovered patients and determine if they have any other detrimental illnesses by longitudinal analysis to safeguard their life in future. It is necessary to follow-up these recovered patients and performs comprehensive assessments for detection and appropriate management towards their psychological, physical, and social realm. This urges us to suggest that it is highly important to provide counselling, moral support as well as a few recommended guidelines to the recovered patients and society to restore to normalcy. Epidemiological, clinical and immunological studies from COVID-19 recovered patients are particularly important to understand the disease and to prepare better for potential outbreaks in the future. Longitudinal studies on a larger cohort would help us to understand the in-depth prognosis as well as the pathogenesis of COVID-19. Also, follow-up studies will help us provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. Hence, we recommend more studies are required to unravel the possible mechanism of COVID-19 infection and the after-effects of it to understand the characteristics of the virus and to develop the necessary precautionary measures to prevent it.", "title": "Follow-up studies in COVID-19 recovered patients - is it mandatory?", "pid": "uqhaxqqh", "bm25_score": 214.0095672607422}, {"text": "PURPOSE: To ascertain delirium prevalence and outcomes in COVID-19. METHODS: We conducted a point-prevalence study in a cohort of COVID-19 inpatients at University College Hospital. Delirium was defined by DSM-IV criteria. The primary outcome was all-cause mortality at 4 weeks; secondary outcomes were physical and cognitive function. RESULTS: In 71 patients (mean age 61, 75% men), 31 (42%) had delirium, of which only 12 (39%) had been recognised by the clinical team. At 4 weeks, 20 (28%) had died, 26 (36%) were interviewed by telephone and 21 (30%) remained as inpatients. Physical function was substantially worse in people after delirium − 50 out of 166 points (95% CI − 83 to − 17, p = 0.01). Mean cognitive scores at follow-up were similar and delirium was not associated with mortality in this sample. CONCLUSIONS: Our findings indicate that delirium is common, yet under-recognised. Delirium is associated with functional impairments in the medium term. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s41999-020-00353-8) contains supplementary material, which is available to authorized users.", "title": "Functional and cognitive outcomes after COVID-19 delirium", "pid": "ix0xi5jb", "bm25_score": 214.00692749023438}, {"text": "By April 2020, COVID-19 lockdowns had restricted the movements of over half the world's population. As health authorities advise people living with chronic conditions to self-isolate because they are at particular risk of serious complications and death, the epidemiological split between communicable and noncommunicable disease is tenuous. We argue that much more is at stake for people living with (multiple) medical conditions than being \"at risk\" of infection of coronavirus. We emphasize the need to attend to the long-term effects of COVID-19, but also the importance of the continued care of people living with other lifelong medical conditions.", "title": "Chronic Living in a Communicable World", "pid": "gmcj27xz", "bm25_score": 214.00323486328125}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - also known as COVID-19 - is primarily known for respiratory illness. While it is clear that patients with moderate to severe cases of COVID-19 will require pulmonary rehabilitation, physiatrists will need to consider effective management plans for COVID-19 survivors with extra-pulmonary involvement. This report will summarize key non-pulmonary considerations to guide rehabilitation clinicians who may be involved in the care of COVID-19 survivors with the best available early evidence.", "title": "COVID-19 Guide for the Rehabilitation Clinician: A Review of Non-Pulmonary Manifestations and Complications", "pid": "kde77s2g", "bm25_score": 214.00296020507812}, {"text": "", "title": "Covid-19 and long term conditions: what if you have cancer, diabetes, or chronic kidney disease?", "pid": "hdjyjaof", "bm25_score": 213.99891662597656}, {"text": "The coronavirus disease-2019 (COVID-19) has become a global pandemic. It has spread to more than 100 countries, and more than 1 million cases have been confirmed. Although coronavirus causes severe respiratory infections in humans, accumulating data have demonstrated cardiac complications and poor outcome in patients with COVID-19. A large percent of patients have underlying cardiovascular disease, and they are at a high risk of developing cardiac complications. The basics of the virus, the clinical manifestations, and the possible mechanisms of cardiac complications in patients with COVID-19 are reviewed. Before an effective vaccine or medicine is available, supportive therapy and identifying patients who are at high risk of cardiac complications are important.", "title": "Coronavirus Disease-2019 (COVID-19) and Cardiovascular Complications", "pid": "wkp58iov", "bm25_score": 213.99708557128906}, {"text": "We identified patients with coronavirus disease 2019 (COVID-19) in a telemedicine clinic who requested ongoing follow-up 6 weeks after symptom onset. Patients with prolonged symptoms often have not returned to work or usual activity. Respiratory symptoms are most common, and underlying asthma and lung disease occur frequently.", "title": "Characterization of prolonged COVID-19 symptoms and patient comorbidities in an outpatient telemedicine cohort", "pid": "fhkr8l4u", "bm25_score": 213.99513244628906}, {"text": "At this time, nurses within hospitals are working hard, but they potentially will have long-term mental health effects as a result of the 2019 novel coronavirus (COVID-19) pandemic. Both short-term interventions, such as daily huddles and debriefings, and long-term interventions, including follow-ups on the mental health of nurses, need to be implemented to prevent mental disorders among nurses during and after the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "The mental turmoil of hospital nurses in the COVID-19 pandemic.", "pid": "1nqa3egs", "bm25_score": 213.97686767578125}, {"text": "", "title": "Opinion: An Increase in Severe Late-Dental Complications May Result from Reliance on Home Dental Remedies During the COVID-19 Pandemic", "pid": "pwrojqju", "bm25_score": 213.96475219726562}, {"text": "This study aimed to investigate the clinical characteristics and to analyse the epidemiological features of coronavirus disease 2019 (COVID-19) patients during convalescence. In this study, we enrolled 71 confirmed cases of COVID-19 who were discharged from hospital and transferred to isolation wards from 6 February to 26 March 2020. They were all employees of Zhongnan Hospital of Wuhan University or their family members of which three cases were <18 years of age. Clinical data were collected and analysed statistically. Forty-one cases (41/71, 57.7%) comprised medical faculty, young and middle-aged patients (aged ⩽60 years) accounted for 81.7% (58/71). The average isolation time period for all adult patients was 13.8 ± 6.1 days. During convalescence, RNA detection results of 35.2% patients (25/71) turned from negative to positive. The longest RNA reversed phase time was 7 days. In all, 52.9% of adult patients (36/68) had no obvious clinical symptoms, and the remaining ones had mild and non-specific clinical symptoms (e.g. cough, sputum, sore throat, disorders of the gastrointestinal tract etc.). Chest CT signs in 89.7% of adult patients (61/68) gradually improved, and in the others, the lesions were eventually absorbed and improved after short-term repeated progression. The main chest CT manifestations of adult patients were normal, GGO or fibre streak shadow, and six patients (8.8%) had extrapulmonary manifestations, but there was no significant correlation with RNA detection results (r = −0.008, P > 0.05). The drug treatment was mainly symptomatic support therapy, and antibiotics and antiviral drugs were ineffective. It is necessary to re-evaluate the isolation time and standard to terminate isolation for discharged COVID-19 patients.", "title": "Epidemiological characteristics of COVID-19 patients in convalescence period", "pid": "ft14aa2n", "bm25_score": 213.9606170654297}, {"text": "This study aimed to investigate the clinical characteristics and to analyse the epidemiological features of coronavirus disease 2019 (COVID-19) patients during convalescence. In this study, we enrolled 71 confirmed cases of COVID-19 who were discharged from hospital and transferred to isolation wards from 6 February to 26 March 2020. They were all employees of Zhongnan Hospital of Wuhan University or their family members of which three cases were <18 years of age. Clinical data were collected and analysed statistically. Forty-one cases (41/71, 57.7%) comprised medical faculty, young and middle-aged patients (aged ⩽60 years) accounted for 81.7% (58/71). The average isolation time period for all adult patients was 13.8 ± 6.1 days. During convalescence, RNA detection results of 35.2% patients (25/71) turned from negative to positive. The longest RNA reversed phase time was 7 days. In all, 52.9% of adult patients (36/68) had no obvious clinical symptoms, and the remaining ones had mild and non-specific clinical symptoms (e.g. cough, sputum, sore throat, disorders of the gastrointestinal tract etc.). Chest CT signs in 89.7% of adult patients (61/68) gradually improved, and in the others, the lesions were eventually absorbed and improved after short-term repeated progression. The main chest CT manifestations of adult patients were normal, GGO or fibre streak shadow, and six patients (8.8%) had extrapulmonary manifestations, but there was no significant correlation with RNA detection results (r = -0.008, P > 0.05). The drug treatment was mainly symptomatic support therapy, and antibiotics and antiviral drugs were ineffective. It is necessary to re-evaluate the isolation time and standard to terminate isolation for discharged COVID-19 patients.", "title": "Epidemiological characteristics of COVID-19 patients in convalescence period", "pid": "rs0bhnuo", "bm25_score": 213.96041870117188}, {"text": "BACKGROUND: Much of the focus regarding the global pandemic of coronavirus disease of 2019 (COVID-19) has been on the cardiovascular, pulmonary, and hematologic complications. However, neurologic complications have arisen as an increasingly recognized area of morbidity and mortality. OBJECTIVE: This brief report summarizes the neurologic complications associated with COVID-19 with an emphasis on the emergency medicine clinician. DISCUSSION: COVID-19 has infected over 3.5 million people and killed over 240,000 people worldwide. While pulmonary complications are profound, the neurologic system is also significantly impacted, with complications including acute cerebrovascular events, encephalitis, Guillain-Barré syndrome, acute necrotizing hemorrhagic encephalopathy, and hemophagocytic lymphohistiocytosis. Additionally, patients on immunosuppressive medications for pre-existing neurologic issues are at an increased risk for complications with COVID-19 infection, and many of the currently proposed COVID-19 therapies can interact with these medications. CONCLUSIONS: When caring for COVID-19 patients, emergency medicine clinicians should be aware of the neurologic complications from COVID-19.", "title": "Neurologic complications of COVID-19", "pid": "bvm1mrdy", "bm25_score": 213.9561767578125}, {"text": "The lockdown measures that were implemented in the spring of 2020 to stop the spread of Covid‐19 are having a huge impact on economies in the UK and around the world. In addition to the direct impact of Covid‐19 on health, the following recession will have an impact on people's health outcomes. This paper reviews economic literature on the longer run health impacts of business cycle fluctuations and recessions. Previous studies show that an economic downturn, which affects people through increased unemployment, lower incomes and increased uncertainty, will have significant consequences on people's health outcomes both in the short and longer term. The health effects caused by these adverse macroeconomic conditions will be complex, and will differ across generations, regions and socioeconomic groups. Groups that are vulnerable to poor health are likely to be hit hardest even if the crisis hit all individuals equally, and we already see that some groups such as young workers and women are worse hit by the recession than others. Government policies during and after the pandemic will play an important role in determining the eventual health consequences. This article is protected by copyright. All rights reserved", "title": "Recessions and health: The long‐term health consequences of responses to the coronavirus", "pid": "ezb7msg8", "bm25_score": 213.9552459716797}, {"text": "In December 2019, a novel coronavirus (SARS-Cov-2) was first reported in Wuhan, China, and rapidly spread around the world, leading to an international emerging public health emergency. As reported from Chinese experiences, approximately 20% of patients had a severe course, requiring intensive care, with an overall case fatality rate of 2.3%. In diagnosis, chest computed tomography most commonly showed ground-glass opacity with or without consolidative patterns. Herein, we report a case of a patient affected by COVID-19 pneumonia referred in the emergency department of our institution on April 4, 2020, with peculiar lung ultrasound findings.", "title": "2019 novel coronavirus (COVID-19) pneumonia complications: the importance of lung ultrasound", "pid": "xvzi1i0v", "bm25_score": 213.9503173828125}, {"text": "In December 2019, a novel coronavirus (SARS-Cov-2) was first reported in Wuhan, China, and rapidly spread around the world, leading to an international emerging public health emergency. As reported from Chinese experiences, approximately 20% of patients had a severe course, requiring intensive care, with an overall case fatality rate of 2.3%. In diagnosis, chest computed tomography most commonly showed ground-glass opacity with or without consolidative patterns.Herein, we report a case of a patient affected by COVID-19 pneumonia referred in the emergency department of our institution on April 4, 2020, with peculiar lung ultrasound findings.", "title": "2019 novel coronavirus (COVID-19) pneumonia complications: the importance of lung ultrasound", "pid": "4p76crrc", "bm25_score": 213.9503173828125}, {"text": "Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can cause neurological complications. We provide a brief overview of these recent observations and discuss some of their possible implications. In particular, given the global dimension of the current pandemic, we highlight the need to consider the possible long-term impact of COVID-19, potentially including neurological and neurodegenerative disorders.", "title": "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and the Central Nervous System", "pid": "prxzcp1x", "bm25_score": 213.9481201171875}, {"text": "The global outbreak of coronavirus disease (COVID-19) has created an unprecedented challenge to the society. Currently, the United States stands as the most affected country, and the entire healthcare system is affected, from emergency department, intensive care unit, post-acute care, outpatient, to home care. Considering the debility, neurological, pulmonary, neuromuscular and cognitive complications, rehabilitation professionals can play an important role in the recovery process for individuals with COVID-19. Clinicians across the nation’s rehabilitation system have already begun working to initiate intensive care unit-based rehabilitation care and develop programs, settings and specialized care to meet the short- and long-term needs of these individuals. We describe the anticipated rehabilitation demands, and the strategies to meet the needs of this population. The complications from COVID-19 can be reduced by (1) delivering interdisciplinary rehabilitation that is initiated early and continued throughout the acute hospital stay, (2) providing patient/family education for self-care after discharge from inpatient rehabilitation at either acute or subacute settings, and (3) continuing rehabilitation care in the outpatient setting, and at home through ongoing therapy either in-person or via telehealth.", "title": "The War on COVID-19 Pandemic: Role of Rehabilitation Professionals and Hospitals", "pid": "f09fxnk9", "bm25_score": 213.94349670410156}, {"text": "", "title": "Recovering from COVID-19: the key issues", "pid": "b2wgo20y", "bm25_score": 213.93675231933594}, {"text": "Background: COVID-19 is still becoming an increasing global threat to public health. More detailed and specific characteristics of COVID-19 are needed to better understand this disease. Additionally, durations of COVID-19, e.g., the average time from exposure to recovery, which is of great value in understanding this disease, has not been reported so far. Aims: To give the information on clinical characteristics and different durations of COVID-19 and to identify the potential risk factors for longer hospitalization duration. Methods: In this retrospective study, we enrolled 77 patients (mean age: 52 years; 44.2% males) with laboratory-confirmed COVID-19 admitted to Beijing YouAn Hospital during 21st Jan and 8th February 2020. Epidemiological, clinical and radiological data on admission were collected; complications and outcomes were followed up until 29th February 2020. The study endpoint was the discharge within two weeks. Cox proportional-hazards regression was performed to identify risk factors for longer hospitalization duration. Results: Of 77 patients, there are 34 (44.2%) males, 24 (31.2%) with comorbidities, 22 (28.6%) lymphopenia, 20 (26.0%) categorized as severe patients, and 28 (36.4%) occurred complications. By the end of follow-up, 64 (83.1%) patients were discharged home after being tested negative for SARS-CoV-2 infections, 8 remained in hospital and 5 died. 36 (46.8%) patients were discharged within 14 days and thus reached the study endpoint, including 34 (59.6%) of 57 non-severe patients and 2 (10%) of 20 severe patients. The overall cumulative probability of the endpoint was 48.3%. Hospital length of stay and duration of exposure to discharge for 64 discharged patients were 13 (10-16.5) and 23 (18-24.5) days, respectively. Multivariable stepwise Cox regression model showed bilateral pneumonia on CT scan, shorter time from the illness onset to admission, the severity of disease and lymphopenia were independently associated with longer hospitalized duration. Conclusions: COVID-19 has significantly shorter duration of disease and hospital length of stay than SARS. Bilateral pneumonia on CT scan, shorter period of illness onset to admission, lymphopenia, the severity of disease are the risk factors for longer hospitalization duration of COVID-19.", "title": "Clinical characteristics and durations of hospitalized patients with COVID-19 in Beijing: a retrospective cohort study", "pid": "n0uwy77g", "bm25_score": 213.9365997314453}, {"text": "Abstract The novel Coronavirus disease 2019 (COVID-19) is an illness caused due to Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The World Health Organization (WHO) has declared this outbreak a global health emergency and as on April 24, 2020, it has spread to 213 countries, with 25,91,015 confirmed cases and 742,855 cases have been recovered from COVID-19. In this dreadful situation our team has already published an article in the Science of the Total Environment, which elaborates the various aspects of the SARS-CoV-2 infection. In this situation, it is imperative to understand the possible outcome of COVID-19 recovered patients and determine if they have any other detrimental illnesses by longitudinal analysis to safeguard their life in future. It is necessary to follow-up these recovered patients and performs comprehensive assessments for detection and appropriate management towards their psychological, physical, and social realm. This urges us to suggest that it is highly important to provide counselling, moral support as well as a few recommended guidelines to the recovered patients and society to restore to normalcy. Epidemiological, clinical and immunological studies from COVID-19 recovered patients are particularly important to understand the disease and to prepare better for potential outbreaks in the future. Longitudinal studies on a larger cohort would help us to understand the in-depth prognosis as well as the pathogenesis of COVID-19. Also, follow-up studies will help us provide more information for the development of vaccines and drugs for these kinds of pandemics in the future. Hence, we recommend more studies are required to unravel the possible mechanism of COVID-19 infection and the after-effects of it to understand the characteristics of the virus and to develop the necessary precautionary measures to prevent it.", "title": "Follow-up studies in COVID-19 recovered patients - is it mandatory?", "pid": "8p9d1c9k", "bm25_score": 213.93487548828125}, {"text": "Objectives Those discharged from hospital after treatment for Covid-19 are likely to have significant and ongoing symptoms, functional impairment and psychological disturbances. There is an immediate need to develop a safe and efficient discharge process and recovery programme. Pulmonary rehabilitation is well placed to deliver a rehabilitation programme for this group but will most likely need to be adapted for the post Covid-19 population. The purpose of this survey was to rapidly identify the components of a post-Covid-19 rehabilitation assessment and elements of a successful rehabilitation programme that would be required to deliver a comprehensive service for those post Covid-19 to inform service delivery. Design A survey comprising a series of closed questions and a free text comments box allowing for a qualitative analysis. Setting Online survey. Participants British Thoracic Society members and multi-professional clinicians, across specialities were invited to take part. Results 1031 participants responded from a broad range of specialities over 6 days. There was overwhelming support for early post discharge from hospital phase of the recovery programme to advise patients about the management of fatigue (95% agreed/ strongly agreed), breathlessness (94%), and mood disturbances (including symptoms of anxiety and depression) 92%. At the 6-8-week time point an assessment was considered important, focusing on the assessment of a broad range of possible symptoms and the need to potentially return to work. Recommendations for the intervention described a holistic programme focusing on symptom management, return of function and return to employment. The free text comments added depth to the survey and the need not to reinvent the wheel rather adapt well established (pulmonary rehabilitation) services to accommodate the needs of the post Covid-19 population. Conclusion The responses indicate the huge interest and the urgent need establish a programme to support and mitigate the long term impact of Covid-19.", "title": "The British Thoracic Society survey of rehabilitation to support recovery of the Post Covid -19 population.", "pid": "s24y9vrw", "bm25_score": 213.93429565429688}, {"text": "Complications of COVID-19 have been particularly severe among older adults, who are the focus of this article. Public policy goals should prioritize pandemic preparedness in nursing homes, as well as civic and local government-based support programs for community-dwelling older adults, to ensure that risk of infection is mitigated while promoting wellness during a period of stress and uncertainty.", "title": "COVID-19 in older adults: clinical, psychosocial, and public health considerations.", "pid": "zg6v74l9", "bm25_score": 213.92938232421875}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic has led to preventive measures worldwide. With the decline of infection rates, less stringent restrictions for sports and exercise are being implemented. COVID-19 is associated with significant cardiovascular complications; however there are limited data on cardiovascular complications and long-term outcomes in both competitive (elite) athletes and highly active individuals. Based on different categories of disease severity (asymptomatic, regional/systemic symptoms, hospitalisation, myocardial damage, and/or myocarditis), in this point-of-view article we offer the (sports) cardiologist or sports physician in the Netherlands a practical guide to pre-participation screening, and diagnostic and management strategies in all athletes >16 years of age after COVID-19 infection.", "title": "Return to sports after COVID-19: a position paper from the Dutch Sports Cardiology Section of the Netherlands Society of Cardiology", "pid": "ele6eq56", "bm25_score": 213.9231719970703}, {"text": "", "title": "Is reinfection possible after recovery from COVID-19?", "pid": "xk73ydqe", "bm25_score": 213.9179229736328}, {"text": "OBJECTIVES: To explore the epidemiological information, clinical characteristics, therapeutic outcomes and temporal progression of laboratory findings in 2019-coronavirus disease (COVID-19) patients exposed to lopinavir. METHODS: We collected data from ten COVID-19 patients admitted between January 22, 2020 and February 11, 2020 at Xixi hospital in Hangzhou, China. RESULTS: Of ten patients, secondary, tertiary and quartus patients emerged; the incubation period was 3-7 days. Mainly initial symptoms were cough and low fever (37.3-38.0°C). An asymptomatic case presented normal radiography, the others had ground glass opacities. All cases (three transferred, seven discharged) were exposed to lopinavir on initial hospitalization. Three patients stopped lopinavir because of adverse effects, two of them deteriorated, one was hospitalized longer than others who with sustained lopinavir use. Levels of potassium, albumin, and lymphocytes were low, but increased persistently after treatment. Eosinophil values were low on initial hospitalization, then all returned to normal before discharge. Viral load of SARS-CoV-2, radiography and eosinophil improved continuously in 3-14, 6-8 and 7-9 days, respectively. CONCLUSIONS: Increasing eosinophils may be an indicator of COVID-19 improvement. The COVID-19 patients may benefit from sustained lopinavir use. More research on a larger scale is needed to verify these points.", "title": "Patients of COVID-19 may benefit from sustained Lopinavir-combined regimen and the increase of Eosinophil may predict the outcome of COVID-19 progression", "pid": "1s63xdcr", "bm25_score": 213.90982055664062}, {"text": "", "title": "Flattening the disability curve: Rehabilitation and recovery after COVID-19 infection", "pid": "7lujm9ch", "bm25_score": 213.90692138671875}, {"text": "", "title": "Flattening the Disability Curve: Rehabilitation and Recovery after COVID-19 Infection", "pid": "w87tgqk1", "bm25_score": 213.90692138671875}, {"text": "Abstract The coronavirus disease 19 (COVID-19) pandemic is a significant psychological stressor in addition to its tremendous impact on every facet of individuals’ lives and organizations in virtually all social and economic sectors worldwide. Fear of illness and uncertainty about the future precipitate anxiety- and stress-related disorders, and several groups have rightfully called for the creation and dissemination of robust mental health screening and treatment programs for the general public and front-line healthcare workers. However, in addition to pandemic-associated psychological distress, the direct effects of the virus itself (several acute respiratory syndrome coronavirus; SARS-CoV-2), and the subsequent host immunologic response, on the human central nervous system (CNS) and related outcomes are unknown. We discuss currently available evidence of COVID-19 related neuropsychiatric sequelae while drawing parallels to past viral pandemic-related outcomes. Past pandemics have demonstrated that diverse types of neuropsychiatric symptoms, such as encephalopathy, mood changes, psychosis, neuromuscular dysfunction, or demyelinating processes, may accompany acute viral infection, or may follow infection by weeks, months, or longer in recovered patients. The potential mechanisms are also discussed, including viral and immunological underpinnings. Therefore, prospective neuropsychiatric monitoring of individuals exposed to SARS-CoV-2 at various points in the life course, as well as their neuroimmune status, are needed to fully understand the long-term impact of COVID-19, and to establish a framework for integrating psychoneuroimmunology into epidemiologic studies of pandemics.", "title": "Are we facing a crashing wave of neuropsychiatric sequelae of COVID-19? Neuropsychiatric symptoms and potential immunologic mechanisms", "pid": "stnva6pv", "bm25_score": 213.90615844726562}]}
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"zzkqb0u2": 0, "zzmfhr2s": 0, "zzpw375i": 1}, "bm25_results": [{"text": "Timely, creditable, and fine-granular case information is vital for local communities and individual citizens to make rational and data-driven responses to the COVID-19 pandemic. This paper presents CovidNet, a COVID-19 tracking project associated with a large scale epidemic dataset, which was initiated by 1Point3Acres. To the best of our knowledge, the project is the only platform providing real-time global case information of more than 4,124 sub-divisions from over 27 countries worldwide with multi-language supports. The platform also offers interactive visualization tools to analyze the full historical case curves in each region. Initially launched as a voluntary project to bridge the data transparency gap in North America in January 2020, this project by far has become one of the major independent sources worldwide and has been consumed by many other tracking platforms. The accuracy and freshness of the dataset is a result of the painstaking efforts from our voluntary teamwork, crowd-sourcing channels, and automated data pipelines. As of May 18, 2020, the project website has been visited more than 200 million times and the CovidNet dataset has empowered over 522 institutions and organizations worldwide in policy-making and academic researches. All datasets are openly accessible for non-commercial purposes at https://coronavirus.1point3acres.com via a formal request through our APIs.", "title": "CovidNet: To Bring Data Transparency in the Era of COVID-19", "pid": "zxvim4t8", "bm25_score": 216.01185607910156}, {"text": "We provide an insight into the open-data resources pertinent to the study of the spread of the Covid-19 pandemic and its control. We identify the variables required to analyze fundamental aspects like seasonal behavior, regional mortality rates, and effectiveness of government measures. Open-data resources, along with data-driven methodologies, provide many opportunities to improve the response of the different administrations to the virus. We describe the present limitations and difficulties encountered in most of the open-data resources. To facilitate the access to the main open-data portals and resources, we identify the most relevant institutions, on a global scale, providing Covid-19 information and/or auxiliary variables (demographics, mobility, etc.). We also describe several open resources to access Covid-19 datasets at a country-wide level (i.e., China, Italy, Spain, France, Germany, US, etc.). To facilitate the rapid response to the study of the seasonal behavior of Covid-19, we enumerate the main open resources in terms of weather and climate variables. We also assess the reusability of some representative open-data sources.", "title": "COVID-19: Open-data resources for monitoring, modeling, and forecasting the epidemic", "pid": "iukudcbo", "bm25_score": 216.0010528564453}, {"text": "As the COVID-19 pandemic continues its march around the world, an unprecedented amount of open data is being generated for genetics and epidemiological research. The unparalleled rate at which many research groups around the world are releasing data and publications on the ongoing pandemic is allowing other scientists to learn from local experiences and data generated in the front lines of the COVID-19 pandemic. However, there is a need to integrate additional data sources that map and measure the role of social dynamics of such a unique world-wide event into biomedical, biological, and epidemiological analyses. For this purpose, we present a large-scale curated dataset of over 152 million tweets, growing daily, related to COVID-19 chatter generated from January 1st to April 4th at the time of writing. This open dataset will allow researchers to conduct a number of research projects relating to the emotional and mental responses to social distancing measures, the identification of sources of misinformation, and the stratified measurement of sentiment towards the pandemic in near real time.", "title": "A large-scale COVID-19 Twitter chatter dataset for open scientific research -- an international collaboration", "pid": "21fhsooy", "bm25_score": 215.98483276367188}, {"text": "As COVID-19 quickly became one of the most concerned global crisis, the demand for data in academic research is also increasing. Currently, there are several open access Twitter datasets, but none of them is dedicated to the institutional and news media Twitter data collection, to fill this blank, we retrieved data from 69 institutional/news media Twitter accounts, 17 of them were related to government and international organizations, 52 of them were news media across North America, Europe and Asia. We believe our open access data can provide researchers more availability to conduct social science research.", "title": "Open access institutional and news media tweet dataset for COVID-19 social science research", "pid": "5o12mbut", "bm25_score": 215.96115112304688}, {"text": "As the COVID-19 pandemic continues its march around the world, an unprecedented amount of open data is being generated for genetics and epidemiological research. The unparalleled rate at which many research groups around the world are releasing data and publications on the ongoing pandemic is allowing other scientists to learn from local experiences and data generated in the front lines of the COVID-19 pandemic. However, there is a need to integrate additional data sources that map and measure the role of social dynamics of such a unique world-wide event into biomedical, biological, and epidemiological analyses. For this purpose, we present a large-scale curated dataset of over 152 million tweets, growing daily, related to COVID-19 chatter generated from January 1st to April 4th at the time of writing. This open dataset will allow researchers to conduct a number of research projects relating to the emotional and mental responses to social distancing measures, the identification of sources of misinformation, and the stratified measurement of sentiment towards the pandemic in near real time.", "title": "A large-scale COVID-19 Twitter chatter dataset for open scientific research -- an international collaboration.", "pid": "1lisdjpm", "bm25_score": 215.94366455078125}, {"text": "This regularly updated survey provides an overview of public resources that offer medical images and metadata of COVID-19 cases. The purpose of this survey is to simplify the access to open COVID-19 image data resources for all scientists currently working on the coronavirus crisis.", "title": "COVID-19: A Survey on Public Medical Imaging Data Resources", "pid": "z0bkpmpk", "bm25_score": 215.7633514404297}, {"text": "The past several years have witnessed a huge surge in the use of social media platforms during mass convergence events such as health emergencies, natural or human-induced disasters. These non-traditional data sources are becoming vital for disease forecasts and surveillance when preparing for epidemic and pandemic outbreaks. In this paper, we present GeoCoV19, a large-scale Twitter dataset containing more than 524 million multilingual tweets posted over a period of 90 days since February 1, 2020. Moreover, we employ a gazetteer-based approach to infer the geolocation of tweets. We postulate that this large-scale, multilingual, geolocated social media data can empower the research communities to evaluate how societies are collectively coping with this unprecedented global crisis as well as to develop computational methods to address challenges such as identifying fake news, understanding communities' knowledge gaps, building disease forecast and surveillance models, among others.", "title": "GeoCoV19: A Dataset of Hundreds of Millions of Multilingual COVID-19 Tweets with Location Information", "pid": "g7dd92bv", "bm25_score": 215.43038940429688}, {"text": "", "title": "Data sharing for novel coronavirus (COVID-19)", "pid": "m2m1ku9t", "bm25_score": 215.34024047851562}, {"text": "", "title": "Open access epidemiological data from the COVID-19 outbreak", "pid": "4c0vh2h1", "bm25_score": 215.26185607910156}, {"text": "The National Center for Advancing Translational Sciences (NCATS) has developed an online open science data portal for its COVID-19 drug repurposing campaign – named OpenData – with the goal of making data across a range of SARS-CoV-2 related assays available in real-time. The assays developed cover a wide spectrum of the SARS-CoV-2 life cycle, including both viral and human (host) targets. In total, over 10,000 compounds are being tested in full concentration-response ranges from across multiple annotated small molecule libraries, including approved drug, repurposing candidates and experimental therapeutics designed to modulate a wide range of cellular targets. The goal is to support research scientists, clinical investigators and public health officials through open data sharing and analysis tools to expedite the development of SARS-CoV-2 interventions, and to prioritize promising compounds and repurposed drugs for further development in treating COVID-19.", "title": "An OpenData portal to share COVID-19 drug repurposing data in real time", "pid": "uh8w5nuj", "bm25_score": 215.25909423828125}, {"text": "The current state of much of the Wuhan pneumonia virus (COVID-19) research shows a regrettable lack of data sharing and considerable analytical obfuscation. This impedes global research cooperation, which is essential for tackling public health emergencies, and requires unimpeded access to data, analysis tools, and computational infrastructure. Here we show that community efforts in developing open analytical software tools over the past ten years, combined with national investments into scientific computational infrastructure, can overcome these deficiencies and provide an accessible platform for tackling global health emergencies in an open and transparent manner. Specifically, we use all COVID-19 genomic data available in the public domain so far to (1) underscore the importance of access to raw data and to (2) demonstrate that existing community efforts in curation and deployment of biomedical software can reliably support rapid, reproducible research during global health crises. All our analyses are fully documented at https://github.com/galaxyproject/SARS-CoV-2.", "title": "No more business as usual: agile and effective responses to emerging pathogen threats require open data and open analytics", "pid": "v0yzur5h", "bm25_score": 215.2226104736328}, {"text": "BACKGROUND: The COVID-19 pandemic constitutes an ongoing, burning Public Health Emergency of International Concern (PHEIC). In 2015, the World Health Organization (WHO) adopted an open-data policy recommendation in such situations. OBJECTIVES: The present cross-sectional meta-research study aimed to assess the availability of open data and metrics and of articles pertaining to the COVID-19 outbreak in five high-impact journals. METHODS: All articles regarding the SARS-CoV-2, published in five high impact journals (Ann Intern Med, BMJ, JAMA, NEJM and Lancet) until March 14, 2020 were retrieved. Meta-data (namely the type of article, number of authors, number of patients, citations, errata, news and social media mentions) were extracted for each article in each journal in a systematic way. Google Scholar and Scopus were used for citations and author metrics respectively, and Altmetrics and PlumX were used for news and social media mentions retrieval. The degree of adherence to the PHEIC open data call was also evaluated. RESULTS: A total of 140 articles were published until March 14, 2020, mostly opinion papers. Sixteen errata followed these publications. The number of authors in each article ranged from 1 to 63, whereas the number of patients with a laboratory-confirmed SARS-CoV-2 infection reached 2,645. The impact of these publications reached a total of 4,210 cumulative crude citations and 342,790 news and social media mentions. Only one publication (0.7%) provided complete open data, while 32 (22.9%) included patient data. CONCLUSIONS: Even though a large number of manuscripts was produced since the pandemic, availability of open data remains restricted.", "title": "Tracing open data in emergencies: the case of the COVID-19 pandemic", "pid": "vhx430l3", "bm25_score": 215.19334411621094}, {"text": "We provide an insight into the open data resources pertinent to the study of the spread of Covid-19 pandemic and its control. We identify the variables required to analyze fundamental aspects like seasonal behaviour, regional mortality rates, and effectiveness of government measures. Open data resources, along with data-driven methodologies, provide many opportunities to improve the response of the different administrations to the virus. We describe the present limitations and difficulties encountered in most of the open-data resources. To facilitate the access to the main open-data portals and resources, we identify the most relevant institutions, at a world scale, providing Covid-19 information and/or auxiliary variables (demographics, mobility, etc.). We also describe several open resources to access Covid-19 data-sets at a country-wide level (i.e. China, Italy, Spain, France, Germany, U.S., etc.). In an attempt to facilitate the rapid response to the study of the seasonal behaviour of Covid-19, we enumerate the main open resources in terms of weather and climate variables. CONCO-Team: The authors of this paper belong to the CONtrol COvid-19 Team, which is composed of different researches from universities of Spain, Italy, France, Germany, United Kingdom and Argentina. The main goal of CONCO-Team is to develop data-driven methods for the better understanding and control of the pandemic.", "title": "Open Data Resources for Fighting COVID-19", "pid": "lysvg3vw", "bm25_score": 215.17205810546875}, {"text": "Over the past several months, the outbreak of COVID-19 has been expanding over the world. A reliable and accurate dataset of the cases is vital for scientists to conduct related research and for policy-makers to make better decisions. We collect the COVID-19 daily reported data from four open sources: the New York Times, the COVID-19 Data Repository by Johns Hopkins University, the COVID Tracking Project at the Atlantic, and the USAFacts, and compare the similarities and differences among them. In addition, we examine the following problems which occur frequently: (1) the order dependencies violation, (2) the delay-reported issue on weekends and/or holidays, and (3) abnormal data point or data period. We also integrate the COVID-19 reported cases with the county-level auxiliary information of the local features from official sources, such as health infrastructure, demographic, socioeconomic, and environment information, which are important for understanding the spread of the virus.", "title": "Comparing and Integrating US COVID-19 Daily Data from Multiple Sources: A County-Level Dataset with Local Characteristics", "pid": "yfuq8na6", "bm25_score": 215.1709747314453}, {"text": "We release our COVID-19 news dataset, containing more than 10,000 links to news articles related to the Coronavirus pandemic published in the Swiss media since early January 2020. This collection can prove beneficial in mining and analysis of the reaction of the Swiss media and the COVID-19 pandemic and extracting insightful information for further research. We hope this dataset helps researchers and the public deliver results that will help analyse the pandemic and potentially lead to a better understanding of the events.", "title": "Lest We Forget: A Dataset of Coronavirus-Related News Headlines in Swiss Media", "pid": "fu373osb", "bm25_score": 215.162353515625}, {"text": "This paper describes the initial COVID-19 open image data collection. It was created by assembling medical images from websites and publications and currently contains 123 frontal view X-rays.", "title": "COVID-19 Image Data Collection", "pid": "53aq480d", "bm25_score": 215.15457153320312}, {"text": "Understanding the COVID-19 pandemic is a multidisciplinary effort that requires a significant number of variables. This dataset comprises (i) sociodemographic characteristics, compiled from 35 datasets obtained at UN Data; (ii) mobility metrics that can assist the analysis of social distancing, from Google Community Mobility Reports and; (iii) daily counts of cases and deaths by COVID-19, from the European Centre for Disease Prevention and Control and the Johns Hopkins University Center for Systems Science and Engineering. This unified dataset ranges from February 15, 2020 to April 26, 2020, a total of 72 days, and is provided as a collection of time series for 131 countries with 192 variables. The pipeline to preprocess and generate the dataset, along with the dataset itself, are versioned with the Data Version Control tool (DVC) and are thus easily reproducible.", "title": "Dataset for country profile and mobility analysis in the assessment of COVID-19 pandemic", "pid": "2llnlr8a", "bm25_score": 215.1492462158203}, {"text": "Governments worldwide have implemented countless policies in response to the COVID-19 pandemic. We present an initial public release of a large hand-coded dataset of over 13,000 such policy announcements across more than 195 countries. The dataset is updated daily, with a 5-day lag for validity checking. We document policies across numerous dimensions, including the type of policy, national versus subnational enforcement, the specific human group and geographical region targeted by the policy, and the time frame within which each policy is implemented. We further analyse the dataset using a Bayesian measurement model, which shows the quick acceleration of the adoption of costly policies across countries beginning in mid-March 2020 through 24 May 2020. We believe that these data will be instrumental for helping policymakers and researchers assess, among other objectives, how effective different policies are in addressing the spread and health outcomes of COVID-19.", "title": "COVID-19 Government Response Event Dataset (CoronaNet v.1.0).", "pid": "4dgvuaxr", "bm25_score": 215.1000213623047}, {"text": "The 2019 coronavirus disease (COVID-19), emerged late December 2019 in China, is now rapidly spreading across the globe. At the time of writing this paper, the number of global confirmed cases has passed two millions and half with over 180,000 fatalities. Many countries have enforced strict social distancing policies to contain the spread of the virus. This have changed the daily life of tens of millions of people, and urged people to turn their discussions online, e.g., via online social media sites like Twitter. In this work, we describe the first Arabic tweets dataset on COVID-19 that we have been collecting since January 1st, 2020. The dataset would help researchers and policy makers in studying different societal issues related to the pandemic. Many other tasks related to behavioral change, information sharing, misinformation and rumors spreading can also be analyzed.", "title": "Large Arabic Twitter Dataset on COVID-19", "pid": "33m59ajn", "bm25_score": 215.06491088867188}, {"text": "Governments worldwide have implemented countless policies in response to the COVID-19 pandemic. We present an initial public release of a large hand-coded dataset of over 13,000 such policy announcements across more than 195 countries. The dataset is updated daily, with a 5-day lag for validity checking. We document policies across numerous dimensions, including the type of policy, national versus subnational enforcement, the specific human group and geographical region targeted by the policy, and the time frame within which each policy is implemented. We further analyse the dataset using a Bayesian measurement model, which shows the quick acceleration of the adoption of costly policies across countries beginning in mid-March 2020 through 24 May 2020. We believe that these data will be instrumental for helping policymakers and researchers assess, among other objectives, how effective different policies are in addressing the spread and health outcomes of COVID-19.", "title": "COVID-19 Government Response Event Dataset (CoronaNet v.1.0)", "pid": "x7v4iwts", "bm25_score": 215.05953979492188}, {"text": "To provide convenient access to epidemiological data on the coronavirus outbreak, we developed an R package, nCov2019 (https://github.com/GuangchuangYu/nCov2019). Besides detailed real-time statistics, it offers access to three data sources with detailed daily statistics from December 1, 2019, for 43 countries and more than 500 Chinese cities. We also developed a web app (http://www.bcloud.org/e/) with interactive plots and simple time-series forecasts. These analytics tools could be useful in informing the public and studying how this and similar viruses spread in populous countries.", "title": "Open-source analytics tools for studying the COVID-19 coronavirus outbreak", "pid": "qtrquuvv", "bm25_score": 215.0478057861328}, {"text": "Across the world's coronavirus disease 2019 (COVID-19) hot spots, the need to streamline patient diagnosis and management has become more pressing than ever. As one of the main imaging tools, chest X-rays (CXRs) are common, fast, non-invasive, relatively cheap, and potentially bedside to monitor the progression of the disease. This paper describes the first public COVID-19 image data collection as well as a preliminary exploration of possible use cases for the data. This dataset currently contains hundreds of frontal view X-rays and is the largest public resource for COVID-19 image and prognostic data, making it a necessary resource to develop and evaluate tools to aid in the treatment of COVID-19. It was manually aggregated from publication figures as well as various web based repositories into a machine learning (ML) friendly format with accompanying dataloader code. We collected frontal and lateral view imagery and metadata such as the time since first symptoms, intensive care unit (ICU) status, survival status, intubation status, or hospital location. We present multiple possible use cases for the data such as predicting the need for the ICU, predicting patient survival, and understanding a patient's trajectory during treatment. Data can be accessed here: https://github.com/ieee8023/covid-chestxray-dataset", "title": "COVID-19 Image Data Collection: Prospective Predictions Are the Future", "pid": "n0y7icl5", "bm25_score": 215.044189453125}, {"text": "Crowdsourcing data can prove of paramount importance in monitoring and controlling the spread of infectious diseases. The recent paper by Sun, Chen and Viboud (2020) is important because it contributes to the understanding of the epidemiology and of the spreading of Covid-19 in a period when most of the epidemic characteristics are still unknown. However, the use of crowdsourcing data raises a number of problems from the statistical point of view which run the risk of invalidating the results and of biasing estimation and hypothesis testing. While the work by Sun, Chen and Viboud (2020) has to be commended, given the importance of the topic for worldwide health security, in this paper we deem important to remark the presence of the possible sources of statistical biases and to point out possible solutions to them", "title": "A Note on Early Epidemiological Analysis of Coronavirus Disease 2019 Outbreak using Crowdsourced Data", "pid": "n5qwsvtr", "bm25_score": 214.914306640625}, {"text": "In December 2019, a novel virus named as COVID-19 emerged in the city of Wuhan, China. In early 2020, the COVID-19 virus spread in all continents of the world except Antarctica causing widespread infections and deaths due to its contagious characteristics and no medically proven treatment. The COVID-19 pandemic has been termed as most consequential global crisis after the World Wars. The first line of defense against the COVID-19 spread are the non-pharmaceutical measures like social distancing and personal hygiene. On the other hand, the medical service providers are the first responders for infected persons with severe symptoms of COVID-19. The great pandemic affecting billions of lives economically and socially has motivated the scientific community to come up with solutions based on computer-aided digital technologies for diagnosis, prevention, and estimation of COVID-19. Some of these efforts focus on statistical and Artificial Intelligence-based analysis of the available data concerning COVID-19. All of these scientific efforts necessitate that the data brought to service for the analysis should be open-source to promote the extension, validation, and collaboration of the work in the fight against the global pandemic. Our survey is motivated by the open-source efforts that can be mainly categorized as: (a) COVID-19 diagnosis from CT scans and X-ray images, (b) COVID-19 case reporting, transmission estimation, and prognosis from epidemiological, demographic, and mobility data, (c) COVID-19 emotional and sentiment analysis from social media, and (d) knowledge-based discovery and semantic analysis from the collection of scholarly articles covering COVID-19. We review and critically analyze works in these directions that are accompanied by open-source data and code. We hope that the article will provide the scientific community with an initiative to start open-source extensible and transparent research in the collective fight against COVID-19.", "title": "COVID-19 Datasets: A Survey and Future Challenges", "pid": "f9eqbaj5", "bm25_score": 214.90036010742188}, {"text": "The COVID-19 Open Research Dataset (CORD-19) is a growing resource of scientific papers on COVID-19 and related historical coronavirus research. CORD-19 is designed to facilitate the development of text mining and information retrieval systems over its rich collection of metadata and structured full text papers. Since its release, CORD-19 has been downloaded over 200K times and has served as the basis of many COVID-19 text mining and discovery systems. In this article, we describe the mechanics of dataset construction, highlighting challenges and key design decisions, provide an overview of how CORD-19 has been used, and describe several shared tasks built around the dataset. We hope this resource will continue to bring together the computing community, biomedical experts, and policy makers in the search for effective treatments and management policies for COVID-19.", "title": "CORD-19: The COVID-19 Open Research Dataset", "pid": "4n6v5kfv", "bm25_score": 214.88397216796875}, {"text": "We present CovidQA, the beginnings of a question answering dataset specifically designed for COVID-19, built by hand from knowledge gathered from Kaggle's COVID-19 Open Research Dataset Challenge. To our knowledge, this is the first publicly available resource of its type, and intended as a stopgap measure for guiding research until more substantial evaluation resources become available. While this dataset, comprising 124 question-article pairs as of the present version 0.1 release, does not have sufficient examples for supervised machine learning, we believe that it can be helpful for evaluating the zero-shot or transfer capabilities of existing models on topics specifically related to COVID-19. This paper describes our methodology for constructing the dataset and presents the effectiveness of a number of baselines, including term-based techniques and various transformer-based models. The dataset is available at http://covidqa.ai/", "title": "Rapidly Bootstrapping a Question Answering Dataset for COVID-19", "pid": "vaeyoxv7", "bm25_score": 214.83694458007812}, {"text": "Cases of a novel coronavirus were first reported in Wuhan, Hubei province, China, in December 2019 and have since spread across the world. Epidemiological studies have indicated human-to-human transmission in China and elsewhere. To aid the analysis and tracking of the COVID-19 epidemic we collected and curated individual-level data from national, provincial, and municipal health reports, as well as additional information from online reports. All data are geo-coded and, where available, include symptoms, key dates (date of onset, admission, and confirmation), and travel history. The generation of detailed, real-time, and robust data for emerging disease outbreaks is important and can help to generate robust evidence that will support and inform public health decision making.", "title": "Epidemiological data from the COVID-19 outbreak, real-time case information", "pid": "irt0wmt2", "bm25_score": 214.83494567871094}, {"text": "The Covid-19 Open Research Dataset (CORD-19) is a growing resource of scientific papers on Covid-19 and related historical coronavirus research. CORD-19 is designed to facilitate the development of text mining and information retrieval systems over its rich collection of metadata and structured full text papers. Since its release, CORD-19 has been downloaded over 75K times and has served as the basis of many Covid-19 text mining and discovery systems. In this article, we describe the mechanics of dataset construction, highlighting challenges and key design decisions, provide an overview of how CORD-19 has been used, and preview tools and upcoming shared tasks built around the dataset. We hope this resource will continue to bring together the computing community, biomedical experts, and policy makers in the search for effective treatments and management policies for Covid-19.", "title": "CORD-19: The Covid-19 Open Research Dataset.", "pid": "pt8nh7wx", "bm25_score": 214.83212280273438}, {"text": "Research into COVID-19 is a big challenge and highly relevant at the moment. New tools are required to assist medical experts in their research with relevant and valuable information. The COVID-19 Open Research Dataset Challenge (CORD-19) is a\"call to action\"for computer scientists to develop these innovative tools. Many of these applications are empowered by entity information, i. e. knowing which entities are used within a sentence. For this paper, we have developed a pipeline upon the latest Named Entity Recognition tools for Chemicals, Diseases, Genes and Species. We apply our pipeline to the COVID-19 research challenge and share the resulting entity mentions with the community.", "title": "A Semantically Enriched Dataset based on Biomedical NER for the COVID19 Open Research Dataset Challenge", "pid": "8lu58q4k", "bm25_score": 214.82972717285156}, {"text": "As the coronavirus disease 2019 (COVID-19) becomes a global pandemic, policy makers must enact interventions to stop its spread. Data driven approaches might supply information to support the implementation of mitigation and suppression strategies. To facilitate research in this direction, we present a machine-readable dataset that aggregates relevant data from governmental, journalistic, and academic sources on the county level. In addition to county-level time-series data from the JHU CSSE COVID-19 Dashboard, our dataset contains more than 300 variables that summarize population estimates, demographics, ethnicity, housing, education, employment and in come, climate, transit scores, and healthcare system-related metrics. Furthermore, we present aggregated out-of-home activity information for various points of interest for each county, including grocery stores and hospitals, summarizing data from SafeGraph. By collecting these data, as well as providing tools to read them, we hope to aid researchers investigating how the disease spreads and which communities are best able to accommodate stay-at-home mitigation efforts. Our dataset and associated code are available at https://github.com/JieYingWu/COVID-19_US_County-level_Summaries.", "title": "A County-level Dataset for Informing the United States' Response to COVID-19", "pid": "rndc2v2b", "bm25_score": 214.78150939941406}, {"text": "BACKGROUND: The COVID‐19 pandemic constitutes an ongoing, burning Public Health Emergency of International Concern (PHEIC). In 2015, the World Health Organization (WHO) adopted an open‐data policy recommendation in such situations. OBJECTIVES: The present cross‐sectional meta‐research study aimed to assess the availability of open data and metrics and of articles pertaining to the COVID‐19 outbreak in five high‐impact journals. METHODS: All articles regarding the SARS‐CoV‐2, published in five high impact journals (Ann Intern Med, BMJ, JAMA, NEJM and Lancet) until March 14, 2020 were retrieved. Meta‐data (namely the type of article, number of authors, number of patients, citations, errata, news and social media mentions) were extracted for each article in each journal in a systematic way. Google Scholar and Scopus were used for citations and author metrics respectively, and Altmetrics and PlumX were used for news and social media mentions retrieval. The degree of adherence to the PHEIC open data call was also evaluated. RESULTS: A total of 140 articles were published until March 14, 2020, mostly opinion papers. Sixteen errata followed these publications. The number of authors in each article ranged from 1 to 63, whereas the number of patients with a laboratory‐confirmed SARS‐CoV‐2 infection reached 2,645. The impact of these publications reached a total of 4,210 cumulative crude citations and 342,790 news and social media mentions. Only one publication (0.7%) provided complete open data, while 32 (22.9%) included patient data. CONCLUSIONS: Even though a large number of manuscripts was produced since the pandemic, availability of open data remains restricted.", "title": "Tracing open data in emergencies: the case of the COVID‐19 pandemic", "pid": "4h2ma00j", "bm25_score": 214.7496337890625}, {"text": "The novel coronavirus (COVID-19) pandemic outbreak is drastically shaping and reshaping many aspects of our life, with a huge impact on our social life. In this era of lockdown policies in most of the major cities around the world, we see a huge increase in people and professional engagement in social media. Social media is playing an important role in news propagation as well as keeping people in contact. At the same time, this source is both a blessing and a curse as the coronavirus infodemic has become a major concern, and is already a topic that needs special attention and further research. In this paper, we provide a multilingual coronavirus (COVID-19) Instagram dataset that we have been continuously collected since March 30, 2020. We are making our dataset available to the research community at Github. We believe that this contribution will help the community to better understand the dynamics behind this phenomenon in Instagram, as one of the major social media. This dataset could also help study the propagation of misinformation related to this outbreak.", "title": "A First Instagram Dataset on COVID-19", "pid": "lqhainz3", "bm25_score": 214.74911499023438}, {"text": "SARS-Cov-2, the deadly and novel virus, which has caused a worldwide pandemic and drastic loss of human lives and economic activities. An open data set called the COVID-19 Open Research Dataset or CORD-19 contains large set full text scientific literature on SARS-CoV-2. The Next Strain consists of a database of SARS-CoV-2 viral genomes from since 12/3/2019. We applied an unique information mining method named lexical link analysis (LLA) to answer the call to action and help the science community answer high-priority scientific questions related to SARS-CoV-2. We first text-mined the CORD-19. We also data-mined the next strain database. Finally, we linked two databases. The linked databases and information can be used to discover the insights and help the research community to address high-priority questions related to the SARS-CoV-2’s genetics, tests, and prevention. Significance Statement In this paper, we show how to apply an unique information mining method lexical link analysis (LLA) to link unstructured (CORD-19) and structured (Next Strain) data sets to relevant publications, integrate text and data mining into a single platform to discover the insights that can be visualized, and validated to answer the high-priority questions of genetics, incubation, treatment, symptoms, and prevention of COVID-19.", "title": "Applying Lexical Link Analysis to Discover Insights from Public Information on COVID-19", "pid": "ovv34qxm", "bm25_score": 214.70933532714844}, {"text": "This paper describes different aspects of novel coronavirus disease (COVID-19), presents visualization of the spread of the infection, and discusses the potential applications of data analytics on this viral infection. Firstly, a literature survey is done on COVID-19 highlighting a number of factors including its origin, its similarity with previous coronaviruses, its transmission capacity, its symptoms, etc. Secondly, data analytics is applied on a dataset of Johns Hopkins University to find out the spread of the viral infection. It is shown here that although the disease started in China in December 2019, the highest number of confirmed cases up to June 04, 2020 is in the USA. Thirdly, the worldwide increase in the number of confirmed cases over time is modelled here using a polynomial regression algorithm with degree 2. Fourthly, classification algorithms are applied on a dataset of 5644 samples provided by Hospital Israelita Albert Einstein of Brazil in order to diagnose COVID-19. It is shown here that multilayer perceptron (MLP), XGBoost and logistic regression can classify COVID-19 patients at an accuracy above 91%. Finally, a discussion is presented on the potential applications of data analytics in several important factors of COVID-19.", "title": "Data analytics for novel coronavirus disease", "pid": "eec649x4", "bm25_score": 214.67654418945312}, {"text": "With the rapid development of COVID-19, people are asked to maintain\"social distance\"and\"stay at home\". In this scenario, more and more social interactions move online, especially on social media like Twitter and Weibo. People post tweets to share information, express opinions and seek help during the pandemic, and these tweets on social media are valuable for studies against COVID19, such as early warning and outbreaks detection. Therefore, in this paper, we release a novel large-scale COVID-19 social media dataset from Weibo called Weibo-COV, covering more than 40 million tweets from 1 December 2019 to 30 April 2020. Moreover, the field information of the dataset is very rich, including basic tweets information, interactive information, location information and retweet network. We hope this dataset can promote studies of COVID-19 from multiple perspectives and enable better and faster researches to suppress the spread of this disease.", "title": "Weibo-COV: A Large-Scale COVID-19 Social Media Dataset from Weibo", "pid": "1bjt64o7", "bm25_score": 214.6536102294922}, {"text": "Abstract In response to the global call for strategic information to understand the novel coronavirus, the dataset presented in this paper is an examination of COVID-19-related knowledge, risk perceptions and precautionary health behavior among Nigerians. The data were generated during the COVID-19 lockdown in the country through a survey distributed via an online questionnaire, assessing socio-demographic information (7 items), knowledge (5 items), information sources (1 item), risk perception (9 items), expected end of lockdown (1 item), and COVID-19 precautionary health behavior (10 items), from 28th March to 4th April, 2020, gathering a total of 1,357 responses. A combination of purposive and snowball techniques helped to select the respondents via Whatsapp and Facebook from 180 cities/towns in the 6 geopolitical zones of Nigeria. The survey data were analyzed using descriptive and inferential statistics. The entire dataset is stored in a Microsoft Excel Worksheet (xlsx) and the questionnaire is attached as a supplementary file. The data will assist in curbing the Coronavirus pandemic by offering evidence for strategic and targeted interventions as well as health policy formulations and implementation.", "title": "Survey data of COVID-19-related Knowledge, Risk Perceptions and Precautionary Behavior among Nigerians", "pid": "pdc2swh6", "bm25_score": 214.5888214111328}, {"text": "The Pandemic of COVID-19, an infectious disease caused by SARS-CoV-2 motivated the scientific community to work together in order to gather, organize, process and distribute data on the novel biomedical hazard. Here, we analyzed how the scientific community responded to this challenge by quantifying distribution and availability patterns of the academic information related to COVID-19. The aim of this study was to assess the quality of the information flow and scientific collaboration, two factors we believe to be critical for finding new solutions for the ongoing pandemic. The RISmed R package, and a custom Python script were used to fetch metadata on articles indexed in PubMed and published on Rxiv preprint server. Scopus was manually searched and the metadata was exported in BibTex file. Publication rate and publication status, affiliation and author count per article, and submission-to-publication time were analysed in R. Biblioshiny application was used to create a world collaboration map. Preliminary data suggest that COVID-19 pandemic resulted in generation of a large amount of scientific data, and demonstrates potential problems regarding the information velocity, availability, and scientific collaboration in the early stages of the pandemic. More specifically, the results indicate precarious overload of the standard publication systems, significant problems with data availability and apparent deficient collaboration. In conclusion, we believe the scientific community could have used the data more efficiently in order to create proper foundations for finding new solutions for the COVID-19 pandemic. Moreover, we believe we can learn from this on the go and adopt open science principles and a more mindful approach to COVID-19-related data to accelerate the discovery of more efficient solutions. We take this opportunity to invite our colleagues to contribute to this global scientific collaboration by publishing their findings with maximal transparency.", "title": "Preliminary analysis of COVID-19 academic information patterns: a call for open science in the times of closed borders", "pid": "ejgdzc70", "bm25_score": 214.57662963867188}, {"text": "The pandemic spread of the COVID-19 virus has, as of 20th of April 2020, reached most countries of the world. In an effort to design informed public health policies, many modelling studies have been performed to predict crucial outcomes of interest, including ICU solicitation, cumulated death counts, etc... The corresponding data analyses however, mostly rely on restricted (openly available) data sources, which typically include daily death rates and confirmed COVID cases time series. In addition, many of these predictions are derived before the peak of the outbreak has been observed yet (as is still currently the case for many countries). In this work, we show that peak phase and data paucity have a substantial impact on the reliability of model predictions. Although we focus on a recent model of the COVID pandemics, our conclusions most likely apply to most existing models, which are variants of the so-called 'Susceptible-Infected-Removed' or SIR framework. Our results highlight the need for performing systematic reliability evaluations for all models that currently inform public health policies. They also motivate a plea for gathering and opening richer and more reliable data time series (e.g., ICU occupancy, negative test rates, social distancing commitment reports, etc).", "title": "On the reliability of model-based predictions in the context of the current COVID epidemic event: impact of outbreak peak phase and data paucity", "pid": "ej8fx52u", "bm25_score": 214.55787658691406}, {"text": "In response to the global call for strategic information to understand the novel coronavirus, the dataset presented in this paper is an examination of COVID-19-related knowledge, risk perceptions and precautionary health behavior among Nigerians. The data were generated during the COVID-19 lockdown in the country through a survey distributed via an online questionnaire, assessing socio-demographic information (7 items), knowledge (5 items), information sources (1 item), risk perception (9 items), expected end of lockdown (1 item), and COVID-19 precautionary health behavior (10 items), from 28th March to 4th April, 2020, gathering a total of 1,357 responses. A combination of purposive and snowball techniques helped to select the respondents via Whatsapp and Facebook from 180 cities/towns in the 6 geopolitical zones of Nigeria. The survey data were analyzed using descriptive and inferential statistics. The entire dataset is stored in a Microsoft Excel Worksheet (xlsx) and the questionnaire is attached as a supplementary file. The data will assist in curbing the Coronavirus pandemic by offering evidence for strategic and targeted interventions as well as health policy formulations and implementation.", "title": "Survey data of COVID-19-related Knowledge, Risk Perceptions and Precautionary Behavior among Nigerians", "pid": "9fia8w7l", "bm25_score": 214.55625915527344}, {"text": "Since the outbreak of coronavirus disease 2019 (COVID-19) in the late 2019, it has affected over 200 countries and billions of people worldwide. This has affected the social life of people owing to enforcements, such as\"social distancing\"and\"stay at home.\"This has resulted in an increasing interaction through social media. Given that social media can bring us valuable information about COVID-19 at a global scale, it is important to share the data and encourage social media studies against COVID-19 or other infectious diseases. Therefore, we have released a multilingual dataset of social media posts related to COVID-19, consisting of microblogs in English and Japanese from Twitter and those in Chinese from Weibo. The data cover microblogs from January 20, 2020, to March 24, 2020. This paper also provides a quantitative as well as qualitative analysis of these datasets by creating daily word clouds as an example of text-mining analysis. The dataset is now available on Github. This dataset can be analyzed in a multitude of ways and is expected to help in efficient communication of precautions related to COVID-19.", "title": "NAIST COVID: Multilingual COVID-19 Twitter and Weibo Dataset", "pid": "o8b1rtux", "bm25_score": 214.54437255859375}, {"text": "Big data could help identify potential clues about the immediate (and future) impact of coronavirus disease 2019, but it is in short supply.", "title": "Tests, surgical masks, hospital beds, and ventilators: add big data to the list of tools to fight the coronavirus that are in short supply.", "pid": "q9nfnzph", "bm25_score": 214.5178680419922}, {"text": "In this paper, we present ArCOV-19, an Arabic COVID-19 Twitter dataset that covers the period from 27th of January till 31st of March 2020. ArCOV-19 is the first publicly-available Arabic Twitter dataset covering COVID-19 pandemic that includes around 748k popular tweets (according to Twitter search criterion) alongside the propagation networks of the most-popular subset of them. The propagation networks include both retweets and conversational threads (i.e., threads of replies). ArCOV-19 is designed to enable research under several domains including natural language processing, information retrieval, and social computing, among others. Preliminary analysis shows that ArCOV-19 captures rising discussions associated with the first reported cases of the disease as they appeared in the Arab world. In addition to the source tweets and the propagation networks, we also release the search queries and the language-independent crawler used to collect the tweets to encourage the curation of similar datasets.", "title": "ArCOV-19: The First Arabic COVID-19 Twitter Dataset with Propagation Networks", "pid": "j530ia4u", "bm25_score": 214.5115509033203}, {"text": "Data has become increasingly important and valuable for both scientists and health authorities searching for answers to the COVID-19 crisis. Due to difficulties in diagnosing this infection in populations around the world, initiatives supported by digital technologies are being developed by governments and private companies to enable the tracking of the public's symptoms, contacts and movements. Considering the current scenario, initiatives designed to support infection surveillance and monitoring are essential and necessary. Nonetheless, ethical, legal and technical questions abound regarding the amount and types of personal data being collected, processed, shared and used in the name of public health, as well as the concomitant or posterior use of this data. These challenges demonstrate the need for new models of responsible and transparent data and technology governance in efforts to control SARS-COV2, as well as in future public health emergencies.", "title": "Personal data usage and privacy considerations in the COVID-19 global pandemic.", "pid": "03nh2f1g", "bm25_score": 214.46005249023438}, {"text": "The worldwide outbreak of COVID-19 has led to great tragedy and poses unprecedented challenges for countries’ healthcare systems. Data has become an important instrument in the global fight against the unprecedented spread of the virus. But how will we ensure a return to previous forms of data privacy once the pandemic subsides?", "title": "Pandemic data challenges", "pid": "copun4j6", "bm25_score": 214.43609619140625}, {"text": "We present Coronavirus disease 2019 (COVID-19) statistics in China dataset: daily statistics of the COVID-19 outbreak in China at the city/county level. For each city/country, we include the six most important numbers for epidemic research: daily new infections, accumulated infections, daily new recoveries, accumulated recoveries, daily new deaths, and accumulated deaths. We cross validate the dataset and the estimate error rate is about 0.04%. We then give several examples to show how to trace the spreading in particular cities or provinces, and also contrast the development of COVID-19 in all cities in China at the early, middle and late stages. We hope this dataset can help researchers around the world better understand the spreading dynamics of COVID-19 at a regional level, to inform intervention and mitigation strategies for policymakers.", "title": "Spatial-Temporal Dataset of COVID-19 Outbreak in China", "pid": "0is1vyhy", "bm25_score": 214.41207885742188}, {"text": "BACKGROUND: We need high-quality data to assess the determinants for COVID-19 severity in people with MS (PwMS). Several studies have recently emerged but there is great benefit in aligning data collection efforts at a global scale. OBJECTIVES: Our mission is to scale-up COVID-19 data collection efforts and provide the MS community with data-driven insights as soon as possible. METHODS: Numerous stakeholders were brought together. Small dedicated interdisciplinary task forces were created to speed-up the formulation of the study design and work plan. First step was to agree upon a COVID-19 MS core data set. Second, we worked on providing a user-friendly and rapid pipeline to share COVID-19 data at a global scale. RESULTS: The COVID-19 MS core data set was agreed within 48 hours. To date, 23 data collection partners are involved and the first data imports have been performed successfully. Data processing and analysis is an on-going process. CONCLUSIONS: We reached a consensus on a core data set and established data sharing processes with multiple partners to address an urgent need for information to guide clinical practice. First results show that partners are motivated to share data to attain the ultimate joint goal: better understand the effect of COVID-19 in PwMS.", "title": "COVID-19 in people with multiple sclerosis: A global data sharing initiative", "pid": "xuuucwgj", "bm25_score": 214.3443603515625}, {"text": "Management of the COVID-19 pandemic has proven to be a significant challenge to policy makers. This is in large part due to uneven reporting and the absence of open-access visualization tools to present local trends and infer healthcare needs. Here we report the development of CovidCounties.org, an interactive web application that depicts daily disease trends at the level of US counties using time series plots and maps. This application is accompanied by a manually curated dataset that catalogs all major public policy actions made at the state-level, as well as technical validation of the primary data. Finally, the underlying code for the site is also provided as open source, enabling others to validate and learn from this work.", "title": "CovidCounties - an interactive, real-time tracker of the COVID-19 pandemic at the level of US counties", "pid": "07v9qign", "bm25_score": 214.34432983398438}, {"text": "As of May 25, 2020, the novel coronavirus disease (called COVID-19) spread to more than 185 countries/regions with more than 348,000 deaths and more than 5,550,000 confirmed cases. In the bioinformatics area, one of the crucial points is the analysis of the virus nucleotide sequences using approaches such as data stream techniques and algorithms. However, to make feasible this approach, it is necessary to transform the nucleotide sequences string to numerical stream representation. Thus, the dataset provides four kinds of data stream representation (DSR) of SARS-CoV-2 virus nucleotide sequences. The dataset provides the DSR of 1557 instances of SARS-CoV-2 virus, 11540 other instances of other viruses from the Virus-Host DB dataset, and three instances of Riboviria viruses from NCBI (Betacoronavirus RaTG13, bat-SL-CoVZC45, and bat-SL-CoVZXC21).", "title": "Data stream dataset of SARS-CoV-2 genome", "pid": "cnndsjyf", "bm25_score": 214.30953979492188}, {"text": "As the COVID-19 pandemic swept over the world, people discussed facts, expressed opinions, and shared sentiments on social media. Since the reaction to COVID-19 in different locations may be tied to local cases, government regulations, healthcare resources and socioeconomic factors, we curated a large geo-tagged Twitter dataset and performed exploratory analysis by location. Specifically, we collected 650,563 unique geo-tagged tweets across the United States (50 states and Washington, D.C.) covering the date range from January 25 to May 10, 2020. Tweet locations enabled us to conduct region-specific studies such as tweeting volumes and sentiment, sometimes in response to local regulations and reported COVID-19 cases. During this period, many people started working from home. The gap between workdays and weekends in hourly tweet volumes inspired us to propose algorithms to estimate work engagement during the COVID-19 crisis. This paper also summarizes themes and topics of tweets in our dataset using both social media exclusive tools (i.e., #hashtags, @mentions) and the latent Dirichlet allocation model. We welcome requests for data sharing and conversations for more insights. Dataset link: http://covid19research.site/geo-tagged_twitter_datasets/", "title": "Is Working From Home The New Norm? An Observational Study Based on a Large Geo-tagged COVID-19 Twitter Dataset", "pid": "es7h7wlk", "bm25_score": 214.30552673339844}, {"text": "", "title": "A Need for Data-driven Public Health Responses to COVID-19.", "pid": "689352fp", "bm25_score": 214.28775024414062}, {"text": "Abstract COVID-19 is a novel and exponentially-growing disease and consequently the accelerated development of knowledge from good data is possible quickly and globally. In order to combat the global pandemic of novel coronavirus disease 2019 (COVID-19), all humans on earth need to make difficult strategic decisions on three very different scales, all fueled by Analytical and Artificial Intelligence-based predictive Models (AAIMs).", "title": "Accelerating the global response against the exponentially growing COVID-19 outbreak through decent data sharing", "pid": "c6ti4d9s", "bm25_score": 214.2667236328125}, {"text": "The database here described contains data of integrated surveillance for the “Coronavirus disease 2019” (abbreviated as COVID-19 by the World Health Organization) in Italy, caused by the novel coronavirus SARS-CoV-2. The database, included in a main folder called COVID-19, has been designed and created by the Italian Civil Protection Department, which currently manages it. The database consists of six folders called ‘aree’ (containing charts of geographical areas interested by containment measures), ‘dati-andamento-nazionale’ (containing data relating to the national trend of SARS-CoV-2 spread), ‘dati-json’ (containing data that summarize the national, provincial and regional trends of SARS-CoV-2 spread), ‘dati-province’ (containing data relating to the provincial trend of SARS-CoV-2 spread), ‘dati-regioni’ (containing data relating to the regional trend of SARS-CoV-2 spread) and ‘schede-riepilogative’ (containing summary sheets relating to the provincial and regional trends of SARS-CoV-2 spread). The Italian Civil Protection Department daily receives data by the Italian Ministry of Health, analyzes them and updates the database. Thus, the database is subject to daily updates and integrations. The database is freely accessible (CC-BY-4.0 license) at https://github.com/pcm-dpc/COVID-19. This database is useful to provide insight on the spread mechanism of SARS-CoV-2, to support organizations in the evaluation of the efficiency of current prevention and control measures, and to support governments in the future prevention decisions.", "title": "COVID-19 in Italy: Dataset of the Italian Civil Protection Department", "pid": "7uhuazcc", "bm25_score": 214.2658233642578}, {"text": "There is an obvious concern globally regarding the fact about the emerging coronavirus 2019 novel coronavirus (2019-nCoV) as a worldwide public health threat. As the outbreak of COVID-19 causes by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) progresses within China and beyond, rapidly available epidemiological data are needed to guide strategies for situational awareness and intervention. The recent outbreak of pneumonia in Wuhan, China, caused by the SARS-CoV-2 emphasizes the importance of analyzing the epidemiological data of this novel virus and predicting their risks of infecting people all around the globe. In this study, we present an effort to compile and analyze epidemiological outbreak information on COVID-19 based on the several open datasets on 2019-nCoV provided by the Johns Hopkins University, World Health Organization, Chinese Center for Disease Control and Prevention, National Health Commission, and DXY. An exploratory data analysis with visualizations has been made to understand the number of different cases reported (confirmed, death, and recovered) in different provinces of China and outside of China. Overall, at the outset of an outbreak like this, it is highly important to readily provide information to begin the evaluation necessary to understand the risks and begin containment activities.", "title": "Analyzing the epidemiological outbreak of COVID-19: A visual exploratory data analysis approach", "pid": "kfy7v56x", "bm25_score": 214.26510620117188}, {"text": "In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market. Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak. The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan. Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics. This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features.", "title": "What we know so far: COVID-19 current clinical knowledge and research", "pid": "3mnmib3o", "bm25_score": 214.2640380859375}, {"text": "During the outbreak time of COVID-19, computed tomography (CT) is a useful manner for diagnosing COVID-19 patients. Due to privacy issues, publicly available COVID-19 CT datasets are highly difficult to obtain, which hinders the research and development of AI-powered diagnosis methods of COVID-19 based on CTs. To address this issue, we build an open-sourced dataset -- COVID-CT, which contains 349 COVID-19 CT images from 216 patients and 463 non-COVID-19 CTs. The utility of this dataset is confirmed by a senior radiologist who has been diagnosing and treating COVID-19 patients since the outbreak of this pandemic. We also perform experimental studies which further demonstrate that this dataset is useful for developing AI-based diagnosis models of COVID-19. Using this dataset, we develop diagnosis methods based on multi-task learning and self-supervised learning, that achieve an F1 of 0.90, an AUC of 0.98, and an accuracy of 0.89. According to the senior radiologist, models with such performance are good enough for clinical usage. The data and code are available at https://github.com/UCSD-AI4H/COVID-CT", "title": "COVID-CT-Dataset: A CT Scan Dataset about COVID-19", "pid": "55nifoqu", "bm25_score": 214.26173400878906}, {"text": "This paper describes BIMCV COVID-19+, a large dataset from the Valencian Region Medical ImageBank (BIMCV) containing chest X-ray images CXR (CR, DX) and computed tomography (CT) imaging of COVID-19+ patients along with their radiological findings and locations, pathologies, radiological reports (in Spanish), DICOM metadata, Polymerase chain reaction (PCR), Immunoglobulin G (IgG) and Immunoglobulin M (IgM) diagnostic antibody tests. The findings have been mapped onto standard Unified Medical Language System (UMLS) terminology and cover a wide spectrum of thoracic entities, unlike the considerably more reduced number of entities annotated in previous datasets. Images are stored in high resolution and entities are localized with anatomical labels and stored in a Medical Imaging Data Structure (MIDS) format. In addition, 10 images were annotated by a team of radiologists to include semantic segmentation of radiological findings. This first iteration of the database includes 1,380 CX, 885 DX and 163 CT studies from 1,311 COVID-19+ patients. This is, to the best of our knowledge, the largest COVID-19+ dataset of images available in an open format. The dataset can be downloaded from http://bimcv.cipf.es/bimcv-projects/bimcv-covid19.", "title": "BIMCV COVID-19+: a large annotated dataset of RX and CT images from COVID-19 patients", "pid": "j9mgdpmd", "bm25_score": 214.25860595703125}, {"text": "Summary We developed a new online database that contains the most updated published scientific literature, online news and reports, CDC and National Institutes of Health (NIH) resources. The tool captures emerging discoveries and applications of genomics, molecular, and other precision medicine and precision public health tools in the investigation and control of coronavirus diseases, including COVID-19, MERS-CoV, and SARS. Availability Coronavirus Disease Portal (CDP) can be freely accessed via https://phgkb.cdc.gov/PHGKB/coVInfoStartPage.action. Contact wyu@cdc.gov", "title": "A New Resource for Genomics and Precision Health Information and Publications on the Investigation and Control of COVID-19 and other Coronaviruses", "pid": "1s0hhx71", "bm25_score": 214.2480926513672}, {"text": "Due to the nature of the data and public interaction, twitter is becoming more and more useful to understand and model various events. The goal of CoronaVis is to use tweets as the information shared by the people to visualize topic modeling, study subjectivity, and to model the human emotions during the COVID-19 pandemic. The main objective is to explore the psychology and behavior of the societies at large which can assist in managing the economic and social crisis during the ongoing pandemic as well as the after-effects of it. The novel coronavirus (COVID-19) pandemic forced people to stay at home to reduce the spread of the virus by maintaining social distancing. However, social media is keeping people connected both locally and globally. People are sharing information (e.g. personal opinions, some facts, news, status, etc.) on social media platforms which can be helpful to understand the various public behavior such as emotions, sentiments, and mobility during the ongoing pandemic. In this work, we develop a live application to observe the tweets on COVID-19 generated from the USA. In this paper, we have generated various data analytics over a period of time to study the changes in topics, subjectivity, and human emotions. We also share a cleaned and processed dataset named CoronaVis Twitter dataset (focused on the United States) available to the research community at https://github.com/mykabir/COVID19. This will enable the community to find more useful insights and create different applications and models to fight with COVID-19 pandemic and future pandemics as well.", "title": "CoronaVis: A Real-time COVID-19 Tweets Data Analyzer and Data Repository", "pid": "iajw2s5w", "bm25_score": 214.238037109375}, {"text": "", "title": "COVID-19 Is a Data Science Issue", "pid": "fvgxzbmx", "bm25_score": 214.23519897460938}, {"text": "Big data could help identify potential clues about the immediate (and future) impact of coronavirus disease 2019, but it is in short supply.", "title": "Tests, surgical masks, hospital beds, and ventilators: add big data to the list of tools to fight the coronavirus that are in short supply", "pid": "5f29q0kk", "bm25_score": 214.2345428466797}, {"text": "The novel coronavirus disease (COVID-19) has rapidly spread around the globe in 2020, with the U.S. becoming the epicenter of COVID-19 cases since late March. As the U.S. begins to gradually resume economic activity, it is imperative for policymakers and power system operators to take a scientific approach to understanding and predicting the impact on the electricity sector. Here, we release a first-of-its-kind cross-domain open-access data hub, integrating data from across all existing U.S. wholesale electricity markets with COVID-19 case, weather, cellular location, and satellite imaging data. Leveraging cross-domain insights from public health and mobility data, we uncover a significant reduction in electricity consumption across that is strongly correlated with the rise in the number of COVID-19 cases, degree of social distancing, and level of commercial activity.", "title": "A Cross-Domain Approach to Analyzing the Short-Run Impact of COVID-19 on the U.S. Electricity Sector", "pid": "kirbycpf", "bm25_score": 214.23350524902344}, {"text": "In response to the COVID-19 pandemic, we established COVID-KOP, a new knowledgebase integrating the existing ROBOKOP biomedical knowledge graph with information from recent biomedical literature on COVID-19 annotated in the CORD-19 collection. COVID-KOP can be used effectively to test new hypotheses concerning repurposing of known drugs and clinical drug candidates against COVID-19. COVID-KOP is freely accessible at https://covidkop.renci.org/. For code and instructions for the original ROBOKOP, see: https://github.com/NCATS-Gamma/robokop.", "title": "COVID-KOP: Integrating Emerging COVID-19 Data with the ROBOKOP Database", "pid": "6txh7jgc", "bm25_score": 214.21429443359375}, {"text": "", "title": "Wuhan Covid19 data - more questions than answers", "pid": "33gd52dv", "bm25_score": 214.20343017578125}, {"text": "This resource paper describes a large dataset covering over 63 million coronavirus-related Twitter posts from more than 13 million unique users since 28 January to 1 July 2020. As strong concerns and emotions are expressed in the tweets, we analyzed the tweets content using natural language processing techniques and machine-learning based algorithms, and inferred seventeen latent semantic attributes associated with each tweet, including 1) ten attributes indicating the tweet's relevance to ten detected topics, 2) five quantitative attributes indicating the degree of intensity in the valence (i.e., unpleasantness/pleasantness) and emotional intensities across four primary emotions of fear, anger, sadness and joy, and 3) two qualitative attributes indicating the sentiment category and the most dominant emotion category, respectively. To illustrate how the dataset can be used, we present descriptive statistics around the topics, sentiments and emotions attributes and their temporal distributions, and discuss possible applications in communication, psychology, public health, economics and epidemiology.", "title": "COVID-19 Twitter Dataset with Latent Topics, Sentiments and Emotions Attributes", "pid": "w61lsdml", "bm25_score": 214.20079040527344}, {"text": "This commentary describes the rapid development of a COVID-19 data dashboard utilising existing Urban Observatory Internet of Things (IoT) data and analytics infrastructure. Existing data capture systems were rapidly repurposed to provide real-time insights into the impacts of lockdown policy on urban governance.", "title": "Smart cities and a data-driven response to COVID-19", "pid": "8vjb0dag", "bm25_score": 214.1914825439453}, {"text": "During its first month, the recently emerged 2019 Wuhan novel coronavirus (2019-nCoV) has already infected many thousands of people in mainland China and worldwide and took hundreds of lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge we leverage the data about the related coronaviruses that is readily available in public databases, and integrate these data into a single computational pipeline. As a result, we provide a comprehensive structural genomics and interactomics road-maps of 2019-nCoV and use these information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community at http://korkinlab.org/wuhan", "title": "Structural genomics and interactomics of 2019 Wuhan novel coronavirus, 2019-nCoV, indicate evolutionary conserved functional regions of viral proteins", "pid": "z3x0c37y", "bm25_score": 214.19110107421875}, {"text": "The coronavirus disease (COVID-19), caused by the SARS-CoV-2 virus, was declared a pandemic by the World Health Organization (WHO) in February 2020. Currently, there are no vaccines or treatments that have been approved after clinical trials. Social distancing measures, including travel bans, school closure, and quarantine applied to countries or regions are being used to limit the spread of the disease and the demand on the healthcare infrastructure. The seclusion of groups and individuals has led to limited access to accurate information. To update the public, especially in South Africa, announcements are made by the minister of health daily. These announcements narrate the confirmed COVID-19 cases and include the age, gender, and travel history of people who have tested positive for the disease. Additionally, the South African National Institute for Communicable Diseases updates a daily infographic summarising the number of tests performed, confirmed cases, mortality rate, and the regions affected. However, the age of the patient and other nuanced data regarding the transmission is only shared in the daily announcements and not on the updated infographic. To disseminate this information, the Data Science for Social Impact research group at the University of Pretoria, South Africa, has worked on curating and applying publicly available data in a way that is computer-readable so that information can be shared to the public - using both a data repository and a dashboard. Through collaborative practices, a variety of challenges related to publicly available data in South Africa came to the fore. These include shortcomings in the accessibility, integrity, and data management practices between governmental departments and the South African public. In this paper, solutions to these problems will be shared by using a publicly available data repository and dashboard as a case study.", "title": "Use of Available Data To Inform The COVID-19 Outbreak in South Africa: A Case Study", "pid": "op4z052p", "bm25_score": 214.1719512939453}, {"text": "The widely spread CoronaVirus Disease (COVID)-19 is one of the worst infectious disease outbreaks in history and has become an emergency of primary international concern. As the pandemic evolves, academic communities have been actively involved in various capacities, including accurate epidemic estimation, fast clinical diagnosis, policy effectiveness evaluation and development of contract tracing technologies. There are more than 23,000 academic papers on the COVID-19 outbreak, and this number is doubling every 20 days while the pandemic is still on-going [1]. The literature, however, at its early stage, lacks a comprehensive survey from a data analytics perspective. In this paper, we review the latest models for analyzing COVID19 related data, conduct post-publication model evaluations and cross-model comparisons, and collect data sources from different projects.", "title": "Data-driven Analytical Models of COVID-2019 for Epidemic Prediction, Clinical Diagnosis, Policy Effectiveness and Contact Tracing: A Survey", "pid": "xe0dhx4o", "bm25_score": 214.1654052734375}, {"text": "While the COVID-19 outbreak was reported to first originate from Wuhan, China, it has been declared as a Public Health Emergency of International Concern (PHEIC) on 30 January 2020 by WHO, and it has spread to over 180 countries by the time of this paper was being composed. As the disease spreads around the globe, it has evolved into a world-wide pandemic, endangering the state of global public health and becoming a serious threat to the global community. To combat and prevent the spread of the disease, all individuals should be well-informed of the rapidly changing state of COVID-19. In the endeavor of accomplishing this objective, a COVID-19 real-time analytical tracker has been built to provide the latest status of the disease and relevant analytical insights. The real-time tracker is designed to cater to the general audience without advanced statistical aptitude. It aims to communicate insights through various straightforward and concise data visualizations that are supported by sound statistical foundations and reliable data sources. This paper aims to discuss the major methodologies which are utilized to generate the insights displayed on the real-time tracker, which include real-time data retrieval, normalization techniques, ARIMA time-series forecasting, and logistic regression models. In addition to introducing the details and motivations of the utilized methodologies, the paper additionally features some key discoveries that have been derived in regard to COVID-19 using the methodologies.", "title": "COVID-19 Real-Time Tracker and Analytical Report", "pid": "js7uvbau", "bm25_score": 214.16290283203125}, {"text": "The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) consortium to bring together scientists with expertise in big data research and epidemiology to develop a COVID-19 Symptom Tracker mobile application that we launched in the UK on March 24, 2020 and the US on March 29, 2020 garnering more than 2.25 million users to date. This mobile application offers data on risk factors, herald symptoms, clinical outcomes, and geographical hot spots. This initiative offers critical proof-of-concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis which is critical for a data-driven response to this public health challenge.", "title": "Rapid implementation of mobile technology for real-time epidemiology of COVID-19", "pid": "mmcszoxb", "bm25_score": 214.15635681152344}, {"text": "BACKGROUND: At the time of this writing, the coronavirus disease (COVID-19) pandemic outbreak has already put tremendous strain on many countries' citizens, resources, and economies around the world. Social distancing measures, travel bans, self-quarantines, and business closures are changing the very fabric of societies worldwide. With people forced out of public spaces, much of the conversation about these phenomena now occurs online on social media platforms like Twitter. OBJECTIVE: In this paper, we describe a multilingual COVID-19 Twitter data set that we are making available to the research community via our COVID-19-TweetIDs GitHub repository. METHODS: We started this ongoing data collection on January 28, 2020, leveraging Twitter's streaming application programming interface (API) and Tweepy to follow certain keywords and accounts that were trending at the time data collection began. We used Twitter's search API to query for past tweets, resulting in the earliest tweets in our collection dating back to January 21, 2020. RESULTS: Since the inception of our collection, we have actively maintained and updated our GitHub repository on a weekly basis. We have published over 123 million tweets, with over 60% of the tweets in English. This paper also presents basic statistics that show that Twitter activity responds and reacts to COVID-19-related events. CONCLUSIONS: It is our hope that our contribution will enable the study of online conversation dynamics in the context of a planetary-scale epidemic outbreak of unprecedented proportions and implications. This data set could also help track COVID-19-related misinformation and unverified rumors or enable the understanding of fear and panic-and undoubtedly more.", "title": "Tracking Social Media Discourse About the COVID-19 Pandemic: Development of a Public Coronavirus Twitter Data Set", "pid": "vy46mpz0", "bm25_score": 214.1563262939453}, {"text": "We describe Mega-COV, a billion-scale dataset from Twitter for studying COVID-19. The dataset is diverse (covers 234 countries), longitudinal (goes as back as 2007), multilingual (comes in 65 languages), and has a significant number of location-tagged tweets (~32M tweets). We release tweet IDs from the dataset, hoping it will be useful for studying various phenomena related to the ongoing pandemic and accelerating viable solutions to associated problems.", "title": "Mega-COV: A Billion-Scale Dataset of 65 Languages For COVID-19", "pid": "lk13v7j6", "bm25_score": 214.15283203125}, {"text": "An ongoing outbreak of a novel coronavirus infection in Wuhan, China since December 2019 has led to 31,516 infected persons and 638 deaths across 25 countries (till 16:00 on February 7, 2020). The virus causing this pneumonia was then named as the 2019 novel coronavirus (2019-nCoV) by the World Health Organization. To promote the data sharing and make all relevant information of 2019-nCoV publicly available, we construct the 2019 Novel Coronavirus Resource (2019nCoVR, https://bigd.big.ac.cn/ncov). 2019nCoVR features comprehensive integration of genomic and proteomic sequences as well as their metadata information from the Global Initiative on Sharing All Influenza Data, National Center for Biotechnology Information, China National GeneBank, National Microbiology Data Center and China National Center for Bioinformation (CNCB)/National Genomics Data Center (NGDC). It also incorporates a wide range of relevant information including scientific literatures, news, and popular articles for science dissemination, and provides visualization functionalities for genome variation analysis results based on all collected 2019-nCoV strains. Moreover, by linking seamlessly with related databases in CNCB/NGDC, 2019nCoVR offers virus data submission and sharing services for raw sequence reads and assembled sequences. In this report, we provide comprehensive descriptions on data deposition, management, release and utility in 2019nCoVR, laying important foundations in aid of studies on virus classification and origin, genome variation and evolution, fast detection, drug development and pneumonia precision prevention and therapy.", "title": "The 2019 novel coronavirus resource", "pid": "dhet9p7s", "bm25_score": 214.14784240722656}, {"text": "SARS-CoV2 is a novel coronavirus, responsible for the COVID-19 pandemic declared by the World Health Organization. Thanks to the latest advancements in the field of molecular and computational techniques and information and communication technologies (ICTs), artificial intelligence (AI) and Big Data can help in handling the huge, unprecedented amount of data derived from public health surveillance, real-time epidemic outbreaks monitoring, trend now-casting/forecasting, regular situation briefing and updating from governmental institutions and organisms, and health facility utilization information. The present review is aimed at overviewing the potential applications of AI and Big Data in the global effort to manage the pandemic.", "title": "How Big Data and Artificial Intelligence Can Help Better Manage the COVID-19 Pandemic", "pid": "lnp8ic9y", "bm25_score": 214.1448974609375}, {"text": "BACKGROUND: At the time of this writing, the coronavirus disease (COVID-19) pandemic outbreak has already put tremendous strain on many countries' citizens, resources, and economies around the world. Social distancing measures, travel bans, self-quarantines, and business closures are changing the very fabric of societies worldwide. With people forced out of public spaces, much of the conversation about these phenomena now occurs online on social media platforms like Twitter. OBJECTIVE: In this paper, we describe a multilingual COVID-19 Twitter data set that we are making available to the research community via our COVID-19-TweetIDs GitHub repository. METHODS: We started this ongoing data collection on January 28, 2020, leveraging Twitter’s streaming application programming interface (API) and Tweepy to follow certain keywords and accounts that were trending at the time data collection began. We used Twitter’s search API to query for past tweets, resulting in the earliest tweets in our collection dating back to January 21, 2020. RESULTS: Since the inception of our collection, we have actively maintained and updated our GitHub repository on a weekly basis. We have published over 123 million tweets, with over 60% of the tweets in English. This paper also presents basic statistics that show that Twitter activity responds and reacts to COVID-19-related events. CONCLUSIONS: It is our hope that our contribution will enable the study of online conversation dynamics in the context of a planetary-scale epidemic outbreak of unprecedented proportions and implications. This data set could also help track COVID-19-related misinformation and unverified rumors or enable the understanding of fear and panic—and undoubtedly more.", "title": "Tracking Social Media Discourse About the COVID-19 Pandemic: Development of a Public Coronavirus Twitter Data Set", "pid": "gva2x8bu", "bm25_score": 214.1431884765625}, {"text": "We present the Neural Covidex, a search engine that exploits the latest neural ranking architectures to provide information access to the COVID-19 Open Research Dataset curated by the Allen Institute for AI. This web application exists as part of a suite of tools that we have developed over the past few weeks to help domain experts tackle the ongoing global pandemic. We hope that improved information access capabilities to the scientific literature can inform evidence-based decision making and insight generation. This paper describes our initial efforts and offers a few thoughts about lessons we have learned along the way.", "title": "Rapidly Deploying a Neural Search Engine for the COVID-19 Open Research Dataset: Preliminary Thoughts and Lessons Learned", "pid": "808as0po", "bm25_score": 214.13345336914062}, {"text": "In response to the COVID-19 pandemic, we established COVID-KOP, a new knowledgebase integrating the existing ROBOKOP biomedical knowledge graph with information from recent biomedical literature on COVID-19 annotated in the CORD-19 collection. COVID-KOP can be used effectively to test new hypotheses concerning repurposing of known drugs and clinical drug candidates against COVID-19. COVID-KOP is freely accessible at https://covidkop.renci.org/. For code and instructions for the original ROBOKOP, see: https://github.com/NCATS-Gamma/robokop.", "title": "COVID-KOP: Integrating Emerging COVID-19 Data with the ROBOKOP Database.", "pid": "dz2qftyv", "bm25_score": 214.12904357910156}, {"text": "ELIXIR, the European research infrastructure for life science data, provides open access to data, tools and workflows in the response to the COVID-19 pandemic. ELIXIR's 23 nodes have reacted swiftly to support researchers in their combined efforts against the pandemic setting out three joint priorities: 1. Connecting national COVID-19 data platforms to create federated European COVID-19 Data Spaces; 2. Fostering good data management to make COVID-19 data open, FAIR and reusable over the long term; 3. Providing open tools, workflows and computational resources to drive reproducible and collaborative science. ELIXIR's strategy is based on the support given by our national nodes - collectively spanning over 200 institutes - to research projects and on partnering with community initiatives to drive development and adoption of good data practice and community driven standards. ELIXIR Nodes provide support activities locally and internationally, from provisioning compute capabilities to helping collect viral sequence data from hospitals. Some Nodes have prioritised access to their national cloud and compute facilities for all COVID-19 research projects, while others have developed tools to search, access and share all data related to the pandemic in a national healthcare setting.", "title": "Connecting data, tools and people across Europe: ELIXIR's response to the COVID-19 pandemic", "pid": "gye8v4ne", "bm25_score": 214.12420654296875}, {"text": "The rapid pace of the coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) Consortium to unite scientists with expertise in big data research and epidemiology to develop the COVID Symptom Study, previously known as the COVID Symptom Tracker, mobile application. This application-which offers data on risk factors, predictive symptoms, clinical outcomes, and geographical hotspots-was launched in the United Kingdom on 24 March 2020 and the United States on 29 March 2020 and has garnered more than 2.8 million users as of 2 May 2020. Our initiative offers a proof of concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis, which is critical for a data-driven response to this public health challenge.", "title": "Rapid implementation of mobile technology for real-time epidemiology of COVID-19", "pid": "pq4zp9cq", "bm25_score": 214.12371826171875}, {"text": "An ongoing outbreak of a novel coronavirus infection in Wuhan, China since December 2019 has led to 31,516 infected persons and 638 deaths across 25 countries (till 16:00 on February 7, 2020). The virus causing this pneumonia was then named as the 2019 novel coronavirus (2019-nCoV) by the World Health Organization. To promote the data sharing and make all relevant information of 2019-nCoV publicly available, we construct the 2019 Novel Coronavirus Resource (2019nCoVR, https://bigd.big.ac.cn/ncov). 2019nCoVR features comprehensive integration of genomic and proteomic sequences as well as their metadata information from the Global Initiative on Sharing All Influenza Data, National Center for Biotechnology Information, China National GeneBank, National Microbiology Data Center and China National Center for Bioinformation (CNCB)/National Genomics Data Center (NGDC). It also incorporates a wide range of relevant information including scientific literatures, news, and popular articles for science dissemination, and provides visualization functionalities for genome variation analysis results based on all collected 2019-nCoV strains. Moreover, by linking seamlessly with related databases in CNCB/NGDC, 2019nCoVR offers virus data submission and sharing services for raw sequence reads and assembled sequences. In this report, we provide comprehensive descriptions on data deposition, management, release and utility in 2019nCoVR, laying important foundations in aid of studies on virus classification and origin, genome variation and evolution, fast detection, drug development and pneumonia precision prevention and therapy.", "title": "The 2019 novel coronavirus resource.", "pid": "5i2dxg8z", "bm25_score": 214.1023406982422}, {"text": "The SARS-CoV-2 pandemic has rapidly saturated healthcare resources across the globe and has led to a restricted screening process, hindering efforts at comprehensive case detection. This has not only facilitated community spread but has also resulted in an underestimation of the true incidence of disease, a statistic which is useful for policy making aimed at controlling the current pandemic and in preparing for future outbreaks. In this perspective, we present a crowdsourced platform developed by us for the true estimation of all SARS-CoV-2 infections in the community, through active self-reporting and layering other authentic datasets. The granularity of data captured by this system could prove to be useful in assisting governments to identify SARS-CoV-2 hotspots in the community facilitating lifting of restrictions in a controlled fashion.", "title": "Hyperlocal Postcode Based Crowdsourced Surveillance Systems in the COVID-19 Pandemic Response", "pid": "0cu6gi44", "bm25_score": 214.10214233398438}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first discovered in late 2019 in Wuhan City, China. The virus may cause novel coronavirus disease 2019 (COVID-19) in symptomatic individuals. Since December of 2019, there have been over 7,000,000 confirmed cases and over 400,000 confirmed deaths worldwide. In the United States (U.S.), there have been over 2,000,000 confirmed cases and over 110,000 confirmed deaths. COVID-19 case data in the United States has been updated daily at the county level since the first case was reported in January of 2020. There currently lacks a study that showcases the novelty of daily COVID-19 surveillance using space-time cluster detection techniques. In this paper, we utilize a prospective Poisson space-time scan statistic to detect daily clusters of COVID-19 at the county level in the contiguous 48 U.S. and Washington D.C. As the pandemic progresses, we generally find an increase of smaller clusters of remarkably steady relative risk. Daily tracking of significant space-time clusters can facilitate decision-making and public health resource allocation by evaluating and visualizing the size, relative risk, and locations that are identified as COVID-19 hotspots.", "title": "Daily Surveillance of COVID-19 using the Prospective Space-Time Scan Statistic in the United States", "pid": "mp5s4fuo", "bm25_score": 214.09669494628906}, {"text": "In December 2019, health authorities in Wuhan, China, identified a cluster of pneumonia cases of unknown aetiology linked to the city's South China Seafood Market. Subsequent investigations revealed a novel coronavirus, SARS-CoV-2, as the causative agent now at the heart of a major outbreak. The rising case numbers have been accompanied by unprecedented public health action, including the wholesale isolation of Wuhan. Alongside this has been a robust scientific response, including early publication of the pathogen genome, and rapid development of highly specific diagnostics. This article will review the new knowledge of SARS-CoV-2 COVID-19 acute respiratory disease, and summarise its clinical features.", "title": "What we know so far: COVID-19 current clinical knowledge and research.", "pid": "sn72mkzq", "bm25_score": 214.09608459472656}, {"text": "", "title": "A Need for Data-driven Public Health Responses to COVID-19", "pid": "1njv37pj", "bm25_score": 214.08746337890625}, {"text": "Despite social distancing and shelter-in-place policies, COVID-19 continues to spread in the United States. A lack of timely information about factors influencing COVID-19 spread and testing has hampered agile responses to the pandemic. We developed How We Feel, an extensible web and mobile application that aggregates self-reported survey responses, to fill gaps in the collection of COVID-19-related data. How We Feel collects longitudinal and geographically localized information on users' health, behavior, and demographics. Here we report results from over 500,000 users in the United States from April 2, 2020 to May 12, 2020. We show that self- reported surveys can be used to build predictive models of COVID-19 test results, which may aid in identification of likely COVID-19 positive individuals. We find evidence among our users for asymptomatic or presymptomatic presentation, as well as for household and community exposure, occupation, and demographics being strong risk factors for COVID-19. We further reveal factors for which users have been SARS-CoV-2 PCR tested, as well as the temporal dynamics of self- reported symptoms and self-isolation behavior in positive and negative users. These results highlight the utility of collecting a diverse set of symptomatic, demographic, and behavioral self- reported data to fight the COVID-19 pandemic.", "title": "Population-scale Longitudinal Mapping of COVID-19 Symptoms, Behavior, and Testing Identifies Contributors to Continued Disease Spread in the United States", "pid": "wrvpoz19", "bm25_score": 214.04579162597656}, {"text": "The coronavirus disease 2019 (COVID-19) has become a public health emergency of international concern affecting 201 countries and territories around the globe. As of April 4, 2020, it has caused a pandemic outbreak with more than 11,16,643 confirmed infections and more than 59,170 reported deaths worldwide. The main focus of this paper is two-fold: (a) generating short term (real-time) forecasts of the future COVID-19 cases for multiple countries; (b) risk assessment (in terms of case fatality rate) of the novel COVID-19 for some profoundly affected countries by finding various important demographic characteristics of the countries along with some disease characteristics. To solve the first problem, we presented a hybrid approach based on autoregressive integrated moving average model and Wavelet-based forecasting model that can generate short-term (ten days ahead) forecasts of the number of daily confirmed cases for Canada, France, India, South Korea, and the UK. The predictions of the future outbreak for different countries will be useful for the effective allocation of health care resources and will act as an early-warning system for government policymakers. In the second problem, we applied an optimal regression tree algorithm to find essential causal variables that significantly affect the case fatality rates for different countries. This data-driven analysis will necessarily provide deep insights into the study of early risk assessments for 50 immensely affected countries.", "title": "Real-time forecasts and risk assessment of novel coronavirus (COVID-19) cases: A data-driven analysis", "pid": "ba6mdgq3", "bm25_score": 214.0419158935547}, {"text": "This dataset contains anonymised human lung computed tomography (CT) scans with COVID-19 related findings, as well as without such findings. A small subset of studies has been annotated with binary pixel masks depicting regions of interests (ground-glass opacifications and consolidations). CT scans were obtained between 1st of March, 2020 and 25th of April, 2020, and provided by municipal hospitals in Moscow, Russia. Permanent link: https://mosmed.ai/datasets/covid19_1110. This dataset is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND 3.0) License. Key words: artificial intelligence, COVID-19, machine learning, dataset, CT, chest, imaging", "title": "MosMedData: Chest CT Scans With COVID-19 Related Findings Dataset", "pid": "0b8250y7", "bm25_score": 214.0399932861328}, {"text": "Data has become increasingly important and valuable for both scientists and health authorities searching for answers to the COVID-19 crisis. Due to difficulties in diagnosing this infection in populations around the world, initiatives supported by digital technologies are being developed by governments and private companies to enable the tracking of the public's symptoms, contacts and movements. Considering the current scenario, initiatives designed to support infection surveillance and monitoring are essential and necessary. Nonetheless, ethical, legal and technical questions abound regarding the amount and types of personal data being collected, processed, shared and used in the name of public health, as well as the concomitant or posterior use of this data. These challenges demonstrate the need for new models of responsible and transparent data and technology governance in efforts to control SARS-COV2, as well as in future public health emergencies.", "title": "Preservação da privacidade no enfrentamento da COVID-19: dados pessoais e a pandemia global./ Preservação da privacidade no enfrentamento da COVID-19: dados pessoais e a pandemia global./ Personal data usage and privacy considerations in the COVID-19 global pandemic", "pid": "d0f7qux9", "bm25_score": 214.0306854248047}, {"text": "", "title": "Open access epidemiologic data and an interactive dashboard to monitor the COVID-19 outbreak in Canada", "pid": "ep79lg0p", "bm25_score": 214.03016662597656}, {"text": "", "title": "Open access epidemiologic data and an interactive dashboard to monitor the COVID-19 outbreak in Canada.", "pid": "6a6m7ye5", "bm25_score": 214.0291290283203}, {"text": "Summary The past few weeks have witnessed a worldwide mobilization of the research community in response to the novel coronavirus (COVID-19). This global response has led to a burst of publications on the pathophysiology of the virus, yet without coordinated efforts to organize this knowledge, it can remain hidden away from individual research groups. By extracting and formalizing this knowledge in a structured and computable form, as in the form of a knowledge graph, researchers can readily reason and analyze this information on a much larger scale. Here, we present the COVID-19 Knowledge Graph, an expansive cause-and-effect network constructed from scientific literature on the new coronavirus that aims to provide a comprehensive view of its pathophysiology. To make this resource available to the research community and facilitate its exploration and analysis, we also implemented a web application and released the KG in multiple standard formats. Availability The COVID-19 Knowledge Graph is publicly available under CC-0 license at https://github.com/covid19kg and https://bikmi.covid19-knowledgespace.de. Contact alpha.tom.kodamullil@scai.fraunhofer.de Supplementary information Supplementary data are available online.", "title": "COVID-19 Knowledge Graph: a computable, multi-modal, cause-and-effect knowledge model of COVID-19 pathophysiology", "pid": "vo0h0tx3", "bm25_score": 214.02587890625}, {"text": "The Covid-19 outbreak, beyond its tragic effects, has changed to an unprecedented extent almost every aspect of human activity throughout the world. At the same time, the pandemic has stimulated enormous amount of research by scientists across various disciplines, seeking to study the phenomenon itself, its epidemiological characteristics and ways to confront its consequences. Information Technology, and particularly Data Science, drive innovation in all related to Covid-19 biomedical fields. Acknowledging that software developers routinely resort to open question and answer communities like Stack Overflow to seek advice on solving technical issues, we have performed an empirical study to investigate the extent, evolution and characteristics of Covid-19 related posts. In particular, through the study of 464 Stack Overflow questions posted mainly in February and March 2020 and leveraging the power of text mining, we attempt to shed light into the interest of developers in Covid-19 related topics and the most popular technological problems for which the users seek information. The findings reveal that indeed this global crisis sparked off an intense and increasing activity in Stack Overflow with most post topics reflecting a strong interest on the analysis of Covid-19 data, primarily using Python technologies.", "title": "A Study of Knowledge Sharing related to Covid-19 Pandemic in Stack Overflow", "pid": "zqbw7uc9", "bm25_score": 214.0254364013672}, {"text": "BACKGROUND: Corona virus disease 2019 (COVID-19) has been announced as a new coronavirus disease by the World Health Organization. At the time of writing this article (April 2020), the world is drastically influenced by the COVID-19. Recently, the COVID-19 Open Research Dataset (CORD-19) was published. For researchers on ID such as ourselves, it is of key interest to learn whether this open research dataset may be used to investigate the virus and its consequences for people with an ID. METHODS: From CORD-19, we identified full-text articles containing terms related to the ID care and applied a text mining technique, specifically the term frequency-inverse document frequency analysis in combination with K-means clustering. RESULTS: Two hundred fifty-nine articles contained one or more of our specified terms related to ID. We were able to cluster these articles related to ID into five clusters on different topics, namely: mental health, viral diseases, diagnoses and treatments, maternal care and paediatrics, and genetics. CONCLUSION: The CORD-19 open research dataset consists of valuable information about not only COVID-19 disease but also ID and the relationship between them. We suggest researchers investigate literature-based discovery approaches on the CORD-19 and develop a new dataset that addresses the intersection of these two fields for further research.", "title": "Coronaviruses and people with intellectual disability: an exploratory data analysis", "pid": "sg8epmf0", "bm25_score": 214.018798828125}, {"text": "In December 2019, a new virus (initially called 'Novel Coronavirus 2019-nCoV' and later renamed to SARS-CoV-2) causing severe acute respiratory syndrome (coronavirus disease COVID-19) emerged in Wuhan, Hubei Province, China, and rapidly spread to other parts of China and other countries around the world, despite China's massive efforts to contain the disease within Hubei. As with the original SARS-CoV epidemic of 2002/2003 and with seasonal influenza, geographic information systems and methods, including, among other application possibilities, online real-or near-real-time mapping of disease cases and of social media reactions to disease spread, predictive risk mapping using population travel data, and tracing and mapping super-spreader trajectories and contacts across space and time, are proving indispensable for timely and effective epidemic monitoring and response. This paper offers pointers to, and describes, a range of practical online/mobile GIS and mapping dashboards and applications for tracking the 2019/2020 coronavirus epidemic and associated events as they unfold around the world. Some of these dashboards and applications are receiving data updates in near-real-time (at the time of writing), and one of them is meant for individual users (in China) to check if the app user has had any close contact with a person confirmed or suspected to have been infected with SARS-CoV-2 in the recent past. We also discuss additional ways GIS can support the fight against infectious disease outbreaks and epidemics.", "title": "Geographical tracking and mapping of coronavirus disease COVID-19/severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic and associated events around the world: how 21st century GIS technologies are supporting the global fight against outbreaks and epidemics", "pid": "oe6daiwx", "bm25_score": 214.0135498046875}, {"text": "The rapid pace of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) presents challenges to the robust collection of population-scale data to address this global health crisis. We established the COronavirus Pandemic Epidemiology (COPE) consortium to bring together scientists with expertise in big data research and epidemiology to develop a COVID-19 Symptom Tracker mobile application that we launched in the UK on March 24, 2020 and the US on March 29, 2020 garnering more than 2.8 million users as of May 2, 2020. This mobile application offers data on risk factors, herald symptoms, clinical outcomes, and geographical hot spots. This initiative offers critical proof-of-concept for the repurposing of existing approaches to enable rapidly scalable epidemiologic data collection and analysis which is critical for a data-driven response to this public health challenge.", "title": "Rapid implementation of mobile technology for real-time epidemiology of COVID-19", "pid": "wfgmvy9i", "bm25_score": 214.01004028320312}, {"text": "", "title": "The challenge of COVID-19 has accelerated the use of new data-sharing technologies", "pid": "98b8m40k", "bm25_score": 213.9970703125}, {"text": "OBJECTIVE: To create an online resource that informs the public of COVID-19 outbreaks in their area. MATERIALS AND METHODS: This R Shiny application aggregates data from multiple resources that track COVID-19 and visualizes them through an interactive, online dashboard. RESULTS: The web resource, called the COVID-19 Watcher, can be accessed at https://covid19watcher.research.cchmc.org/. It displays COVID-19 data from every county and 188 metropolitan areas in the U.S. Features include rankings of the worst affected areas and auto-generating plots that depict temporal changes in testing capacity, cases, and deaths. DISCUSSION: The Centers for Disease Control and Prevention (CDC) do not publish COVID-19 data for local municipalities, so it is critical that academic resources fill this void so the public can stay informed. The data used have limitations and likely underestimate the scale of the outbreak. CONCLUSIONS: The COVID-19 Watcher can provide the public with real-time updates of outbreaks in their area.", "title": "An Interactive Online Dashboard for Tracking COVID-19 in U.S. Counties, Cities, and States in Real Time", "pid": "9kb1tt5d", "bm25_score": 213.98281860351562}, {"text": "", "title": "Reply to Nepomuceno et al.: A renewed call for detailed social and demographic COVID-19 data from all countries", "pid": "8kb5weqa", "bm25_score": 213.98251342773438}, {"text": "ELIXIR, the European research infrastructure for life science data, provides open access to data, tools and workflows in the response to the COVID-19 pandemic. ELIXIR’s 23 nodes have reacted swiftly to support researchers in their combined efforts against the pandemic setting out three joint priorities: 1. Connecting national COVID-19 data platforms to create federated European COVID-19 Data Spaces; 2. Fostering good data management to make COVID-19 data open, FAIR and reusable over the long term; 3. Providing open tools, workflows and computational resources to drive reproducible and collaborative science. ELIXIR’s strategy is based on the support given by our national nodes - collectively spanning over 200 institutes - to research projects and on partnering with community initiatives to drive development and adoption of good data practice and community driven standards. ELIXIR Nodes provide support activities locally and internationally, from provisioning compute capabilities to helping collect viral sequence data from hospitals. Some Nodes have prioritised access to their national cloud and compute facilities for all COVID-19 research projects, while others have developed tools to search, access and share all data related to the pandemic in a national healthcare setting.", "title": "Connecting data, tools and people across Europe: ELIXIR’s response to the COVID-19 pandemic", "pid": "qj7e5o19", "bm25_score": 213.98153686523438}, {"text": "Public information search data from sources such as Google Trends affords researchers a perspective on what society does not know, or what society wants to find out prompted by, or in response to, developments in societal communication and news media events. In times of crisis, online public information search thus offers a window into the most urgent concerns of, and demands by society. By extension, such data offers a window into upcoming, and currently pressing demands on businesses, policymakers and researchers. This research note aims to illustrate some of these themes with a visual-based overview of the current COVID-19 / Coronavirus crisis.", "title": "Online Information Search During COVID-19", "pid": "as74qa0l", "bm25_score": 213.98025512695312}]}
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The spike (S) glycoprotein of betacoronavirus SARS-CoV-2 is a homotrimeric class I fusion protein that exists in a metastable conformation for cleavage by host cell proteases furin and TMPRSS2, thereby undergoing substantial structural rearrangement for ACE2 host cell receptor binding and subsequent viral entry by membrane fusion. The S protein is densely decorated with N-linked glycans protruding from the trimer surface that affect S protein folding, processing by host cell proteases and the elicitation of humoral immune response. Deep insight into the sophisticated structure of SARS-CoV-2 S protein may provide a blueprint for vaccination strategies, as reviewed herein.", "title": "Structural features of coronavirus SARS-CoV-2 spike protein: Targets for vaccination", "pid": "ust578fc", "bm25_score": 220.1727752685547}, {"text": "Entry of SARS-CoV-2, etiological agent of COVID-19, in the host cell is driven by the interaction of its spike protein with human ACE2 receptor and a serine protease, TMPRSS2. Although complex between SARS-CoV-2 spike protein and ACE2 has been structurally resolved, the molecular details of the SARS-CoV-2 and TMPRSS2 complex are still elusive. TMPRSS2 is responsible for priming of the viral spike protein that entails cleavage of the spike protein at two potential sites, Arg685/Ser686 and Arg815/Ser816. The present study aims to investigate the conformational details of complex between TMPRSS2 and SARS-CoV-2 spike protein, in order to discern the finer details of the priming of viral spike and to point candidate drug targets. Briefly, full length structural model of TMPRSS2 was developed and docked against the resolved structure of SARS-CoV-2 spike protein with directional restraints of both cleavage sites. The docking simulations showed that TMPRSS2 interacts with the two different loops of SARS-CoV-2 spike protein, each containing different cleavage sites. Key functional residues of TMPRSS2 (His296, Ser441 and Ser460) were found to interact with immediate flanking residues of cleavage sites of SARS-CoV-2 spike protein. Compared to the N-terminal cleavage site (Arg685/Ser686), TMPRSS2 region that interact with C-terminal cleavage site (Arg815/Ser816) of the SARS-CoV-2 spike protein was predicted as relatively more druggable. In summary, the present study provide structural characteristics of molecular complex between human TMPRSS2 and SARS-CoV-2 spike protein and points to the candidate drug targets that could further be exploited to direct structure base drug designing.", "title": "Structural Basis of SARS-CoV-2 Spike Protein Priming by TMPRSS2", "pid": "34ljq0qt", "bm25_score": 220.14112854003906}, {"text": "The spike (S) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is required for cell entry and is the major focus for vaccine development. We combine cryo electron tomography, subtomogram averaging and molecular dynamics simulations to structurally analyze S in situ. Compared to recombinant S, the viral S is more heavily glycosylated and occurs predominantly in a closed pre-fusion conformation. We show that the stalk domain of S contains three hinges that give the globular domain unexpected orientational freedom. We propose that the hinges allow S to scan the host cell surface, shielded from antibodies by an extensive glycan coat. The structure of native S contributes to our understanding of SARS-CoV-2 infection and the development of safe vaccines. The large scale tomography data set of SARS-CoV-2 used for this study is therefore sufficient to resolve structural features to below 5 Ångstrom, and is publicly available at EMPIAR-10453.", "title": "In situ structural analysis of SARS-CoV-2 spike reveals flexibility mediated by three hinges", "pid": "otovxksn", "bm25_score": 219.87083435058594}, {"text": "A novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) has emerged as a human pathogen, causing global pandemic and resulting in over 400,000 deaths worldwide. The surface spike protein of SARS-CoV-2 mediates the process of coronavirus entry into human cells by binding angiotensin-converting enzyme 2 (ACE2). Due to the critical role in viral-host interaction and the exposure of spike protein, it has been a focus of most vaccines’ developments. However, the structural and biochemical studies of the spike protein are challenging because it is thermodynamically metastable1. Here, we develop a new pipeline that automatically identifies mutants that thermodynamically stabilize the spike protein. Our pipeline integrates bioinformatics analysis of conserved residues, motion dynamics from molecular dynamics simulations, and other structural analysis to identify residues that significantly contribute to the thermodynamic stability of the spike protein. We then utilize our previously developed protein design tool, Eris, to predict thermodynamically stabilizing mutations in proteins. We validate the ability of our pipeline to identify protein stabilization mutants through known prefusion spike protein mutants. We finally utilize the pipeline to identify new prefusion spike protein stabilization mutants.", "title": "Prefusion spike protein stabilization through computational mutagenesis", "pid": "86hv27vh", "bm25_score": 219.77288818359375}, {"text": "Spike protein (S protein) is the virus 'key' to infect cells being able to strongly bind to the human angiotensin-converting enzyme2 (ACE2), as it has been reported. In fact, Spike structure and function is known to be highly important for cell infection as well as entering the brain. Growing evidence indicates that different types of coronaviruses not only affect the respiratory system, but they might also invade the central nervous system (CNS). However, very few evidence have been so far reported on the presence of COVID-19 in the brain and the potential exploitation, by this virus, of lung to brain axis to reach neurons has not completely understood. In this article we assessed the SARS-CoV and SARS-CoV-2 Spike protein sequence, structure and electrostatic potential using computational approaches. Our results showed that the S proteins of SARS-CoV-2 and SARS-CoV are highly similar, sharing a sequence identity of 77%. In addition, we found that the SARS-CoV-2 S protein is slightly more positively charged than that of SARS-CoV since it contains four more positively charged residues and five less negatively charged residues which may lead to an increased affinity to bind to negatively charged regions of other molecules through non-specific and specific interactions. Analyzing of the S protein binds to the host ACE2 receptor showed a 30% higher binding energy for SARS-CoV-2 than the SARS-CoV S protein. These results might be useful for understanding the mechanism of cell entry, blood brain barrier crossing and clinical features related to the CNS infection by SARS-CoV-2.", "title": "Considerations around the SARS-CoV-2 Spike Protein with particular attention to COVID-19 brain infection and neurological symptoms.", "pid": "2bz78yl1", "bm25_score": 219.75726318359375}, {"text": "Spike protein (S protein) is the virus 'key' to infect cells being able to strongly bind to the human angiotensin-converting enzyme2 (ACE2), as it has been reported. In fact, Spike structure and function is known to be highly important for cell infection as well as entering the brain. Growing evidence indicates that different types of coronaviruses not only affect the respiratory system, but they might also invade the central nervous system (CNS). However, very few evidence have been so far reported on the presence of COVID-19 in the brain and the potential exploitation, by this virus, of lung to brain axis to reach neurons has not completely understood. In this article we assessed the SARS-CoV and SARS-CoV-2 Spike protein sequence, structure and electrostatic potential using computational approaches. Our results showed that the S proteins of SARS-CoV-2 and SARS-CoV are highly similar, sharing a sequence identity of 77%. In addition, we found that the SARS-CoV-2 S protein is slightly more positively charged than that of SARS-CoV since it contains four more positively charged residues and five less negatively charged residues which may lead to an increased affinity to bind to negatively charged regions of other molecules through non-specific and specific interactions. Analyzing of the S protein binds to the host ACE2 receptor showed a 30% higher binding energy for SARS-CoV-2 than the SARS-CoV S protein. These results might be useful for understanding the mechanism of cell entry, blood brain barrier crossing and clinical features related to the CNS infection by SARS-CoV-2.", "title": "Considerations around the SARS-CoV-2 Spike Protein with particular attention to COVID-19 brain infection and neurological symptoms", "pid": "t4bqmgcl", "bm25_score": 219.737060546875}, {"text": "Motivation The recent emergence of the novel SARS-coronavirus 2 (SARS-CoV-2) and its international spread pose a global health emergency. The viral spike (S) glycoprotein binds the receptor (angiotensin-converting enzyme 2) ACE2 and promotes SARS-CoV-2 entry into host cells. The trimeric S protein binds the receptor using the distal receptor-binding domain (RBD) causing conformational changes in S protein that allow priming by host cell proteases. Unravelling the dynamic structural features used by SARS-CoV-2 for entry might provide insights into viral transmission and reveal novel therapeutic targets. Using structures determined by X-ray crystallography and cryo-EM, we performed structural analysis and atomic comparisons of the different conformational states adopted by the SARS-CoV-2-RBD. Results Here, we determined the key structural components induced by the receptor and characterized their intramolecular interactions. We show that κ-helix (also known as polyproline II) is a predominant structure in the binding interface and in facilitating the conversion to the active form of the S protein. We demonstrate a series of conversions between switch-like κ-helix and β-strand, and conformational variations in a set of short α-helices which affect the proximal hinge region. This conformational changes lead to an alternating pattern in conserved disulfide bond configurations positioned at the hinge, indicating a possible disulfide exchange, an important allosteric switch implicated in viral entry of various viruses, including HIV and murine coronavirus. The structural information presented herein enables us to inspect and understand the important dynamic features of SARS-CoV-2-RBD and propose a novel potential therapeutic strategy to block viral entry. Overall, this study provides guidance for the design and optimization of structure-based intervention strategies that target SARS-CoV-2.", "title": "Structural basis of SARS-CoV-2 spike protein induced by ACE2", "pid": "yfn9vaan", "bm25_score": 219.7302703857422}, {"text": "SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.", "title": "The biological characteristics of SARS-CoV-2 spike protein Pro330-Leu650", "pid": "ufmzv9f4", "bm25_score": 219.65283203125}, {"text": "Covid-19 pandemic outbreak is the reason of the current world health crisis. The development of effective antiviral compounds and vaccines requires detailed descriptive studies of the SARS-CoV-2 proteins. The SARS-CoV-2 spike (S) protein mediates virion binding to the human cells through its interaction with the ACE2 cell surface receptor and is one of the prime immunization targets. A functional virion is composed of three S1 and three S2 subunits created by furin cleavage of the spike protein at R682, a polybasic cleavage sites that differs from the SARS-CoV spike protein of 2002. We observe that the spike protein is O-glycosylated on a threonine (T678) near the furin cleavage site occupied by core-1 and core-2 structures. In addition, we have identified eight additional O-glycopeptides on the spike glycoprotein and we confirmed that the spike protein is heavily N-glycosylated. Our recently developed LC-MS/MS methodology allowed us to identify LacdiNAc structural motifs on all occupied N-glycopeptides and polyLacNAc structures on six glycopeptides of the spike protein. In conclusion, our study substantially expands the current knowledge of the spike protein’s glycosylation and enables the investigation of the influence of the O-glycosylation on its proteolytic activation.", "title": "N and O glycosylation of the SARS-CoV-2 spike protein", "pid": "ssffvlrl", "bm25_score": 219.5199737548828}, {"text": "The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10 - 25 January) 2020. We also applied structural bioinformatics to assess D614G potential impact on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.", "title": "Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide", "pid": "zu46bdpu", "bm25_score": 219.4813232421875}, {"text": "SARS-CoV-2 is the cause of the worldwide outbreak of COVID-19 that has been characterized as a pandemic by the WHO. Since the first report of COVID-19 on December 31, 2019, 179,111 cases were confirmed in 160 countries/regions with 7,426 deaths as of March 17, 2020. However, there have been no vaccines approved in the world to date. In this study, we analyzed the biological characteristics of the SARS-CoV-2 Spike protein, Pro330-Leu650 (SARS-CoV-2-SPL), using biostatistical methods. SARS-CoV-2-SPL possesses a receptor-binding region (RBD) and important B (Ser438-Gln506, Thr553-Glu583, Gly404-Aps427, Thr345-Ala352, and Lys529-Lys535) and T (9 CD4 and 11 CD8 T cell antigenic determinants) cell epitopes. High homology in this region between SARS-CoV-2 and SARS-CoV amounted to 87.7%, after taking the biological similarity of the amino acids into account and eliminating the receptor-binding motif (RBM). The overall topology indicated that the complete structure of SARS-CoV-2-SPL was with RBM as the head, and RBD as the trunk and the tail region. SARS-CoV-2-SPL was found to have the potential to elicit effective B and T cell responses. Our findings may provide meaningful guidance for SARS-CoV-2 vaccine design.", "title": "The biological characteristics of SARS-CoV-2 Spike protein Pro330-Leu650", "pid": "vhl5adaw", "bm25_score": 219.4492950439453}, {"text": "The 2019 novel coronavirus (2019-nCoV/SARS-CoV-2) originally arose as part of a major outbreak of respiratory disease centered on Hubei province, China. It is now a global pandemic and is a major public health concern. Taxonomically, SARS-CoV-2 was shown to be a Betacoronavirus (lineage B) closely related to SARS-CoV and SARS-related bat coronaviruses, and it has been reported to share a common receptor with SARS-CoV (ACE-2). Subsequently, betacoronaviruses from pangolins were identified as close relatives to SARS-CoV-2. Here, we perform structural modeling of the SARS-CoV-2 spike glycoprotein. Our data provide support for the similar receptor utilization between SARS-CoV-2 and SARS-CoV, despite a relatively low amino acid similarity in the receptor binding module. Compared to SARS-CoV and all other coronaviruses in Betacoronavirus lineage B, we identify an extended structural loop containing basic amino acids at the interface of the receptor binding (S1) and fusion (S2) domains. We suggest this loop confers fusion activation and entry properties more in line with betacoronaviruses in lineages A and C, and be a key component in the evolution of SARS-CoV-2 with this structural loop affecting virus stability and transmission.", "title": "Phylogenetic Analysis and Structural Modeling of SARS-CoV-2 Spike Protein Reveals an Evolutionary Distinct and Proteolytically Sensitive Activation Loop", "pid": "vembiw2k", "bm25_score": 219.39306640625}, {"text": "The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has led to accelerated efforts to develop therapeutics, diagnostics, and vaccines to mitigate this public health emergency. A key target of these efforts is the spike (S) protein, a large trimeric class I fusion protein that is metastable and difficult to produce recombinantly in large quantities. Here, we designed and expressed over 100 structure-guided spike variants based upon a previously determined cryo-EM structure of the prefusion SARS-CoV-2 spike. Biochemical, biophysical and structural characterization of these variants identified numerous individual substitutions that increased protein yields and stability. The best variant, HexaPro, has six beneficial proline substitutions leading to ~10-fold higher expression than its parental construct and is able to withstand heat stress, storage at room temperature, and multiple freeze-thaws. A 3.2 Å-resolution cryo-EM structure of HexaPro confirmed that it retains the prefusion spike conformation. High-yield production of a stabilized prefusion spike protein will accelerate the development of vaccines and serological diagnostics for SARS-CoV-2.", "title": "Structure-based Design of Prefusion-stabilized SARS-CoV-2 Spikes", "pid": "g81ylcxq", "bm25_score": 219.3534393310547}, {"text": "The ongoing SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic has created urgent needs for intervention strategies to control the crisis. The spike (S) protein of the virus forms a trimer and catalyzes fusion between viral and target cell membranes - the first key step of viral infection. Here we report two cryo-EM structures, both derived from a single preparation of the full-length S protein, representing the prefusion (3.1Å resolution) and postfusion (3.3Å resolution) conformations, respectively. The spontaneous structural transition to the postfusion state under mild conditions is independent of target cells. The prefusion trimer forms a tightly packed structure with three receptor-binding domains clamped down by a segment adjacent to the fusion peptide, significantly different from recently published structures of a stabilized S ectodomain trimer. The postfusion conformation is a rigid tower-like trimer, but decorated by N-linked glycans along its long axis with almost even spacing, suggesting possible involvement in a mechanism protecting the virus from host immune responses and harsh external conditions. These findings advance our understanding of how SARS-CoV-2 enters a host cell and may guide development of vaccines and therapeutics.", "title": "Distinct conformational states of SARS-CoV-2 spike protein", "pid": "muwwyktk", "bm25_score": 219.18995666503906}, {"text": "In this study, the encoding sequences of SARS-CoV spike protein were analyzed by bioinformatics methods, the structural characteristics and functions were forecasted based on available data. It suggests that the fragment of spike glycoprotein (S401-659) may be crucial for viral attachment and may be a major immunodominant epitope. Then the fragment was amplified and subcloned into expression vector pET28a(+) and pPIC9K. These two plasmids pET28a(+)-S and pPIC9K-S were transformed to E.coli strain BL21(DE3)-star and Pichia pastoris, respectively. SDS-PAGE and Western blot analysis showed that the recombinant protein was successfully expressed. The denatured inclusion bodies were purified with Ni-NTA chelate agarose and its purity can reach 90%.", "title": "[A preliminary study of the structure prediction and expression of SARS-CoV spike protein].", "pid": "x55bdcy5", "bm25_score": 219.16250610351562}, {"text": "The year 2020 has seen a major and sustained outbreak of a novel betacoronavirus (severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2) infection that causes fever, severe respiratory illness and pneumonia, a disease called COVID-19. At the time of writing, the death toll was greater than 120 000 worldwide with more than 2 million documented infections. The genome of the CoV encodes a number of structural proteins that facilitate cellular entry and assembly of virions, of which the spike protein S appears to be critical for cellular entry. The spike protein guides the virus to attach to the host cell. The spike protein contains a receptor-binding domain (RBD), a fusion domain and a transmembrane domain. The RBD of spike protein S binds to Angiotensin Converting Enzyme 2 (ACE2) to initiate cellular entry. The spike protein of SARS-CoV-2 shows more than 90% amino acid similarity to the pangolin and bat CoVs and these also use ACE2 as a receptor. Binding of the spike protein to ACE2 exposes the cleavage sites to cellular proteases. Cleavage of the spike protein by transmembrane protease serine 2 and other cellular proteases initiates fusion and endocytosis. The spike protein contains an addition furin cleavage site that may allow it to be 'preactivated' and highly infectious after replication. The fundamental role of the spike protein in infectivity suggests that it is an important target for vaccine development, blocking therapy with antibodies and diagnostic antigen-based tests. This review briefly outlines the structure and function of the 2019 novel CoV/SARS-CoV-2 spike protein S.", "title": "Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein", "pid": "50hqr249", "bm25_score": 219.16238403320312}, {"text": "Pandemic coronavirus disease 2019 (COVID-19) is caused by the emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), for which there are no efficacious vaccines or therapeutics that are urgently needed. We expressed three versions of spike (S) proteins—receptor binding domain (RBD), S1 subunit and S ectodomain—in insect cells. RBD appears monomer in solutions, whereas S1 and S associate into homotrimer with substantial glycosylation. The three proteins confer excellent antigenicity with six convalescent COVID-19 patient sera. Cryo-electron microscopy (cryo-EM) analyses indicate that the SARS-CoV-2 S trimer dominate in a unique conformation distinguished from the classic prefusion conformation of coronaviruses by the upper S1 region at lower position ~15 Å proximal to viral membrane. Such conformation is proposed as an early prefusion state for the SARS-CoV-2 spike that may broaden the knowledge of coronavirus and facilitate vaccine development.", "title": "Characterization of the SARS-CoV-2 Spike in an Early Prefusion Conformation", "pid": "i9r77o70", "bm25_score": 219.1491241455078}, {"text": "Abstract What began with a sign of pneumonia-related respiratory disorders in China has now become a pandemic named by WHO as Covid-19 known to be caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The SARS-CoV-2 are newly emerged β coronaviruses belonging to the Coronaviridae family. SARS-CoV-2 has a positive viral RNA genome expressing open reading frames that code for structural and non-structural proteins. The spike, nucleocapsid, membrane, and envelope proteins are structural proteins. The S1 subunit of spike protein facilitates ACE2 mediated virus attachment and S2 subunit for membrane fusion. The presence of glutamine, asparagine, leucine, phenylalanine and serine amino in SARS-CoV-2 enhanced ACE2 binding. The N protein is composed of a serine-rich linker region sandwiched between N terminal (NTD) and C terminal (CTD). These terminals play a role in viral entry and its processing post entry. The NTD of SARS-CoV-2 N protein forms orthorhombic crystals and binds to the viral genome. The linker region contains phosphorylation sites that regulate its functioning. The CTD promotes nucleocapsid formation. Envelope proteins contain an NTD, hydrophobic domain and C terminal which form viroporins needed for viral assembly. Membrane proteins hydrophilic C terminal and amphipathic N terminal. Its long-form promotes spike incorporations and interaction with E facilitate virion production. As each protein is essential in viral functioning, this review describes the insights of SARS-CoV-2 structural proteins that would help in developing therapeutic strategies by targeting each protein to curb the rapidly growing pandemic.", "title": "Structural Proteins in Severe Acute Respiratory Syndrome Coronavirus-2", "pid": "7axo7k51", "bm25_score": 219.07568359375}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions are surrounded by a lipid bilayer from which spike (S) protein trimers protrude. Heavily glycosylated S trimers bind the ACE2 receptor and mediate entry of virions into target cells. S exhibits extensive conformational flexibility: it modulates the exposure of its receptor binding site and later undergoes complete structural rearrangement to drive fusion of viral and cellular membranes. The structures and conformations of soluble, overexpressed, purified S proteins have been studied in detail using cryo-electron microscopy. The structure and distribution of S on the virion surface, however, has not been characterised. Here we applied cryo-electron microscopy and tomography to image intact SARS-CoV-2 virions, determining the high-resolution structure, conformational flexibility and distributions of S trimers in situ on the virion surface. These results provide a basis for understanding the conformations of S present on the virion, and for studying their interactions with neutralizing antibodies.", "title": "Structures, conformations and distributions of SARS-CoV-2 spike protein trimers on intact virions", "pid": "g6jyqiep", "bm25_score": 219.01812744140625}, {"text": "n a piece of research accomplished with astonishing speed, scientists from the University of Texas at Austin and the National Institutes of Health have released a cryo-electron microscopy (cryo-EM) structure of part of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus that has infected tens of thousands of people and killed more than 2,000 since the end of December (Science 2020, DOI: 10 1126/science abb2507) The part of the virus imaged, called the spike protein, helps the virus attach to and infect human cells, and the determination of its structure comes just weeks after the virus’s genome sequence was published The breakthrough is a huge step toward developing a vaccine against the virus as well as treatments for COVID-19, the disease that it causes, the researchers say UT Austin’s Jason McLellan and his colleagues, who have spent many years studying other coronaviruses, had already figured out how to use select", "title": "Structure of novel coronavirus’s spike protein solved", "pid": "oq79dfhr", "bm25_score": 219.01751708984375}, {"text": "Severe acute respiratory syndrome coronavirus is a newly emergent virus responsible for a recent outbreak of an atypical pneumonia. The coronavirus spike protein, an enveloped glycoprotein essential for viral entry, belongs to the class I fusion proteins and is characterized by the presence of two heptad repeat (HR) regions, HR1 and HR2. These two regions are understood to form a fusion-active conformation similar to those of other typical viral fusion proteins. This hairpin structure likely juxtaposes the viral and cellular membranes, thus facilitating membrane fusion and subsequent viral entry. The fusion core protein of severe acute respiratory syndrome coronavirus spike protein was crystallized, and the structure was determined at 2.8 A of resolution. The fusion core is a six-helix bundle with three HR2 helices packed against the hydrophobic grooves on the surface of central coiled coil formed by three parallel HR1 helices in an oblique antiparallel manner. This structure shares significant similarity with the fusion core structure of mouse hepatitis virus spike protein and other viral fusion proteins, suggesting a conserved mechanism of membrane fusion. Drug discovery strategies aimed at inhibiting viral entry by blocking hairpin formation, which have been successfully used in human immunodeficiency virus 1 inhibitor development, may be applicable to the inhibition of severe acute respiratory syndrome coronavirus on the basis of structural information provided here. The relatively deep grooves on the surface of the central coiled coil will be a good target site for the design of viral fusion inhibitors.", "title": "Crystal structure of severe acute respiratory syndrome coronavirus spike protein fusion core.", "pid": "is9b0csy", "bm25_score": 219.00340270996094}, {"text": "The year 2020 has seen a major and sustained outbreak of a novel betacoronavirus (severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2) infection that causes fever, severe respiratory illness and pneumonia, a disease called Covid-19. At the time of writing, the death toll was greater than 120 000 worldwide with more than 2 million documented infections. The genome of the CoV encodes a number of structural proteins that facilitate cellular entry and assembly of virions, of which the spike protein S appears to be critical for cellular entry. The spike protein guides the virus to attach to the host cell. The spike protein contains a receptor-binding domain (RBD), a fusion domain and a transmembrane domain. The RBD of spike protein S binds to Angiotensin Converting Enzyme 2 (ACE2) to initiate cellular entry. The spike protein of SARS-CoV-2 shows more than 90% amino acid similarity to the pangolin and bat CoVs and these also use ACE2 as a receptor. Binding of the spike protein to ACE2 exposes the cleavage sites to cellular proteases. Cleavage of the spike protein by transmembrane protease serine 2 and other cellular proteases initiates fusion and endocytosis. The spike protein contains an addition furin cleavage site that may allow it to be 'preactivated' and highly infectious after replication. The fundamental role of the spike protein in infectivity suggests that it is an important target for vaccine development, blocking therapy with antibodies and diagnostic antigen-based tests. This review briefly outlines the structure and function of the 2019 novel CoV/SARS-CoV-2 spike protein S.", "title": "Gene of the month: the 2019-nCoV/SARS-CoV-2 novel coronavirus spike protein.", "pid": "40ejbv5j", "bm25_score": 218.99940490722656}, {"text": "[Image: see text] Recent crystal structure data for protein–protein interactions featuring the SARS-CoV-2 spike protein will inevitably trigger a new wave of research in this area that was not possible before. This Viewpoint outlines a few of the ways that it is already happening.", "title": "Blocking Coronavirus 19 Infection via the SARS-CoV-2 Spike Protein: Initial Steps", "pid": "908d8bax", "bm25_score": 218.97024536132812}, {"text": "Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) is causing an unprecedented global pandemic demanding the urgent development of therapeutic strategies. Microarray binding experiments using an extensive heparan sulfate (HS) oligosaccharide library showed the spike of SARS-CoV-2 can bind HS in a length- and sequence-dependent manner. Hexa- and octasaccharides composed of IdoA2S-GlcNS6S repeating units were identified as optimal ligands. Surface plasma resonance (SPR) showed the SARS-CoV-2 spike protein binds with higher affinity to heparin (KD 55 nM) compared to the receptor binding domain (RBD, KD 1 µM) alone. An octasaccharide composed of IdoA2S-GlcNS6S could inhibit spike-heparin interaction with an IC50 of 38 nM. Our data supports a model in which the RBD of the spike of SARS-CoV-2 confers sequence specificity for HS expressed by target cells whereas an additional HS binding site in the S1/S2 proteolytic cleavage site enhances the avidity of binding. Collectively, our results highlight the potential of using HS oligosaccharides as a therapeutic agent by inhibiting SARS-CoV-2 binding to target cells.", "title": "SARS-CoV-2 spike protein binds heparan sulfate in a length- and sequence-dependent manner", "pid": "1h9ewx5j", "bm25_score": 218.96139526367188}, {"text": "The envelope glycoprotein, termed the spike protein, of severe acute respiratory syndrome coronavirus (SARS-CoV) is known to mediate viral entry. Similar to other class 1 viral fusion proteins, the heptad repeat regions of SARS-CoV spike are thought to undergo conformational changes from a prefusion form to a subsequent post-fusion form that enables fusion of the viral and host membranes. Recently, the structure of a post-fusion form of SARS-CoV spike, which consists of isolated domains of heptad repeats 1 and 2 (HR1 and HR2), has been determined by x-ray crystallography. To date there is no structural information for the prefusion conformations of SARS-CoV HR1 and HR2. In this work we present the NMR structure of the HR2 domain (residues 1141-1193) from SARS-CoV (termed S2-HR2) in the presence of the co-solvent trifluoroethanol. We find that in the absence of HR1, S2-HR2 forms a coiled coil symmetric trimer with a complex molecular mass of 18 kDa. The S2-HR2 structure, which is the first example of the prefusion form of coronavirus envelope, supports the current model of viral membrane fusion and gives insight into the design of structure-based antagonists of SARS.", "title": "Solution structure of the severe acute respiratory syndrome-coronavirus heptad repeat 2 domain in the prefusion state.", "pid": "jfq7820g", "bm25_score": 218.95083618164062}, {"text": "Severe acute respiratory syndrome (SARS) is a novel infectious disease caused by the SARS-associated coronavirus (SARS-CoV). There are four major structural proteins in the SARS-CoV, including the nucleocapsid, spike, membrane, and small envelope proteins. In this study, two sets of truncated fragments of spike protein were generated, the first were approximately 210-bp nonoverlapping fragments and the second were overlapping segments of 750 to 900 bp. From these 23 fragments, we identified a fragment of 259 amino acids (amino acids 441 to 700) that is a major immunodominant epitope. This fragment was highly expressed, and the purified fragment C could detect all 33 SARS patient serum samples tested, collected from 7 to 60 days after the onset of fever, but had no reactivity with all 66 healthy human serum samples tested. Thus, fragment C of spike protein was identified as an immunodominant antigen and could be used for serological detection of SARS-CoV infection.", "title": "Immunological characterization of the spike protein of the severe acute respiratory syndrome coronavirus.", "pid": "lr9mwb7m", "bm25_score": 218.9353790283203}, {"text": "The newly emergent SARS-CoV-2 coronavirus is closely related to SARS-CoV which emerged in 2002. Studies on coronaviruses in general, and SARS in particular, have identified the virus spike protein (S) as being central to virus tropism, to the generation of a protective antibody response and to the unambiguous detection of past infections. As a result of this centrality SARS-CoV-2 S protein has a role in many aspects of research from vaccines to diagnostic tests. We describe a number of recombinant forms of SARS-CoV-2 S expressed in commonly available expression systems and their preliminary use in diagnostics and epitope mapping. These sources may find use in the current and future analysis of the virus and the Covid-19 disease it causes.", "title": "Recombinant SARS-CoV-2 spike proteins for sero-surveillance and epitope mapping", "pid": "e20gtx0z", "bm25_score": 218.9238739013672}, {"text": "Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease caused by a novel coronavirus, SARS-coronavirus (SARS-CoV). The SARS-CoV spike (S) protein is composed of two subunits; the S1 subunit contains a receptor-binding domain that engages with the host cell receptor angiotensin-converting enzyme 2 and the S2 subunit mediates fusion between the viral and host cell membranes. The S protein plays key parts in the induction of neutralizing-antibody and T-cell responses, as well as protective immunity, during infection with SARS-CoV. In this Review, we highlight recent advances in the development of vaccines and therapeutics based on the S protein.", "title": "The spike protein of SARS-CoV — a target for vaccine and therapeutic development", "pid": "48ay8yl3", "bm25_score": 218.92066955566406}, {"text": "The recent emergence of a novel coronavirus (SARS-CoV-2) is causing a severe global health threat characterized by severe acute respiratory syndrome (Covid-19). At the moment, there is no specific treatment for this disease, and vaccines are still under development. The structural protein Spike is essential for virus infection and has been used as the main target for vaccine and serological diagnosis test development. We analysed 2363 sequences of the Spike protein from SARS-CoV-2 isolates and identified variability in 44 amino acid residues and their worldwide distribution in all continents. We used the three-dimensional structure of the homo-trimer model to predict conformational epitopes of B-cell, and sequence of Spike protein Wuhan-Hu-1 to predict linear epitopes of T-Cytotoxic and T-Helper cells. We identified 45 epitopes with amino acid variations. Finally, we showed the distribution of mutations within the epitopes. Our findings can help researches to identify more efficient strategies for the development of vaccines, therapies, and serological diagnostic tests based on the Spike protein of Sars-Cov-2.", "title": "SARS-CoV-2 mutations and where to find them: An in silico perspective of structural changes and antigenicity of the Spike protein", "pid": "srgi9jc6", "bm25_score": 218.87484741210938}, {"text": "Corona virus spike protein S is a large homo-trimeric protein embedded in the membrane of the virion particle. Protein S binds to angiotensin-converting-enzyme 2, ACE2, of the host cell, followed by proteolysis of the spike protein, drastic protein conformational change with exposure of the fusion peptide of the virus, and entry of the virion into the host cell. The structural elements that govern conformational plasticity of the spike protein are largely unknown. Here, we present a methodology that relies upon graph and centrality analyses, augmented by bioinformatics, to identify and characterize large H-bond clusters in protein structures. We apply this methodology to protein S ectodomain and find that, in the closed conformation, the three protomers of protein S bring the same contribution to an extensive central network of H-bonds, has a relatively large H-bond cluster at the receptor binding domain, and a cluster near a protease cleavage site. Markedly different H-bonding at these three clusters in open and pre-fusion conformations suggest dynamic H-bond clusters could facilitate structural plasticity and selection of a protein S protomer for binding to the host receptor, and proteolytic cleavage. From analyses of spike protein sequences we identify patches of histidine and carboxylate groups that could be involved in transient proton binding.", "title": "A graph-based approach identifies dynamic H-bond communication networks in spike protein S of SARS-CoV-2", "pid": "f4z91s03", "bm25_score": 218.86941528320312}, {"text": "SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S; we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable precleavage form of human S and about 1,000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.", "title": "SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects", "pid": "3damlwoj", "bm25_score": 218.8162078857422}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters into the cells through its spike proteins binding to human angiotensin-converting enzyme 2 (ACE2) protein and causes virus infection in host cells. Until now, there are no available antiviral drugs have been reported that can effectively block virus infection. The study aimed to discover the potential compounds to prevent viral spike proteins to bind to the human ACE2 proteins from Taiwan Database of Extracts and Compounds (TDEC) by structure-based virtual screening. In this study, to rapidly discover potential inhibitors against SARS-CoV-2 spike proteins, the molecular docking calculation was performed by AutoDock Vina program. Herein, we found that 39 potential compounds may have good binding affinities and can respectively bind to the viral receptor-binding domain (RBD) of spike protein in the prefusion conformation and spike-ACE2 complex protein in silico. Among those compounds, especially natural products thioflexibilolide A and candidine that were respectively isolated from the soft corals Sinularia flexibilis and Phaius mishmensis may have better binding affinity than others. This study provided the predictions that these compounds may have the potential to prevent SARS-CoV-2 spike protein from entry into cells.", "title": "The discovery of potential natural products for targeting SARS-CoV-2 spike protein by virtual screening", "pid": "4skamxby", "bm25_score": 218.810546875}, {"text": "SARS-CoV-2 is thought to have emerged from bats, possibly via a secondary host. Here, we investigate the relationship of spike (S) glycoprotein from SARS-CoV-2 with the S protein of a closely related bat virus, RaTG13. We determined cryo-EM structures for RaTG13 S and for both furin-cleaved and uncleaved SARS-CoV-2 S; we compared these with recently reported structures for uncleaved SARS-CoV-2 S. We also biochemically characterized their relative stabilities and affinities for the SARS-CoV-2 receptor ACE2. Although the overall structures of human and bat virus S proteins are similar, there are key differences in their properties, including a more stable precleavage form of human S and about 1,000-fold tighter binding of SARS-CoV-2 to human receptor. These observations suggest that cleavage at the furin-cleavage site decreases the overall stability of SARS-CoV-2 S and facilitates the adoption of the open conformation that is required for S to bind to the ACE2 receptor.", "title": "SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects.", "pid": "guxbf60n", "bm25_score": 218.80233764648438}, {"text": "Statistical and epidemiological data imply temperature sensitivity of the SARS-CoV-2 coronavirus. However, the molecular level understanding of the virus structure at different temperature is still not clear. Spike protein is the outermost structural protein of the SARS-CoV-2 virus which interacts with the Angiotensin Converting Enzyme 2 (ACE2), a human receptor, and enters the respiratory system. In this study, we performed an all atom molecular dynamics simulation to study the effect of temperature on the structure of the Spike protein. After 200ns of simulation at different temperatures, we came across some interesting phenomena exhibited by the protein. We found that the solvent exposed domain of Spike protein, namely S1, is more mobile than the transmembrane domain, S2. Structural studies implied the presence of several charged residues on the surface of N-terminal Domain of S1 which are optimally oriented at 10-30 °C. Bioinformatics analyses indicated that it is capable of binding to other human receptors and should not be disregarded. Additionally, we found that receptor binding motif (RBM), present on the receptor binding domain (RBD) of S1, begins to close around temperature of 40 °C and attains a completely closed conformation at 50 °C. The closed conformation disables its ability to bind to ACE2, due to the burying of its receptor binding residues. Our results clearly show that there are active and inactive states of the protein at different temperatures. This would not only prove beneficial for understanding the fundamental nature of the virus, but would be also useful in the development of vaccines and therapeutics. Graphical Abstract Highlights Statistical and epidemiological evidence show that external climatic conditions influence the SARS-CoV infectivity, but we still lack a molecular level understanding of the same. Here, we study the influence of temperature on the structure of the Spike glycoprotein, the outermost structural protein, of the virus which binds to the human receptor ACE2. Results show that the Spike’s S1 domain is very sensitive to external atmospheric conditions compared to the S2 transmembrane domain. The N-terminal domain comprises of several solvent exposed charged residues that are capable of binding to human proteins. The region is specifically stable at temperatures ranging around 10-30° C. The Receptor Binding Motif adopts a closed conformation at 40°C and completely closes at higher temperatures making it unsuitable of binding to human receptors", "title": "Investigation of the effect of temperature on the structure of SARS-Cov-2 Spike Protein by Molecular Dynamics Simulations", "pid": "nsp53lv6", "bm25_score": 218.79653930664062}, {"text": "What began with a sign of pneumonia-related respiratory disorders in China has now become a pandemic named by WHO as Covid-19 known to be caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). The SARS-CoV-2 are newly emerged ß coronaviruses belonging to the Coronaviridae family. SARS-CoV-2 has a positive viral RNA genome expressing open reading frames that code for structural and non-structural proteins. The structural proteins include spike (S), nucleocapsid (N), membrane (M), and envelope (E) proteins. The S1 subunit of S protein facilitates ACE2 mediated virus attachment while S2 subunit promotes membrane fusion. The presence of glutamine, asparagine, leucine, phenylalanine and serine amino acids in SARS-CoV-2 enhances ACE2 binding. The N protein is composed of a serine-rich linker region sandwiched between N Terminal Domain (NTD) and C Terminal Domain (CTD). These terminals play a role in viral entry and its processing post entry. The NTD forms orthorhombic crystals and binds to the viral genome. The linker region contains phosphorylation sites that regulate its functioning. The CTD promotes nucleocapsid formation. The E protein contains a NTD, hydrophobic domain and CTD which form viroporins needed for viral assembly. The M protein possesses hydrophilic C terminal and amphipathic N terminal. Its long-form promotes spike incorporations and the interaction with E facilitates virion production. As each protein is essential in viral functioning, this review describes the insights of SARS-CoV-2 structural proteins that would help in developing therapeutic strategies by targeting each protein to curb the rapidly growing pandemic.", "title": "Structural Proteins in Severe Acute Respiratory Syndrome Coronavirus-2", "pid": "9sbrxzxu", "bm25_score": 218.78091430664062}, {"text": "The novel betacoronavirus SARS-CoV-2 is the etiological agent of the current pandemic COVID-19. Like other coronaviruses, this novel virus relies on the surface Spike glycoprotein to access the host cells, mainly through the interaction of its Receptor Binding Domain (RBD) with the human angiotensin-converting enzyme 2 (ACE2). Therefore, molecular entities able to interfere with binding of the SARS-CoV-2 Spike protein to ACE2 have a great potential to inhibit viral entry. Starting from the available structural data on the interaction between SARS-CoV-2 Spike protein and the host ACE2 receptor, we here engineered a mini-protein with the aim of creating a soluble and stable Spike interactor. This mini-protein, which was recombinantly produced in high yields, possesses a stable α helical conformation and is able to interact with the RBD of glycosylated Spike protein from SARS-CoV-2 with nanomolar affinity, as measured by microscale thermophoresis. By plugging the Spike protein, our mini-protein constitutes a valid tool for the development of treatments against different types of coronavirus.", "title": "An engineered stable mini-protein to plug SARS-Cov-2 Spikes", "pid": "5ftpxlfe", "bm25_score": 218.7348175048828}, {"text": "The corona-like spikes or peplomers on the surface of the virion under electronic microscope are the most striking features of coronaviruses. The S (spike) protein is the largest structural protein, with 1,255 amino acids, in the viral genome. Its structure can be divided into three regions: a long N-terminal region in the exterior, a characteristic transmembrane (TM) region, and a short C-terminus in the interior of a virion. We detected fifteen substitutions of nucleotides by comparisons with the seventeen published SARS-CoV genome sequences, eight (53.3%) of which are non-synonymous mutations leading to amino acid alternations with predicted physiochemical changes. The possible antigenic determinants of the S protein are predicted, and the result is confirmed by ELISA (enzyme-linked immunosorbent assay) with synthesized peptides. Another profound finding is that three disulfide bonds are defined at the C-terminus with the N-terminus of the E (envelope) protein, based on the typical sequence and positions, thus establishing the structural connection with these two important structural proteins, if confirmed. Phylogenetic analysis reveals several conserved regions that might be potent drug targets.", "title": "The Structural Characterization and Antigenicity of the S Protein of SARS-CoV", "pid": "hc0ma2cq", "bm25_score": 218.72068786621094}, {"text": "SARS-CoV-2 has a zoonotic origin and was transmitted to humans via an undetermined intermediate host, leading to infections in humans and other mammals. To enter host cells, the viral spike protein (S-protein) binds to its receptor, ACE2, and is then processed by TMPRSS2. Whilst receptor binding contributes to the viral host range, S-protein:ACE2 complexes from other animals have not been investigated widely. To predict infection risks, we modelled S-protein:ACE2 complexes from 215 vertebrate species, calculated changes in the energy of the complex caused by mutations in each species, relative to human ACE2, and correlated these changes with COVID-19 infection data. We also analysed structural interactions to better understand the key residues contributing to affinity. We predict that mutations are more detrimental in ACE2 than TMPRSS2. Finally, we demonstrate phylogenetically that human SARS-CoV-2 strains have been isolated in animals. Our results suggest that SARS-CoV-2 can infect a broad range of mammals, but few fish, birds or reptiles. Susceptible animals could serve as reservoirs of the virus, necessitating careful ongoing animal management and surveillance.", "title": "SARS-CoV-2 spike protein predicted to form complexes with host receptor protein orthologues from a broad range of mammals", "pid": "sygnmiun", "bm25_score": 218.718994140625}, {"text": "The spike protein (S) of SARS coronavirus (SARS-CoV) attaches the virus to its cellular receptor, angiotensin-converting enzyme 2 (ACE2). A defined receptor-binding domain (RBD) on S mediates this interaction. The crystal structure at 2.9 angstrom resolution of the RBD bound with the peptidase domain of human ACE2 shows that the RBD presents a gently concave surface, which cradles the N-terminal lobe of the peptidase. The atomic details at the interface between the two proteins clarify the importance of residue changes that facilitate efficient cross-species infection and human-to-human transmission. The structure of the RBD suggests ways to make truncated disulfide-stabilized RBD variants for use in the design of coronavirus vaccines.", "title": "Structure of SARS coronavirus spike receptor-binding domain complexed with receptor.", "pid": "hmswnrgg", "bm25_score": 218.69688415527344}, {"text": "The emergence in 2003 of a new coronavirus (CoV) responsible for the atypical pneumonia termed severe acute respiratory syndrome (SARS) was a stark reminder that hitherto unknown viruses have the potential to cross species barriers to become new human pathogens. Here we describe the SARS-CoV 'spike' structure determined by single-particle cryo-EM, along with the docked atomic structures of the receptor-binding domain and prefusion core. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nsmb1123) contains supplementary material, which is available to authorized users.", "title": "Architecture of the SARS coronavirus prefusion spike", "pid": "tpn5cg4n", "bm25_score": 218.6934051513672}, {"text": "Abstract Severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is a newly identified member of Family Coronaviridae. Coronavirus envelope spike protein S is a class I viral fusion protein which is characterized by the existence of two heptad repeat regions (HR1 and HR2) (forming a complex called fusion core). Here we report that by using in vitro bio-engineering techniques, SARS-CoV HR1 and HR2 bind to each other and form a typical 6-helix bundle. The HR2, either as a synthetic peptide or as a GST-fusion polypeptide, is a potent inhibitor of virus entry. The results do show that SARS-CoV follows the general fusion mechanism of class I viruses and this lays the ground for identification of virus fusion/entry inhibitors for this devastating emerging virus.", "title": "Following the rule: formation of the 6-helix bundle of the fusion core from severe acute respiratory syndrome coronavirus spike protein and identification of potent peptide inhibitors", "pid": "16upcncw", "bm25_score": 218.69049072265625}, {"text": "Coronaviruses are a class of virus responsible of the recent outbreak of Human Severe Acute Respiratory Syndrome. The molecular machinery behind the viral entry and thus infectivity is based on the formation of the complex of virus spike protein with the angiotensin-converting enzyme 2 (ACE2). The detection of putative allosteric sites on the viral spike protein can trace the path to develop allosteric drugs to weaken the strength of the spike-ACE2 interface and, thus, reduce the viral infectivity. In this work we present results of the application of the Protein Contact Network (PCN) paradigm to the complex SARS-CoV spike - ACE2 relative to both 2003 SARS and the recent 2019 - CoV. Results point to a specific region, present in both structures, that is predicted to act as allosteric site modulating the binding of the spike protein with ACE2.", "title": "Mapping active allosteric loci SARS-CoV Spike Proteins by means of Protein Contact Networks", "pid": "nrx9wqwg", "bm25_score": 218.68936157226562}, {"text": "This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2' spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles' heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried out suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding sites. The enzyme 11ß-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets.", "title": "COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles' heel conserved region to minimize probability of escape mutations and drug resistance", "pid": "8y4j510s", "bm25_score": 218.6876220703125}, {"text": "The rapid and escalating spread of SARS coronavirus 2 (SARS-CoV-2) poses an immediate public health emergency. The viral spike protein S binds ACE2 on host cells to initiate molecular events that release the viral genome intracellularly. Soluble ACE2 inhibits entry of both SARS and SARS-2 coronaviruses by acting as a decoy for S binding sites, and is a candidate for therapeutic, prophylactic and diagnostic development. Using deep mutagenesis, variants of ACE2 are identified with increased binding to the receptor binding domain of S. Mutations are found across the interface, in the N90-glycosylation motif, and at buried sites where they are predicted to enhance local folding and presentation of the interaction epitope. When single substitutions are combined, large increases in binding can be achieved. The mutational landscape offers a blueprint for engineering high affinity proteins and peptides that block receptor binding sites on S to meet this unprecedented challenge.", "title": "The sequence of human ACE2 is suboptimal for binding the S spike protein of SARS coronavirus 2", "pid": "jalijjmg", "bm25_score": 218.66098022460938}, {"text": "Abstract This paper continues a recent study of the spike protein sequence of the COVID-19 virus (SARS-CoV-2). It is also in part an introductory review to relevant computational techniques for tackling viral threats, using COVID-19 as an example. Q-UEL tools for facilitating access to knowledge and bioinformatics tools were again used for efficiency, but the focus in this paper is even more on the virus. Subsequence KRSFIEDLLFNKV of the S2′ spike glycoprotein proteolytic cleavage site continues to appear important. Here it is shown to be recognizable in the common cold coronaviruses, avian coronaviruses and possibly as traces in the nidoviruses of reptiles and fish. Its function or functions thus seem important to the coronaviruses. It might represent SARS-CoV-2 Achilles’ Heel, less likely to acquire resistance by mutation, as has happened in some early SARS vaccine studies discussed in the previous paper. Preliminary conformational analysis of the receptor (ACE2) binding site of the spike protein is carried suggesting that while it is somewhat conserved, it appears to be more variable than KRSFIEDLLFNKV. However compounds like emodin that inhibit SARS entry, apparently by binding ACE2, might also have functions at several different human protein binding studies. The enzyme 11β-hydroxysteroid dehydrogenase type 1 is again argued to be a convenient model pharmacophore perhaps representing an ensemble of targets, and it is noted that it occurs both in lung and alimentary tract. Perhaps it benefits the virus to block an inflammatory response by inhibiting the dehydrogenase, but a fairly complex web involves several possible targets.", "title": "COVID-19 Coronavirus spike protein analysis for synthetic vaccines, a peptidomimetic antagonist, and therapeutic drugs, and analysis of a proposed achilles’ heel conserved region to minimize probability of escape mutations and drug resistance", "pid": "xvfl7ycj", "bm25_score": 218.64418029785156}, {"text": "We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified thirteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.", "title": "Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2", "pid": "4hmecfi0", "bm25_score": 218.61892700195312}, {"text": "A novel coronavirus (SARS-coronavirus, SARS-CoV) was discovered in association with cases of severe acute respiratory syndrome (SARS) recently. The first step in coronavirus infection is binding of the viral spike protein to certain receptor on host cells. The spike protein is the main surface antigen of the coronavirus and there should be antibodies against spike protein in patients serum. Thus, to develop and expression protein fragment from spike protein gene are the purposes of this experiment. Partial spike gene fragments (751-1925 bp, 2005-3410 bp, 1-1925 bp and 32-3659 bp) and its intact gene were cloned into pET32 or pGEX vectors, and transformed into competent Escherichia coli BL21(DE3) (pLysS), respectively. 63, 78, 98, 160 and 164 kD fusion proteins were successfully expressed with amounts of 35%, 34%, 24%, 17% and 5% of total cell protein. The soluble parts of the cell crude extract were then partially purified by GST affinity chromatography.", "title": "[Expression and purification of recombinant SARS coronavirus spike protein].", "pid": "s2zn7k75", "bm25_score": 218.61569213867188}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus responsible for the COVID-19 pandemic. Despite recent advances in the structural elucidation of SARS-CoV-2 proteins and the complexes of the spike (S) proteins with the cellular receptor ACE2 or neutralizing antibodies, detailed architecture of the intact virus remains to be unveiled. Here we report the molecular assembly of the authentic SARS-CoV-2 virus using cryo-electron tomography (cryo-ET) and subtomogram averaging (STA). Native structures of the S proteins in both pre- and postfusion conformations were determined to average resolutions of 9-11 Å. Compositions of the N-linked glycans from the native spikes were analyzed by mass spectrometry, which revealed highly similar overall processing states of the native glycans to that of the recombinant glycoprotein glycans. The in situ architecture of the ribonucleoproteins (RNP) and its higher-order assemblies were revealed. These characterizations have revealed the architecture of the SARS-CoV-2 virus to an unprecedented resolution, and shed lights on how the virus packs its ~30 Kb long single-segmented RNA in the ~80 nm diameter lumen. Overall, the results unveiled the molecular architecture and assembly of the SARS-CoV-2 in native context.", "title": "Molecular architecture of the SARS-CoV-2 virus", "pid": "oo0pzspi", "bm25_score": 218.61221313476562}, {"text": "The SARS coronavirus (SARS-CoV) spike is the largest known viral spike molecule, and shares a similar function with all class 1 viral fusion proteins. Previous structural studies of membrane fusion proteins have largely used crystallography of static molecular fragments, in isolation of their transmembrane domains. In this study we have produced purified, irradiated SARS-CoV virions that retain their morphology, and are fusogenic in cell culture. We used cryo-electron microscopy and image processing to investigate conformational changes that occur in the entire spike of intact virions when they bind to the viral receptor, angiotensin-converting enzyme 2 (ACE2). We have shown that ACE2 binding results in structural changes that appear to be the initial step in viral membrane fusion, and precisely localized the receptor-binding and fusion core domains within the entire spike. Furthermore, our results show that receptor binding and subsequent membrane fusion are distinct steps, and that each spike can bind up to three ACE2 molecules. The SARS-CoV spike provides an ideal model system to study receptor binding and membrane fusion in the native state, employing cryo-electron microscopy and single-particle image analysis.", "title": "Conformational Reorganization of the SARS Coronavirus Spike Following Receptor Binding: Implications for Membrane Fusion", "pid": "mcsdem7y", "bm25_score": 218.59400939941406}, {"text": "SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is a novel coronavirus causing an outbreak of COVID-19 globally in the past six months. A relatively higher divergence on the spike protein of SASR-CoV-2 enables it to transmit across species efficiently. We particularly believe that the adaptive mutations of the receptor-binding domain (RBD) of spike protein in SARS-CoV-2 might be essential to its high transmissibility among humans. Thus here we collected 2,142 high-quality genome sequences of SARS-CoV-2 from 160 regions in over 50 countries and reconstructed their phylogeny, and also analyzed the interaction between the polymorphisms of spike protein and human ACE2 (hACE2). Phylogenetic analysis of SARS-CoV-2 and coronavirus in other hosts show SARS-CoV-2 is highly possible originated from Bat-CoV (RaTG13) found in horseshoe bat and a recombination event may occur on the spike protein of Pangolin-CoV to imbue it the ability to infect humans. Moreover, compared to the S gene of SARS-CoV-2, it is more conserved in the direct-binding sites of RBD and we noticed that spike protein of SARS-CoV-2 may under a consensus evolution to adapt to human hosts better. 3,860 amino acid mutations in spike protein RBD (T333-C525) of SARS-CoV-2 were simulated and their stability and affinity binding to hACE2 (S19-D615) were calculated. Our analysis indicates SARS-CoV-2 could infect humans from different populations with no preference, and a higher divergence in the spike protein of SARS-CoV-2 at the early stage of this pandemic may be a good indicator that could show the pathway of SARS-CoV-2 transmitting from the natural reservoir to human beings.", "title": "Binding Ability Prediction between Spike Protein and Human ACE2 Reveals the Adaptive Strategy of SARS-CoV-2 in Humans", "pid": "d3rrnjz2", "bm25_score": 218.59329223632812}, {"text": "The pandemic of SARS-CoV-2 has caused a high number of deaths in the world. To combat it, it is necessary to develop a better understanding of how the virus infects host cells. Infection normally starts with the attachment of the virus to cell-surface glycans like heparan sulfate (HS) and sialic acid-containing oligosaccharides. In this study, we examined and compared the binding of the subunits and spike (S) proteins of SARS-CoV-2 and SARS-CoV, MERS-CoV to these glycans. Our results revealed that the S proteins and subunits can bind to HS in a sulfation-dependent manner, the length of HS is not a critical factor for the binding, and no binding with sialic acid residues was detected. Overall, this work suggests that HS binding may be a general mechanism for the attachment of these coronaviruses to host cells, and supports the potential importance of HS in infection and in the development of antiviral agents against these viruses.", "title": "Binding of the SARS-CoV-2 Spike Protein to Glycans", "pid": "6e3j0pn7", "bm25_score": 218.5903778076172}, {"text": "SARS-CoV-2, the causative agent of COVID-19 pandemic, is an RNA virus prone to mutations. Interaction of SARS-CoV-2 Spike (S) protein with the host cell receptor, Angiotensin-I Converting Enzyme 2 (ACE2) is pivotal for attachment and entry of the virus. Yet, natural mutations acquired on S protein during the pandemic and their impact on viral infectivity, transmission dynamics and disease pathogenesis remains poorly understood. Here, we analysed 2952 SARS-CoV-2 genomes across the globe, and identified a total of 1815 non-synonymous mutations in the S-protein that fall into 54 different types. We observed that six of these distinct mutations were located in the Receptor Binding Domain (RBD) region that directly engages host ACE2. Molecular phylogenetic analysis revealed that these RBD mutations cluster into distinct phyletic clades among global subtypes of SARS-CoV-2 implying possible emergence of novel sublineages of the strain. Structure-guided homology modelling and docking analysis predicted key molecular rearrangements in the ACE2 binding interface of RBD mutants that could result in altered virus-host interactions. We propose that our findings could be significant in understanding disease dynamics and in developing vaccines, antibodies and therapeutics for COVID-19. Importance COVID-19 pandemic shows considerable variations in disease transmission and pathogenesis globally, yet reasons remain unknown. Our study identifies key S-protein mutations prevailing in SARS-CoV-2 strain that could alter viral attachment and infectivity. We propose that the interplay of these mutations could be one of the factors driving global variations in COVID-19 spread. In addition, the mutations identified in this study could be an important indicator in predicting efficacies of vaccines, antibodies and therapeutics that target SARS-CoV-2 RBD-ACE2 interface.", "title": "Structural and Functional Implications of Spike Protein Mutational Landscape in SARS-CoV-2", "pid": "40xsypzt", "bm25_score": 218.58493041992188}, {"text": "A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.", "title": "Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor", "pid": "m3j0kv0t", "bm25_score": 218.57391357421875}, {"text": "Abstract The SARS-CoV spike protein, a glycoprotein essential for viral entry, is a primary target for vaccine and drug development. Two peptides denoted HR-N(SN50) and HR-C(SC40), corresponding to the Leu/Ile/Val-rich heptad-repeat regions from the N-terminal and C-terminal segments of the SARS-CoV spike S2 sequence, respectively, were synthesized and predicted to form trimeric assembly of hairpin-like structures. The polyclonal antibodies produced by recombinant S2 protein were tested for antigenicity of the two heptad repeats. We report here the first crystallographic study of the SARS spike HR-N/HR-C complex. The crystal belongs to the triclinic space group P1 and the data-set collected to 2.98Å resolution showed noncrystallographic pseudo-222 and 3-fold symmetries. Based on these data, comparative modeling of the SARS-CoV fusion core was performed. The immunological and structural information presented herein may provide a more detailed understanding of the viral fusion mechanism as well as the development of effective therapy against SARS-CoV infection.", "title": "Immunological, structural, and preliminary X-ray diffraction characterizations of the fusion core of the SARS-coronavirus spike protein", "pid": "19h2i631", "bm25_score": 218.5691680908203}, {"text": "At the end of 2019, the SARS-CoV-2 induces an ongoing outbreak of pneumonia in China1, even more spread than SARS-CoV infection2. The entry of SARS-CoV into host cells mainly depends on the cell receptor (ACE2) recognition and spike protein cleavage-induced cell membrane fusion3,4. The spike protein of SARS-CoV-2 also binds to ACE2 with a similar affinity, whereas its spike protein cleavage remains unclear5,6. Here we show that an insertion sequence in the spike protein of SARS-CoV-2 enhances the cleavage efficiency, and besides pulmonary alveoli, intestinal and esophagus epithelium were also the target tissues of SARS-CoV-2. Compared with SARS-CoV, we found a SPRR insertion in the S1/S2 protease cleavage sites of SARS-CoV-2 spike protein increasing the cleavage efficiency by the protein sequence aligment and furin score calculation. Additionally, the insertion sequence facilitates the formation of an extended loop which was more suitable for protease recognition by the homology modeling and molicular docking. Furthermore, the single-cell transcriptomes identified that ACE2 and TMPRSSs are highly coexpressed in AT2 cells of lung, along with esophageal upper epithelial cells and absorptive enterocytes. Our results provide the bioinformatics evidence for the increased spike protein cleavage of SARS-CoV-2 and indicate its potential target cells.", "title": "The insert sequence in SARS-CoV-2 enhances spike protein cleavage by TMPRSS", "pid": "pm8usc55", "bm25_score": 218.5464324951172}, {"text": "Severe respiratory syndrome coronavirus 2 (SARS-CoV-2) infection presents an immense global health problem. Spike (S) protein of coronavirus is the primary determinant of its entry into the host as it consists of both receptor binding and fusion domain. While tissue tropism, host range, and pathogenesis of coronavirus are primarily controlled by the interaction of S protein with the cell receptor, it is possible that proteolytic activation of S protein by host cell proteases also plays a decisive role. The host-cell proteases have shown to be involved in the proteolysis of S protein and cleaving it into two functional subunits, S1 and S2, during the maturation process. In the present study, the interaction of S protein of SARS-CoV-2 with different host proteases like furin, cathepsin B, and plasmin has been analyzed. Incorporation of the furin cleavage site (R-R-A-R) in the S protein in SARS-CoV-2 has been studied by mutating the individual amino acid. Our results suggest the polytropic nature of the S protein of SARS-CoV-2. Our analysis indicated that a single amino acid substitution in the polybasic cleavage site of S protein perturb the binding of cellular proteases. This mutation study might help to generate an attenuated SARS-CoV-2. Besides, targeting of host proteases by inhibitors may result in a practical approach to stop the cellular spread of SARS-CoV-2 and to develop its antiviral.", "title": "Insight towards the effect of the multibasic cleavage site of SARS-CoV-2 spike protein on cellular proteases", "pid": "gcwecehu", "bm25_score": 218.5458221435547}, {"text": "The spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.", "title": "Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: Similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism", "pid": "vy1obqyp", "bm25_score": 218.5239715576172}, {"text": "The spread of COVID-19 caused by the SARS-CoV-2 outbreak has been growing since its first identification in December 2019. The publishing of the first SARS-CoV-2 genome made a valuable source of data to study the details about its phylogeny, evolution, and interaction with the host. Protein-protein binding assays have confirmed that Angiotensin-converting enzyme 2 (ACE2) is more likely to be the cell receptor through which the virus invades the host cell. In the present work, we provide an insight into the interaction of the viral spike Receptor Binding Domain (RBD) from different coronavirus isolates with host ACE2 protein. By calculating the binding energy score between RBD and ACE2, we highlighted the putative jump in the affinity from a progenitor form of SARS-CoV-2 to the current virus responsible for COVID-19 outbreak. Our result was consistent with previously reported phylogenetic analysis and corroborates the opinion that the interface segment of the spike protein RBD might be acquired by SARS-CoV-2 via a complex evolutionary process rather than a progressive accumulation of mutations. We also highlighted the relevance of Q493 and P499 amino acid residues of SARS-CoV-2 RBD for binding to human ACE2 and maintaining the stability of the interface. Moreover, we show from the structural analysis that it is unlikely for the interface residues to be the result of genetic engineering. Finally, we studied the impact of eight different variants located at the interaction surface of ACE2, on the complex formation with SARS-CoV-2 RBD. We found that none of them is likely to disrupt the interaction with the viral RBD of SARS-CoV-2.", "title": "Interaction of the spike protein RBD from SARS-CoV-2 with ACE2: similarity with SARS-CoV, hot-spot analysis and effect of the receptor polymorphism", "pid": "wynyrumi", "bm25_score": 218.5239715576172}, {"text": "The emergence and rapid worldwide spread of the novel coronavirus disease, COVID-19, has prompted concerted efforts to find successful treatments. The causative virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), uses its spike (S) protein to gain entry into host cells. Therefore, the S protein presents a viable target to develop a directed therapy. Here, we deployed an integrated artificial intelligence with molecular dynamics simulation approach to provide new details of the S protein structure. Based on a comprehensive structural analysis of S proteins from SARS-CoV-2 and previous human coronaviruses, we found that the protomer state of S proteins is structurally flexible. Without the presence of a stabilizing beta sheet from another protomer chain, two regions in the S2 domain and the hinge connecting the S1 and S2 subunits lose their secondary structures. Interestingly, the region in the S2 domain was previously identified as an immunodominant site in the SARS-CoV-1 S protein. We anticipate that the molecular details elucidated here will assist in effective therapeutic development for COVID-19.", "title": "Distinct Structural Flexibility within SARS-CoV-2 Spike Protein Reveals Potential Therapeutic Targets", "pid": "klb8oe9q", "bm25_score": 218.5194091796875}, {"text": "The coronavirus spike protein is a multifunctional molecular machine that mediates coronavirus entry into host cells. It first binds to a receptor on the host cell surface through its S1 subunit and then fuses viral and host membranes through its S2 subunit. Two domains in S1 from different coronaviruses recognize a variety of host receptors, leading to viral attachment. The spike protein exists in two structurally distinct conformations, prefusion and postfusion. The transition from prefusion to postfusion conformation of the spike protein must be triggered, leading to membrane fusion. This article reviews current knowledge about the structures and functions of coronavirus spike proteins, illustrating how the two S1 domains recognize different receptors and how the spike proteins are regulated to undergo conformational transitions. I further discuss the evolution of these two critical functions of coronavirus spike proteins, receptor recognition and membrane fusion, in the context of the corresponding functions from other viruses and host cells.", "title": "Structure, Function, and Evolution of Coronavirus Spike Proteins.", "pid": "cvp10nx0", "bm25_score": 218.50491333007812}, {"text": "The trimeric spike (S) protein of SARS-CoV-2 is the primary focus of most vaccine design and development efforts. Due to intrinsic instability typical of class I fusion proteins, S tends to prematurely refold to the post-fusion conformation, compromising immunogenic properties and prefusion trimer yields. To support ongoing vaccine development efforts, we report the structure-based design of soluble S trimers, with increased yields and stabilities, based on introduction of single point mutations and disulfide-bridges. We identify two regions in the S-protein critical for the protein’s stability: the heptad repeat region 1 of the S2 subunit and subunit domain 1 at the interface with S2. We combined a minimal selection of mostly interprotomeric mutations to create a stable S-closed variant with a 6.4-fold higher expression than the parental construct while no longer containing a heterologous trimerization domain. The cryo-EM structure reveals a correctly folded, predominantly closed pre-fusion conformation. Highly stable and well producing S protein and the increased understanding of S protein structure will support vaccine development and serological diagnostics.", "title": "Stabilizing the Closed SARS-CoV-2 Spike Trimer", "pid": "h90c721k", "bm25_score": 218.50413513183594}, {"text": "The current emergence of the novel coronavirus pandemic caused by SARS-CoV-2 demands the development of new therapeutic strategies to prevent rapid progress of mortalities. The coronavirus spike (S) protein, which facilitates viral attachment, entry and membrane fusion is heavily glycosylated and plays a critical role in the elicitation of the host immune response. The spike protein is comprised of two protein subunits (S1 and S2), which together possess 22 potential N-glycosylation sites. Herein, we report the glycosylation mapping on spike protein subunits S1 and S2 expressed on human cells through high resolution mass spectrometry. We have characterized the quantitative N-glycosylation profile on spike protein and interestingly, observed unexpected O-glycosylation modifications on the receptor binding domain (RBD) of spike protein subunit S1. Even though O-glycosylation has been predicted on the spike protein of SARS-CoV-2, this is the first report of experimental data for both the site of O-glycosylation and identity of the O-glycans attached on the subunit S1. Our data on the N- and O- glycosylation is strengthened by extensive manual interpretation of each glycopeptide spectra in addition to using bioinformatics tools to confirm the complexity of glycosylation in the spike protein. The elucidation of the glycan repertoire on the spike protein provides insights into the viral binding studies and more importantly, propels research towards the development of a suitable vaccine candidate.", "title": "Deducing the N- and O- glycosylation profile of the spike protein of novel coronavirus SARS-CoV-2", "pid": "6nkp2aov", "bm25_score": 218.4586944580078}, {"text": "The current emergence of the novel coronavirus pandemic caused by SARS-CoV-2 demands the development of new therapeutic strategies to prevent rapid progress of mortalities. The coronavirus spike (S) protein, which facilitates viral attachment, entry and membrane fusion is heavily glycosylated and plays a critical role in the elicitation of the host immune response. The spike protein is comprised of two protein subunits (S1 and S2), which together possess 22 potential N-glycosylation sites. Herein, we report the glycosylation mapping on spike protein subunits S1 and S2 expressed on human cells through high resolution mass spectrometry. We have characterized the quantitative N-glycosylation profile on spike protein and interestingly, observed unexpected O-glycosylation modifications on the receptor binding domain (RBD) of spike protein subunit S1. Even though O-glycosylation has been predicted on the spike protein of SARS-CoV-2, this is the first report of experimental data for both the site of O-glycosylation and identity of the O-glycans attached on the subunit S1. Our data on the N- and O-glycosylation is strengthened by extensive manual interpretation of each glycopeptide spectra in addition to using bioinformatics tools to confirm the complexity of glycosylation in the spike protein. The elucidation of the glycan repertoire on the spike protein provides insights into the viral binding studies and more importantly, propels research towards the development of a suitable vaccine candidate.", "title": "Deducing the N- and O- glycosylation profile of the spike protein of novel coronavirus SARS-CoV-2", "pid": "f0xsisdg", "bm25_score": 218.4586944580078}, {"text": "The trimeric SARS coronavirus (SARS-CoV) surface spike (S) glycoprotein consisting of three S1-S2 heterodimers binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition. Here, we report the structure of the SARS-CoV S glycoprotein in complex with its host cell receptor ACE2 revealed by cryo-electron microscopy (cryo-EM). The complex structure shows that only one receptor-binding domain of the trimeric S glycoprotein binds ACE2 and adopts a protruding “up” conformation. In addition, we studied the structures of the SARS-CoV S glycoprotein and its complexes with ACE2 in different in vitro conditions, which may mimic different conformational states of the S glycoprotein during virus entry. Disassociation of the S1-ACE2 complex from some of the prefusion spikes was observed and characterized. We also characterized the rosette-like structures of the clustered SARS-CoV S2 trimers in the postfusion state observed on electron micrographs. Structural comparisons suggested that the SARS-CoV S glycoprotein retains a prefusion architecture after trypsin cleavage into the S1 and S2 subunits and acidic pH treatment. However, binding to the receptor opens up the receptor-binding domain of S1, which could promote the release of the S1-ACE2 complex and S1 monomers from the prefusion spike and trigger the pre- to postfusion conformational transition.", "title": "Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2", "pid": "g28eq99t", "bm25_score": 218.44488525390625}, {"text": "Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2002 as a highly transmissible pathogenic human betacoronavirus. The viral spike glycoprotein (S) utilizes angiotensin-converting enzyme 2 (ACE2) as a host protein receptor and mediates fusion of the viral and host membranes, making S essential to viral entry into host cells and host species tropism. As SARS-CoV enters host cells, the viral S is believed to undergo a number of conformational transitions as it is cleaved by host proteases and binds to host receptors. We recently developed stabilizing mutations for coronavirus spikes that prevent the transition from the pre-fusion to post-fusion states. Here, we present cryo-EM analyses of a stabilized trimeric SARS-CoV S, as well as the trypsin-cleaved, stabilized S, and its interactions with ACE2. Neither binding to ACE2 nor cleavage by trypsin at the S1/S2 cleavage site impart large conformational changes within stabilized SARS-CoV S or expose the secondary cleavage site, S2′.", "title": "Stabilized coronavirus spikes are resistant to conformational changes induced by receptor recognition or proteolysis", "pid": "gz38qibg", "bm25_score": 218.44424438476562}, {"text": "COVID-19 is a highly contagious disease caused by a novel coronavirus SARS-CoV-2. The interaction between SARS-CoV-2 spike protein and the host cell surface receptor ACE2 is responsible for mediating SARS-CoV-2 infection. By analyzing the spike-hACE2 interacting surface, we predicted many hot spot residues that make major contributions to the binding affinity. Mutations on most of these residues are likely to be deleterious, leading to less infectious virus strains that may suffer from negative selection. Meanwhile, several residues with mostly advantageous mutations have been predicted. It is more probable that mutations on these residues increase the transmission ability of the virus by enhancing spike-hACE2 interaction. So far, only a limited number of mutations has been reported in this region. However, the list of hot spot residues with predicted downstream effects from this study can still serve as a tracking list for SARS-CoV-2 evolution studies. Coincidentally, one advantageous mutation, p.476G>S, started to surge in the last couple of weeks based on the data submitted to the public domain, indicating that virus strains with increased transmission ability may have already spread.", "title": "SARS-CoV-2 Spike Glycoprotein Receptor Binding Domain is Subject to Negative Selection with Predicted Positive Selection Mutations", "pid": "m6f3soiz", "bm25_score": 218.42575073242188}, {"text": "Many of the SARS-CoV-2 proteins have related counterparts across the Severe Acute Respiratory Syndrome (SARS-CoV) family. One such protein is non-structural protein 9 (Nsp9), which is thought to mediate viral replication, overall virulence, and viral genomic RNA reproduction. We sought to better characterize the SARS-CoV-2 Nsp9 and subsequently solved its X-ray crystal structure, in an apo form and, unexpectedly, in a peptide-bound form with a sequence originating from a rhinoviral 3C protease sequence (LEVL). The SARS-CoV-2 Nsp9 structure revealed the high level of structural conservation within the Nsp9 family. The exogenous peptide binding site is close to the dimer interface and impacted the relative juxtapositioning of the monomers within the homodimer. We have established a protocol for the production of SARS-CoV-2 Nsp9, determined its structure, and identified a peptide-binding site that warrants further study to understanding Nsp9 function.", "title": "Crystal Structure of the SARS-CoV-2 Non-structural Protein 9, Nsp9", "pid": "8sy4j2py", "bm25_score": 218.42074584960938}, {"text": "We constructed complex models of SARS-CoV-2 spike protein binding to pangolin or human ACE2, the receptor for virus transmission, and estimated the binding free energy changes using molecular dynamics simulation. SARS-CoV-2 can bind to both pangolin and human ACE2, but has a significantly lower binding affinity for pangolin ACE2 due to the increased binding free energy (9.5 kcal mol-1). Human ACE2 is among the most polymorphous genes, for which we identified 317 missense single-nucleotide variations (SNVs) from the dbSNP database. Three SNVs, E329G (rs143936283), M82I (rs267606406) and K26R (rs4646116), had a significant reduction in binding free energy, which indicated higher binding affinity than wild-type ACE2 and greater susceptibility to SARS-CoV-2 infection for people with them. Three other SNVs, D355N (rs961360700), E37K (rs146676783) and I21T (rs1244687367), had a significant increase in binding free energy, which indicated lower binding affinity and reduced susceptibility to SARS-CoV-2 infection.", "title": "Molecular simulation of SARS-CoV-2 spike protein binding to pangolin ACE2 or human ACE2 natural variants reveals altered susceptibility to infection.", "pid": "d4rekhom", "bm25_score": 218.4197540283203}, {"text": "Abstract The coronavirus spike glycoprotein is a class I membrane fusion protein with two characteristic heptad repeat regions (HR1 and HR2) in its ectodomain. Here, we report the X-ray structure of a previously characterized HR1/HR2 complex of the severe acute respiratory syndrome coronavirus spike protein. As expected, the HR1 and HR2 segments are organized in antiparallel orientations within a rod-like molecule. The HR1 helices form an exceptionally long (120 Å) internal coiled coil stabilized by hydrophobic and polar interactions. A striking arrangement of conserved asparagine and glutamine residues of HR1 propagates from two central chloride ions, providing hydrogen-bonding “zippers” that strongly constrain the path of the HR2 main chain, forcing it to adopt an extended conformation at either end of a short HR2 α-helix.", "title": "Central ions and lateral asparagine/glutamine zippers stabilize the post-fusion hairpin conformation of the SARS coronavirus spike glycoprotein", "pid": "3laov764", "bm25_score": 218.40052795410156}, {"text": "Summary Many of the SARS-CoV-2 proteins have related counterparts across the Severe Acute Respiratory Syndrome (SARS-CoV) family. One such protein is non-structural protein 9 (Nsp9), which is thought to mediate viral replication, overall virulence and viral genomic RNA reproduction. We sought to better characterise the SARS-CoV-2 Nsp9 and subsequently solved its X-ray crystal structure, in an apo-form and, unexpectedly, in a peptide-bound form with a sequence originating from a rhinoviral 3C protease sequence (LEVL). The SARS-CoV-2 Nsp9 structure revealed the high level of structural conservation within the Nsp9 family. The exogenous peptide binding site is close to the dimer interface and impacted the relative juxtapositioning of the monomers within the homodimer. We have established a protocol for the production of SARS-CoV-2 Nsp9, determined its structure and identified a peptide-binding site that warrants further study to understanding Nsp9 function.", "title": "Crystal structure of the SARS-CoV-2 non-structural protein 9, Nsp9", "pid": "e0o2lbbw", "bm25_score": 218.39495849609375}, {"text": "SARS-CoV-2 spike protein (S) is associated with the entry of virus inside the host cell by recruiting its loop dominant receptor binding domain (RBD) and interacting with the host ACE2 receptor. Our study deploying a two-tier approach encompassing evolutionary and structural analysis provides a comprehensive picture of the RBD, which could be of potential use for better understanding the RBD and address its druggability issues. Resorting to an ensemble of sequence space exploratory tools including co-evolutionary analysis and deep mutational scans we provide a quantitative insight into the evolutionarily constrained subspace of the RBD sequence space. Guided by structure network analysis and Monte Carlo simulation we highlight regions inside the RBD, which are critical for providing structural integrity and conformational flexibility of the binding cleft. We further deployed fuzzy C-means clustering by plugging the evolutionary and structural features of discrete structure blocks of RBD to understand which structure blocks share maximum overlap based on their evolutionary and structural features. Deploying this multi-tier interlinked approach, which essentially distilled the evolutionary and structural features of RBD, we highlight discrete region, which could be a potential druggable pocket thereby destabilizing the structure and addressing evolutionary routes.", "title": "An exploration of the SARS-CoV-2 spike receptor binding domain (RBD) – a complex palette of evolutionary and structural features", "pid": "fa96qw24", "bm25_score": 218.3925018310547}, {"text": "The 2019 novel severe respiratory syndrome coronavirus-2 (SARS-CoV-2) outbreak has caused a large number of deaths with thousands of confirmed cases worldwide. The present study followed computational approaches to identify B- and T-cell epitopes for spike glycoprotein of SARS-CoV-2 by its interactions with the human leukocyte antigen alleles. We identified twenty-four peptide stretches on the SARS-CoV-2 spike protein that are well conserved among the reported strains. The S protein structure further validated the presence of predicted peptides on the surface. Out of which twenty are surface exposed and predicted to have reasonable epitope binding efficiency. The work could be useful for understanding the immunodominant regions in the surface protein of SARS-CoV-2 and could potentially help in designing some peptide-based diagnostics.", "title": "Understanding the B and T cells epitopes of spike protein of severe respiratory syndrome coronavirus-2: A computational way to predict the immunogens", "pid": "ch004jxy", "bm25_score": 218.38462829589844}, {"text": "The recent emergence of a novel coronavirus associated with an ongoing outbreak of pneumonia (Covid-2019) resulted in infections of more than 72,000 people and claimed over 1,800 lives. Coronavirus spike (S) glycoprotein trimers promote entry into cells and are the main target of the humoral immune response. We show here that SARS-CoV-2 S mediates entry in VeroE6 cells and in BHK cells transiently transfected with human ACE2, establishing ACE2 as a functional receptor for this novel coronavirus. We further demonstrate that the receptor-binding domains of SARS-CoV-2 S and SARS-CoV S bind with similar affinities to human ACE2, which correlates with the efficient spread of SARS-CoV-2 among humans. We found that the SARS-CoV-2 S glycoprotein harbors a furin cleavage site at the boundary between the S1/S2 subunits, which is processed during biogenesis and sets this virus apart from SARS-CoV and other SARS-related CoVs. We determined a cryo-electron microscopy structure of the SARS-CoV-2 S ectodomain trimer, demonstrating spontaneous opening of the receptor-binding domain, and providing a blueprint for the design of vaccines and inhibitors of viral entry. Finally, we demonstrate that SARS-CoV S murine polyclonal sera potently inhibited SARS-CoV-2 S-mediated entry into target cells, thereby indicating that cross-neutralizing antibodies targeting conserved S epitopes can be elicited upon vaccination.", "title": "Structure, function and antigenicity of the SARS-CoV-2 spike glycoprotein", "pid": "yaow639d", "bm25_score": 218.3826141357422}, {"text": "Here we have generated 3D structures of glycoforms of the spike (S) glycoprotein from SARS-CoV-2, based on reported 3D structures and glycomics data for the protein produced in HEK293 cells. We also analyze structures for glycoforms representing those present in the nascent glycoproteins (prior to enzymatic modifications in the Golgi), as well as those that are commonly observed on antigens present in other viruses. These models were subjected to molecular dynamics (MD) simulation to determine the extent to which glycan microheterogeneity impacts the antigenicity of the S glycoprotein. Lastly, we have identified peptides in the S glycoprotein that are likely to be presented in human leukocyte antigen (HLA) complexes, and discuss the role of S protein glycosylation in potentially modulating the adaptive immune response to the SARS-CoV-2 virus or to a related vaccine. The 3D structures show that the protein surface is extensively shielded from antibody recognition by glycans, with the exception of the ACE2 receptor binding domain, and also that the degree of shielding is largely insensitive to the specific glycoform. Despite the relatively modest contribution of the glycans to the total molecular weight (17% for the HEK293 glycoform) the level of surface shielding is disproportionately high at 42%.", "title": "Analysis of the SARS-CoV-2 spike protein glycan shield: implications for immune recognition", "pid": "rwlpkf7n", "bm25_score": 218.37379455566406}, {"text": "Many human viral diseases are a consequence of a zoonotic event. Some of the diseases caused by these zoonotic events have affected millions of people around the world, some of which have resulted in high rates of morbidity/mortality in humans. Changes in the viral proteins that function as ligands of the host receptor may promote the spillover between species. The most recent of these zoonotic events that have caused an ongoing epidemic of high magnitude is the Covid-19 epidemics caused by SARS-CoV-2. The aim of this study was to determine the mutation(s) in the sequence of the spike protein of the SARS-CoV-2 that might be favoring human to human transmission. An in silico approach was performed, and changes were detected in the S1 subunit of the receptor-binding domain of spike. The observed changes have significant effect on SARS-CoV-2 spike/ACE2 interaction and produce a reduction in the binding energy, compared to the one of the Bat-CoV to this receptor. The data presented in this study suggest a higher affinity of the SARS-Cov-2 spike protein to the human ACE2 receptor, compared to the one of Bat-CoV spike and ACE2. This could be the cause of the rapid viral spread of SARS-CoV-2 in humans.", "title": "Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: An in silico analysis", "pid": "ldf7uso2", "bm25_score": 218.37158203125}, {"text": "The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected in S, 12 variations were located at the N-terminal domain (NTD) and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin-converting enzyme 2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "title": "Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach", "pid": "c5fygzvz", "bm25_score": 218.36245727539062}, {"text": "Summary The pandemic coronavirus SARS-CoV-2 threatens public health worldwide. The viral spike protein mediates SARS-CoV-2 entry into host cells and harbors a S1/S2 cleavage site containing multiple arginine residues (multibasic) not found in closely related animal coronaviruses. However, the role of this multibasic cleavage site in SARS-CoV-2 infection is unknown. Here, we report that the cellular protease furin cleaves the spike protein at the S1/S2 site and that cleavage is essential for S-protein-mediated cell-cell fusion and entry into human lung cells. Moreover, optimizing the S1/S2 site increased cell-cell, but not virus-cell, fusion, suggesting that the corresponding viral variants might exhibit increased cell-cell spread and potentially altered virulence. Our results suggest that acquisition of a S1/S2 multibasic cleavage site was essential for SARS-CoV-2 infection of humans and identify furin as a potential target for therapeutic intervention.", "title": "A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells", "pid": "1n0qw2a5", "bm25_score": 218.36195373535156}, {"text": "The Spike is a hallmark coronavirus protein that determines virus fusion, entry and spread in the host, and thus holds clues for the rapid spread of the SARS-CoV-2 pandemic. We have investigated the Spike from six β-coronaviruses, including the SARS-CoV-2, and find that their surface-exposed fusion peptides constituting the fusion loop are spatially organized contiguous to each other to work synergistically for triggering the virus-host membrane fusion process. The SARS-CoV-2 fusion peptides have unique physicochemical properties, accrued in part from the presence of consecutive prolines that impart backbone rigidity which aids the virus fusogenicity. The specific contribution of these prolines has been inferred from comparative studies of their deletion mutant in a fellow murine β-coronavirus MHV-A59 that show significantly diminished fusogenicity in vitro and associated pathogenesis in vivo. The Spike cleavage-linked priming and fusogenic conformational transition steered by the fusion loop may be critical for the SARS-CoV-2 spread. Summary The Spike protein on the SARS-CoV-2 surface is the prime mediator of COVID-191 because of its central role in virus-host attachment, virus-entry, and virus-spread2. The contagious nature of SARS-CoV-2 infection has been attributed to dense glycosylation of the Spike glycoprotein3, its high affinity of binding to human ACE2 receptor4, and cleavage5. While these may be imperative, it does not explain the uncontrolled infectivity. Here we show that properties of the fusion peptides constituting the fusion loop of SARS-CoV-2 Spike that triggers the virus fusion, distinguishes it from the other five β-coronaviruses. The SARS-CoV-2 Spike trimer surface is relatively more hydrophobic, including the surface contributed by the fusion peptides. The fusion peptides are structurally rigid owing to its consecutive prolines, aromatic/hydrophobic clusters, a stretch of consecutive β-branched amino acids, and the hydrogen bonds. The role of rigidity accrued from the presence of consecutive prolines contributing to virus fusogenicity can be deciphered from our previous murine β-coronavirus, MHV-A59 studies6. The synergy brought about by the global location of the surface exposed fusion peptides, their physicochemical features, and the fusogenic conformational transition appears to drive the fusion process, which may explain the severity of the infection and widespread nature of the COVID-19 pandemic.", "title": "Spike protein fusion loop controls SARS-CoV-2 fusogenicity and infectivity", "pid": "7xd0msyk", "bm25_score": 218.3529052734375}, {"text": "The COVID-19 caused by SARS-CoV-2 has spread globally and caused tremendous loss of lives and properties, and it is of utmost urgency to understand its propagation process and to find ways to slow down the epidemic. In this work, we used a coarse-grained model to calculate the binding free energy of SARS-CoV-2 or SARS-CoV to their human receptor ACE2. The investigation of the free energy contribution of the interacting residues indicates that the residues located outside the receptor binding domain are the source of the stronger binding of the novel virus. Thus, the current results suggest that the essential evolution of SARS-CoV-2 happens remotely from the binding domain at the spike protein trimeric body. Such evolution may facilitate the conformational change and the infection process that occurs after the virus is bound to ACE2. By studying the binding pattern between SARS-CoV antibody m396 and SARS-CoV-2, it is found that the remote energetic contribution is missing, which might explain the absence of cross-reactivity of such antibodies.", "title": "Critical Differences between the Binding Features of the Spike Proteins of SARS-CoV-2 and SARS-CoV", "pid": "chl7ykkc", "bm25_score": 218.329833984375}, {"text": "Novel coronavirus 2019 (2019-nCoV), also known as SARS-CoV-2), leads high morbidity and mortality in global epidemics. Four structural proteins (surface glycoprotein (QIQ22760.1), envelop glycoprotein (QIQ22762.1), nucleocapsid phosphoprotein (QIQ22768.1) and membrane glycoprotein (QIQ22763.1)) of SARS-CoV-2 are extracted from the NCBI database and further analyzed with ExPASy ProtParam tool. Lucien is the highest in envelope, surface and membrane glycoprotein that is an optimal environment for rapid virus fixation on host cell's surface to the receptor molecule. Transmembrane region prediction was performed by SOSUI server. For all structural proteins, except nucleocapsid Phosphoprotein, the trans-membrane prediction indicates that the virus can enter the host easily. Domain analysis was done by SMART tool. Domain information helps in the function of the viral protein. Lastly, the 3D structure prediction was carried out by Swiss Model and the result validation was achieved by PROCHECK. Such models are the starting point of the community for structural drug and vaccine designs as well as virtual computational screening.", "title": "Bioinformatics Study on Structural Proteins of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) For Better Understanding the Vaccine Development", "pid": "ien7z5gd", "bm25_score": 218.3151397705078}, {"text": "Coronavirus disease 2019 (COVID-19), caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. The viral spike protein binds the host receptor angiotensin-converting enzyme 2 (ACE2) via the receptor-binding domain (RBD), and thus is believed to be a major target to block viral entry. Both SARS-CoV-2 and SARS-CoV share this mechanism. Here we functionally analyzed the key amino acid residues located within receptor binding motif of RBD that may interact with human ACE2 and available neutralizing antibodies. The in vivo experiments showed that immunization with either the SARS-CoV RBD or SARS-CoV-2 RBD was able to induce strong clade-specific neutralizing antibodies in mice; however, the cross-neutralizing activity was much weaker, indicating that there are distinct antigenic features in the RBDs of the two viruses. This finding was confirmed with the available neutralizing monoclonal antibodies against SARS-CoV or SARS-CoV-2. It is worth noting that a newly developed SARS-CoV-2 human antibody, HA001, was able to neutralize SARS-CoV-2, but failed to recognize SARS-CoV. Moreover, the potential epitope residues of HA001 were identified as A475 and F486 in the SARS-CoV-2 RBD, representing new binding sites for neutralizing antibodies. Overall, our study has revealed the presence of different key epitopes between SARS-CoV and SARS-CoV-2, which indicates the necessity to develop new prophylactic vaccine and antibody drugs for specific control of the COVID-19 pandemic although the available agents obtained from the SARS-CoV study are unneglectable.", "title": "Key residues of the receptor binding motif in the spike protein of SARS-CoV-2 that interact with ACE2 and neutralizing antibodies", "pid": "73inqtb9", "bm25_score": 218.31295776367188}, {"text": "Spike protein is one of the major structural proteins of severe acute respiratory syndrome-coronavirus. It is essential for the interaction of the virons with host cell receptors and subsequent fusion of the viral envelop with host cell membrane to allow infection. Some spike proteins of coronavirus, such as MHV, HCoV-OC43, AIBV and BcoV, are proteolytically cleaved into two subunits, S1 and S2. In contrast, TGV, FIPV and HCoV-229E are not. Many studies have shown that the cleavage of spike protein seriously affects its function. In order to investigate the maturation and proteolytic processing of the S protein of SARS CoV, we generated S1 and S2 subunit specific antibodies (Abs) as well as N, E and 3CL protein-specific Abs. Our results showed that the antibodies could efficiently and specifically bind to their corresponding proteins from E.coli expressed or lysate of SARS-CoV infected Vero-E6 cells by Western blot analysis. Furthermore, the anti-S1 and S2 Abs were proved to be capable of binding to SARS CoV under electron microscope observation. When S2 Ab was used to perform immune precipitation with lysate of SARS-CoV infected cells, a cleaved S2 fragment was detected with S2-specific mAb by Western blot analysis. The data demonstrated that the cleavage of S protein was observed in the lysate, indicating that proteolytic processing of S protein is present in host cells.", "title": "The spike protein of severe acute respiratory syndrome (SARS) is cleaved in virus infected Vero-E6 cells", "pid": "fy1lqk00", "bm25_score": 218.28555297851562}, {"text": "The pandemic coronavirus SARS-CoV-2 threatens public health worldwide. The viral spike protein mediates SARS-CoV-2 entry into host cells and harbors a S1/S2 cleavage site containing multiple arginine residues (multibasic) not found in closely related animal coronaviruses. However, the role of this multibasic cleavage site in SARS-CoV-2 infection is unknown. Here, we report that the cellular protease furin cleaves the spike protein at the S1/S2 site and that cleavage is essential for S-protein-mediated cell-cell fusion and entry into human lung cells. Moreover, optimizing the S1/S2 site increased cell-cell, but not virus-cell, fusion, suggesting that the corresponding viral variants might exhibit increased cell-cell spread and potentially altered virulence. Our results suggest that acquisition of a S1/S2 multibasic cleavage site was essential for SARS-CoV-2 infection of humans and identify furin as a potential target for therapeutic intervention.", "title": "A Multibasic Cleavage Site in the Spike Protein of SARS-CoV-2 Is Essential for Infection of Human Lung Cells", "pid": "twtt9wtd", "bm25_score": 218.26431274414062}, {"text": "Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19) has rapidly spread to the entire world within a few months. The origin of SARS-CoV-2 has been related to the lineage B Betacoronavirus SARS-CoV and SARS-related coronaviruses found in bats. Early characterizations of the SARS-CoV-2 genome revealed the existence of a distinct 4 amino acid insert within the spike (S) protein (underlined, SPRRAR↓S), at the S1/S2 site located at the interface between the S1 receptor binding subunit and the S2 fusion subunit. Notably, this insert appears to be a distinguishing feature among SARS-related sequences and introduces a potential cleavage site for the protease furin. Here, we investigate the potential role of this novel S1/S2 cleavage site and present direct biochemical evidence for proteolytic processing by a variety of proteases. We discuss these findings in the context of the origin of SARS-CoV-2, viral stability and transmission.", "title": "Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 site", "pid": "on70zzn0", "bm25_score": 218.26353454589844}, {"text": "The recent severe acute respiratory syndrome, known as Corona Virus Disease 2019 (COVID-19) has spread so much rapidly and severely to induce World Health Organization (WHO) to declare state of emergency over the new coronavirus SARS-CoV-2 pandemic. While several countries have chosen the almost complete lock-down for slowing down SARS-CoV-2 spread, scientific community is called to respond to the devastating outbreak by identifying new tools for diagnosis and treatment of the dangerous COVID-19. With this aim we performed an in silico comparative modeling analysis, which allows to gain new insights about the main conformational changes occurring in the SARS-CoV-2 spike protein, at the level of the receptor binding domain (RBD), along interactions with human cells angiotensin converting enzyme 2 (ACE2) receptor, that favour human cell invasion. Furthermore, our analysis provides i) an ideal pipeline to identify already characterized antibodies that might target SARS-CoV-2 spike RBD, for preventing interactions with the human ACE2, and ii) instructions for building new possible neutralizing antibodies, according to chemical/physical space restraints and complementary determining regions (CDR) mutagenesis of the identified existing antibodies. The proposed antibodies show in silico a high affinity for SARS-CoV-2 spike RBD and can be used as reference antibodies also for building new high affinity antibodies against present and future coronavirus able to invade human cells through interactions of their spike proteins with the human ACE2. More in general, our analysis provides indications for the set-up of the right biological molecular context for investigating spike RBD-ACE2 interactions for the development of new vaccines, diagnosis kits and other treatments based on the usage or the targeting of SARS-CoV-2 spike protein.", "title": "Protein structure analysis of the interactions between SARS-CoV-2 spike protein and the human ACE2 receptor: from conformational changes to novel neutralizing antibodies", "pid": "mswmkgl4", "bm25_score": 218.25523376464844}, {"text": "There is a well-known and established link between high lipopolysaccharide (LPS) levels in blood and the metabolic syndrome (MS). MS is a risk factor for developing severe COVID-19 and acute respiratory distress syndrome (ARDS). Here we define an interaction between SARS-CoV-2 Spike (S) protein and LPS and its link to aggravated inflammation in vitro and in vivo. Electrophoresis under native conditions demonstrated that SARS-CoV-2 S protein binds to Escherichia coli LPS, forming high molecular weight aggregates. Microscale thermophoresis analysis further defined the interaction, having a KD of ~47 nM, similar to the observed affinity between LPS and the human receptor CD14. Moreover, S protein, when combined with low levels of LPS, boosted nuclear factor-kappa B (NF-κB) and cytokine responses in monocytic THP-1 cells and human blood, respectively. In an experimental model of localized inflammation, employing NF-κB reporter mice and in vivo bioimaging, S protein in conjunction with LPS significantly increased the inflammatory response when compared with S protein and LPS alone. Apart from providing information on LPS as a ligand for S protein, our results are of relevance for studies on comorbidities involving bacterial endotoxins, such as the MS, or co-existing acute and chronic infections in COVID-19 patients.", "title": "SARS-CoV-2 Spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity", "pid": "30dr8z9k", "bm25_score": 218.24415588378906}, {"text": "Abstract The S1 and S2 subunits of the spike glycoprotein of the coronavirus which is responsible for the severe acute respiratory syndrome (SARS) have been modelled, even though the corresponding amino acid sequences were not suitable for tertiary structure predictions with conventional homology and/or threading procedures. An indirect search for a protein structure to be used as a template for 3D modelling has been performed on the basis of the genomic organisation similarity generally exhibited by coronaviruses. The crystal structure of Clostridium botulinum neurotoxin B appeared to be structurally adaptable to human and canine coronavirus spike protein sequences and it was successfully used to model the two subunits of SARS coronavirus spike glycoprotein. The overall shape and the surface hydrophobicity of the two subunits in the obtained models suggest the localisation of the most relevant regions for their activity.", "title": "Molecular modelling of S1 and S2 subunits of SARS coronavirus spike glycoprotein", "pid": "imyfo83x", "bm25_score": 218.23207092285156}, {"text": "Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS is a novel coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I transmembrane glycoprotein that mediates initial host binding via the cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the subsequent membrane fusion events required for cell entry. Here we report the crystal structure of the S1 receptor binding domain (RBD) in complex with a neutralizing antibody, 80R, at 2.3 A resolution, as well as the structure of the uncomplexed S1 RBD at 2.2 A resolution. We show that the 80R-binding epitope on the S1 RBD overlaps very closely with the ACE2-binding site, providing a rationale for the strong binding and broad neutralizing ability of the antibody. We provide a structural basis for the differential effects of certain mutations in the spike protein on 80R versus ACE2 binding, including escape mutants, which should facilitate the design of immunotherapeutics to treat a future SARS outbreak. We further show that the RBD of S1 forms dimers via an extensive interface that is disrupted in receptor- and antibody-bound crystal structures, and we propose a role for the dimer in virus stability and infectivity.", "title": "Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R.", "pid": "eara96ch", "bm25_score": 218.20986938476562}, {"text": "Many of the proteins produced by SARS-CoV-2 have related counterparts across the Severe Acute Respiratory Syndrome (SARS-CoV) family. One such protein is non-structural protein 9 (Nsp9), which is thought to mediate both viral replication and virulence. Current understanding suggests that Nsp9 is involved in viral genomic RNA reproduction. Nsp9 is thought to bind RNA via a fold that is unique to this class of betacoronoaviruses although the molecular basis for this remains ill-defined. We sought to better characterise the SARS-CoV-2 Nsp9 protein and subsequently solved its X-ray crystal structure, in an apo-form and, unexpectedly, in a peptide-bound form with a sequence originating from a rhinoviral 3C protease sequence (LEVL). The structure of the SARS-CoV-2 Nsp9 revealed the high level of structural conservation within the Nsp9 family. The exogenous peptide binding site is close to the dimer interface and impacted on the relative juxtaposition of the monomers within the homodimer. Together we have established a protocol for the production of SARS-CoV-2 Nsp9, determined its structure and identified a peptide-binding site that may warrant further study from the perspective of understanding Nsp9 function.", "title": "Crystal structure of the SARS-CoV-2 non-structural protein 9, Nsp9", "pid": "beoseizn", "bm25_score": 218.1976318359375}, {"text": "The causative agent of severe acute respiratory syndrome (SARS) has been identified as SARS-associated coronavirus (SARS-CoV). To evaluate the molecular mechanisms involved in the viral infection, in this study, we investigated the role of SARS-CoV Spike (S) protein in the regulation of cyclooxygenase-2 (COX-2). Expression of COX-2 stimulated by the S protein was verified by RT-PCR and western blot assay. To explore the relationship between S and COX-2, we constructed a series of plasmids containing truncated N-terminal fragments of the SARS-CoV S gene (designated from Sa to Si), which encoded truncated S proteins, and investigated whether these truncated proteins could induce effective expression of COX-2 in 293T cells. Our results showed that S(d) that encoded a truncated S protein with 422 amino acid residues (from 1 to 422 aa), a part of 672 amino-acid S1 subunit is crucial for the induction of COX-2 expression. Immunofluorescence examinations also give the evidence that these N terminal 422 amino acids of the S protein were also required for the correct localization of the protein. We also compared S protein sequences of SARS-CoV isolated during the SARS break with that from palm civets, a possible source of SARS-CoV found in humans. S protein residues (344, 360), which mutated in the epitome from palm civet to human being were characterized in 3D modeling of 252–375 amino acid fragment. Collectively, these results indicate that S protein of SARS-CoV induces the expression of COX-2 and an N-terminal fragment of the Spike protein is crucial for the induction. Our finding may provide clue for the induction of inflammation by SARS-CoV and cast insight into the severity of the SARS epidemic.", "title": "Amino acids 1 to 422 of the spike protein of SARS associated coronavirus are required for induction of cyclooxygenase-2", "pid": "2d7l26tl", "bm25_score": 218.1880340576172}, {"text": "One notable feature of the SARS-CoV-2 genome, the spike (S) protein of SARS-CoV-2 has a polybasic furin cleavage site (FCS) at its S1-S2 boundary through the insertion of 12 nucleotides encoding four amino acid residues PRRA. Quite intriguingly, this polybasic FCS is absent in coronaviruses of the same clade as SARS-CoV-2. Thus, with currently available experimental structural data for S protein, this short article presents a set of comprehensive structural characterization of the insertion of FCS into S protein, and argues against a hypothesis of the origin of SARS-CoV-2 from purposeful manipulation: (1), the inserted FCS is spatially located at a random coil loop region, mostly distantly solvent-exposed (instead of deeply buried), with no structural proximity to the other part of the S protein; (2), the insertion of FCS itself does not alter, neither stabilize nor de-stabilize, the three-dimensional structure of S; (3), the net result here is the insertion of a furin cleavage site into S protein, whose S1 and S2 subunits will still be strongly electrostatically bonded together from a structural and biophysical point of view, even if the polybasic FCS is actually cleaved by furin protease before or after viral cell entry.", "title": "Delving deep into the structural aspects of a furin cleavage site inserted into the spike protein of SARS-CoV-2: A structural biophysical perspective", "pid": "30bc6f4r", "bm25_score": 218.184326171875}, {"text": "A novel and highly pathogenic coronavirus (SARS-CoV-2) has caused an outbreak in Wuhan city, Hubei province of China since December 2019, and soon spread nationwide and spilled over to other countries around the world1-3. To better understand the initial step of infection at an atomic level, we determined the crystal structure of the SARS-CoV-2 spike receptor-binding domain (RBD) bound to the cell receptor ACE2 at 2.45 Å resolution. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also utilizes ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are critical for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly argue for convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies targeting the RBD are also analysed with the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.", "title": "Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor.", "pid": "h2zpl0qt", "bm25_score": 218.18211364746094}, {"text": "The newly identified SARS-CoV-2 has now been reported from around 183 countries with more than a million confirmed human cases including more than 68000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins have gotten substantial attention recently. Spike glycoprotein is widely considered as a possible target to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment tools. In this study, 483 unique variations have been identified among the genomes including 25 non-synonymous mutations and one deletion in the spike protein of SARS-CoV-2. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction with receptor molecules. In addition, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on our findings, potential inhibitors can be designed and tested targeting these proposed sites of variation.", "title": "Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach", "pid": "vf32wxkx", "bm25_score": 218.17770385742188}, {"text": "The spike (S) glycoprotein of severe acute respiratory syndrome coronavirus (SARS-CoV) is a major target in the development of diagnostic assays and vaccines, but its antigenic and immunogenic properties remain unclear. Seven SARS-CoV spike proteins (S, SQ, S1, RBD, S2, S2Q, and CX) were generated using the modified vaccinia virus (Tiantan strain) as a vector, and their antigenicity and immunogenicity were evaluated. The secreted SQ protein in which the transmembrane domain was deleted, as well as the full-length spike protein, showed the most potential to induce the production of neutralizing antibody (nAb) in mice. S1 and RBD proteins initialized significantly lower levels of nAb production. In addition, the S proteins were recognized specifically by the sera of convalescent patients with SARS, and that of mice immunized with inactivated SARS-CoV, but did not react with anti-sera of HCoV-OC43 or HCoV-229E, or sera from healthy donors (although RBD showed a false-positive in 1 of 55 control samples of human sera). Our results demonstrate that SQ protein may be an effective vaccine candidate and a convenient and safe diagnostic antigen for SARS-CoV.", "title": "SARS-CoV spike proteins expressed by the vaccinia virus Tiantan strain: secreted sq protein induces robust neutralization antibody in mice.", "pid": "f5ami32g", "bm25_score": 218.17262268066406}, {"text": "The spike (S) protein of SARS-CoV-2 mediates receptor binding and cell entry and is the dominant target of the immune system. S exhibits substantial conformational flexibility. It transitions from closed to open conformations to expose its receptor binding site, and subsequently from prefusion to postfusion conformations to mediate fusion of viral and cellular membranes. S protein derivatives are components of vaccine candidates and diagnostic assays, as well as tools for research into the biology and immunology of SARS-CoV-2. Here we have designed mutations in S which allow production of thermostable, crosslinked, S protein trimers that are trapped in the closed, pre-fusion, state. We have determined the structures of crosslinked and non-crosslinked proteins, identifying two distinct closed conformations of the S trimer. We demonstrate that the designed, thermostable, closed S trimer can be used in serological assays. This protein has potential applications as a reagent for serology, virology and as an immunogen.", "title": "A thermostable, closed, SARS-CoV-2 spike protein trimer", "pid": "oqixb26h", "bm25_score": 218.16290283203125}, {"text": "With the help of novel processing workflows and algorithms, we have obtained a better understanding of the flexibility and conformational dynamics of the SARS-CoV-2 spike in the prefusion state. We have re-analyzed previous cryo-EM data combining 3D clustering approaches with ways to explore a continuous flexibility space based on 3D Principal Component Analysis. These advanced analyses revealed a concerted motion involving the receptor-binding domain (RBD), N-terminal domain (NTD), and subdomain 1 and 2 (SD1 & SD2) around the previously characterized 1-RBD-up state, which have been modeled as elastic deformations. We show that in this dataset there are not well-defined, stable, spike conformations, but virtually a continuum of states moving in a concerted fashion. We obtained an improved resolution ensemble map with minimum bias, from which we model by flexible fitting the extremes of the change along the direction of maximal variance. Moreover, a high-resolution structure of a recently described biochemically stabilized form of the spike is shown to greatly reduce the dynamics observed for the wild-type spike. Our results provide new detailed avenues to potentially restrain the spike dynamics for structure-based drug and vaccine design and at the same time give a warning of the potential image processing classification instability of these complicated datasets, having a direct impact on the interpretability of the results.", "title": "Continuous flexibility analysis of SARS-CoV-2 Spike prefusion structures", "pid": "o58kbiqv", "bm25_score": 218.1612548828125}, {"text": "AIM: The COVID-19 pandemic is caused by infection with the SARS-CoV-2 virus. The major mutation detected to date in the SARS-CoV-2 viral envelope spike protein, which is responsible for virus attachment to the host and is also the main target for host antibodies, is a mutation of an aspartate (D) at position 614 found frequently in Chinese strains to a glycine (G). We sought to infer health impact of this mutation. RESULT: Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilise a specific conformation of the viral spike, within which the key host receptor binding site is more accessible. CONCLUSION: These results imply that G614 is a more pathogenic strain of SARS-CoV-2, which may influence vaccine design. The prevalence of this form of the virus should also be included in epidemiologic models predicting the COVID-19 health burden and fatality over time in specific regions. Physicians should be aware of this characteristic of the virus to anticipate the clinical course of infection.", "title": "SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate", "pid": "273ppceg", "bm25_score": 218.1556854248047}, {"text": "Severe acute respiratory syndrome (SARS) coronavirus (SCoV) spike (S) protein is the major surface antigen of the virus and is responsible for receptor binding and the generation of neutralizing antibody. To investigate SCoV S protein, full-length and individual domains of S protein were expressed on the surface of insect cells and were characterized for cleavability and reactivity with serum samples obtained from patients during the convalescent phase of SARS. S protein could be cleaved by exogenous trypsin but not by coexpressed furin, suggesting that the protein is not normally processed during infection. Reactivity was evident by both flow cytometry and Western blot assays, but the pattern of reactivity varied according to assay and sequence of the antigen. The antibody response to SCoV S protein involves antibodies to both linear and conformational epitopes, with linear epitopes associated with the carboxyl domain and conformational epitopes associated with the amino terminal domain. Recombinant SCoV S protein appears to be a suitable antigen for the development of an efficient and sensitive diagnostic test for SARS, but our data suggest that assay format and choice of S antigen are important considerations.", "title": "Cleavage and Serum Reactivity of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein", "pid": "qcu73sdu", "bm25_score": 218.15545654296875}, {"text": "As cell-invading molecular machinery, coronavirus spike proteins pose an evolutionary conundrum due to their high divergence. In this study, we determined the cryo-EM structure of avian infectious bronchitis coronavirus (IBV) spike protein from the γ-genus. The trimeric IBV spike ectodomain contains three receptor-binding S1 heads and a trimeric membrane-fusion S2 stalk. While IBV S2 is structurally similar to those from the other genera, IBV S1 possesses structural features that are unique to different other genera, thereby bridging these diverse spikes into an evolutionary spectrum. Specifically, among different genera, the two domains of S1, the N-terminal domain (S1-NTD) and C-terminal domain (S1-CTD), diverge from simpler tertiary structures and quaternary packing to more complex ones, leading to different functions of the spikes in receptor usage and membrane fusion. Based on the above structural and functional comparisons, we propose that the evolutionary spectrum of coronavirus spikes follows the order of α-, δ-, γ-, and β-genus. This study has provided insight into the evolutionary relationships among coronavirus spikes and deepened our understanding of their structural and functional diversity.", "title": "Cryo-EM structure of infectious bronchitis coronavirus spike protein reveals structural and functional evolution of coronavirus spike proteins", "pid": "s0wmll4q", "bm25_score": 218.1503448486328}, {"text": "The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin converting enzyme-2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "title": "Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach", "pid": "w5ytp1q7", "bm25_score": 218.1441650390625}]}
{"idx": 36, "qid": "37", "q_text": "What is the result of phylogenetic analysis of SARS-CoV-2 genome sequence?", "qrels": {"000tfenb": 0, "005b2j4b": 0, "023h20vk": 2, "02opdk0m": 0, "03agubzq": 0, "03eod3df": 1, "04bi0d50": 2, "07arhrv9": 0, "09dh938k": 0, "09r8xd0u": 0, "09ubsq2k": 0, "0a8sz7zb": 0, "0b7zb12r": 0, "0c8znvcf": 0, "0chuwvg6": 0, "0d9hzmyk": 0, "0e1wmy41": 2, "nnpzvcda": 0, "0gmtnkbh": 0, "0hxan9rw": 1, "0nh58odf": 1, "0p7mvljv": 0, "20ak2zsy": 0, "0pzjyrdf": 0, "0qn4c5t3": 2, "0s7oq0uv": 2, "0sm0r4v8": 0, "0t9ok1jb": 0, "0v1appqr": 2, "0vam15pt": 0, "0vnpodgu": 2, "0x90yubt": 2, "0xruezf2": 1, "0ydpwdpz": 1, "0zeppske": 0, "12540n1s": 2, "127c5bve": 1, "12dcftwt": 2, "dqyjdast": 2, "13ir7swr": 2, "13tc3loo": 0, "146matzr": 2, "16swzibp": 1, "18b2foud": 0, "19zimnoa": 0, "1abp6oom": 0, "1c38o79q": 0, "oubeywbn": 2, "1dxu14b1": 2, "1ef1cxc8": 0, "1evug4fr": 0, "1fxrmuzl": 1, "1fz039a5": 0, "1h1hwbos": 0, "6advof00": 0, "1iq1j47x": 0, "oi2cm546": 2, "ldyg241o": 0, 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As of May 2020, Turkey is among the top ten countries with the most cases. A comprehensive genomic characterization of the virus isolates in Turkey is yet to be carried out. Here, we built a phylogenetic tree with globally obtained 15,277 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes. We identified the subtypes based on the phylogenetic clustering in comparison with the previously annotated classifications. We performed a phylogenetic analysis of the first thirty SARS-CoV-2 genomes isolated and sequenced in Turkey. We suggest that the first introduction of the virus to the country is earlier than the first reported case of infection. Virus genomes isolated from Turkey are dispersed among most types in the phylogenetic tree. We find two of the seventeen sub-clusters enriched with the isolates of Turkey, which likely have spread expansively in the country. Finally, we traced virus genomes based on their phylogenetic placements. This analysis suggested multiple independent international introductions of the virus and revealed a hub for the inland transmission. We released a web application to track the global and interprovincial virus spread of the isolates from Turkey in comparison to thousands of genomes worldwide.", "title": "Phylogenetic Analysis of SARS-CoV-2 Genomes in Turkey", "pid": "7u97in7o", "bm25_score": 219.31472778320312}, {"text": "Background The origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still a debatable topic. The association of the virus spread from the market is supported by the close relation of genome sequences of environmental surface samples with virus samples from earliest patients by phylogenetic analysis. Objectives To have an insight into the SARS-CoV-2 genome sequences reported from India for better understanding on their epidemiology and virulence. Methods Genome sequences of Indian isolates of SARS-CoV-2 were analyzed to understand their phylogeny and divergence with respect to other isolates reported from other countries. Amino acid sequences of individual open reading frames (ORFs) from SARS-CoV-2 Indian isolates were aligned with sequences of isolates reported from other countries to identify the mutations occurred in Indian isolates. Results Our analysis suggests that Indian SARS-CoV-2 isolates are closely related to isolates reported from other parts of the world. Most ORFs are highly conserved; mutations were also detected in some ORFs. We found that most isolates reported from India have key mutations at 614th position of the S protein and 84th position of the ORF 8, which has been reported to be associated with high virulence and high transmission rate. Conclusion An attempt was made to understand the SARS-CoV-2 virus reported from India. SARS-CoV-2 reported from India was closely similar to other SARS-CoV-2 reported from other parts of the world, which suggests that vaccines and other therapeutic methods generated from other countries might work well in India. In addition, available sequence data suggest that majority of Indian isolates are capable of high transmission and virulence.", "title": "Genome analysis of SARS-CoV-2 isolates occurring in India: Present scenario.", "pid": "bcx51aci", "bm25_score": 219.2664794921875}, {"text": "COVID-19 has effectively spread worldwide. As of May 2020, Turkey is among the top ten countries with the most cases. A comprehensive genomic characterization of the virus isolates in Turkey is yet to be carried out. Here, we built a phylogenetic tree with globally obtained 15,277 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes. We identified the subtypes based on the phylogenetic clustering in comparison with the previously annotated classifications. We performed a phylogenetic analysis of the first 30 SARS-CoV-2 genomes isolated and sequenced in Turkey. We suggest that the first introduction of the virus to the country is earlier than the first reported case of infection. Virus genomes isolated from Turkey are dispersed among most types in the phylogenetic tree. We find 2 of the seventeen subclusters enriched with the isolates of Turkey, which likely have spread expansively in the country. Finally, we traced virus genomes based on their phylogenetic placements. This analysis suggested multiple independent international introductions of the virus and revealed a hub for the inland transmission. We released a web application to track the global and interprovincial virus spread of the isolates from Turkey in comparison to thousands of genomes worldwide.", "title": "Phylogenetic analysis of SARS-CoV-2 genomes in Turkey", "pid": "m3505b5w", "bm25_score": 219.22268676757812}, {"text": "Background: The origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still a debatable topic. The association of the virus spread from the market is supported by the close relation of genome sequences of environmental surface samples with virus samples from earliest patients by phylogenetic analysis. Objectives: To have an insight into the SARS-CoV-2 genome sequences reported from India for better understanding on their epidemiology and virulence. Methods: Genome sequences of Indian isolates of SARS-CoV-2 were analyzed to understand their phylogeny and divergence with respect to other isolates reported from other countries. Amino acid sequences of individual open reading frames (ORFs) from SARS-CoV-2 Indian isolates were aligned with sequences of isolates reported from other countries to identify the mutations occurred in Indian isolates. Results: Our analysis suggests that Indian SARS-CoV-2 isolates are closely related to isolates reported from other parts of the world. Most ORFs are highly conserved; mutations were also detected in some ORFs. We found that most isolates reported from India have key mutations at 614th position of the S protein and 84th position of the ORF 8, which has been reported to be associated with high virulence and high transmission rate. Conclusion: An attempt was made to understand the SARS-CoV-2 virus reported from India. SARS-CoV-2 reported from India was closely similar to other SARS-CoV-2 reported from other parts of the world, which suggests that vaccines and other therapeutic methods generated from other countries might work well in India. In addition, available sequence data suggest that majority of Indian isolates are capable of high transmission and virulence.", "title": "Genome analysis of SARS-CoV-2 isolates occurring in India: Present scenario", "pid": "2nvk7glh", "bm25_score": 219.15542602539062}, {"text": "Over 10,000 viral genome sequences of the SARS-CoV-2 virus have been made readily available during the ongoing coronavirus pandemic since the initial genome sequence of the virus was released on the open access Virological website (http://virological.org/) early on January 11. We utilize the published data on the single stranded RNAs of 11, 132 SARS-CoV-2 patients in the GISAID (Elbe and Buckland-Merrett, 2017; Shu and McCauley, 2017) database, which contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Among many important research questions which are currently being investigated, one aspect pertains to the genetic characterization/classification of the virus. We analyze data on the nucleotide sequencing of the virus and geographic information of a subset of 7, 640 SARS-CoV-2 patients without missing entries that are available in the GISAID database. Instead of modelling the mutation rate, applying phylogenetic tree approaches, etc., we here utilize a model-free clustering approach that compares the viruses at a genome-wide level. We apply principal component analysis to a similarity matrix that compares all pairs of these SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index (Jaccard, 1901; Tan et al., 2005; Prokopenko et al., 2016; Schlauch et al., 2017). Our analysis results of the SARS-CoV-2 genome data illustrates the geographic and chronological progression of the virus, starting from the first cases that were observed in China to the current wave of cases in Europe and North America. We also observe that, based on their sequence data, the SARS-CoV-2 viruses cluster in distinct genetic subgroups. It is the subject of ongoing research to examine whether the genetic subgroup could be related to diseases outcome and its potential implications for vaccine development.", "title": "Unsupervised cluster analysis of SARS-CoV-2 genomes reflects its geographic progression and identifies distinct genetic subgroups of SARS-CoV-2 virus", "pid": "xnamt7q4", "bm25_score": 219.04263305664062}, {"text": "The current global pandemic COVID-19, caused by SARS-CoV-2, has resulted in millions of infections worldwide in a few months. Global efforts to tackle this situation have produced a tremendous body of genomic data, which can be used for tracing transmission routes, characterization of isolates, and monitoring variants with potential for unusual virulence. Several groups have analyzed these genomes using different approaches. However, as new data become available, the research community needs a pipeline to perform a set of routine analyses, that can quickly incorporate new genome sequences and update the analysis reports. We developed a programmatic tool, CoVa, with this objective. It is a fast, accurate and user-friendly utility to perform a variety of genome analyses on hundreds of SARS-CoV-2 sequences. Using CoVa, we define a modified sequence typing nomenclature and identify sites under positive selection. Further analysis identified some peptides and sites showing geographical patterns of selection. Specifically, we show differences in sequence type distribution between sequences from India and those from the rest of the world. We also show that several sites show signatures of positive selection uniquely in sequences from India. Preliminary evolutionary analysis, using features that will be incorporated into CoVa in the near future, show a mutation rate of 7.4 × 10−4 substitutions/site/year, confirm a temporal signal with a November 2019 origin of SARS-CoV-2, and a heterogeneity in the geographical distribution of Indian samples.", "title": "SARS-CoV-2 sequence typing, evolution and signatures of selection using CoVa, a Python-based command-line utility", "pid": "w8vs7s28", "bm25_score": 219.0286407470703}, {"text": "OBJECTIVE: To analyze the evolution and variation of SARS-CoV-2 during the epidemic starting at the end of 2019. METHODS: We downloaded the full-length genome sequence of SARS-CoV-2 from the databases of GISAID and NCBI. Using the software for bioinformatics including MEGA-X, BEAST, and TempEst, we constructed the genomic evolution tree, inferred the time evolution signal of the virus, calculated the tMRCA time of the virus and analyzed the selection pressure of the virus during evolution. RESULTS: The phylogenetic tree showed that SARS-CoV-2 belonged to the Sarbecovirus subgenus of ß Coronavirus genus together with bat coronavirus BetaCoV/bat/Yunnan/RaTG13/2013, bat-SL-CoVZC45, bat-SL-CoVZXC21 and SARS-CoV. The genomic sequences of SARS-CoV-2 isolated from the ongoing epidemic showed a weak time evolution signal with an average tMRCA time of 73 days (95% CI: 38.9-119.3 days). No positive time evolution signal was found between SARS-CoV-2 and BetaCoV/bat/Yunnan/RaTG13/2013, but the former virus had a strong positive temporal evolution relationship with bat-SL-CoVZC45 and SARS-CoV. The major cause for mutations of SARS-CoV-2 was the pressure of purification selection during the epidemic. CONCLUSIONS: SARS-CoV-2 may have emerged as early as November, 2019, originating most likely from bat-associated coronavirus. This finding may provide evidence for tracing the sources and evolution of the virus.", "title": "[Analysis of variation and evolution of SARS-CoV-2 genome]", "pid": "fofy6whl", "bm25_score": 218.9714813232422}, {"text": "BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been growing exponentially, affecting over 4 million people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published both in scientific journals and through non-peer-reviewed channels to investigate the genetic heterogeneity and spatiotemporal dissemination of SARS-CoV-2. However, a systematic investigation of phylogenetic information and sampling bias in the available data is lacking. Although the number of available genome sequences of SARS-CoV-2 is growing daily and the sequences show increasing phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution. OBJECTIVE: The objective of this study was to determine the quality of the currently available SARS-CoV-2 full genome data in terms of sampling bias as well as phylogenetic and temporal signals to inform and guide the scientific community. METHODS: We used maximum likelihood-based methods to assess the presence of sufficient information for robust phylogenetic and phylogeographic studies in several SARS-CoV-2 sequence alignments assembled from GISAID (Global Initiative on Sharing All Influenza Data) data released between March and April 2020. RESULTS: Although the number of high-quality full genomes is growing daily, and sequence data released in April 2020 contain sufficient phylogenetic information to allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 data sets still present severe limitations. CONCLUSIONS: At the present time, studies assessing within-country spread or transmission clusters should be considered preliminary or hypothesis-generating at best. Hence, current reports should be interpreted with caution, and concerted efforts should continue to increase the number and quality of sequences required for robust tracing of the epidemic.", "title": "A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis", "pid": "dqyjdast", "bm25_score": 218.9610595703125}, {"text": "OBJECTIVE To analyze the evolution and variation of SARS-CoV-2 during the epidemic starting at the end of 2019. METHODS We downloaded the full-length genome sequence of SARS-CoV-2 from the databases of GISAID and NCBI. Using the software for bioinformatics including MEGA-X, BEAST, and TempEst, we constructed the genomic evolution tree, inferred the time evolution signal of the virus, calculated the tMRCA time of the virus and analyzed the selection pressure of the virus during evolution. RESULTS The phylogenetic tree showed that SARS-CoV-2 belonged to the Sarbecovirus subgenus of β Coronavirus genus together with bat coronavirus BetaCoV/bat/Yunnan/RaTG13/2013, bat-SL-CoVZC45, bat-SL-CoVZXC21 and SARS-CoV. The genomic sequences of SARS-CoV-2 isolated from the ongoing epidemic showed a weak time evolution signal with an average tMRCA time of 73 days (95% CI: 38.9-119.3 days). No positive time evolution signal was found between SARS-CoV-2 and BetaCoV/bat/Yunnan/RaTG13/2013, but the former virus had a strong positive temporal evolution relationship with bat-SL-CoVZC45 and SARS-CoV. The major cause for mutations of SARS-CoV-2 was the pressure of purification selection during the epidemic. CONCLUSIONS SARS-CoV-2 may have emerged as early as November, 2019, originating most likely from bat-associated coronavirus. This finding may provide evidence for tracing the sources and evolution of the virus.", "title": "[Analysis of variation and evolution of SARS-CoV-2 genome].", "pid": "h8abjsxr", "bm25_score": 218.9532012939453}, {"text": "Impact of mutations on the evolution of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) are needed for ongoing global efforts to track and trace the current pandemic, in order to enact effective prevention and treatment options. SARS-Co-V-2 viral genomes were detected and sequenced from 18 Romanian patients suffering from coronavirus disease-2019. Viral Spike S glycoprotein sequences were used to generate model structures and assess the role of mutations on protein stability. We integrated the phylogenetic tree within the available European SARS-Co-V-2 genomic sequences. We further provide an epidemiological overview of the pre-existing conditions that are lethal in relevant Romanian patients. Non-synonymous mutations in the viral Spike glycoprotein relating to infectivity are constructed in models of protein structures. Continuing search to limit and treat SARS-CoV-2 benefit from our contribution in delineating the viral Spike glycoprotein mutations, as well as from assessment of their role on protein stability or complex formation with human receptor angiotensin-converting enzyme 2. Our results help implement and extend worldwide genomic surveillance of coronavirus disease-2019.", "title": "Whole-Genome Sequences of the Severe Acute Respiratory Syndrome Coronavirus-2 obtained from Romanian patients between March and June of 2020", "pid": "uhru7rn8", "bm25_score": 218.9404296875}, {"text": "The SARS-CoV-2 pandemic has been growing exponentially, affecting nearly 900 thousand people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published, in scientific journals as well as through non-peer reviewed channels, to investigate SARS-CoV-2 genetic heterogeneity and spatiotemporal dissemination. We examined full genome sequences currently available to assess the presence of sufficient information for reliable phylogenetic and phylogeographic studies in countries with the highest toll of confirmed cases. Although number of-available full-genomes is growing daily, and the full dataset contains sufficient phylogenetic information that would allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 datasets still present severe limitations. Studies assessing within country spread or transmission clusters should be considered preliminary at best, or hypothesis generating. Hence the need for continuing concerted efforts to increase number and quality of the sequences required for robust tracing of the epidemic. Significance Statement Although genome sequences of SARS-CoV-2 are growing daily and contain sufficient phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution.", "title": "A snapshot of SARS-CoV-2 genome availability up to 30th March, 2020 and its implications", "pid": "8vl0okiv", "bm25_score": 218.72866821289062}, {"text": "Recently the first genome sequence for a Severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2 isolate from Bangladesh became available. The sequencing was carried out by the Child Health Research Foundation and provided the first insight into the genetic details of the viral strain responsible for the SARS-CoV-2 infections in Bangladesh. Here we carried out a comparative study were we explored the phylogenetic relationship between the Bangladeshi isolate with other isolates from different parts of the world. Afterwards we identified single nucleotide variants in the Bangladeshi isolate, using the Wuhan virus reference sequence. We found a total of 9 variants in the Bangladeshi isolate using 2 separate tools. Barring 2, the rest of these variants were also observed in other isolates from different countries. Most of the variants occurred in the ORF1ab gen. Another noteworthy finding was a sequence of three consecutive variants in the N protein gene that were observed in other isolates as well. Lastly the phylogenetic analysis revealed a close relationship between the Bangladeshi isolate and those from Taiwan, Kazakhstan, Greece, California, Spain, Israel, and Sri Lanka.", "title": "Genome Analysis of SARS-CoV-2 Isolate from Bangladesh", "pid": "gygi11gk", "bm25_score": 218.7233123779297}, {"text": "The COVID-19 pandemic spread very fast around the world. A few days after the first detected case in South Africa, an infection started a large hospital outbreak in Durban, KwaZulu-Natal. Phylogenetic analysis of SARS-CoV-2 genomes can be used to trace the path of transmission within a hospital. It can also identify the source of the outbreak and provide lessons to improve infection prevention and control strategies. In this manuscript, we outline the obstacles we encountered in order to genotype SARS-CoV-2 in real-time during an urgent outbreak investigation. In this process, we encountered problems with the length of the original genotyping protocol, reagent stockout and sample degradation and storage. However, we managed to set up three different library preparation methods for sequencing in Illumina. We also managed to decrease the hands on library preparation time from twelve to three hours, which allowed us to complete the outbreak investigation in just a few weeks. We also fine-tuned a simple bioinformatics workflow for the assembly of high-quality genomes in real-time. In order to allow other laboratories to learn from our experience, we released all of the library preparation and bioinformatics protocols publicly and distributed them to other laboratories of the South African Network for Genomics Surveillance (SANGS) consortium.", "title": "Whole Genome Sequencing of SARS-CoV-2: Adapting Illumina Protocols for Quick and Accurate Outbreak Investigation During a Pandemic", "pid": "lsqg65ez", "bm25_score": 218.66091918945312}, {"text": "BACKGROUND & OBJECTIVES: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has globally affected 195 countries. In India, suspected cases were screened for SARS-CoV-2 as per the advisory of the Ministry of Health and Family Welfare. The objective of this study was to characterize SARS-CoV-2 sequences from three identified positive cases as on February 29, 2020. METHODS: Throat swab/nasal swab specimens for a total of 881 suspected cases were screened by E gene and confirmed by RdRp (1), RdRp (2) and N gene real-time reverse transcription-polymerase chain reactions and next-generation sequencing. Phylogenetic analysis, molecular characterization and prediction of B- and T-cell epitopes for Indian SARS-CoV-2 sequences were undertaken. RESULTS: Three cases with a travel history from Wuhan, China, were confirmed positive for SARS-CoV-2. Almost complete (29,851 nucleotides) genomes of case 1, case 3 and a fragmented genome for case 2 were obtained. The sequences of Indian SARS-CoV-2 though not identical showed high (~99.98%) identity with Wuhan seafood market pneumonia virus (accession number: NC 045512). Phylogenetic analysis showed that the Indian sequences belonged to different clusters. Predicted linear B-cell epitopes were found to be concentrated in the S1 domain of spike protein, and a conformational epitope was identified in the receptor-binding domain. The predicted T-cell epitopes showed broad human leucocyte antigen allele coverage of A and B supertypes predominant in the Indian population. INTERPRETATION & CONCLUSIONS: The two SARS-CoV-2 sequences obtained from India represent two different introductions into the country. The genetic heterogeneity is as noted globally. The identified B- and T-cell epitopes may be considered suitable for future experiments towards the design of vaccines and diagnostics. Continuous monitoring and analysis of the sequences of new cases from India and the other affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.", "title": "Full-genome sequences of the first two SARS-CoV-2 viruses from India", "pid": "vhb280gz", "bm25_score": 218.65325927734375}, {"text": "Background & objectives: Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has globally affected 195 countries. In India, suspected cases were screened for SARS-CoV-2 as per the advisory of the Ministry of Health and Family Welfare. The objective of this study was to characterize SARS-CoV-2 sequences from three identified positive cases as on February 29, 2020. Methods: Throat swab/nasal swab specimens for a total of 881 suspected cases were screened by E gene and confirmed by RdRp (1), RdRp (2) and N gene real-time reverse transcription-polymerase chain reactions and next-generation sequencing. Phylogenetic analysis, molecular characterization and prediction of B- and T-cell epitopes for Indian SARS-CoV-2 sequences were undertaken. Results: Three cases with a travel history from Wuhan, China, were confirmed positive for SARS-CoV-2. Almost complete (29,851 nucleotides) genomes of case 1, case 3 and a fragmented genome for case 2 were obtained. The sequences of Indian SARS-CoV-2 though not identical showed high (~99.98%) identity with Wuhan seafood market pneumonia virus (accession number: NC 045512). Phylogenetic analysis showed that the Indian sequences belonged to different clusters. Predicted linear B-cell epitopes were found to be concentrated in the S1 domain of spike protein, and a conformational epitope was identified in the receptor-binding domain. The predicted T-cell epitopes showed broad human leucocyte antigen allele coverage of A and B supertypes predominant in the Indian population. Interpretation & conclusions: The two SARS-CoV-2 sequences obtained from India represent two different introductions into the country. The genetic heterogeneity is as noted globally. The identified B- and T-cell epitopes may be considered suitable for future experiments towards the design of vaccines and diagnostics. Continuous monitoring and analysis of the sequences of new cases from India and the other affected countries would be vital to understand the genetic evolution and rates of substitution of the SARS-CoV-2.", "title": "Full-genome sequences of the first two SARS-CoV-2 viruses from India", "pid": "35wfw3zn", "bm25_score": 218.65325927734375}, {"text": "Different tree-building methods consistently place the SARS corona-virus (SARS-CoV) as a basal Group 2 coronavirus rather than as an ungrouped species as concluded by others. Detailed comparisons of the SARS-CoV genomic sequence with those of six other coronaviruses failed to find evidence of recombination or genomic rearrangement using computational methods designed for that purpose.", "title": "The phylogeny of SARS coronavirus", "pid": "wr7vrild", "bm25_score": 218.63046264648438}, {"text": "Coronaviruses are responsible on respiratory diseases in animal and human. The combination of numerical encoding techniques and digital signal processing methods are becoming increasingly important in handling large genomic data. In this paper, we propose to analyze the SARS-CoV-2 genomic signature using the combination of different nucleotide representations and signal processing tools in the aim to identify its genetic origin. The sequence of SARS-CoV-2 was compared with 21 relevant sequences including bat, yak and pangolin coronavirus sequences. In addition, we developed a new algorithm to locate the nucleotide modifications. The results show that the Bat and Pangolin coronaviruses were the most related to SARS-CoV-2 with 96% and 86% of identity all along the genome. Within the S gene sequence, the Pangolin sequence presents local highest nucleotide identity. Those findings suggest genesis of SARS-Cov-2 through evolution from bat and pangolin strains. This study offers new ways to automatically characterize viruses.", "title": "Comparative genomic signature representations of the emerging COVID-19 coronavirus and other coronaviruses: High identity and possible recombination between Bat and Pangolin coronaviruses", "pid": "6ydswv0a", "bm25_score": 218.59381103515625}, {"text": "BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been growing exponentially, affecting over 4 million people and causing enormous distress to economies and societies worldwide. A plethora of analyses based on viral sequences has already been published both in scientific journals and through non–peer-reviewed channels to investigate the genetic heterogeneity and spatiotemporal dissemination of SARS-CoV-2. However, a systematic investigation of phylogenetic information and sampling bias in the available data is lacking. Although the number of available genome sequences of SARS-CoV-2 is growing daily and the sequences show increasing phylogenetic information, country-specific data still present severe limitations and should be interpreted with caution. OBJECTIVE: The objective of this study was to determine the quality of the currently available SARS-CoV-2 full genome data in terms of sampling bias as well as phylogenetic and temporal signals to inform and guide the scientific community. METHODS: We used maximum likelihood–based methods to assess the presence of sufficient information for robust phylogenetic and phylogeographic studies in several SARS-CoV-2 sequence alignments assembled from GISAID (Global Initiative on Sharing All Influenza Data) data released between March and April 2020. RESULTS: Although the number of high-quality full genomes is growing daily, and sequence data released in April 2020 contain sufficient phylogenetic information to allow reliable inference of phylogenetic relationships, country-specific SARS-CoV-2 data sets still present severe limitations. CONCLUSIONS: At the present time, studies assessing within-country spread or transmission clusters should be considered preliminary or hypothesis-generating at best. Hence, current reports should be interpreted with caution, and concerted efforts should continue to increase the number and quality of sequences required for robust tracing of the epidemic.", "title": "A Snapshot of SARS-CoV-2 Genome Availability up to April 2020 and its Implications: Data Analysis", "pid": "hze05jnf", "bm25_score": 218.58883666992188}, {"text": "The novel coronavirus (CoV), severe acute respiratory syndrome (SARS)-CoV-2 is an international public health emergency. Until now, the intermediate host and mechanisms of the interspecies jump of this virus are unknown. Phylogenetic analysis of all available bat CoV complete genomes was performed to analyze the relationships between bat CoV and SARS-CoV-2. To suggest a possible intermediate host, another phylogenetic reconstruction of CoV genomes obtained from animals that were hypothetically commercialized in the Chinese markets was also carried out. Moreover, mutation analysis was executed to suggest genomic regions that may have permitted the adaptation of SARS-CoV-2 to the human host. The phylogenetic analysis demonstrated that SARS-CoV-2 formed a cluster with the bat CoV isolate RaTG13. Possible CoV interspecies jumps among bat isolates were also observed. The phylogenetic tree reconstructed from CoV strains belonging to different animals demonstrated that SARS-CoV-2, bat RaTG13, and pangolin CoV genomes formed a monophyletic cluster, demonstrating that pangolins may be suggested as SARS-CoV-2 intermediate hosts. Three AA substitutions localized in the S1 portion of the S gene were observed, some of which have been correlated to structural modifications of the S protein which may facilitate SARS-CoV-2 tropism to human cells. Our analysis shows the tight relationship between SARS-CoV-2 and bat SARS-like strains. It also hypothesizes that pangolins might have been possible intermediate hosts of the infection. Some of the observed AA substitutions in the S-binding protein may serve as possible adaptation mutations in humans but more studies are needed to elucidate their function.", "title": "The novel coronavirus SARS-CoV-2: From a zoonotic infection to coronavirus disease 2019", "pid": "5qn5h7p5", "bm25_score": 218.56991577148438}, {"text": "BACKGROUND The aim of the current study was to investigate and track the SARS-CoV-2 in Iranian Coronavirus Disease 2019 (COVID-19) patients using molecular and phylogenetic methods. METHODS We enrolled seven confirmed cases of COVID-19 patients for the phylogenetic assessment of the SARS-CoV-2 in Iran. The nsp-2, nsp-12, and S genes were amplified using one-step RT-PCR and sequenced using Sanger sequencing method. Popular bioinformatics software were used for sequences alignment and analysis as well as phylogenetic construction. RESULTS The mean age of the patients in the present study was 60.42 ± 9.94 years and 57.1% (4/7) were male. The results indicated high similarity between Iranian and Chinese strains. We could not find any particular polymorphisms in the assessed regions of the three genes. Phylogenetic trees by neighbor-joining and maximum likelihood method of nsp-2, nsp-12, and S genes showed that there are not any differences between Iranian isolates and those of other countries. CONCLUSION As a preliminary phylogenetic study in Iranian SARS-CoV-2 isolates, we found that these isolates are closely related to the Chinese and reference sequences. Also, no sensible differences were observed between Iranian isolates and those of other countries. Further investigations are recommended using more comprehensive methods and larger sample sizes.", "title": "SARS-CoV-2 molecular and phylogenetic analysis in COVID-19 patients: A preliminary report from Iran.", "pid": "mjxs395h", "bm25_score": 218.5591278076172}, {"text": "BACKGROUND: The aim of the current study was to investigate and track the SARS-CoV-2 in Iranian Coronavirus Disease 2019 (COVID-19) patients using molecular and phylogenetic methods. METHODS: We enrolled seven confirmed cases of COVID-19 patients for the phylogenetic assessment of the SARS-CoV-2 in Iran. The nsp-2, nsp-12, and S genes were amplified using one-step RT-PCR and sequenced using Sanger sequencing method. Popular bioinformatics software were used for sequences alignment and analysis as well as phylogenetic construction. RESULTS: The mean age of the patients in the present study was 60.42 ± 9.94 years and 57.1% (4/7) were male. The results indicated high similarity between Iranian and Chinese strains. We could not find any particular polymorphisms in the assessed regions of the three genes. Phylogenetic trees by neighbor-joining and maximum likelihood method of nsp-2, nsp-12, and S genes showed that there are not any differences between Iranian isolates and those of other countries. CONCLUSION: As a preliminary phylogenetic study in Iranian SARS-CoV-2 isolates, we found that these isolates are closely related to the Chinese and reference sequences. Also, no sensible differences were observed between Iranian isolates and those of other countries. Further investigations are recommended using more comprehensive methods and larger sample sizes.", "title": "SARS-CoV-2 Molecular and Phylogenetic analysis in COVID-19 patients: A preliminary report from Iran", "pid": "jhlnwoml", "bm25_score": 218.5472869873047}, {"text": "Objective: To obtain the genome sequences of SARS-CoV-2 in respiratory specimens in Guangdong Province with next-generation sequencing (NGS) and analyze the factors influencing sequencing. Methods: Eight upper and lower respiratory tract specimens were collected from patients with SARS-CoV-2 infection in Guangdong Province in January 2020. RNA library construction was used to obtain the genome sequences of SARS-CoV-2. A bio-informatics software package (CLC Genomics Workbench 12.0) was used to analyze and compare the genomic sequences. Results: Five SARS-CoV-2 genome sequences were obtained from the eight specimens and two were obtained from lower respiratory tract specimens. The nucleotide homology to SARS-CoV-2 was 97.74%-99.90%. The Ct values were lower, while the sequencing depth, coverage, relative abundance and genome integrity were higher in sequencing the SARS-CoV-2 in lower respiratory tract specimens. Conclusions: The low Ct value of SARS-CoV-2 in the samples was good for sequencing.", "title": "Whole genome sequencing of SARS-CoV-2 isolated in Guangdong Province and factors influencing the sequencing/ 广东省新型冠状病毒全基因组序列测定及其影响因素分析", "pid": "2k7gckj2", "bm25_score": 218.54515075683594}, {"text": "OBJECTIVE: Severe acute respiratory syndrome (SARS) is caused by a new coronavirus. Genomic sequence analysis will provide the molecular epidemiology and help to develop vaccines. METHODS: We developed a rapid method to amplify and sequence the whole SARS-CoV genome from clinical specimens. The technique employed one-step multiplex RT-PCR to amplify the whole SARS-CoV genome, and then nested PCR was performed to amplify a 2-kb region separately. The PCR products were sequenced. RESULTS: We sequenced the genomes of SARS-CoV from 3 clinical specimens obtained in Taiwan. The sequences were similar to those reported by other groups, except that 17 single nucleotide variations and two 2-nucleotide deletions, and a 1-nucleotide deletion were found. All the variations in the clinical specimens did not alter the amino acid sequence. Of these 17 sequenced variants, two loci (positions 26203 and 27812) were segregated together as a specific genotype-T:T or C:C. Phylogenetic analysis showed two major clusters of SARS patients in Taiwan. CONCLUSION: We developed a very economical and rapid method to sequence the whole genome of SARS-CoV, which can avoid cultural influence. From our results, SARS patients in Taiwan may be infected from two different origins.", "title": "SARS-CoV Infection Was from at Least Two Origins in the Taiwan Area", "pid": "79uxm3bg", "bm25_score": 218.50701904296875}, {"text": "", "title": "Reply to Sánchez-Pacheco et al., Chookajorn, and Mavian et al.: Explaining phylogenetic network analysis of SARS-CoV-2 genomes", "pid": "5nhh01wa", "bm25_score": 218.49810791015625}, {"text": "Abstract Coronaviruses are responsible on respiratory diseases in animal and human. The combination of numerical encoding techniques and digital signal processing methods are becoming increasingly important in handling large genomic data. In this paper, we propose to analyze the SARS-CoV-2 genomic signature using the combination of different nucleotide representations and signal processing tools in the aim to identify its genetic origin. The sequence of SARS-CoV-2 was compared with 21 relevant sequences including bat, yak and pangolin coronavirus sequences. In addition, we developed a new algorithm to locate the nucleotide modifications. The results show that the Bat and Pangolin coronaviruses were the most related to SARS-CoV-2 with 96% and 86% of identity all along the genome. Within the S gene sequence, the Pangolin sequence presents local highest nucleotide identity. Those findings suggest genesis of SARS-Cov-2 through evolution from bat and pangolin strains. This study offers new ways to automatically characterize viruses.", "title": "Comparative genomic signature representations of the emerging COVID-19 coronavirus and other coronaviruses: High identity and possible recombination between Bat and Pangolin coronaviruses", "pid": "13ir7swr", "bm25_score": 218.4906005859375}, {"text": "The wave of COVID-19 is a big threat to the human population. Presently, the world is going through different phases of lock down in order to stop this wave of pandemic; India being no exception. We have also started the lock down on 23rd March 2020. In this current situation, apart from social distancing only a vaccine can be the proper solution to serve the population of human being. Thus it is important for all the nations to perform the genome-wide analysis in order to identify the genetic variation in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) so that proper vaccine can be designed. This fast motivated us to analyze publicly available 566 Indian complete or near complete SARS-CoV-2 genomes to find the mutation points as substitution, deletion and insertion. In this regard, we have performed the multiple sequence alignment in presence of reference sequence from NCBI. After the alignment, a consensus sequence is build to analyze each genome in order to identify the mutation points. As a consequence, we have found 933 substitutions, 2449 deletions and 2 insertions, in total 3384 unique mutation points, in 566 genomes across 29.9 K bp. Further, it has been classified into three groups as 100 clusters of mutations (mostly deletions), 1609 point mutations as substitution, deletion and insertion and 64 SNPs. These outcomes are visualized using BioCircos and bar plots as well as plotting entropy value of each genomic location. Moreover, phylogenetic analysis has also been performed to see the evolution of SARS-CoV-2 virus in India. It also shows the wide variation in tree which indeed vivid in genomic analysis. Finally, these SNPs can be the useful target for virus classification, designing and defining the effective dose of vaccine for the heterogeneous population.", "title": "Genome-wide analysis of Indian SARS-CoV-2 genomes for the identification of genetic mutation and SNP", "pid": "lt0uo7q3", "bm25_score": 218.490478515625}, {"text": "In December 2019, a novel human-infecting coronavirus (SARS-CoV-2) was recognized in China. In a few months, SARS-CoV-2 has caused thousands of disease cases and deaths in several countries. Phylogenetic analyses indicated that SARS-CoV-2 clusters with SARS-CoV in the Sarbecovirus subgenus and viruses related to SARS-CoV-2 were identified from bats and pangolins. Coronaviruses have long and complex genomes with high plasticity in terms of gene content. To date, the coding potential of SARS-CoV-2 remains partially unknown. We thus used available sequences of bat and pangolin viruses to determine the selective events that shaped the genome structure of SARS-CoV-2 and to assess its coding potential. By searching for signals of significantly reduced variability at synonymous sites (dS), we identified six genomic regions, one of these corresponding to the programmed -1 ribosomal frameshift. The most prominent signal of dS reduction was observed within the E gene. A genome-wide analysis of conserved RNA structures indicated that this region harbors a putative functional RNA element that is shared with the SARS-CoV lineage. Additional signals of reduced dS indicated the presence of internal ORFs. Whereas the presence ORF9a (internal to N) was previously proposed by homology with a well characterized protein of SARS-CoV, ORF3h (for hypothetical, within ORF3a) was not previously described. The predicted product of ORF3h has 90% identity with the corresponding predicted product of SARS-CoV and displays features suggestive of a viroporin. Finally, analysis of the putative ORF10 revealed high dN/dS (3.82) in SARS-CoV-2 and related coronaviruses. In the SARS-CoV lineage, the ORF is predicted to encode a truncated protein and is neutrally evolving. These data suggest that ORF10 encodes a functional protein in SARS-CoV-2 and that positive selection is driving its evolution. Experimental analyses will be necessary to validate and characterize the coding and non-coding functional elements we identified.", "title": "Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses", "pid": "dbem6cfo", "bm25_score": 218.4453125}, {"text": "This manuscript is based on the method we developed urgently to deal with the research requirement in the conflict between achieving a complete genome sequence for the evolutionary history of SARS-CoV-2 study and the low viral RNA concentration. Here, in this manuscript, we developed a set of SARS-CoV-2 enrichment probes to increase the sensitivity of sequence-based virus detection and characterization via obtaining the comprehensive genome sequence. Following the CDC health and safety guidelines, we test the concept using the culturing supernatant contain SARS-CoV-2 particles, and its full-length sequence was used for further analysis. The fraction of SARS-CoV-2 endogenous DNA was 93.47% with Cluster Factor about 1.1, which demonstrate that the numbers of mapped reads to SARS-CoV-2 reference sequence significantly increased, compared to metagenomic sequencing technology, following SARS-CoV-2 probe enrichment. Moreover, based on the high-quality sequence, we discussed the heterozygosity and viral expression during replication of coronavirus, and its phylogenetic relationship with other selected high-quality samples from The Genome Variation Map (GVM) (on 2020/03/22). We believe this manuscript is valuable for all the researchers who are interested in using clinical warp samples to obtain the high coverage of SARS-CoV-2 genome sequence with a relatively low concentration of viral particles. This would allow the clinician to correlate the diagnostic data with molecular monitoring in viral evolutional, the most importantly, to track the functional mutation of SARS-CoV-2.", "title": "A High-Coverage SARS-CoV-2 Genome Sequence Acquired by Target Capture Sequencing", "pid": "yb6if23t", "bm25_score": 218.38563537597656}, {"text": "The coronavirus disease (COVID-19) belongs to the family Severe Acute Respiratory Syndrome (SARS-CoV). It can be more severe for some persons and can lead to pneumonia or breathing difficulties resulting in the death of immune-compromised patients. We performed a phylogenomic and phylogeographic tree from the collected datasets. Phylogenomic analysis or sequence-based phylogeny showed an evolutionary relationship between the geographical strains. The phylogenomic tree grouped into two major clades consists of various isolates of SARS-CoV-2 and Bat SARS-like coronavirus, Bat coronavirus, and Pangolin coronavirus. The phylogenetic neighbor of newly sequenced Indian strains (Accession: MT012098.1, MT050493.1) was revealed to identify the variations between the nCoV-19 strains. The results showed keen evidence that SARS-CoV-2 has evolved from Bat SARS-like coronavirus. The evolutionary history and comparative proteomic analysis provide a new avenue for the current scientific research related to the coronavirus.", "title": "Phylogenomic proximity and comparative proteomic analysis of SARS-CoV-2", "pid": "ltar1aa5", "bm25_score": 218.36688232421875}, {"text": "A pandemic caused by the SARS-CoV2 is being experienced by the whole world since December, 2019. A thorough understanding beyond just sequential similarities among the protein coding genes of SARS-CoV2 is important in order to differentiate or relate to the other known CoVs of the same genus. In this study, we compare three genomes namely MT012098 (India-Kerala), MT050493 (India-Kerala), MT358637 (India-Gujrat) from India with NC_045512 (China-Wuhan) to view the spatial as well as molecular arrangements of nucleotide bases of all the genes embedded in these four genomes. Based on different features extracted for each gene embedded in these genomes, corresponding phylogenetic relationships have been built up. Differences in phylogenetic tree arrangement with individual gene suggest that three genomes of Indian origin have come from three different origins or the evolution of viral genome is very fast process. This study would also help to understand the virulence factors, disease pathogenicity, origin and transmission of the SARS-CoV2.", "title": "On spatial molecular arrangements of SARS-CoV2 genomes of Indian patients", "pid": "k2juhyex", "bm25_score": 218.32846069335938}, {"text": "BACKGROUND: SARS-CoV-2 is a new coronavirus that has spread globally, infecting more than 150000 people, and being declared pandemic by the WHO. We provide here bio-informatic, evolutionary analysis of 351 available sequences of its genome with the aim of mapping genome structural variations and the patterns of selection. METHODS: A Maximum likelihood tree has been built and selective pressure has been investigated in order to find any mutation developed during the SARS-CoV-2 epidemic that could potentially affect clinical evolution of the infection. FINDING: We have found in more recent isolates the presence of two mutations affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures. INTERPRETATION: One of the two mutations, likely developed within the genome during virus spread, could affect virus intracellular survival. Genome follow-up of SARS-CoV-2 spread is urgently needed in order to identify mutations that could significantly modify virus pathogenicity.", "title": "Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy", "pid": "su5tlg3l", "bm25_score": 218.31573486328125}, {"text": "The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10 - 25 January) 2020. We also applied structural bioinformatics to assess D614G potential impact on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.", "title": "Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide", "pid": "zu46bdpu", "bm25_score": 218.30332946777344}, {"text": "Four signature groups of single-nucleotide variants (SNVs) were identified using two-way clustering method in about twenty thousand high quality and high coverage SARS-CoV-2 complete genome sequences. Some frequently occurred SNVs predominate but are mutually exclusively presented in patients from different countries and areas. These major SNV signatures exhibited distinguished evolution patterns overtime. Although it was rare, our data indicated possible cross-infections with multiple groups of SNVs existed simultaneously in some patients, suggesting infections from different SARS-CoV-2 clades or potential re-combination of SARS-CoV-2 sequences. Interestingly nucleotide substitutions among SARS-CoV-2 genomes tend to occur at the sites where one bat RaTG13 coronavirus sequences differ from Wuhan-Hu-1 genome, indicating the tolerance of mutations on those sites or suggesting that major viral strains might exist between Wuhan-Hu-1 and RaTG13 coronavirus.", "title": "Distinct genetic spectrums and evolution patterns of SARS-CoV-2", "pid": "xly61tfw", "bm25_score": 218.30186462402344}, {"text": "Covid-19 infection, which spread to the whole world in December 2019 and is still active, caused more than 250 thousand deaths in the world today. Researches on this subject have been focused on analyzing the genetic structure of the virus, developing vaccines, the course of the disease, and its source. In this study, RNA sequences belonging to the SARS-CoV-2 virus are transformed into gene motifs with two basic image processing algorithms and classified with the convolutional neural network (CNN) models. The CNN models achieved an average of 98% Area Under Curve(AUC) value was achieved in RNA sequences classified as Asia, Europe, America, and Oceania. The resulting artificial neural network model was used for phylogenetic analysis of the variant of the virus isolated in Turkey. The classification results reached were compared with gene alignment values in the GISAID database, where SARS-CoV-2 virus records are kept all over the world. Our experimental results have revealed that now the detection of the geographic distribution of the virus with the CNN models might serve as an efficient method.", "title": "SARS-CoV-2 virus RNA sequence classification and geographical analysis with convolutional neural networks approach", "pid": "yl6qynnm", "bm25_score": 218.29632568359375}, {"text": "Abstract As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to disperse globally with worrisome speed, identifying amino acid variations in the virus could help to understand the characteristics of it. Here, we studied 489 SARS-CoV-2 genomes obtained from 32 countries from the Nextstrain database and performed phylogenetic tree analysis by clade, country, and genotype of the surface spike glycoprotein (S protein) at site 614. We found that virus strains from mainland China were mostly distributed in Clade B and Clade undefined in the phylogenetic tree, with very few found in Clade A. In contrast, Clades A2 (one case) and A2a (112 cases) predominantly contained strains from European regions. Moreover, Clades A2 and A2a differed significantly from those of mainland China in age of infected population (P = 0.0071, mean age 40.24 to 46.66), although such differences did not exist between the US and mainland China. Further analysis demonstrated that the variation of the S protein at site 614 (QHD43416.1: p.614D>G) was a characteristic of stains in Clades A2 and A2a. Importantly, this variation was predicted to have neutral or benign effects on the function of the S protein. In addition, global quality estimates and 3D protein structures tended to be different between the two S proteins. In summary, we identified different genomic epidemiology among SARS-CoV-2 strains in different clades, especially in an amino acid variation of the S protein at 614, revealing potential viral genome divergence in SARS-CoV-2 strains.", "title": "Amino acid variation analysis of surface spike glycoprotein at 614 in SARS-CoV-2 strains", "pid": "gquo184w", "bm25_score": 218.28489685058594}, {"text": "The newly identified SARS-CoV-2 has now been reported from around 183 countries with more than a million confirmed human cases including more than 68000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins have gotten substantial attention recently. Spike glycoprotein is widely considered as a possible target to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment tools. In this study, 483 unique variations have been identified among the genomes including 25 non-synonymous mutations and one deletion in the spike protein of SARS-CoV-2. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction with receptor molecules. In addition, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on our findings, potential inhibitors can be designed and tested targeting these proposed sites of variation.", "title": "Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach", "pid": "vf32wxkx", "bm25_score": 218.26475524902344}, {"text": "COVID-A9 is an infection disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid expansion worldwide. In this study we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 using 22 virus genome sequences reported by three different laboratories in Morocco till the date 07/06/2020 as well as (40366) virus genomes from all around the world. The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations of which 30 were missense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred one time in our sequences with no record in other sequence worldwide. These mutations should be investigated to figure out their potential effects on all around the world virulence. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses pertaining to clade 20A, 9 to clade 20B and 2 to clade 20C. This finding suggest that the epidemic spread in Morocco did not show a predominant SARS-CoV-2 route. For multiple and unrelated introductions of SARS-CoV-2 into Morocco via different routes have occurred, giving rise to the diversity of virus genomes in the country. Furthermore, very likely, the SARS-CoV-2 virus circulated in cryptic way in Morocco starting from the fifteen January before the discovering of the first case the second of March.", "title": "Genetic Diversity and Genomic Epidemiology of SARS-COV-2 in Morocco", "pid": "zb1pzdd0", "bm25_score": 218.23855590820312}, {"text": "The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3’-to-5’ exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.", "title": "Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13", "pid": "3h1o0oz3", "bm25_score": 218.22781372070312}, {"text": "Abstract Background SARS-CoV-2 is a new coronavirus that has spread globally, infecting more than 150000 people, and being declared pandemic by the WHO. We provide here bio-informatic, evolutionary analysis of 351 available sequences of its genome with the aim of mapping genome structural variations and the patterns of selection. Methods A Maximum likelihood tree has been built and selective pressure has been investigated in order to find any mutation developed during the SARS-CoV-2 epidemic that could potentially affect clinical evolution of the infection. Finding We have found in more recent isolates the presence of two mutations affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures. Interpretation One of the two mutations, likely developed within the genome during virus spread, could affect virus intracellular survival. Genome follow-up of SARS-CoV-2 spread is urgently needed in order to identify mutations that could significantly modify virus pathogenicity.", "title": "Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy", "pid": "tldg8c94", "bm25_score": 218.22164916992188}, {"text": "The origin of the severe acute respiratory syndrome‐coronavirus (SARS‐CoV) remains unclear. Evidence based on Bayesian scanning plots and phylogenetic analysis using maximum likelihood (ML) and Bayesian methods indicates that SARS‐CoV, for the largest part of the genome (∼80%), is more closely related to Group II coronaviruses sequences, whereas in three regions in the ORF1ab gene it shows no apparent similarity to any of the previously characterized groups of coronaviruses. There is discordant phylogenetic clustering of SARS‐CoV and coronaviruses sequences, throughout the genome, compatible with either ancient recombination events or altered evolutionary rates in different lineages, or a combination of both. J. Med. Virol. 74:369–372, 2004. © 2004 Wiley‐Liss, Inc.", "title": "Phylogenetic analysis of the full‐length SARS‐CoV sequences: Evidence for phylogenetic discordance in three genomic regions", "pid": "arp07mck", "bm25_score": 218.18325805664062}, {"text": "To investigate the evolutionary history of the recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China, a total of 70 genomes of virus strains from China and elsewhere with sampling dates between 24 December 2019 and 3 February 2020 were analyzed. To explore the potential intermediate animal host of the SARS-CoV-2 virus, we reanalyzed virome data sets from pangolins and representative SARS-related coronaviruses isolates from bats, with particular attention paid to the spike glycoprotein gene. We performed phylogenetic, split network, transmission network, likelihood-mapping, and comparative analyses of the genomes. Based on Bayesian time-scaled phylogenetic analysis using the tip-dating method, we estimated the time to the most recent common ancestor and evolutionary rate of SARS-CoV-2, which ranged from 22 to 24 November 2019 and 1.19 to 1.31 × 10-3 substitutions per site per year, respectively. Our results also revealed that the BetaCoV/bat/Yunnan/RaTG13/2013 virus was more similar to the SARS-CoV-2 virus than the coronavirus obtained from the two pangolin samples (SRR10168377 and SRR10168378). We also identified a unique peptide (PRRA) insertion in the human SARS-CoV-2 virus, which may be involved in the proteolytic cleavage of the spike protein by cellular proteases, and thus could impact host range and transmissibility. Interestingly, the coronavirus carried by pangolins did not have the RRAR motif. Therefore, we concluded that the human SARS-CoV-2 virus, which is responsible for the recent outbreak of COVID-19, did not come directly from pangolins.", "title": "Evolutionary history, potential intermediate animal host, and cross-species analyses of SARS-CoV-2", "pid": "rvr86c6c", "bm25_score": 218.16465759277344}, {"text": "Abstract A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.", "title": "Genomic characterization of a novel SARS-CoV-2", "pid": "vjfquvlu", "bm25_score": 218.13198852539062}, {"text": "The phylogenetic clustering of 95 SARS-CoV-2 sequences from the first 3 months of the pandemic reveals insights into the early evolution of the virus and gives first indications of how the variants are globally distributed. Variants might become a challenge in terms of diagnostics, immunology, and effectiveness of drugs. All available whole genome sequence data from the NCBI database (March 16, 2020) were phylogenetically analyzed, and gene prediction as well as analysis of selected variants were performed. Antigenic regions and the secondary protein structure were predicted for selected variants. While some clusters are presenting the same variant with 100% identical bases, other SARS-CoV-2 lineages show a beginning diversification and phylogenetic clustering due to base substitutions and deletions in the genomes. First molecular epidemiological investigations are possible with the results by adding metadata as travelling history to the presented data. The advantage of variants in source tracing can be a challenge in terms of virulence, immune response, and immunological memory. Variants of viruses often show differences in virulence or antigenicity. This must also be considered in decisions like herd immunity. Diagnostic methods might not work if the variations or deletions are in target regions for the detection of the pathogen. One base substitution was detected in a primer binding site.", "title": "Early Phylogenetic Diversification of SARS-CoV-2: Determination of Variants and the Effect on Epidemiology, Immunology, and Diagnostics.", "pid": "3sxlvoxf", "bm25_score": 218.13070678710938}, {"text": "The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin converting enzyme-2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "title": "Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach", "pid": "w5ytp1q7", "bm25_score": 218.11181640625}, {"text": "As the coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), rages across the world, killing hundreds of thousands and infecting millions, researchers are racing against time to elucidate the viral genome. Some Bangladeshi institutes are also in this race, sequenced a few isolates of the virus collected from Bangladesh. Here, we present a genomic analysis of 14 isolates. The analysis revealed that SARS-CoV-2 isolates sequenced from Dhaka and Chittagong were the lineage of Europe and the Middle East, respectively. Our analysis identified a total of 42 mutations, including three large deletions, half of which were synonymous. Most of the missense mutations in Bangladeshi isolates found to have weak effects on the pathogenesis. Some mutations may lead the virus to be less pathogenic than the other countries. Molecular docking analysis to evaluate the effect of the mutations on the interaction between the viral spike proteins and the human ACE2 receptor, though no significant interaction was observed. This study provides some preliminary insights into the origin of Bangladeshi SARS-CoV-2 isolates, mutation spectrum and its possible pathomechanism, which may give an essential clue for designing therapeutics and management of COVID-19 in Bangladesh.", "title": "Genetic analysis of SARS-CoV-2 isolates collected from Bangladesh: insights into the origin, mutation spectrum, and possible pathomechanism", "pid": "8ow952d8", "bm25_score": 218.109619140625}, {"text": "", "title": "Median-joining network analysis of SARS-CoV-2 genomes is neither phylogenetic nor evolutionary", "pid": "wvkbihj8", "bm25_score": 218.10589599609375}, {"text": "In a phylogenetic network analysis of 160 complete human severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) genomes, we find three central variants distinguished by amino acid changes, which we have named A, B, and C, with A being the ancestral type according to the bat outgroup coronavirus. The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia. The network faithfully traces routes of infections for documented coronavirus disease 2019 (COVID-19) cases, indicating that phylogenetic networks can likewise be successfully used to help trace undocumented COVID-19 infection sources, which can then be quarantined to prevent recurrent spread of the disease worldwide.", "title": "Phylogenetic network analysis of SARS-CoV-2 genomes", "pid": "d5qzzvy3", "bm25_score": 218.1018829345703}, {"text": "A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.", "title": "Genomic characterization of a novel SARS-CoV-2", "pid": "mp3196kj", "bm25_score": 218.08413696289062}, {"text": "Starting around December 2019, an epidemic of pneumonia, which was named COVID-19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full-length genomic sequences of SARAS-CoV-2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS-CoV-2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%-100%) at the nucleotide level and 99.99% (99.79%-100%) at the amino acid level. Although overall variation in open-reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS-COV-2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS-CoV-2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS-CoV-2 infection in the future.", "title": "The establishment of reference sequence for SARS-CoV-2 and variation analysis", "pid": "g1zxlaer", "bm25_score": 218.08126831054688}, {"text": "Abstract Background Phyloepidemiologic approaches have given specific insight to understanding emergence and evolution of infection. Knowledge on the outbreak and spread of SARS-CoV-2 in Nigeria would assist in providing preventive measures to reduce transmission among populations at risk. Therefore, this study aimed at investigating the evolution of SARS-CoV-2 in Nigeria. Materials and Method A total of 39 complete genomes of SARS-CoV-2 were retrieved from the GISAID EpiFluTM database on March 29th 2020 to investigate its evolution in Nigeria. Sequences were selected based on the travel history of the patient and the collection date. Other sequences were not selected because they were short, contained artefacts, not from original source or had insufficient information. Evolutionary history was inferred using Maximum Likelihood method based on the General Time Reversible model. Phylogenetic tree was constructed to determine the common ancestor of each strain. Results The phylogenetic analysis showed the strain in Nigeria clustered in a monophyletic clade with a Wuhan sublineage. Nucleotide alignment also showed a 100% similarity indicating a common origin of evolution. Comparative analysis showed 27,972 (93.6%) identical sites and 97.6% pairwise identity with the consensus. Conclusion The study evidently showed the entire outbreak of COVID-19 infection in Nigeria stemmed from a single introduction sharing consensus similarity with the reference SARS-CoV-2 human genome from Wuhan. Preventive measures that can limit the spread of the infection among populations at risk should be implemented.", "title": "Phyloevolutionary analysis of SARS-CoV-2 in Nigeria", "pid": "aejbfk3l", "bm25_score": 218.0758514404297}, {"text": "The novel human coronavirus (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic worldwide. The increasing sequencing data have shown abundant single nucleotide variations in SARS-CoV-2 genome. However, it is difficult to quickly analyze genomic variation and screen key mutations of SARS-CoV-2. In this study, we developed a visual program, named BioAider, for quick and convenient sequence annotation and mutation analysis on multiple genome-sequencing data. Using BioAider, we conducted a comprehensive genome variation analysis on 3,240 sequences of SARS-CoV-2 genome. Herein, we detected 14 substitution hotspots within SARS-CoV-2 genome, including 10 non-synonymous and 4 synonymous ones. Among these hotspots, NSP13-Y541C was predicted to be a crucial substitution which might affect the unwinding activity of NSP13, a key protein for viral replication. Besides, we also found 3 groups of potentially linked substitution hotspots which were worth further study. In particular, we discovered a SR-rich region (aa 184-204) on the N protein of SARS-CoV-2 distinct from SARS-CoV, indicating more complex replication mechanism and unique N-M interaction of SARS-CoV-2. Interestingly, the quantity of SRXX repeat fragments in the SR-rich region well reflected the evolutionary relationship among SARS-CoV-2 and SARS-CoV-2 related animal coronaviruses, providing further evidence of its animal origin. Overall, we developed an efficient tool for rapid identification of mutations, identified substitution hotspots in SARS-CoV-2 genomes, and detected a distinctive polymorphism SR-rich region in N protein. This tool and the detected hotspots could facilitate the viral genomic study and may contribute for screening antiviral target sites.", "title": "Characterization of the substitution hotspots in SARS-CoV-2 genome using BioAider and detection of a SR-rich region in N protein providing further evidence of its animal origin", "pid": "hib30ct6", "bm25_score": 218.07411193847656}, {"text": "Research efforts of the ongoing SARS-CoV-2 pandemic have focused on viral genome sequence analysis to understand how the virus spread across the globe. Here, we assess three recently identified SARS-CoV-2 genomes in Beijing from June 2020 and attempt to determine the origin of these genomes, made available in the GISAID database. The database contains fully or partially sequenced SARS-CoV-2 samples from laboratories around the world. Including the three new samples and excluding samples with missing annotations, we analyzed 7, 643 SARS-CoV-2 genomes. Using principal component analysis computed on a similarity matrix that compares all pairs of the SARS-CoV-2 nucleotide sequences at all loci simultaneously, using the Jaccard index, we find that the newly discovered virus genomes from Beijing are in a genetic cluster that consists mostly of cases from Europe and South(east) Asia. The sequences of the new cases are most related to virus genomes from a small number of cases from China (March 2020), cases from Europe (February to early May 2020), and cases from South(east) Asia (May to June 2020). These findings could suggest that the original cases of this genetic cluster originated from China in March 2020 and were re-introduced to China by transmissions from samples from South(east) Asia between April and June 2020.", "title": "Unsupervised cluster analysis of SARS-CoV-2 genomes indicates that recent (June 2020) cases in Beijing are from a genetic subgroup that consists of mostly European and South(east) Asian samples, of which the latter are the most recent", "pid": "4oa0gsos", "bm25_score": 218.06460571289062}, {"text": "The first Indian cases of COVID-19 caused by SARS-Cov-2 were reported in February 29, 2020 with a history of travel from Wuhan, China and so far above 4500 deaths have been attributed to this pandemic. The objectives of this study were to characterize Indian SARS-CoV-2 genome-wide nucleotide variations, trace ancestries using phylogenetic networks and correlate state-wise distribution of viral haplotypes with differences in mortality rates. A total of 305 whole genome sequences from 19 Indian states were downloaded from GISAID. Sequences were aligned using the ancestral Wuhan-Hu genome sequence (NC_045512.2). A total of 633 variants resulting in 388 amino acid substitutions were identified. Allele frequency spectrum, and nucleotide diversity (π) values revealed the presence of higher proportions of low frequency variants and negative Tajima’s D values across ORFs indicated the presence of population expansion. Network analysis highlighted the presence of two major clusters of viral haplotypes, namely, clade G with the S:D614G, RdRp: P323L variants and a variant of clade L [Lv] having the RdRp:A97V variant. Clade G genomes were found to be evolving more rapidly into multiple sub-clusters including clade GH and GR and were also found in higher proportions in three states with highest mortality rates namely, Gujarat, Madhya Pradesh and West Bengal.", "title": "Phylogenetic clustering of the Indian SARS-CoV-2 genomes reveals the presence of distinct clades of viral haplotypes among states", "pid": "9slpoyz7", "bm25_score": 218.05899047851562}, {"text": "The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present study highlights the genomic, proteomic, pathogenesis, and therapeutic strategies in SARS-CoV-2 infection. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins has been performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, which makes available drugs ineffective.", "title": "Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach", "pid": "1evug4fr", "bm25_score": 218.0507354736328}, {"text": "From an isolated epidemic, COVID-19 has now emerged as a global pandemic. The availability of genomes in the public domain following the epidemic provides a unique opportunity to understand the evolution and spread of the SARS-CoV-2 virus across the globe. The availability of whole genomes from multiple states in India prompted us to analyse the phylogenetic clusters of genomes in India. We performed whole-genome sequencing for 64 genomes making a total of 361 genomes from India, followed by phylogenetic clustering, substitution analysis, and dating of the different phylogenetic clusters of viral genomes. We describe a distinct phylogenetic cluster (Clade I / A3i) of SARS-CoV-2 genomes from India, which encompasses 41% of all genomes sequenced and deposited in the public domain from multiple states in India. Globally 3.5% of genomes, which till date could not be mapped to any distinct known cluster fall in this newly defined clade. The cluster is characterized by a core set of shared genetic variants – C6312A (T2016K), C13730T (A88V/A97V), C23929T, and C28311T (P13L). Further, the cluster is also characterized by a nucleotide substitution rate of 1.4 × 10−3 variants per site per year, lower than the prevalent A2a cluster, and predominantly driven by variants in the E and N genes and relative sparing of the S gene. Epidemiological assessments suggest that the common ancestor emerged in the month of February 2020 and possibly resulted in an outbreak followed by countrywide spread, as evidenced by the low divergence of the genomes from across the country. To the best of our knowledge, this is the first comprehensive study characterizing the distinct and predominant cluster of SARS-CoV-2 in India.", "title": "A distinct phylogenetic cluster of Indian SARS-CoV-2 isolates", "pid": "x6hln4wk", "bm25_score": 218.03604125976562}, {"text": "We sequenced the 29,751-base genome of the severe acute respiratory syndrome (SARS)-associated coronavirus known as the Tor2 isolate. The genome sequence reveals that this coronavirus is only moderately related to other known coronaviruses, including two human coronaviruses, HCoV-OC43 and HCoV-229E. Phylogenetic analysis of the predicted viral proteins indicates that the virus does not closely resemble any of the three previously known groups of coronaviruses. The genome sequence will aid in the diagnosis of SARS virus infection in humans and potential animal hosts (using polymerase chain reaction and immunological tests), in the development of antivirals (including neutralizing antibodies), and in the identification of putative epitopes for vaccine development.", "title": "The Genome sequence of the SARS-associated coronavirus.", "pid": "flu3lrif", "bm25_score": 218.02113342285156}, {"text": "Abstract In December 2019, a novel human-infecting coronavirus (SARS-CoV-2) was recognized in China. In a few months, SARS-CoV-2 has caused thousands of disease cases and deaths in several countries. Phylogenetic analyses indicated that SARS-CoV-2 clusters with SARS-CoV in the Sarbecovirus subgenus and viruses related to SARS-CoV-2 were identified from bats and pangolins. Coronaviruses have long and complex genomes with high plasticity in terms of gene content. To date, the coding potential of SARS-CoV-2 remains partially unknown. We thus used available sequences of bat and pangolin viruses to determine the selective events that shaped the genome structure of SARS-CoV-2 and to assess its coding potential. By searching for signals of significantly reduced variability at synonymous sites (dS), we identified six genomic regions, one of these corresponding to the programmed −1 ribosomal frameshift. The most prominent signal of dS reduction was observed within the E gene. A genome-wide analysis of conserved RNA structures indicated that this region harbors a putative functional RNA element that is shared with the SARS-CoV lineage. Additional signals of reduced dS indicated the presence of internal ORFs. Whereas the presence ORF9a (internal to N) was previously proposed by homology with a well characterized protein of SARS-CoV, ORF3h (for hypothetical, within ORF3a) was not previously described. The predicted product of ORF3h has 90% identity with the corresponding predicted product of SARS-CoV and displays features suggestive of a viroporin. Finally, analysis of the putative ORF10 revealed high dN/dS (3.82) in SARS-CoV-2 and related coronaviruses. In the SARS-CoV lineage, the ORF is predicted to encode a truncated protein and is neutrally evolving. These data suggest that ORF10 encodes a functional protein in SARS-CoV-2 and that positive selection is driving its evolution. Experimental analyses will be necessary to validate and characterize the coding and non-coding functional elements we identified.", "title": "Coding potential and sequence conservation of SARS-CoV-2 and related animal viruses", "pid": "zaxjj9q7", "bm25_score": 218.0104522705078}, {"text": "The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected in S, 12 variations were located at the N-terminal domain (NTD) and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin-converting enzyme 2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "title": "Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach", "pid": "c5fygzvz", "bm25_score": 217.9925537109375}, {"text": "OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has been rapidly spreading worldwide. Although the causal relationship among mutations and the features of SARS-CoV-2 such as rapid transmission, pathogenicity, and tropism, remains unclear, our results of genomic mutations in SARS-CoV-2 may help to interpret the interaction between genomic characterization in SARS-CoV-2 and infectivity with the host. METHODS: A total of 4,254 genomic sequences of SARS-CoV-2 were collected from the Global Initiative on Sharing all Influenza Data (GISAID). Multiple sequence alignment for phylogenetic analysis and comparative genomic approach for mutation analysis were conducted using Molecular Evolutionary Genetics Analysis (MEGA), and an in-house program based on Perl language, respectively. RESULTS: Phylogenetic analysis of SARS-CoV-2 strains indicated that there were 3 major clades including S, V, and G, and 2 subclades (G.1 and G.2). There were 767 types of synonymous and 1,352 types of non-synonymous mutation. ORF1a, ORF1b, S, and N genes were detected at high frequency, whereas ORF7b and E genes exhibited low frequency. In the receptor-binding domain (RBD) of the S gene, 11 non-synonymous mutations were observed in the region adjacent to the angiotensin converting enzyme 2 (ACE2) binding site. CONCLUSION: It has been reported that the rapid infectivity and transmission of SARS-CoV-2 associated with host receptor affinity are derived from several mutations in its genes. Without these genetic mutations to enhance evolutionary adaptation, species recognition, host receptor affinity, and pathogenicity, it would not survive. It is expected that our results could provide an important clue in understanding the genomic characteristics of SARS-CoV-2.", "title": "Genome-Wide Identification and Characterization of Point Mutations in the SARS-CoV-2 Genome", "pid": "shn7vx3d", "bm25_score": 217.98709106445312}, {"text": "AIM Recently, more SARS-CoV virus genome sequences are released to the GenBank database. The aim of this study is to reveal the evolution forces of SARS-CoV virus by analyzing the nucleotide mutations in these sequences. METHODS We obtained 20 SARS-CoV virus genome sequences from NCBI database, and calculated the ratio of non-synonymous nucleotide substitution per non-synonymous site (Ka) and synonymous nucleotide substitution per synonymous site (Ks) for SARS-CoV virus genes. RESULTS The Ka/Ks ratios for replicase polyprotein ORF1a, ORF1b, and spike protein gene are 1.09 (P=0.6501), 0.38 (P=0.0074), 0.65 (P=0.0685) respectively. CONCLUSION SARS-CoV virus replicase polyprotein ORF1b is undergoing negative selection; negative selection force is also probably operating on spike protein gene. These results provide basis for future developing a new drug and vaccine against SARS.", "title": "Mutation analysis of 20 SARS virus genome sequences: evidence for negative selection in replicase ORF1b and spike gene.", "pid": "8r5wopu9", "bm25_score": 217.97909545898438}, {"text": "Monitoring the mutation dynamics of SARS-CoV-2 is critical for the development of effective approaches to contain the pathogen. By analyzing 106 SARS-CoV-2 and 39 SARS genome sequences, we provided direct genetic evidence that SARS-CoV-2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. This represents the first report of a significant SARS-CoV-2 mutant, and raises the alarm that the ongoing vaccine development may become futile in future epidemic if more mutations were identified. Highlights Based on the currently available genome sequence data, we proved that SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002-2003 outbreak. The spike (S) protein encoding gene of SARS-COV-2 is found relatively more conserved than other protein-encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. We confirmed a previously reported rearrangement in the S protein arrangement of SARS-COV-2, and propose that this rearrangement should have occurred between human SARS-CoV and a bat SARS-CoV, at a time point much earlier before SARS-COV-2 transmission to human. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020.", "title": "Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity", "pid": "t8q99tlq", "bm25_score": 217.9684600830078}, {"text": "During the past three months, a new coronavirus (SARS-CoV-2) epidemic has been growing exponentially, affecting over 100 thousand people worldwide, and causing enormous distress to economies and societies of affected countries. A plethora of analyses based on viral sequences has already been published, in scientific journals as well as through non-peer reviewed channels, to investigate SARS-CoV-2 genetic heterogeneity and spatiotemporal dissemination. We examined all full genome sequences currently available to assess the presence of sufficient information for reliable phylogenetic and phylogeographic studies. Our analysis clearly shows severe limitations in the present data, in light of which any finding should be considered, at the very best, preliminary and hypothesis-generating. Hence the need for avoiding stigmatization based on partial information, and for continuing concerted efforts to increase number and quality of the sequences required for robust tracing of the epidemic.", "title": "Regaining perspective on SARS-CoV-2 molecular tracing and its implications", "pid": "szg12wfa", "bm25_score": 217.9623260498047}, {"text": "The emerging global infectious COVID-19 coronavirus disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. For understanding the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. We present an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The SNP genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. Our method serves a promising tool for monitoring and tracking the epidemic of pathogenic viruses in their gradual and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.", "title": "Genotyping coronavirus SARS-CoV-2: methods and implications", "pid": "ulygq434", "bm25_score": 217.95909118652344}, {"text": "Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA State) and Australia (VIC). A total of 30 datasets (60%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA next-generation sequencing samples. Sequencing samples from North America in GenBank (22 April 2020) present this signature with up to 39% allele frequencies among samples (n = 1,359). Australian variant signatures were more diverse than USA samples, but still, clonal events were found in these samples. Mutations in the helicase, encoded by the ORF1ab gene in SARS-CoV-2 were predominant, among others, suggesting that these regions are actively evolving. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.", "title": "Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions", "pid": "0xruezf2", "bm25_score": 217.95492553710938}, {"text": "BACKGROUND: More than 2 months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence. METHODS: To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, WA were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2. RESULTS: Within 36 h our results showed clear identification of a novel human Betacoronavirus, closely related to known Betacoronaviruses of bats, in laboratory-proven cases of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Samples negative for SARS-CoV-2 by RT-PCR were also negative by metagenomic analysis, and positive for Rhinovirus A and C. Unlike targeted SARS-CoV-2 qRT-PCR testing, metagenomic analysis of these SARS-CoV-2 negative samples identified candidate etiological agents for the patients' respiratory symptoms. CONCLUSION: Taken together, these results demonstrate the value of metagenomic analysis in the monitoring and response to this and future viral pandemics.", "title": "Metagenomic Analysis Reveals Clinical SARS-CoV-2 Infection and Bacterial or Viral Superinfection and Colonization", "pid": "lsowgp2e", "bm25_score": 217.9483642578125}, {"text": "The recent zoonotic coronavirus virus outbreak of a novel type [COVID 19] has necessitated the adequate understanding of the evolutionary pathway of zoonotic viruses which adversely affects human populations for therapeutic constructs to combat the pandemic now and in the future. We analyzed conserved domains of the severe acute respiratory coronavirus 2 [SARS-CoV2] for possible targets of viral entry inhibition in host cells, evolutionary relationship of human coronavirus [229E] and zoonotic coronaviruses with SAR-CoV2 as well as evolutionary relationship between selected SARS-CoV 2 genomic data. Conserved domains with antagonistic action on host innate antiviral cellular mechanisms in SARS-CoV 2 include nsp 11, nsp 13 etc. Also, multiple sequence alignments of the spike [S] gene protein of selected candidate zoonotic coronaviruses alongside the S gene protein of the SARs-CoV2 revealed closest evolutionary relationship [95.6%] with pangolin coronaviruses [S] gene. Clades formed between Wuhan SARS-CoV2 phylogeny data and five others suggests viral entry trajectory while revealing genomic and protein SARS CoV 2 data from Philippines as early ancestors. Therefore, phylogeny of SARS-CoV 2 genomic data suggests profiling in diverse populations with and without the outbreak alongside migration history and racial background for mutation tracking and dating of viral subtype divergence which is essential for effective management of present and future zoonotic coronavirus outbreaks.", "title": "In-silico nucleotide and protein analyses of S-gene region in selected zoonotic coronaviruses reveal conserved domains and evolutionary emergence with trajectory course of viral entry from SARS-CoV2 genomic data", "pid": "bmwgq7py", "bm25_score": 217.94554138183594}, {"text": "Objectives To reveal epidemic trend and possible origins of SARS-CoV-2 by exploring its evolution and molecular characteristics based on a large number of genomes since it has infected millions of people and spread quickly all over the world. Methods Various evolution analysis methods were employed. Results The estimated Ka/Ks ratio of SARS-CoV-2 is 1.008 or 1.094 based on 622 or 3624 SARS-CoV-2 genomes, and the time to the most recent common ancestor (tMRCA) was inferred in late September 2019. Further 9 key specific sites of highly linkage and four major haplotypes H1, H2, H3 and H4 were found. The Ka/Ks, detected population size and development trends of each major haplotype showed H3 and H4 subgroups were going through a purify evolution and almost disappeared after detection, indicating H3 and H4 might have existed for a long time, while H1 and H2 subgroups were going through a near neutral or neutral evolution and globally increased with time. Notably the frequency of H1 was generally high in Europe and correlated to death rate (r>0.37). Conclusions In this study, the evolution and molecular characteristics of more than 16000 genomic sequences provided a new perspective for revealing epidemiology of SARS-CoV-2.", "title": "Comprehensive evolution and molecular characteristics of a large number of SARS-CoV-2 genomes revealed its epidemic trend and possible origins", "pid": "npcu4wq1", "bm25_score": 217.9451141357422}, {"text": "SARS-CoV, as the pathogeny of severe acute respiratory syndrome (SARS), is a mystery that the origin of the virus is still unknown even a few isolates of the virus were completely sequenced. To explore the genesis of SARS-CoV, the FDOD method previously developed by us was applied to comparing complete genomes from 12 SARS-CoV isolates to those from 12 previously identified coronaviruses and an unrooted phylogenetic tree was constructed. Our results show that all SARS-CoV isolates were clustered into a clique and previously identified coronaviruses formed the other clique. Meanwhile, the three groups of coronaviruses depart from each other clearly in our tree that is consistent with the results of prevenient papers. Differently, from the topology of the phylogenetic tree we found that SARS-CoV is more close to group 1 within genus coronavirus. The topology map also shows that the 12 SARS-CoV isolates may be divided into two groups determined by the association with the SARS-CoV from the Hotel M in Hong Kong that may give some information about the infectious relationship of the SARS.", "title": "Phylogeny of SARS-CoV as inferred from complete genome comparison", "pid": "x9az3twa", "bm25_score": 217.9438934326172}, {"text": "The sudden emergence of severe respiratory disease, caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has recently become a public health emergency. Genome sequence analysis of SARS-CoV-2 revealed its close resemblance to the earlier reported SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). However, initial testing of the drugs used against SARS-CoV and MERS-CoV has been ineffective in controlling SARS-CoV-2. The present review looks to highlight the differences in genomic, proteomic, pathogenesis, and therapeutic strategies of SARS-CoV-2. We have carried out sequence analysis of potential drug target proteins in SARS-CoV-2 and, compared them with SARS-CoV-1 and MERS viruses. Analysis of mutations in the coding and non-coding regions, genetic diversity, and pathogenicity of SARS-CoV-2 has also been done. A detailed structural analysis of drug target proteins was performed to gain insights into the mechanism of pathogenesis, structure-function relationships, and the development of structure-guided therapeutic approaches. The cytokine profiling and inflammatory signalling are different in the case of SARS-CoV-2 infection. We also highlighted possible therapies and their mechanism of action followed by clinical manifestation. Our analysis suggests a minimal variation in the genome sequence of SARS-CoV-2, may be responsible for a drastic change in the structures of target proteins, makes available drugs ineffective.", "title": "Insights into SARS-CoV-2 genome, structure, evolution, pathogenesis and therapies: Structural genomics approach", "pid": "dfydh7sf", "bm25_score": 217.941650390625}, {"text": "The pandemic COVID-19 caused by the zoonotic virus SARS-CoV-2 has devastated countries worldwide, infecting more than 4.5 million people and leading to more than 300,000 deaths. Whole genome sequencing (WGS) is an effective tool to monitor emerging strains and provide information for intervention, thus help to inform outbreak control decisions. Here, we reported the first effort to sequence and de novo assemble the whole genome of SARS-CoV-2 using PacBio’s SMRT sequencing technology in Vietnam. We also presented the annotation results and a brief analysis of the variants found in our SARS-CoV-2 strain, which was isolated from a Vietnamese patient. The sequencing was successfully completed and de novo assembled in less than 30 hours, resulting in one contig with no gap and a length of 29,766 bp. All detected variants as compared to the NCBI reference were highly accurate as confirmed by Sanger sequencing. The results have shown the potential of long read sequencing to provide high quality WGS data to support public health responses, and advance understanding of this and future pandemics.", "title": "WHOLE-GENOME SEQUENCING AND DE NOVO ASSEMBLY OF A 2019 NOVEL CORONAVIRUS (SARS-COV-2) STRAIN ISOLATED IN VIETNAM", "pid": "eoa3dkoz", "bm25_score": 217.9274139404297}, {"text": "During its first two and a half months, the recently emerged 2019 novel coronavirus, SARS-CoV-2, has already infected over one-hundred thousand people worldwide and has taken more than four thousand lives. However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions. Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop. To expedite the advancement of our knowledge, we leveraged data about the related coronaviruses that is readily available in public databases and integrated these data into a single computational pipeline. As a result, we provide comprehensive structural genomics and interactomics roadmaps of SARS-CoV-2 and use this information to infer the possible functional differences and similarities with the related SARS coronavirus. All data are made publicly available to the research community.", "title": "Structural Genomics of SARS-CoV-2 Indicates Evolutionary Conserved Functional Regions of Viral Proteins", "pid": "fvirvpyl", "bm25_score": 217.9195556640625}, {"text": "Knowledge of the evolution of pathogens is of great medical and biological significance to the prevention, diagnosis, and therapy of infectious diseases. In order to understand the origin and evolution of the SARS-CoV (severe acute respiratory syndrome-associated coronavirus), we collected complete genome sequences of all viruses available in GenBank, and made comparative analyses with the SARS-CoV. Genomic signature analysis demonstrates that the coronaviruses all take the TGTT as their richest tetranucleotide except the SARS-CoV. A detailed analysis of the forty-two complete SARS-CoV genome sequences revealed the existence of two distinct genotypes, and showed that these isolates could be classified into four groups. Our manual analysis of the BLASTN results demonstrates that the HE (hemagglutinin-esterase) gene exists in the SARS-CoV, and many mutations made it unfamiliar to us.", "title": "Evolution and Variation of the SARS-CoV Genome", "pid": "8oz6bgz4", "bm25_score": 217.9126739501953}, {"text": "To investigate the evolutionary history of the current pandemic outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a total of 137 genomes of coronavirus strains with release dates between January 2019 and 25 March 2020, were analyzed. To investigate the potential intermediate host of the SARS-CoV-2, we analyzed spike glycoprotein sequences from different animals, with particular emphasis on bats. We performed phylogenetic analysis and structural reconstruction of the spike glycoproteins with subsequent alignment and comparison. Our phylogenetic results revealed that SARS-CoV-2 was more similar to the bats' betacoronavirus isolates: HKU5-related from Pipistrellus abramus and HKU4-related from Tylonycteris pachypus. We also identified a yak betacoronavirus strain, YAK/HY24/CH/2017, as the closest match in the comparison of the structural models of spike glycoproteins. Interestingly, a set of unique features has been described for this particular strain of the yak betacoronavirus. Therefore, our results suggest that the human SARS-CoV-2, responsible for the current outbreak of COVID-19, could also come from yak as an intermediate host.", "title": "SARS-CoV-2: Structural diversity, phylogeny, and potential animal host identification of spike glycoprotein", "pid": "d9qtn37b", "bm25_score": 217.91165161132812}, {"text": "BACKGROUND: More than two months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence. METHODS: To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, Washington were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2. RESULTS: Within 36 hours our results showed clear identification of a novel human Betacoronavirus, closely related to known Betacoronaviruses of bats, in laboratory-proven cases of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Samples negative for SARS-CoV-2 by RT-PCR were also negative by metagenomic analysis, and positive for Rhinovirus A and C. Unlike targeted SARS-CoV-2 qRT-PCR testing, metagenomic analysis of these SARS-CoV-2 negative samples identified candidate etiological agents for the patients’ respiratory symptoms. CONCLUSION: Taken together, these results demonstrate the value of metagenomic analysis in the monitoring and response to this and future viral pandemics.", "title": "Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization", "pid": "m0fjt483", "bm25_score": 217.86160278320312}, {"text": "Genomic analysis of SARS-CoV-2 sequences is crucial in determining the effectiveness of prudent safer at home measures in the United States (US). By haplotype analysis of 6,356 US isolates, we identified a pattern of strongly localized outbreaks at the city-, state-, and country-levels, and temporal transmissions. This points to the effectiveness of existing travel restriction policies and public health measures in controlling the transmission of SARS-CoV-2.", "title": "Comprehensive genome analysis of 6,000 USA SARS-CoV-2 isolates reveals haplotype signatures and localized transmission patterns by state and by country", "pid": "ydl44zg8", "bm25_score": 217.8585205078125}, {"text": "The COVID-19 pandemic has spread across the globe at an alarming rate in the last four months. However, unlike any of the previous global outbreaks the availability of hundreds of SARS-CoV-2 sequences provides us with a unique opportunity to understand viral evolution in real time. We analysed 480 full-length (>29000 nt) sequences from the 1575 SARS-CoV-2 sequences available and identified 37 single-nucleotide substitutions occurring in >1% of the genomes. Majority of the substitutions were C to T or G to A. We identify C/Gs with an upstream TTT trinucleotide motif as hotspots for mutations in the SARS-CoV-2 genome. Interestingly, two of the 37 substitutions occur within highly conserved secondary structures in the 5’ and 3’ untranslated regions that are critical for the virus life cycle. Furthermore, clustering analysis revealed unique geographical distribution of SARS-CoV-2 variants defined by their mutation profile. Of note, we observed several co-occurring mutations that almost never occur individually. We define 3 mutually exclusive lineages (A1, B1 and C1) of SARS-CoV-2 which account for about three quarters of the genomes analysed. We identify lineage-defining leading mutations in the SARS-CoV-2 genome which precede the occurrence of sub-lineage defining trailing mutations. The identification of mutually exclusive lineage-defining mutations with geographically restricted patterns of distribution has potential implications for diagnosis, pathogenesis and vaccine design. Our work provides novel insights on the temporal evolution of SARS-CoV-2.", "title": "Mutation landscape of SARS-CoV-2 reveals three mutually exclusive clusters of leading and trailing single nucleotide substitutions", "pid": "miujzgtd", "bm25_score": 217.85845947265625}, {"text": "The emerging global infectious COVID-19 disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. To understand the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. This study presents an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The single-nucleotide polymorphism (SNP) genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. The proposed method serves an effective tool for monitoring and tracking the epidemic of pathogenic viruses in their global and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.", "title": "Genotyping coronavirus SARS-CoV-2: methods and implications", "pid": "leyqhma0", "bm25_score": 217.857177734375}, {"text": "OBJECTIVE To perform variation and phylogenetics analysis on the SARS-CoV genome sequence (PUMC01) isolated in the Peking Union Medical College Hospital. METHODS The cDNA library of SARS-CoV (PUMC01 isolate) was constructed by means of random-priming strategy. Random selected plasmid was sequenced and the genome sequence of SARS-CoV-PUMC01 was assembled by conventional methods (The Genebank Accession No. of SARS-CoV-PUMC01 is AY350750). The variation and phylogenetics analysis were performed by comparing the PUMC01 sequence with other SARS-CoV isolates. RESULTS Ten variation sites were found by comparing PUMC01 isolate with Tor2 and Urbani isolates. In phylogenetic analysis of 18 SARS-CoV isolates, two classes were observed and there is different differential time between these two classes and the different isolates in each class. CONCLUSIONS The evidence of phylogenetic analysis of different SARS-CoV isolates from different region is instructive for understanding the clinical relations between the different isolates and the transmission chain of SARS-CoV.", "title": "[Analysis on the SARS-CoV genome of PUMC01 isolate].", "pid": "agox0lbq", "bm25_score": 217.85391235351562}, {"text": "Abstract The emerging global infectious COVID-19 disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. To understand the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. This study presents an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The single-nucleotide polymorphism (SNP) genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. The proposed method serves an effective tool for monitoring and tracking the epidemic of pathogenic viruses in their global and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.", "title": "Genotyping coronavirus SARS-CoV-2: Methods and implications", "pid": "jujrazsr", "bm25_score": 217.85218811035156}, {"text": "The rooting of the SARS-CoV-2 phylogeny is important for understanding the origin and early spread of the virus. Previously published phylogenies have used different rootings that do not always provide consistent results. We use several different strategies for rooting the SARS-CoV-2 tree and provide measures of statistical uncertainty for all methods. We show that methods based on the molecular clock tend to place the root in the B clade, while methods based on outgroup rooting tend to place the root in the A clade. The results from the two approaches are statistically incompatible, possibly as a consequence of deviations from a molecular clock or excess back-mutations. We also show that none of the methods provide strong statistical support for the placement of the root in any particular edge of the tree. Our results suggest that inferences on the origin and early spread of SARS-CoV-2 based on rooted trees should be interpreted with caution.", "title": "Assessing uncertainty in the rooting of the SARS-CoV-2 phylogeny", "pid": "55loucvc", "bm25_score": 217.85165405273438}, {"text": "Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive repository. Up until March 27, 2020, we downloaded 53 illumina datasets, mostly from China, USA (Washington DC) and Australia (Victoria). Of 30 high quality datasets, 27 datasets (90%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA sequencing samples. Sequencing samples from USA in GenBank present this signature with 50% allele frequencies among samples. Australian mutation signatures were more diverse than USA samples, but still, clonal events were found in those samples. Mutations in the helicase and orf1a coding regions from SARS-CoV-2 were predominant, among others, suggesting that these proteins are prone to evolve by natural selection. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.", "title": "Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions", "pid": "gfwqog3x", "bm25_score": 217.84532165527344}, {"text": "Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S(2) domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in S(D) domain) and G1124V (in S(2) subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird’s eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12038-020-00046-1) contains supplementary material, which is available to authorized users.", "title": "Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility", "pid": "6dsx7pey", "bm25_score": 217.81588745117188}, {"text": "The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu TM database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau ( &#964;) using the formula t= &#964;/2 u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.", "title": "Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data", "pid": "gy78e87y", "bm25_score": 217.81045532226562}, {"text": "BACKGROUND China announced an outbreak of new coronavirus in the city of Wuhan on December 31, 2019; lash to now, the virus transmission has become pandemic worldwide. Severe cases from Huanan Seafood Wholesale market in Wuhan were confirmed pneumonia with a novel coronavirus. (2019-nCoV). Understanding the molecular mechanisms of genome selection and packaging is critical for developing antiviral strategies. Thus, we defined the correlation in ten SARS-CoV2 sequences from different countries to analyze the genomic patterns of disease origin and evolution aiming for development new control pandemic processes. METHODS We apply genomic analysis to observe SARS-Co-V2 sequences from GenBank (http:// www.ncbi.nim.nih.gov/genebank/): MN 908947 China, C1), MN985325 (USA:WA, UW), MN996527 (China, C2), MT007544 (Australia:Victoria, A1), MT027064 (USA:CA, UC), MT039890 (South Korea, K1), MT066175 (Taiwan,T1), MT066176 (Taiwan, T2), LC528232 (Japan, J1), and LC528233 (Japan, J2) for genomic sequence alignment an analysis. Multiple Sequence Alignment by Clustalw (https://www.genome.jp/tools-bin/clustalw) web is applied as our alignment tool. RESULTS We analyze ten sequences from NCBI database by genome alignment and find no difference in amino acid sequences within M and N proteins. There are two amino acid variances in Spike protein region. One mutation found from south Korea sequence is verified. Two possible \"L\" and \"S\" SNP found in ORF1ab and ORF8 regions are detected CONCLUSION:: We perform genomic analysis and comparative multiple sequence of SARS-CoV-2. Studies about the biological symptoms of SARS-CoV-2 in clinic animal and humans will manipulate an understanding the origin of pandemic crisis.", "title": "Genomic Analysis and Comparative Multiple Sequence of SARS-CoV2.", "pid": "zzi2xv3p", "bm25_score": 217.8008575439453}, {"text": "A coding-complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate was revealed. The sample for the virus was isolated from a female patient from Dhaka, Bangladesh, suffering from coronavirus disease-2019 (COVID-19).", "title": "Coding-Complete Genome Sequence of SARS-CoV-2 Isolate from Bangladesh by Sanger Sequencing.", "pid": "kc8j8h5e", "bm25_score": 217.7986297607422}, {"text": "The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFlu(TM) database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau (τ) using the formula t=τ/2u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.", "title": "Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data", "pid": "127c5bve", "bm25_score": 217.7969970703125}, {"text": "A novel coronavirus has been identified as the cause of the outbreak of severe acute respiratory syndrome (SARS). Previous phylogenetic analyses based on sequence alignments show that SARS‐CoVs form a new group distantly related to the other three groups of previously characterized coronaviruses. In this aritcle, a new approach based on the 2D graphical representation of the whole genome sequence is proposed to analyze the phylogenetic relationships of coronaviruses. The evolutionary distances are obtained through measuring the differences among the two‐dimensional curves. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1196–1202, 2006", "title": "Coronavirus phylogeny based on 2D graphical representation of DNA sequence", "pid": "plsspth8", "bm25_score": 217.7958526611328}, {"text": "During its first two and a half months, the recently emerged 2019 novel coronavirus, SARS-CoV-2, has already infected over one-hundred thousand people worldwide and has taken more than four thousand lives However, the swiftly spreading virus also caused an unprecedentedly rapid response from the research community facing the unknown health challenge of potentially enormous proportions Unfortunately, the experimental research to understand the molecular mechanisms behind the viral infection and to design a vaccine or antivirals is costly and takes months to develop To expedite the advancement of our knowledge, we leveraged data about the related coronaviruses that is readily available in public databases and integrated these data into a single computational pipeline As a result, we provide comprehensive structural genomics and interactomics roadmaps of SARS-CoV-2 and use this information to infer the possible functional differences and similarities with the related SARS coronavirus All data are made publicly available to the research community", "title": "Structural Genomics of SARS-CoV-2 Indicates Evolutionary Conserved Functional Regions of Viral Proteins", "pid": "5wp3wz6s", "bm25_score": 217.7794647216797}, {"text": "The recent global outbreak of viral pneumonia designated as Coronavirus Disease 2019 (COVID-19) by coronavirus (SARS-CoV-2) has threatened global public health and urged to investigate its source. Whole genome analysis of SARS-CoV-2 revealed ~96% genomic similarity with bat CoV (RaTG13) and clustered together in phylogenetic tree. Furthermore, RaTGl3 also showed 97.43% spike protein similarity with SARS-CoV-2 suggesting that RaTGl3 is the closest strain. However, RBD and key amino acid residues supposed to be crucial for human-to-human and cross-species transmission are homologues between SARS-CoV-2 and pangolin CoVs. These results from our analysis suggest that SARS-CoV-2 is a recombinant virus of bat and pangolin CoVs. Moreover, this study also reports mutations in coding regions of 125 SARS-CoV-2 genomes signifying its aptitude for evolution. In short, our findings propose that homologous recombination has been occurred between bat and pangolin CoVs that triggered cross-species transmission and emergence of SARS-CoV-2, and, during the ongoing outbreak, SARS-CoV-2 is still evolving for its adaptability.", "title": "Evidence of the Recombinant Origin and Ongoing Mutations in Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)", "pid": "fw4pmaoc", "bm25_score": 217.77235412597656}, {"text": "World Health Organization (WHO) declared COVID-19 as a pandemic disease on March 11, 2020. Comparison of genome sequences from diverse locations allows us to identify the genetic diversity among viruses which would help in ascertaining viral virulence, disease pathogenicity, origin and spread of the SARS-CoV-2 between countries. The aim of this study is to ascertain the genetic diversity among Indian SARS-CoV-2 isolates. Initial examination of the phylogenetic data of SARS-CoV-2 genomes (n=3123) from different continents deposited at GISAID (Global Initiative on Sharing All Influenza Data) revealed multiple origin for Indian isolates. An in-depth analysis of 449 viral genomes derived from samples representing countries from USA, Europe, China, East Asia, South Asia, Oceania, Middle East regions and India revealed that most Indian samples are divided into two clusters (A and B) with cluster A showing more similarity to samples from Oceania and Kuwait and the cluster B grouping with countries from Europe, Middle East and South Asia. Diversity analysis of viral clades, which are characterized by specific non-synonymous mutations in viral proteins, discovered that the cluster A Indian samples belong to I clade (V378I in ORF1ab), which is an Oceania clade with samples having Iran connections and the cluster B Indian samples belong to G clade (D614G in Spike protein), which is an European clade. Thus our study identifies that the Indian SARS-CoV-2 viruses belong to I and G clades with potential origin to be countries mainly from Oceania, Europe, Middle East and South Asia regions, which strongly implying the spread of virus through most travelled countries. The study also emphasizes the importance of pathogen genomics through phylogenetic analysis to discover viral genetic diversity and understand the viral transmission dynamics with eventual grasp on viral virulence and disease pathogenesis.", "title": "Genomics of Indian SARS-CoV-2: Implications in genetic diversity, possible origin and spread of virus", "pid": "i758v1vb", "bm25_score": 217.7535858154297}, {"text": "One of the reasons for the fast spread of SARS-CoV-2 is the lack of accuracy in detection tools in the clinical field. Molecular techniques, such as quantitative real-time RT-PCR and nucleic acid sequencing methods, are widely used to identify pathogens. For this particular virus, however, they have an overall unsatisfying detection rate, due to its relatively recent emergence and still not completely understood features. In addition, SARS-CoV-2 is remarkably similar to other Coronaviruses, and it can present with other respiratory infections, making identification even harder. To tackle this issue, we propose an assisted detection test, combining molecular testing with deep learning. The proposed approach employs a state-of-the-art deep convolutional neural network, able to automatically create features starting from the genome sequence of the virus. Experiments on data from the Novel Coronavirus Resource (2019nCoVR) show that the proposed approach is able to correctly classify SARS-CoV-2, distinguishing it from other coronavirus strains, such as MERS-CoV, HCoV-NL63, HCoV-OC43, HCoV-229E, HCoV-HKU1, and SARS-CoV regardless of missing information and errors in sequencing (noise). From a dataset of 553 complete genome non-repeated sequences that vary from 1,260 to 31,029 bps in length, the proposed approach classifies the different coronaviruses with an average accuracy of 98.75% in a 10-fold cross-validation, identifying SARS-CoV-2 with an AUC of 98%, specificity of 0.9939 and sensitivity of 1.00 in a binary classification. Then, using the same basis, we classify SARS-CoV-2 from 384 complete viral genome sequences with human host, that contain the gene ORF1ab from the NCBI with a 10-fold accuracy of 98.17%, a specificity of 0.9797 and sensitivity of 1.00. Furthermore, an in-depth analysis of the results allow us to identify base pairs sequences that are unique to SARS-CoV-2 and do not appear in other virus strains, that could then be used as a base for designing new primers and examined by experts to extract further insights. These preliminary results seem encouraging enough to identify deep learning as a promising research venue to develop assisted detection tests for SARS-CoV-2. At this end the interaction between viromics and deep learning, will hopefully help to solve global infection problems. In addition, we offer our code and processed data to be used for diagnostic purposes by medical doctors, virologists and scientists involved in solving the SARS-CoV-2 pandemic. As more data become available we will update our system.", "title": "Accurate Identification of SARS-CoV-2 from Viral Genome Sequences using Deep Learning", "pid": "c2lljdi7", "bm25_score": 217.74961853027344}, {"text": "We describe fifteen major mutation events from 2,058 high-quality SARS-CoV-2 genomes deposited up to March 31st, 2020. These events define five major clades (G, I, S, D and V) of globally-circulating viral populations, representing 85.7% of all sequenced cases, which we can identify using a 10 nucleotide genetic classifier or barcode. We applied this barcode to 4,000 additional genomes deposited between March 31st and April 15th and classified successfully 95.6% of the clades demonstrating the utility of this approach. An analysis of amino acid variation in SARS-CoV-2 ORFs provided evidence of substitution events in the viral proteins involved in both host-entry and genome replication. The systematic monitoring of dynamic changes in the SARS-CoV-2 genomes of circulating virus populations over time can guide therapeutic and prophylactic strategies to manage and contain the virus and, also, with available efficacious antivirals and vaccines, aid in the monitoring of circulating genetic diversity as we proceed towards elimination of the agent. The barcode will add the necessary genetic resolution to facilitate tracking and monitoring of infection clusters to distinguish imported and indigenous cases and thereby aid public health measures seeking to interrupt transmission chains without the requirement for real-time complete genomes sequencing.", "title": "The genomic variation landscape of globally-circulating clades of SARS-CoV-2 defines a genetic barcoding scheme", "pid": "drqhuhk4", "bm25_score": 217.7485809326172}, {"text": "Tracing the history of molecular changes in coronaviruses using phylogenetic methods can provide powerful insights into the patterns of modification to sequences that underlie alteration to selective pressure and molecular function in the SARS-CoV (severe acute respiratory syndrome coronavirus) genome. The topology and branch lengths of the phylogenetic relationships among the family Coronaviridae, including SARS-CoV, have been estimated using the replicase polyprotein. The spike protein fragments S1 (involved in receptor-binding) and S2 (involved in membrane fusion) have been found to have different mutation rates. Fragment S1 can be further divided into two regions (S1A, which comprises approximately the first 400 nucleotides, and S1B, comprising the next 280) that also show different rates of mutation. The phylogeny presented on the basis of S1B shows that SARS-CoV is closely related to MHV (murine hepatitis virus), which is known to bind the murine receptor CEACAM1. The predicted structure, accessibility and mutation rate of the S1B region is also presented. Because anti-SARS drugs based on S2 heptads have short half-lives and are difficult to manufacture, our findings suggest that the S1B region might be of interest for anti-SARS drug discovery.", "title": "Phylogenomics and bioinformatics of SARS-CoV", "pid": "ukuia48s", "bm25_score": 217.73727416992188}, {"text": "SARS-CoV-2 is a betacoronavirus that is responsible for the COVID-19 pandemic. The genome of SARS-CoV-2 was reported recently, but its transcriptomic architecture is unknown. Utilizing two complementary sequencing techniques, we here present a high-resolution map of the SARS-CoV-2 transcriptome and epitranscriptome. DNA nanoball sequencing shows that the transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical. In addition to the genomic RNA and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces a large number of transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Using nanopore direct RNA sequencing, we further find at least 41 RNA modification sites on viral transcripts, with the most frequent motif being AAGAA. Modified RNAs have shorter poly(A) tails than unmodified RNAs, suggesting a link between the internal modification and the 3′ tail. Functional investigation of the unknown ORFs and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2. Highlights We provide a high-resolution map of SARS-CoV-2 transcriptome and epitranscriptome using nanopore direct RNA sequencing and DNA nanoball sequencing. The transcriptome is highly complex owing to numerous recombination events, both canonical and noncanonical. In addition to the genomic and subgenomic RNAs common in all coronaviruses, SARS-CoV-2 produces transcripts encoding unknown ORFs. We discover at least 41 potential RNA modification sites with an AAGAA motif.", "title": "The architecture of SARS-CoV-2 transcriptome", "pid": "wt4pxu08", "bm25_score": 217.73318481445312}, {"text": "Human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin isolated strain, GD410721, in the receptor binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead it suggests a recombination into RaTG13. We also find a 14-fold increase in the dN/dS ratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of non-synonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence, is 51.71 years (95% C.I., 28.11-75.31) and 37.02 years (95% C.I., 18.19-55.85), respectively.", "title": "Synonymous mutations and the molecular evolution of SARS-Cov-2 origins", "pid": "z11exbyu", "bm25_score": 217.7296142578125}, {"text": "Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S2 domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in SD domain) and G1124V (in S2 subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird's eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India.", "title": "Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility.", "pid": "02cfyuf4", "bm25_score": 217.7149658203125}, {"text": "Background SARS-CoV-2 most likely evolved from a bat beta-coronavirus and started infecting humans in December 2019. Since then it has rapidly infected people around the world, with more than 4.5 million confirmed cases by the middle of May 2020. Early genome sequencing of the virus has enabled the development of molecular diagnostics and the commencement of therapy and vaccine development. The analysis of the early sequences showed relatively few evolutionary selection pressures. However, with the rapid worldwide expansion into diverse human populations, significant genetic variations are becoming increasingly likely. The current limitations on social movement between countries also offers the opportunity for these viral variants to become distinct strains with potential implications for diagnostics, therapies and vaccines. Methods We used the current sequencing archives (NCBI and GISAID) to investigate 15,487 whole genomes, looking for evidence of strain diversification and selective pressure. Results We used 6,294 SNPs to build a phylogenetic tree of SARS-CoV-2 diversity and noted strong evidence for the existence of two major clades and six sub-clades, unevenly distributed across the world. We also noted that convergent evolution has potentially occurred across several locations in the genome, showing selection pressures, including on the spike glycoprotein where we noted a potentially critical mutation that could affect its binding to the ACE2 receptor. We also report on mutations that could prevent current molecular diagnostics from detecting some of the sub-clades. Conclusion The worldwide whole genome sequencing effort is revealing the challenge of developing SARS-CoV-2 containment tools suitable for everyone and the need for data to be continually evaluated to ensure accuracy in outbreak estimations.", "title": "Controlling the SARS-CoV-2 outbreak, insights from large scale whole genome sequences generated across the world", "pid": "tutit2bc", "bm25_score": 217.71484375}, {"text": "Background With the gradual reopening of economies and resumption of social life, robust surveillance mechanisms should be implemented to control the ongoing COVID-19 pandemic. Unlike RT-qPCR, SARS-CoV-2 Whole Genome Sequencing (cWGS) has the added advantage of identifying cryptic origins of the virus, and the extent of community-based transmissions versus new viral introductions, which can in turn influence public health policy decisions. However, practical and cost considerations of cWGS should be addressed before it can be widely implemented. Methods We performed shotgun transcriptome sequencing using RNA extracted from nasopharyngeal swabs of patients with COVID-19, and compared it to targeted SARS-CoV-2 full genome amplification and sequencing with respect to virus detection, scalability, and cost-effectiveness. To track virus origin, we used open-source multiple sequence alignment and phylogenetic tools to compare the assembled SARS-CoV-2 genomes to publicly available sequences. Results We show a significant improvement in whole genome sequencing data quality and viral detection using amplicon-based target enrichment of SARS-CoV-2. With enrichment, more than 99% of the sequencing reads mapped to the viral genome compared to an average of 0.63% without enrichment. Consequently, a dramatic increase in genome coverage was obtained using significantly less sequencing data, enabling higher scalability and significant cost reductions. We also demonstrate how SARS-CoV-2 genome sequences can be used to determine their possible origin through phylogenetic analysis including other viral strains. Conclusions SARS-CoV-2 whole genome sequencing is a practical, cost-effective, and powerful approach for population-based surveillance and control of viral transmission in the next phase of the COVID-19 pandemic.", "title": "SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission", "pid": "8klkojpo", "bm25_score": 217.714111328125}, {"text": "The complete genome sequence of a novel coronavirus (severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) isolate obtained from a nasopharyngeal swab from a patient with COVID-19 in Bangladesh is reported.", "title": "Complete Genome Sequence of a Novel Coronavirus (SARS-CoV-2) Isolate from Bangladesh", "pid": "o1ky8tyv", "bm25_score": 217.71109008789062}, {"text": "Covid-19 pandemic, caused by the sars-cov-2 strain of coronavirus, has affected millions of people all over the world and taken thousands of lives. It is of utmost importance that the character of this deadly virus be studied and its nature be analysed. We present here an analysis pipeline comprising phylogenetic analysis on strains of this novel virus to track its evolutionary history among the countries uncovering several interesting relationships, followed by a classification exercise to identify the virulence of the strains and extraction of important features from its genetic material that are used subsequently to predict mutation at those interesting sites using deep learning techniques. In a nutshell, we have prepared an analysis pipeline for hCov genome sequences leveraging the power of machine intelligence and uncovered what remained apparently shrouded by raw data.", "title": "Analyzing hCov genome sequences: Applying Machine Intelligence and beyond", "pid": "0x90yubt", "bm25_score": 217.69862365722656}]}
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"zlro6tel": 2, "zlxqt7qy": 0, "vkbyc7xd": 2, "zmp0dpv0": 2, "znrhobb2": 1, "zolwjl9u": 0, "zph6r4il": 0, "zpo1nffy": 1, "6o1vaf3d": 0, "zra8fixl": 2, "9ve8bj4r": 1, "zsem29ss": 1, "zsyi98t0": 1, "zt5alyy2": 2, "zte7w9yy": 1, "zu6xmuql": 2, "zwftmuj3": 2, "zwqycuw4": 1, "zwvutq57": 1, "zwy2wym7": 2, "zy9lb7d9": 2}, "bm25_results": [{"text": "The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic Patient throat swabs were tested daily for SARS-CoV-2 with the virus persisting for 3-4 weeks in all three patients Cytokine analyses of whole blood revealed increased cytokine expression in the single more severe case However, most inflammatory gene expression peaked after respiratory function nadir, except those in the IL1 pathway Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T-cell activation that could exacerbate disease or prolong the infection Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19 This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies", "title": "A dynamic immune response shapes COVID-19 progression", "pid": "uxehz43v", "bm25_score": 216.82464599609375}, {"text": "The inflammatory response to SARS-coronavirus-2 (SARS-CoV-2) infection is thought to underpin COVID-19 pathogenesis. We conducted daily transcriptomic profiling of three COVID-19 cases and found that the early immune response in COVID-19 patients is highly dynamic. Patient throat swabs were tested daily for SARS-CoV-2, with the virus persisting for 3 to 4 weeks in all three patients. Cytokine analyses of whole blood revealed increased cytokine expression in the single most severe case. However, most inflammatory gene expression peaked after respiratory function nadir, except expression in the IL1 pathway. Parallel analyses of CD4 and CD8 expression suggested that the pro-inflammatory response may be intertwined with T cell activation that could exacerbate disease or prolong the infection. Collectively, these findings hint at the possibility that IL1 and related pro-inflammatory pathways may be prognostic and serve as therapeutic targets for COVID-19. This work may also guide future studies to illuminate COVID-19 pathogenesis and develop host-directed therapies.", "title": "A Dynamic Immune Response Shapes COVID-19 Progression", "pid": "xm0n9iu4", "bm25_score": 216.8231964111328}, {"text": "IMPACT STATEMENT: In late 2019, a novel virus called SARS-CoV-2, expanded globally from Wuhan, China and was declared a pandemic on 11 March 2020 by the WHO. The mechanism of virus entry inside the host cell depends upon the cellular proteases including cathepsins, HAT, and TMPRSS2, which splits up the spike protein and causes further penetration. MERS coronavirus uses DPP4, while coronavirus HCoV-NL63 and SARS-CoV and SARS-CoV-2 employ ACE-2 as the key receptor. Cytokine storm syndrome was analyzed in critically ill nCOVID-19 patients and it is presented with high inflammatory mediators, systemic inflammation, and multiple organ failure. Among various inflammatory mediators, the level of interleukins (IL-2, IL-7, IL-10), G-CSF, MIP1A, MCP1, and TNF-&#945; was reported to be higher in critically ill patients. Understanding this molecular mechanism of ILs, T cells, and dendritic cells will be helpful to design immunotherapy and novel drugs for the treatment of nCOVID-19 infection.", "title": "Role of inflammatory markers in corona virus disease (COVID-19) patients: A review", "pid": "qk5mrmrd", "bm25_score": 216.7901611328125}, {"text": "The COVID-19 pandemic caused by infection with SARS-CoV-2 has led to more than 200,000 deaths worldwide. Several studies have now established that the hyperinflammatory response induced by SARS-CoV-2 is a major cause of disease severity and death in infected patients. Macrophages are a population of innate immune cells that sense and respond to microbial threats by producing inflammatory molecules that eliminate pathogens and promote tissue repair. However, a dysregulated macrophage response can be damaging to the host, as is seen in the macrophage activation syndrome induced by severe infections, including in infections with the related virus SARS-CoV. Here we describe the potentially pathological roles of macrophages during SARS-CoV-2 infection and discuss ongoing and prospective therapeutic strategies to modulate macrophage activation in patients with COVID-19.", "title": "Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages", "pid": "jfkyfmst", "bm25_score": 216.73916625976562}, {"text": "IMPACT STATEMENT In late 2019, a novel virus called SARS-CoV-2, expanded globally from Wuhan, China and was declared a pandemic on 11 March 2020 by the WHO. The mechanism of virus entry inside the host cell depends upon the cellular proteases including cathepsins, HAT, and TMPRSS2, which splits up the spike protein and causes further penetration. MERS coronavirus uses DPP4, while coronavirus HCoV-NL63 and SARS-CoV and SARS-CoV-2 employ ACE-2 as the key receptor. Cytokine storm syndrome was analyzed in critically ill nCOVID-19 patients and it is presented with high inflammatory mediators, systemic inflammation, and multiple organ failure. Among various inflammatory mediators, the level of interleukins (IL-2, IL-7, IL-10), G-CSF, MIP1A, MCP1, and TNF-α was reported to be higher in critically ill patients. Understanding this molecular mechanism of ILs, T cells, and dendritic cells will be helpful to design immunotherapy and novel drugs for the treatment of nCOVID-19 infection.", "title": "Role of inflammatory markers in corona virus disease (COVID-19) patients: A review.", "pid": "8gzcrrml", "bm25_score": 216.72462463378906}, {"text": "The current COVID-19 pandemic began in December 2019 in Wuhan (China) and rapidly extended to become a global sanitary and economic emergency. Its etiological agent is the coronavirus SARS-CoV-2. COVID-19 presents a wide spectrum of clinical manifestations, which ranges from an asymptomatic infection to a severe pneumonia accompanied by multisystemic failure that can lead to a patient's death. The immune response to SARS-CoV-2 is known to involve all the components of the immune system that together appear responsible for viral elimination and recovery from the infection. Nonetheless, such immune responses are implicated in the disease's progression to a more severe and lethal process. This review describes the general aspects of both COVID-19 and its etiological agent SARS-CoV-2, stressing the similarities with other severe coronavirus infections, such as SARS and MERS, but more importantly, pointing toward the evidence supporting the hypothesis that the clinical spectrum of COVID-19 is a consequence of the corresponding variable spectrum of the immune responses to the virus. The critical point where progression of the disease ensues appears to center on loss of the immune regulation between protective and altered responses due to exacerbation of the inflammatory components. Finally, it appears possible to delineate certain major challenges deserving of exhaustive investigation to further understand COVID-19 immunopathogenesis, thus helping to design more effective diagnostic, therapeutic, and prophylactic strategies.", "title": "Immune Response, Inflammation, and the Clinical Spectrum of COVID-19", "pid": "pjjrgn05", "bm25_score": 216.60792541503906}, {"text": "Currently, we are on a global pandemic of Coronavirus disease-2019 (COVID-19) which causes fever, dry cough, fatigue and acute respiratory distress syndrome (ARDS) that may ultimately lead to the death of the infected. Current researches on COVID-19 continue to highlight the necessity for further understanding the virus-host synergies. In this study, we have highlighted the key cytokines induced by coronavirus infections. We have demonstrated that genes coding interleukins (Il-1&#945;, Il-1ß, Il-6, Il-10), chemokine (Ccl2, Ccl3, Ccl5, Ccl10), and interferon (Ifn-&#945;2, Ifn-ß1, Ifn2) upsurge significantly which in line with the elevated infiltration of T cells, NK cells and monocytes in SARS-Cov treated group at 24 hours. Also, interleukins (IL-6, IL-23&#945;, IL-10, IL-7, IL-1&#945;, IL-1ß) and interferon (IFN-&#945;2, IFN2, IFN-γ) have increased dramatically in MERS-Cov at 24 hours. A similar cytokine profile showed the cytokine storm served a critical role in the infection process. Subsequent investigation of 463 patients with COVID-19 disease revealed the decreased amount of total lymphocytes, CD3+, CD4+, and CD8+ T lymphocytes in the severe type patients which indicated COVID-19 can impose hard blows on human lymphocyte resulting in lethal pneumonia. Thus, taking control of changes in immune factors could be critical in the treatment of COVID-19.", "title": "Immune environment modulation in pneumonia patients caused by coronavirus: SARS-CoV, MERS-CoV and SARS-CoV-2", "pid": "xrcvyu87", "bm25_score": 216.55694580078125}, {"text": "Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1ß-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1ß-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.", "title": "Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19", "pid": "3dpdg5ls", "bm25_score": 216.55645751953125}, {"text": "The novel Coronavirus Disease 2019 (COVID-19), that began in Wuhan Province, China was labelled as an International Public Health Emergency on January 30, 2020 and later was declared a pandemic by the World Health Organisation (WHO) on March 11, 2020. The causative agent, SARS-CoV-2 was the third coronavirus responsible for causing major disease outbreaks in human population after Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) caused by SARS-CoV and MERS-CoV respectively. The patients of COVID-19 present with a clinical feature resembling mild form of viral pneumonia which in certain cases progress to a severe form characterised by adult respiratory distress syndrome (ARDS) and/or multiorgan failure leading to death. The transition from mild to severe form of COVID-19 is affected by a lot of factors like age, co-morbidities etc. In the absence of an absolute cure, it is essential to explore the molecular pathogenesis of the disease to identify people at risk of developing severity so that alternative treatment modalities may be planned. The aim of this review is to provide an update on the general characteristics of SARS-CoV-2 and highlight the inflammatory changes and immune dysregulation that may help in identification of molecular predictors of disease severity.", "title": "Inflammation, Immunity and Immunogenetics in COVID-19: A Narrative Review", "pid": "zy9lb7d9", "bm25_score": 216.5249786376953}, {"text": "Coronavirus Disease 2019 (COVID-19) has sparked a global pandemic, affecting more than 4 million people worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute lung injury (ALI) and even acute respiratory distress syndrome (ARDS); with a fatality of 7.0 %. Accumulating evidence suggested that the progression of COVID-19 is associated with lymphopenia and excessive inflammation, and a subset of severe cases might exhibit cytokine storm triggered by secondary hemophagocytic lymphohistiocytosis (sHLH). Furthermore, secondary bacterial infection may contribute to the exacerbation of COVID-19. We recommend using both IL-10 and IL-6 as the indicators of cytokine storm, and monitoring the elevation of procalcitonin (PCT) as an alert for initiating antibacterial agents. Understanding the dynamic progression of SARS-CoV-2 infection is crucial to determine an effective treatment strategy to reduce the rising mortality of this global pandemic.", "title": "Biochemical indicators of coronavirus disease 2019 exacerbation and the clinical implications", "pid": "j25rvp1i", "bm25_score": 216.5072021484375}, {"text": "Although most SARS-CoV-2-infected individuals experience mild coronavirus disease 2019 (COVID-19), some patients suffer from severe COVID-19, which is accompanied by acute respiratory distress syndrome and systemic inflammation. To identify factors driving severe progression of COVID-19, we performed single-cell RNA-seq using peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, patients with mild or severe COVID-19, and patients with severe influenza. Patients with COVID-19 exhibited hyper-inflammatory signatures across all types of cells among PBMCs, particularly up-regulation of the TNF/IL-1β-driven inflammatory response as compared to severe influenza. In classical monocytes from patients with severe COVID-19, type I IFN response co-existed with the TNF/IL-1β-driven inflammation, and this was not seen in patients with milder COVID-19. Interestingly, we documented type I IFN-driven inflammatory features in patients with severe influenza as well. Based on this, we propose that the type I IFN response plays a pivotal role in exacerbating inflammation in severe COVID-19.", "title": "Immunophenotyping of COVID-19 and influenza highlights the role of type I interferons in development of severe COVID-19.", "pid": "bqvn3ceq", "bm25_score": 216.48178100585938}, {"text": "Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.", "title": "The potential role of Th17 immune responses in coronavirus immunopathology and vaccine-induced immune enhancement", "pid": "5jl6ltfj", "bm25_score": 216.4097900390625}, {"text": "Summary The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection has posed a severe threat to global public health. It is unclear how the human immune system responds to this infection. Here, we used metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight COVID-19 cases. The expression of proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous IFN-inducible genes (ISGs). These ISGs exhibit immunopathogenic potential, with overrepresentation of genes involved in inflammation. The transcriptome data was also used to estimate immune cell populations, revealing increases in activated dendritic cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection could further our understanding of disease pathogenesis and point towards antiviral strategies.", "title": "Heightened innate immune responses in the respiratory tract of COVID-19 patients", "pid": "ri9ncm86", "bm25_score": 216.38845825195312}, {"text": "The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection have posed a severe threat to global public health. It is unclear how the human immune system responds to this infection. Here, we used metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight COVID-19 cases. The expression of proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous IFN-stimulated genes (ISGs). These ISGs exhibit immunopathogenic potential, with overrepresentation of genes involved in inflammation. The transcriptome data was also used to estimate immune cell populations, revealing increases in activated dendritic cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection could further our understanding of disease pathogenesis and point toward antiviral strategies.", "title": "Heightened Innate Immune Responses in the Respiratory Tract of COVID-19 Patients", "pid": "19pz3kli", "bm25_score": 216.33213806152344}, {"text": "Pathogenic human coronavirus infections, such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV), cause high morbidity and mortality 1,2. Recently, a severe pneumonia-associated respiratory syndrome caused by a new coronavirus was reported at December 2019 (2019-nCoV) in the city Wuhan, Hubei province, China3–5, which was also named as pneumonia-associated respiratory syndrome (PARS)6. Up to 9th of February 2020, at least 37, 251 cases have been reported with 812 fatal cases according to the report from China CDC. However, the immune mechanism that potential orchestrated acute mortality from patients of 2019-nCoV is still unknown. Here we show that after the 2019-nCoV infection, CD4+T lymphocytes are rapidly activated to become pathogenic T helper (Th) 1 cells and generate GM-CSF etc. The cytokines environment induces inflammatory CD14+CD16+ monocytes with high expression of IL-6 and accelerates the inflammation. These aberrant and excessive immune cells may enter the pulmonary circulation in huge numbers and play an immune damaging role to causing lung functional disability and quick mortality. Our results demonstrate that excessive non-effective host immune responses by pathogenic T cells and inflammatory monocytes may associate with severe lung pathology. Therefore, we suggest that monoclonal antibody that targets the GM-CSF or interleukin 6 receptor may potentially curb immunopathology caused by 2019-nCoV and consequently win more time for virus clearance.", "title": "Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus", "pid": "anls8gri", "bm25_score": 216.32533264160156}, {"text": "Currently there is no effective antiviral therapy for SARS-CoV-2 infection, which frequently leads to fatal inflammatory responses and acute lung injury. Here, we discuss the various mechanisms of SARS-CoV-mediated inflammation. We also assume that SARS-CoV-2 likely shares similar inflammatory responses. Potential therapeutic tools to reduce SARS-CoV-2-induced inflammatory responses include various methods to block FcR activation. In the absence of a proven clinical FcR blocker, the use of intravenous immunoglobulin to block FcR activation may be a viable option for the urgent treatment of pulmonary inflammation to prevent severe lung injury. Such treatment may also be combined with systemic anti-inflammatory drugs or corticosteroids. However, these strategies, as proposed here, remain to be clinically tested for effectiveness.", "title": "Understanding SARS-CoV-2-Mediated Inflammatory Responses: From Mechanisms to Potential Therapeutic Tools", "pid": "b0u07692", "bm25_score": 216.32266235351562}, {"text": "The novel coronavirus disease 2019 has rapidly increased in pandemic scale since it first appeared in Wuhan, China, in December 2019. In these troubled days the scientific community is asking for rapid replies to prevent and combat the emergency. It is generally accepted that only achieving a better understanding of the interactions between the virus and the host immune response and of the pathogenesis of infection is crucial to identify valid therapeutic tools to control virus entry, replication, and spread as well as to impair its lethal effects. On the basis of recent research progress of severe acute respiratory syndrome coronavirus 2 and the results on previous coronaviruses, in this contribution we underscore some of the main unsolved problems, mostly focusing on pathogenetic aspects and host immunity to the virus. On this basis, we also touch important aspects regarding the immune response in asymptomatic subjects, the immune evasion of severe acute respiratory syndrome coronavirus 2 in severe patients, and differences in disease severity by age and sex.", "title": "COVID-19: Unanswered questions on immune response and pathogenesis", "pid": "08ftq7hl", "bm25_score": 216.3165740966797}, {"text": "Abstract Increasing evidence points to host Th17 inflammatory responses as contributing to the severe lung pathology and mortality of lower respiratory tract infections from coronaviruses. This includes host inflammatory and cytokine responses to COVID-19 caused by the SARS-2 coronavirus (SARS CoV2). From studies conducted in laboratory animals, there are additional concerns about immune enhancement and the role of potential host immunopathology resulting from experimental human COVID-19 vaccines. Here we summarize evidence suggesting there may be partial overlap between the underlying immunopathologic processes linked to both coronavirus infection and vaccination, and a role for Th17 in immune enhancement and eosinophilic pulmonary immunopathology. Such findings help explain the link between viral-vectored coronavirus vaccines and immune enhancement and its reduction through alum adjuvants. Additional research may also clarify links between COVID-19 pulmonary immunopathology and heart disease.", "title": "The Potential Role of Th17 Immune Responses in Coronavirus Immunopathology and Vaccine-induced Immune Enhancement", "pid": "8o884nyp", "bm25_score": 216.3043212890625}, {"text": "BACKGROUND AND AIMS: The outbreak of the new coronavirus, SARS-CoV-2, causes a respiratory disease and individuals with pre-existing cardiometabolic disorders display worse prognosis through the infection course. The aim of this minireview is to present epidemiological data related to metabolic comorbidities in association with the SARS-CoV-2. METHODS: This is a narrative mini-review with Pubmed search until April 23, 2020 using the keywords COVID-19, SARS-CoV-2, treatment of coronavirus and following terms: diabetes mellitus, obesity, arterial hypertension, ACE-inhibitors, cytokine storm, immune response and vitamin D. RESULTS: Studies indicate that obese individuals are more likely to develop infections, and that adipose tissue serves as a pathogen reservoir. In diabetic individuals higher rate of inflammatory processes is seen due to constant glucose recognition by C type lectin receptors. Hypertensive individuals, usually grouped with other conditions, are treated with drugs to reduce blood pressure mostly through ACEi and ARB, that leads to increased ACE2 expression, used by SARS-CoV-2 for human's cell entry. Until now, the studies have shown that individuals with those conditions and affected by COVID-19 present an uncontrolled release of pro-inflammatory cytokines and an unbalanced immune response, leading to the cytokine storm phenomenon. Vitamin D is highlighted as a potential therapeutic target, because in addition to acting on the immune system, it plays an important role in the control of cardiometabolic diseases. CONCLUSION: Currently, since there is no proven and effective antiviral therapy for SARS-CoV-2, the efforts should focus on controlling inflammatory response and reduce the risks of associated complications.", "title": "Mechanism of inflammatory response in associated comorbidities in COVID-19", "pid": "cn3bpmwj", "bm25_score": 216.229248046875}, {"text": "Clinical evidence indicates that the fatal outcome observed with severe acute respiratory syndrome-coronavirus-2 infection often results from alveolar injury that impedes airway capacity and multi-organ failure-both of which are associated with the hyperproduction of cytokines, also known as a cytokine storm or cytokine release syndrome. Clinical reports show that both mild and severe forms of disease result in changes in circulating leukocyte subsets and cytokine secretion, particularly IL-6, IL-1ß, IL-10, TNF, GM-CSF, IP-10 (IFN-induced protein 10), IL-17, MCP-3, and IL-1ra. Not surprising, therapies that target the immune response and curtail the cytokine storm in coronavirus 2019 (COVID-19) patients have become a focus of recent clinical trials. Here we review reports on leukocyte and cytokine data associated with COVID-19 disease in 3939 patients in China and describe emerging data on immunopathology. With an emphasis on immune modulation, we also look at ongoing clinical studies aimed at blocking proinflammatory cytokines; transfer of immunosuppressive mesenchymal stem cells; use of convalescent plasma transfusion; as well as immunoregulatory therapy and traditional Chinese medicine regimes. In examining leukocyte and cytokine activity in COVID-19, we focus in particular on how these levels are altered as the disease progresses (neutrophil NETosis, macrophage, T cell response, etc.) and proposed consequences to organ pathology (coagulopathy, etc.). Viral and host interactions are described to gain further insight into leukocyte biology and how dysregulated cytokine responses lead to disease and/or organ damage. By better understanding the mechanisms that drive the intensity of a cytokine storm, we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.", "title": "Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts", "pid": "nmdko4nl", "bm25_score": 216.22256469726562}, {"text": "We demonstrate that the general clinical conditions, risk factors and numerous pathological and biological features of COVID-19 are analogous with various disorders caused by the uncontrolled formation of neutrophil extracellular traps and their by-products. Given the rapid evolution of this disease's symptoms and its lethality, we hypothesize that SARS-CoV2 evades innate immune response causing COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. This work allows us to propose new strategies for treating the pandemic.", "title": "SARS-CoV2 may evade innate immune response, causing uncontrolled neutrophil extracellular traps formation and multi-organ failure.", "pid": "va8kg3kb", "bm25_score": 216.2225341796875}, {"text": "Pathogenic human coronavirus infections, such as severe acute respiratory syndrome CoV (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV), cause high morbidity and mortality1, 2 Recently, a severe pneumonia-associated respiratory syndrome caused by a new coronavirus (SARS-CoV-2) was reported at December 2019 in the city Wuhan, Hubei province, China3, 4, 5, which was also named as pneumonia-associated respiratory syndrome (PARS)6 and can cause coronavirus disease 2019 (COVID-19) to seriously endanger human health Up to 24th of February 2020, at least 77779 cases have been reported with 2666 fatal cases according to the report from China CDC However, the immune mechanism that potential orchestrated acute mortality from COVID-19 patients is still unknown Here we show that after the SARS-CoV-2 infection, CD4+ T lymphocytes are rapidly activated to become pathogenic T helper (Th) 1 cells and generate GM-CSF etc The cytokines environment induces inflammatory CD14+CD16+ monocytes with high expression of IL-6 and accelerate the inflammation Given that large amount of inflammatory cells infiltrations have been observed in lungs from severe COVID-19 patients7, 8, these aberrant pathogenic Th1 cells and inflammatory monocytes may enter the pulmonary circulation in huge numbers and play an immune damaging role to causing lung functional disability and quick mortality Our results demonstrate that excessive non-effective host immune responses by pathogenic T cells and inflammatory monocytes may associate with severe lung pathology Thus, we suggest that monoclonal antibodies targeting GM-CSF or interleukin 6 may be effective in blocking inflammatory storms and, therefore, be a promising treatment of severe COVID-19 patients", "title": "Pathogenic T cells and inflammatory monocytes incite inflammatory storm in severe COVID-19 patients", "pid": "iqx0rxun", "bm25_score": 216.2157745361328}, {"text": "Currently, we are on a global pandemic of Coronavirus disease-2019 (COVID-19) which causes fever, dry cough, fatigue and acute respiratory distress syndrome (ARDS) that may ultimately lead to the death of the infected. Current researches on COVID-19 continue to highlight the necessity for further understanding the virus-host synergies. In this study, we have highlighted the key cytokines induced by coronavirus infections. We have demonstrated that genes coding interleukins (Il-1α, Il-1β, Il-6, Il-10), chemokine (Ccl2, Ccl3, Ccl5, Ccl10), and interferon (Ifn-α2, Ifn-β1, Ifn2) upsurge significantly which in line with the elevated infiltration of T cells, NK cells and monocytes in SARS-Cov treated group at 24 hours. Also, interleukins (IL-6, IL-23α, IL-10, IL-7, IL-1α, IL-1β) and interferon (IFN-α2, IFN2, IFN-γ) have increased dramatically in MERS-Cov at 24 hours. A similar cytokine profile showed the cytokine storm served a critical role in the infection process. Subsequent investigation of 463 patients with COVID-19 disease revealed the decreased amount of total lymphocytes, CD3+, CD4+, and CD8+ T lymphocytes in the severe type patients which indicated COVID-19 can impose hard blows on human lymphocyte resulting in lethal pneumonia. Thus, taking control of changes in immune factors could be critical in the treatment of COVID-19.", "title": "Immune environment modulation in pneumonia patients caused by coronavirus: SARS-CoV, MERS-CoV and SARS-CoV-2", "pid": "2w5ws14b", "bm25_score": 216.19482421875}, {"text": "Coronavirus disease 2019 (COVID-19), caused by an outbreak of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in Wuhan, China, has led to an unprecedented health and economic crisis worldwide. To develop treatments that can stop or lessen the symptoms and severity of SARS-CoV-2 infection, it is critical to understand how the virus behaves inside human cells, and so far studies in this area remain scarce. A recent study investigated translatome and proteome host cell changes induced in vitro by SARS-CoV-2. Here, we use the publicly available proteomics data from this study to re-analyze the in vitro cellular consequences of SARS-CoV-2 infection by impact pathways analysis and network analysis. Notably, proteins linked to the inflammatory response, but also proteins related to chromosome segregation during mitosis, were found to be altered in response to viral infection. Upregulation of inflammatory response proteins is in line with the propagation of inflammatory reaction and lung injury that is observed in advanced stages of COVID-19 patients and which worsens with age.", "title": "Re-analysis of SARS-CoV-2-infected host cell proteomics time-course data by impact pathway analysis and network analysis: a potential link with inflammatory response", "pid": "3sbr1et1", "bm25_score": 216.13397216796875}, {"text": "The pandemic caused by SARS-COV2 Virus/COVID-19, which was initially reported in China in December 2019, has become a major global health concern. COVID-19 can manifest with cytokine storm - an exaggerated systemic inflammatory phenomenon due to over-production of proinflammatory cytokines by immune cells that results in diffuse inflammatory lung disease and acute respiratory distress syndrome. It may be complicated by septic shock and subsequent multi-organ failure. Based on the most recently published evidence, this article will review and discuss comprehensive information on its clinical manifestations, laboratory tests, potential therapeutics, and prevention guidelines.", "title": "2019 Novel Coronavirus Pandemic: What Do We Know?", "pid": "k3w39apy", "bm25_score": 216.11505126953125}, {"text": "The lung is a key target of the cytokine storm that can be triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the widespread clinical syndrome known as coronavirus disease 2019 (COVID-19). Indeed, in some patients, SARS-CoV-2 promotes a dysfunctional immune response that dysregulates the cytokine secretory pattern. Hypercytokinemia underlies the hyperinflammatory state leading to injury of alveolar epithelial cells and vascular endothelial cells, as well as to lung infiltration sustained by neutrophils and macrophages. Within such a pathogenic context, interleukin-6 (IL-6) and other cytokines/chemokines play a pivotal pro-inflammatory role. Therefore, cytokines and their receptors, as well as cytokine-dependent intracellular signalling pathways can be targeted by potential therapies aimed to relieve the heavy burden of cytokine storm. In particular, the anti-IL-6-receptor monoclonal antibody tocilizumab is emerging as one of the most promising pharmacologic treatments. The reviews of this paper are available via the supplemental material section.", "title": "Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications", "pid": "o9xh6bqz", "bm25_score": 216.10916137695312}, {"text": "The 2019 coronavirus disease (COVID-19) pandemic caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has created an unprecedented global crisis for the infrastructure sectors, including economic, political, healthcare, education, and research systems. Although over 90% of infected individuals are asymptomatic or manifest noncritical symptoms and will recover from the infection, those individuals presenting with critical symptoms are in urgent need of effective treatment options. Emerging data related to mechanism of severity and potential therapies for patients presenting with severe symptoms are scattered and therefore require a comprehensive analysis to focus research on developing effective therapeutics. A critical literature review suggests that the severity of SARS-CoV-2 infection is associated with dysregulation of inflammatory immune responses, which in turn inhibits the development of protective immunity to the infection. Therefore, the use of therapeutics that modulate inflammation without compromising the adaptive immune response could be the most effective therapeutic strategy.", "title": "COVID-19 as an Acute Inflammatory Disease", "pid": "hczmytse", "bm25_score": 216.1032257080078}, {"text": "COVID-19 is often related to hyperinflammation that drives lung or multiorgan injury. The immunopathological mechanisms that cause excessive inflammation are under investigation and constantly updated. Here, a gene network approach was used on recently published data sets to identify possible COVID-19 inflammatory mechanisms and bioactive genes. First, network analysis of putative SARS-CoV-2 cellular receptors led to the mining of a neutrophil-response signature and relevant inflammatory genes. Second, analysis of RNA-seq data sets of lung cells infected with SARS-CoV-2 revealed that infected cells expressed neutrophil-attracting chemokines. Third, analysis of RNA-seq data sets of bronchoalveolar lavage fluid cells from COVID-19 patients identified upregulation of neutrophil genes and chemokines. Different inflammatory genes mined here, including TNFR, IL-8, CXCR1, CXCR2, ADAM10, GPR84, MME, ANPEP, and LAP3, might be druggable targets in efforts to limit SARS-CoV-2 inflammation in severe clinical cases. The possible role of neutrophils in COVID-19 inflammation needs to be studied further.", "title": "COVID-19 Hyperinflammation: What about Neutrophils?", "pid": "9l5ajo4q", "bm25_score": 216.0994873046875}, {"text": "Emerging of the COVID-19 pandemic has raised interests in the field of biology and pathogenesis of coronaviruses; including interactions between host immune reactions specific, and viral factors. Deep knowledge about the interaction between coronaviruses and the host factors could be useful to provide a better support for the disease sufferers and be advantageous for managing and treatment of the lung infection caused by the virus. At this study, we reviewed the updated information on the pathogenesis of the COVID-19 and the immune responses toward it, with a special focus on structure, genetics, and viral accessory proteins, viral replication, viral receptors, the human immune reactions, cytopathic effects, and host-related factors.", "title": "A contemporary review on pathogenesis and immunity of COVID-19 infection", "pid": "owby50fr", "bm25_score": 216.09832763671875}, {"text": "Interleukin-6 (IL-6), known as an inflammatory cytokine, can be involved in many innate and adaptive immune responses. The role of IL-6 in the pathogenesis of the novel coronavirus disease 2019 (COVID-19) has recently received much more attention due to the spread of the virus and its pandemic potential. Cytokine storm is among the most critical pathological events in patients affected with coronaviruses (CoVs), i.e., severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and COVID-19, causing inflammation-induced lung injury and also occurring as a result of dysregulation of immune responses to the mentioned viruses. IL-6, along with some other inflammatory cytokines, including IL-1 beta (β), IL-8, and tumor necrosis factor-alpha (TNF-α), as well as inflammatory chemokines, can significantly contribute to, fever, lymphopenia, coagulation, lung injury, and multi-organ failure (MOF). Therefore, researchers are to explore novel approaches to treat the disease through targeting of IL-6 and its receptors based on prior experience of other disorders. In this review article, the latest findings on the role of IL-6 in the pathogenesis of COVID-19, as well as therapeutic perspectives, were summarized and discussed.", "title": "The bio-mission of interleukin-6 in the pathogenesis of COVID-19: A brief look at potential therapeutic tactics", "pid": "8leknnvc", "bm25_score": 216.0840606689453}, {"text": "RATIONALE: Coronavirus disease 2019 (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood. OBJECTIVES: To define the cytokine profile of COVID-19, and to identify evidence of immunometabolic alterations in those with severe illness. METHODS: Levels of interleukin (IL)-1ß, IL-6, IL-8, IL-10 and soluble TNF receptor 1 (sTNFR1) were assessed in plasma from healthy volunteers, hospitalized-but-stable COVID-19 patients (COVIDstable), COVID-19 patients requiring intensive care unit (ICU) admission (COVIDICU) and individuals with severe community-acquired pneumonia requiring ICU support (CAPICU). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of alpha-1 antitrypsin (AAT) to COVID-19 was also evaluated. MAIN RESULTS: IL-1ß, IL-6, IL-8 and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable, and demonstrated higher levels of IL-1ß, IL-6 and sTNFR1 - but lower IL-10 - than CAPICU. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2, phosphorylated PKM2, HIF-1&#945; and lactate. The production and sialylation of AAT increased in COVID-19, but this anti-inflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P<0.0001). In critically unwell COVID-19 patients, increases in IL-6:AAT predicted prolonged ICU stay and mortality, while improvement in IL-6:AAT was associated with clinical resolution (P<0.0001). CONCLUSIONS: The COVID-19 cytokinemia is distinct from that of other types of pneumonia leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).", "title": "Characterization of the Inflammatory Response to Severe COVID-19 Illness", "pid": "z2l2vn1o", "bm25_score": 216.08139038085938}, {"text": "Since the WHO declared COVID-19 a pandemic, a great effort has been made to understand this serious disease. Thousands of studies are being devoted to understanding its epidemiology, its molecular characteristics, its mechanisms, and the clinical evolution of this viral infection. However, little has been published on its pathogenesis and the host response mechanisms in the progress of the disease. Therefore, we propose a hypothesis based on strong scientific documentation, associating oxidative stress with changes found in patients with COVID-19, such as its participation in the amplification and perpetuation of the cytokine storm, coagulopathy, and cell hypoxia. Finally, we suggest a therapeutic strategy to reduce oxidative stress using antioxidants, NFkB inhibitors, Nrf2 activators, and iron complexing agents. We believe that this hypothesis can guide new studies and therapeutic strategies on this topic.", "title": "SARS-CoV-2 infection pathogenesis is related to oxidative stress as a response to aggression", "pid": "lkhmgfnc", "bm25_score": 216.078369140625}, {"text": "We demonstrate that the general clinical conditions, risk factors and numerous pathological and biological features of COVID-19 are analogous with various disorders caused by the uncontrolled formation of neutrophil extracellular traps and their by-products. Given the rapid evolution of this disease's symptoms and its lethality, we hypothesize that SARS-CoV2 evades innate immune response causing COVID-19 progresses under just such an amplifier loop, leading to a massive, uncontrolled inflammation process. This work allows us to propose new strategies for treating the pandemic.", "title": "SARS-CoV2 may evade innate immune response, causing uncontrolled neutrophil extracellular traps formation and multi-organ failure", "pid": "faz6icy3", "bm25_score": 216.07545471191406}, {"text": "Abstract Coronavirus Disease 2019 (COVID-19) was first identified in China at the end of 2019. Acute respiratory distress syndrome (ARDS) represents the most common and serious complication of COVID-19. Cytokine storms are a pathophysiological feature of COVID-19 and play an important role in distinguishing hyper-inflammatory subphenotypes of ARDS. Accordingly, in this review, we focus on hyper-inflammatory host responses in ARDS that play a critical role in the differentiated development of COVID-19. Furthermore, we discuss inflammation-related indicators that have the potential to identify hyper-inflammatory subphenotypes of COVID-19, especially for those with a high risk of ARDS. Finally, we explore the possibility of improving the quality of monitoring and treatment of COVID-19 patients and in reducing the incidence of critical illness and mortality via better distinguishing hyper- and hypo-inflammatory subphenotypes of COVID-19.", "title": "Coronavirus Disease 2019 (COVID-19): Cytokine Storms, Hyper-Inflammatory Phenotypes, and Acute Respiratory Distress Syndrome", "pid": "c5co9cfq", "bm25_score": 216.07122802734375}, {"text": "Background Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or \"cytokine storm\". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear. Methods Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). Findings In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were 3 deaths (17.8+/-10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and 1 serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p<0.0001 for both) and higher neutrophils and lower lymphocyte levels (p= 0.04 and p=0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. Interpretation Higher inflammatory markers, more superimposed infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI therapy. Despite the confounding factors, this study suggests that therapy time in anti-cytokine randomized clinical trials will be key.", "title": "Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: results from a single Italian Centre study on tocilizumab versus standard of care.", "pid": "d4wzmrz4", "bm25_score": 216.05580139160156}, {"text": "The disease known as coronavirus disease 19 (COVID-19), potentially caused by an outbreak of the severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in Wuhan, China, has hit the world hard, and has led to an unprecedent health and economic crisis. In order to develop treatment options able to stop or ameliorate SARS-CoV-2 effects, we need to understand the biology of the virus inside cells, but this kind of studies are still scarce. A recent study investigated translatome and proteome host cell changes induced in vitro by SARS-CoV-2. In the present study, we use the publicly available proteomics data from this study to re-analyze the mechanisms altered by the virus infection by impact pathways analysis and network analysis. Proteins linked to inflammatory response, but also proteins related to chromosome segregation during mitosis, were found to be regulated. The up-regulation of the inflammatory-related proteins observed could be linked to the propagation of inflammatory reaction and lung injury that is observed in advanced stages of COVID-19 patients.", "title": "Re-analysis of SARS-CoV-2 infected host cell proteomics time-course data by impact pathway analysis and network analysis. A potential link with inflammatory response", "pid": "ym44s4oc", "bm25_score": 216.05088806152344}, {"text": "H7N9 influenza A virus (IAV)-infected human cases are increasing and reported over 200 mortalities since its first emergence in 2013. Host inflammatory response contributes to the clearance of influenza virus; meanwhile, the induced “cytokine storm” also leads to pathological lesions. However, what inflammation-related response of the host for H7N9 influenza A virus infection to survival from injures of exuberant cytokine release is still obscure. In this research, expression pattern and histological distribution of inflammation-related genes, RIP3, NLRP3, IL-1β, TNF-α, Slit2 and Robo4 in the lung of BALB/c mice infected with two H7N9 IAV strains with only a PB2 residue 627 difference were investigated, as well as the histopathological injury of the lung. Results showed that significantly higher expression level of NLRP3, RIP3, IL-1β and TNF-α in H7N9-infected groups compared with the control would play a key role in driving lung pathological lesion. While the expression level of Slit2 and Robo4 in H7N9 rV(K627E) group had significantly increased trend than V(K627) which might be the main factor to inhibit the interstitial pneumonia and infiltration. Also, H7N9 induced the histopathological changes in the lung of infected mice, and RIP3, NLRP3, IL-1β, TNF-α, Slit2 and Robo4 showed cell-specific distribution in the lung. The results will provide basic data for further research on the mechanism of inflammatory response and understanding of the role of site 627 in PB2 in H7N9 IAVs infection. In addition, enhancing the resilience of the host vascular system to the inflammatory response by regulation of Slit2–Robo4 signaling pathway might provide a novel strategy for H7N9 IAVs infection.", "title": "Expression of inflammation-related genes in the lung of BALB/c mice response to H7N9 influenza A virus with different pathogenicity", "pid": "pyrfgggz", "bm25_score": 216.03318786621094}, {"text": "The immune response to SARS-CoV2 is under intense investigation, but not fully understood att this moment. Severe disease is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5-7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome, rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Systems-level analyses are required to simultaneously capture all immune cell populations and the many protein mediators by which cells communicate. Since every patient analyzed will be captured at different stages of his or her infection, longitudinal monitoring of the immune response is critical. Here we report on a systems-level blood immunomonitoring study of 39 adult patients, hospitalized with severe COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFNg-Eosinophil axis activated prior to lung hyperinflammation and changes in cell-cell coregulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.", "title": "Systems-level immunomonitoring from acute to recovery phase of severe COVID-19", "pid": "xwlpb3db", "bm25_score": 216.0322723388672}, {"text": "Abstract The novel coronavirus disease 2019 (COVID-19) has rapidly increased in pandemic scale since it first appeared in Wuhan, China, in December 2019. In these troubled days the scientific community is asking rapid replies to prevent and combat the emergency. It is generally accepted that only achieving a better understanding of the interactions between the virus and host immune response and of the pathogenesis of infection is crucial to identify valid therapeutic tools to control virus entry, replication and spread as well as to impair its lethal effects. Based on the recent research progress of SARS-CoV-2 and the results on previous coronaviruses, in this contribution we underscore some of the main unsolved problems, mostly focusing on pathogenetic aspects and host immunity to the virus. On this basis, we also touch important aspects regarding the immune response in asymptomatic subjects, the immune-evasion of SARS-CoV-2 in severe patients and differences in disease severity by age and gender.", "title": "COVID-19: unanswered questions on immune response and pathogenesis", "pid": "l8380adr", "bm25_score": 216.03123474121094}, {"text": "COVID-19 is associated with 5.1% mortality. Although the virological, epidemiological, clinical, and management outcome features of COVID-19 patients have been defined rapidly, the inflammatory and immune profiles require definition as they influence pathogenesis and clinical expression of COVID-19. Here we show lymphopenia, selective loss of CD4+ T cells, CD8+ T cells and NK cells, excessive T-cell activation and high expression of T-cell inhibitory molecules are more prominent in severe cases than in those with mild disease. CD8+ T cells in patients with severe disease express high levels of cytotoxic molecules. Histochemical studies of lung tissue from one fatality show sub-anatomical distributions of SARS-CoV-2 RNA and massive infiltration of T cells and macrophages. Thus, aberrant activation and dysregulation of CD8+ T cells occur in patients with severe COVID-19 disease, an effect that might be for pathogenesis of SARS-CoV-2 infection and indicate that immune-based targets for therapeutic interventions constitute a promising treatment for severe COVID-19 patients.", "title": "Immunological and inflammatory profiles in mild and severe cases of COVID-19", "pid": "j6jb4j3b", "bm25_score": 216.019775390625}, {"text": "Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy. In this paper, we present an immunothrombosis model of COVID-19. We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients.", "title": "Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis", "pid": "p298vft5", "bm25_score": 216.0041961669922}, {"text": "Abstract Influenza virus infection is characterized by symptoms ranging from mild congestion and body aches to severe pulmonary edema and respiratory failure. While the majority of those exposed have minor symptoms and recover with little morbidity, an estimated 500,000 people succumb to IAV-related complications each year worldwide. In these severe cases, an exaggerated inflammatory response, known as “cytokine storm”, occurs which results in damage to the respiratory epithelial barrier and development of acute respiratory distress syndrome (ARDS). Data from retrospective human studies as well as experimental animal models of influenza virus infection highlight the fine line between an excessive and an inadequate immune response, where the host response must balance viral clearance with exuberant inflammation. Current pharmacological modulators of inflammation, including corticosteroids and statins, have not been successful in improving outcomes during influenza virus infection. We have reported that the amplitude of the inflammatory response is regulated by Linear Ubiquitin Assembly Complex (LUBAC) activity and that dampening of LUBAC activity is protective during severe influenza virus infection. Therapeutic modulation of LUBAC activity may be crucial to improve outcomes during severe influenza virus infection, as it functions as a molecular rheostat of the host response. Here we review the evidence for modulating inflammation to ameliorate influenza virus infection-induced lung injury, data on current anti-inflammatory strategies, and potential new avenues to target viral inflammation and improve outcomes.", "title": "Targeting the Linear Ubiquitin Assembly Complex to Modulate the Host Response and Improve Influenza A Virus Induced Lung Injury", "pid": "zieuc7vk", "bm25_score": 215.98899841308594}, {"text": "Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients' lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.", "title": "Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients", "pid": "5nx2l9kf", "bm25_score": 215.9873809814453}, {"text": "Influenza virus infection is characterized by symptoms ranging from mild congestion and body aches to severe pulmonary edema and respiratory failure. While the majority of those exposed have minor symptoms and recover with little morbidity, an estimated 500,000 people succumb to IAV-related complications each year worldwide. In these severe cases, an exaggerated inflammatory response, known as \"cytokine storm\", occurs which results in damage to the respiratory epithelial barrier and development of acute respiratory distress syndrome (ARDS). Data from retrospective human studies as well as experimental animal models of influenza virus infection highlight the fine line between an excessive and an inadequate immune response, where the host response must balance viral clearance with exuberant inflammation. Current pharmacological modulators of inflammation, including corticosteroids and statins, have not been successful in improving outcomes during influenza virus infection. We have reported that the amplitude of the inflammatory response is regulated by Linear Ubiquitin Assembly Complex (LUBAC) activity and that dampening of LUBAC activity is protective during severe influenza virus infection. Therapeutic modulation of LUBAC activity may be crucial to improve outcomes during severe influenza virus infection, as it functions as a molecular rheostat of the host response. Here we review the evidence for modulating inflammation to ameliorate influenza virus infection-induced lung injury, data on current anti-inflammatory strategies, and potential new avenues to target viral inflammation and improve outcomes.", "title": "Targeting the Linear Ubiquitin Assembly Complex to Modulate the Host Response and Improve Influenza A Virus Induced Lung Injury", "pid": "apj9hv4v", "bm25_score": 215.98655700683594}, {"text": "BACKGROUND Severe acute respiratory coronavirus 2 (SARS-CoV-2) caused coronavirus disease 2019 (COVID-19) has become a pandemic. This study addressed the clinical and immunopathological characteristics of severe COVID-19. METHODS Sixty-nine COVID-19 patients were classified into as severe and non-severe groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from two deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations. RESULTS Circulating cytokines, including IL8, IL6, TNFα, IP10, MCP1, and RANTES, were significantly elevated in severe COVID-19 patients. Dynamic IL6 and IL8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II, type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4+ and CD8+ T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues. CONCLUSIONS A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both SARS-CoV-2 caused cytopathy and immunopathologic damage. Strategies that encourage pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of severe COVID-19 patients.", "title": "Clinical and pathological investigation of severe COVID-19 patients.", "pid": "2ik1rbto", "bm25_score": 215.9838104248047}, {"text": "Background The pathogenesis of COVID-19, caused by a novel strain of coronavirus (SARS-CoV-2), involves a complex host-virus interaction and is characterised by an exaggerated immune response, the specific components of which are poorly understood. Here we report the outcome of a longitudinal immune profiling study in hospitalised patients during the peak of the COVID-19 pandemic in the UK and show the relationship between immune responses and severity of the clinical presentation. Methods The Coronavirus Immune Response and Clinical Outcomes (CIRCO) study was conducted at four hospitals in Greater Manchester. Patients with SARS-CoV-2 infection, recruited as close to admission as possible, provided peripheral blood samples at enrolment and sequentially thereafter. Fresh samples were assessed for immune cells and proteins in whole blood and serum. Some samples were also stimulated for 3 hours with LPS and analysed for intracellular proteins. Results were stratified based on patient-level data including severity of symptoms and date of reported symptom onset. Findings Longitudinal analysis showed a very high neutrophil to T cell ratio and abnormal activation of monocytes in the blood, which displayed high levels of the cell cycle marker, Ki67 and low COX-2. These properties all reverted in patient with good outcome. Unexpectedly, multiple aspects of inflammation were diminished as patients progressed in severity and time, even in ITU patients not recovering. Interpretation This is the first detailed longitudinal analysis of COVID-19 patients of varying severity and outcome, revealing common features and aspects that track with severity. Patients destined for a severe outcome can be identified at admission when still displaying mild-moderate symptoms. We provide clues concerning pathogenesis that should influence clinical trials and therapeutics. Targeting pathways involved in neutrophil and monocyte release from the bone marrow should be tested in patients with COVID-19. Funding: The Kennedy Trust for Rheumatology Research, The Wellcome Trust, The Royal Society, The BBSRC, National Institute for Health Research (NIHR) Biomedical Research Centres (BRC).", "title": "Longitudinal immune profiling reveals distinct features of COVID-19 pathogenesis", "pid": "p3st70u3", "bm25_score": 215.97901916503906}, {"text": "Background: The recent outbreak of coronavirus disease 2019 (COVID-19) has been rapidly spreading on a global scale and poses a great threat to human health. Acute respiratory distress syndrome, characterized by a rapid onset of generalized inflammation, is the leading cause of mortality in patients with COVID-19. We thus aimed to explore the effect of risk factors on the severity of the disease, focusing on immune-inflammatory parameters, which represent the immune status of patients. Methods: A comprehensive systematic search for relevant studies published up to April 2020 was performed by using the PubMed, Web of Science, EMBASE, and China National Knowledge Internet (CNKI) databases. After extracting all available data of immune-inflammatory indicators, we statistically analyzed the risk factors of severe and non-severe COVID-19 patients with a meta-analysis. Results: A total of 4,911 patients from 29 studies were included in the final meta-analysis. The results demonstrated that severe patients tend to present with increased white blood cell (WBC) and neutrophil counts, neutrophil-lymphocyte ratio (NLR), procalcitonin (PCT), C-reaction protein (CRP), erythrocyte sedimentation rate (ESR), and Interleukin-6 (IL-6) and a decreased number of total lymphocyte and lymphocyte subtypes, such as CD4+ T lymphocyte and CD8+ T lymphocyte, compared to the non-severe patients. In addition, the WBC count>10 × 10(9)/L, lymphocyte count<1 × 10(9)/L, PCT>0.5 ng/mL, and CRP>10 mg/L were risk factors for disease progression in patients with COVID-19 (WBC count>10 × 10(9)/L: OR = 2.92, 95% CI: 1.96–4.35; lymphocyte count<1 × 10(9)/L: OR = 4.97, 95% CI: 3.53–6.99; PCT>0.5 ng/mL: OR = 6.33, 95% CI: 3.97–10.10; CRP>10 mg/L: OR = 3.51, 95% CI: 2.38–5.16). Furthermore, we found that NLR, as a novel marker of systemic inflammatory response, can also help predict clinical severity in patients with COVID-19 (OR = 2.50, 95% CI: 2.04–3.06). Conclusions: Immune-inflammatory parameters, such as WBC, lymphocyte, PCT, CRP, and NLR, could imply the progression of COVID-19. NLR has taken both the levels of neutrophil and lymphocyte into account, indicating a more complete, accurate, and reliable inspection efficiency; surveillance of NLR may help clinicians identify high-risk COVID-19 patients at an early stage.", "title": "Immune-Inflammatory Parameters in COVID-19 Cases: A Systematic Review and Meta-Analysis", "pid": "9knsva7e", "bm25_score": 215.97833251953125}, {"text": "Novel coronavirus disease-2019 (COVID-19) is a highly contagious respiratory-related disease induced by the newly emerged virus SARS-CoV-2. Given that inflammatory immune cells may induce severe lung injury, the involvement of immune factors in the pathogenesis of the disease cannot be overestimated. It has been demonstrated that coronaviruses (CoVs) have developed mechanisms of immune evasion, making them invisible to the immune system at an early stage of infection. The mechanism relies on inhibition of the anti-viral response of type I interferons (IFNs), which supports uncontrolled viral replication in epithelial cells. There is growing body of evidence that the fatal hyperinflammation ('cytokine storm') responsible for the severe course of COVID-19 is a consequence of massive SARS-CoV-2 replication rather than inappropriate hyperresponsiveness of the immune system. Therefore, a dampened innate anti-viral immune response seems to be the primary cause of the delayed critical cascade of uncontrolled immune events leading to fulminating systemic inflammation. The occurrence of virus transmission even in asymptomatic subjects infected with SARS-CoV-2 clearly strengthens the evidence for a key role of sufficient immune control of viral replication in a subset of cases (e.g. in children, a population with highly effective innate immune responses). Although administration of immunomodulatory therapeutics is recommended under certain conditions in the guidelines of COVID-19 management, controversies regarding treatment protocols in immunocompromised patients infected with SARS-CoV-2 still exist. Extended knowledge of clinicians on the dysregulated immune response, which is a driver of the COVID-19 outcome, may improve both therapeutic protocols and the prognosis of SARS-CoV-2 infected patients.", "title": "Dysregulation of the immune system as a driver of the critical course of the novel coronavirus disease 2019", "pid": "5ad4rm3y", "bm25_score": 215.9783172607422}, {"text": "Novel coronavirus disease-2019 (COVID-19) is a highly contagious respiratory-related disease induced by the newly emerged virus SARS-CoV-2. Given that inflammatory immune cells may induce severe lung injury, the involvement of immune factors in the pathogenesis of the disease cannot be overestimated. It has been demonstrated that coronaviruses (CoVs) have developed mechanisms of immune evasion, making them invisible to the immune system at an early stage of infection. The mechanism relies on inhibition of the anti-viral response of type I interferons (IFNs), which supports uncontrolled viral replication in epithelial cells. There is growing body of evidence that the fatal hyperinflammation ('cytokine storm') responsible for the severe course of COVID-19 is a consequence of massive SARS-CoV-2 replication rather than inappropriate hyperresponsiveness of the immune system. Therefore, a dampened innate anti-viral immune response seems to be the primary cause of the delayed critical cascade of uncontrolled immune events leading to fulminating systemic inflammation. The occurrence of virus transmission even in asymptomatic subjects infected with SARS-CoV-2 clearly strengthens the evidence for a key role of sufficient immune control of viral replication in a subset of cases (e.g. in children, a population with highly effective innate immune responses). Although administration of immunomodulatory therapeutics is recommended under certain conditions in the guidelines of COVID-19 management, controversies regarding treatment protocols in immunocompromised patients infected with SARS-CoV-2 still exist. Extended knowledge of clinicians on the dysregulated immune response, which is a driver of the COVID-19 outcome, may improve both therapeutic protocols and the prognosis of SARS-CoV-2 infected patients.", "title": "Dysregulation of the immune system as a driver of the critical course of the novel coronavirus disease 2019.", "pid": "1zq0aels", "bm25_score": 215.9781036376953}, {"text": "Abstract Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy. In this paper, we present an immunothrombosis model of COVID-19. We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients.", "title": "Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis", "pid": "7vqnqp83", "bm25_score": 215.97755432128906}, {"text": "Circulating in China and 158 other countries and areas, the ongoing COVID-19 outbreak has caused devastating mortality and posed a great threat to public health. However, efforts to identify effectively supportive therapeutic drugs and treatments has been hampered by our limited understanding of host immune response for this fatal disease. To characterize the transcriptional signatures of host inflammatory response to SARS-CoV-2 (HCoV-19) infection, we carried out transcriptome sequencing of the RNAs isolated from the bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cells (PBMC) specimens of COVID-19 patients. Our results reveal distinct host inflammatory cytokine profiles to SARS-CoV-2 infection in patients, and highlight the association between COVID-19 pathogenesis and excessive cytokine release such as CCL2/MCP-1, CXCL10/IP-10, CCL3/MIP-1A, and CCL4/MIP1B. Furthermore, SARS-CoV-2 induced activation of apoptosis and P53 signalling pathway in lymphocytes may be the cause of patients’ lymphopenia. The transcriptome dataset of COVID-19 patients would be a valuable resource for clinical guidance on anti-inflammatory medication and understanding the molecular mechansims of host response.", "title": "Transcriptomic characteristics of bronchoalveolar lavage fluid and peripheral blood mononuclear cells in COVID-19 patients", "pid": "0daf0i75", "bm25_score": 215.9735565185547}, {"text": "OBJECTIVE: Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or \"cytokine storm\". Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. METHODS: Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). RESULTS: In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were three deaths (17.8 ± 10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and one serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p < 0.0001 for both) and higher neutrophils and lower lymphocyte levels (p = 0.04 and p = 0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. CONCLUSION: Higher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key.", "title": "Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: Results from a single Italian Centre study on tocilizumab versus standard of care", "pid": "xa25e1ew", "bm25_score": 215.96376037597656}, {"text": "Background Infection with SARS-CoV-2 manifests itself as a mild respiratory tract infection in the majority of individuals, which progresses to a severe pneumonia and acute respiratory distress syndrome (ARDS) in 10-15% of patients. Inflammation plays a crucial role in the pathogenesis of ARDS, with immune dysregulation in severe COVID-19 leading to a hyperinflammatory response. A comprehensive understanding of the inflammatory process in COVID-19 is lacking. Methods In this prospective, multicenter observational study, patients with PCR-proven or clinically presumed COVID-19 admitted to the intensive care unit (ICU) or clinical wards were included. Demographic and clinical data were obtained and plasma was serially collected. Concentrations of IL-6, TNF-, complement components C3a, C3c and the terminal complement complex (TCC) were determined in plasma by ELISA. Additionally, 269 circulating biomarkers were assessed using targeted proteomics. Results were compared between ICU and non ICU patients. Findings A total of 119 (38 ICU and 91 non ICU) patients were included. IL-6 plasma concentrations were elevated in COVID-19 (ICU vs. non ICU, median 174.5 pg/ml [IQR 94.5-376.3 vs. 40.0 pg/ml [16.5-81.0]), whereas TNF- concentrations were relatively low and not different between ICU and non ICU patients (median 24.0 pg/ml [IQR 16.5-33.5] and 21.5 pg/ml [IQR 16.0-33.5], respectively). C3a and terminal complement complex (TCC) concentrations were significantly higher in ICU vs. non ICU patients (median 556.0 ng/ml [IQR 333.3-712.5]) vs. 266.5 ng/ml [IQR 191.5-384.0 for C3a and 4506 mAU/ml [IQR 3661-6595 vs. 3582 mAU/ml [IQR 2947-4300] for TCC) on the first day of blood sampling. Targeted proteomics demonstrated that IL-6 (logFC 2.2), several chemokines and hepatocyte growth factor (logFC 1.4) were significantly upregulated in ICU vs. non ICU patients. In contrast, stem cell factor was significantly downregulated (logFC -1.3) in ICU vs. non ICU patients, as were DPP4 (logFC -0.4) and protein C inhibitor (log FC -1.0), the latter two factors also being involved in the regulation of the kinin-kallikrein pathway. Unsupervised clustering pointed towards a homogeneous pathogenetic mechanism in the majority of patients infected with SARS-CoV-2, with patient clustering mainly based on disease severity. Interpretation We identified important pathways involved in dysregulation of inflammation in patients with severe COVID-19, including the IL-6, complement system and kinin-kallikrein pathways. Our findings may aid the development of new approaches to host-directed therapy.", "title": "A systems approach to inflammation identifies therapeutic targets in SARS-CoV-2 infection", "pid": "jutof78v", "bm25_score": 215.9630126953125}, {"text": "OBJECTIVE: Approximately 5% of patients with coronavirus disease 2019 (COVID-19) develop a life-threatening pneumonia that often occurs in the setting of increased inflammation or “cytokine storm”. Anti-cytokine treatments are being evaluated but optimal patient selection remains unclear, and the aim of our study is to address this point. METHODS: Between February 29 to April 6, 2020, 111 consecutive hospitalized patients with COVID-19 pneumonia were evaluated in a single centre retrospective study. Patients were divided in two groups: 42 severe cases (TOCI) with adverse prognostic features including raised CRP and IL-6 levels, who underwent anti-cytokine treatments, mostly tocilizumab, and 69 standard of care patients (SOC). RESULTS: In the TOCI group, all received anti-viral therapy and 40% also received glucocorticoids. In TOCI, 62% of cases were ventilated and there were 3 deaths (17.8 ± 10.6 days, mean follow up) with 7/26 cases remaining on ventilators, without improvement, and 17/26 developed bacterial superinfection. One fatality occurred in the 15 TOCI cases treated on noninvasive ventilation and 1 serious bacterial superinfection. Of the 69 cases in SOC, there was no fatalities and no bacterial complications. The TOCI group had higher baseline CRP and IL-6 elevations (p < 0.0001 for both) and higher neutrophils and lower lymphocyte levels (p = 0.04 and p = 0.001, respectively) with the TOCI ventilated patients having higher markers than non-ventilated TOCI patients. CONCLUSION: Higher inflammatory markers, more infections and worse outcomes characterized ventilated TOCI cases compared to ward based TOCI. Despite the confounding factors, this suggests that therapy time in anti-cytokine randomized trials will be key.", "title": "Profiling COVID-19 pneumonia progressing into the cytokine storm syndrome: results from a single Italian Centre study on tocilizumab versus standard of care", "pid": "2xnq1oq7", "bm25_score": 215.96231079101562}, {"text": "The current pandemic of COVID-19 has caused severe morbidity and mortality across the globe. People with a smoking history have severe disease outcomes by COVID-19 infection. Epidemiological studies show that old age and pre-existing disease conditions (hypertension and diabetes) result in severe disease outcome and mortality amongst COVID-19 patients. Evidences suggest that the S1 domain of the SARS-CoV-2 (causative agent of COVID-19) membrane spike has a high affinity towards the angiotensin-converting enzyme 2 (ACE2) receptor found on the host’s lung epithelium. Likewise, TMPRSS2 protease has been shown to be crucial for viral activation thus facilitating the viral engulfment. The viral entry has been shown to cause ‘cytokine storm’ involving excessive production of pro-inflammatory cytokines/chemokines including IL-6, TNF-α, IFN-γ, IL-2, IL-7, IP-10, MCP-3 or GM-CSF, which is augmented by smoking. Future research could target these inflammatory-immunological responses to develop effective therapy for COVID-19. This mini-review provides a consolidated account on the role of inflammation and immune responses, proteases, and epithelial permeability by smoking and vaping during SARS-CoV2 infection with future directions of research, and provides a list of the potential targets for therapies particularly controlling cytokine storms in the lung.", "title": "SARS-CoV-2 COVID-19 susceptibility and lung inflammatory storm by smoking and vaping", "pid": "n0d9b50t", "bm25_score": 215.95904541015625}, {"text": "The pandemic caused by SARS-COV2 Virus/COVID-19, which was initially reported in China in December 2019, has become a major global health concern COVID-19 can manifest with cytokine storm - an exaggerated systemic inflammatory phenomenon due to over-production of proinflammatory cytokines by immune cells that results in diffuse inflammatory lung disease and acute respiratory distress syndrome It may be complicated by septic shock and subsequent multi-organ failure Based on the most recently published evidence, this article will review and discuss comprehensive information on its clinical manifestations, laboratory tests, potential therapeutics, and prevention guidelines", "title": "2019 Novel Coronavirus Pandemic: What Do We Know?", "pid": "8lnb2tnz", "bm25_score": 215.95896911621094}, {"text": "BACKGROUND: The rapid outbreak of coronavirus disease 2019 (COVID-19) has turned into a public health emergency of international concern. Epidemiological research has shown that sex is associated with the severity of COVID-19, but the underlying mechanism of sex predisposition remains poorly understood. We aim to study the gendered differences in inflammation reaction, and the association with severity and mortality of COVID-19. METHODS: In this retrospective study, we enrolled 548 COVID-19 inpatients from Tongji Hospital from 26 January to 5 February 2020, and followed up to 3 March 2020. Epidemiological, demographic and clinical features, and inflammatory indexes were collected and compared between males and females. The Cox proportional hazard regression model was applied to identify the gendered effect on mortality of COVID-19 after adjusting for age, comorbidity, and smoking history. The multiple linear regression method was used to explore the influence of sex on inflammation reaction. RESULTS: Males had higher mortality than females did (22.2% vs 10.4%), with an hazard ratio of 1.923 (95% confidence interval, 1.181-3.130); elder age and comorbidity were significantly associated with decease of COVID-19 patients. Excess inflammation reaction was related to severity of COVID-19. Male patients had greater inflammation reaction, with higher levels of interleukin 10, tumor necrosis factor-&#945;, lactose dehydrogenase, ferritin, and hyper-sensitive C-reactive protein, but a lower lymphocyte count than females adjusted by age and comorbidity. CONCLUSIONS: Sex, age, and comorbidity are critical risk factors for mortality of COVID-19. Excess innate immunity and proinflammation activity, and deficiency in adaptive immunity response promote males, especially elder males, to develop a cytokine storm, causing potential acute respiratory distressed syndrome, multiple organ failure and decease.", "title": "Gendered effects on inflammation reaction and outcome of COVID-19 patients in Wuhan", "pid": "j6v0zaa7", "bm25_score": 215.95797729492188}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the genus Betacoronavirus within the family Coronaviridae. It is an enveloped single-stranded positive-sense RNA virus. Since December of 2019, a global expansion of the infection has occurred with widespread dissemination of coronavirus disease 2019 (COVID-19). COVID-19 often manifests as only mild cold-like symptomatology, but severe disease with complications occurs in 15% of cases. Respiratory failure occurs in severe disease that can be accompanied by a systemic inflammatory reaction characterized by inflammatory cytokine release. In severe cases, fatality is caused by the rapid development of severe lung injury characteristic of acute respiratory distress syndrome (ARDS). Although ARDS is a complication of SARS-CoV-2 infection, it is not viral replication or infection that causes tissue injury; rather, it is the result of dysregulated hyperinflammation in response to viral infection. This pathology is characterized by intense, rapid stimulation of the innate immune response that triggers activation of the Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome pathway and release of its products including the proinflammatory cytokines IL-6 and IL-1β. Here we review the literature that describes the pathogenesis of severe COVID-19 and NLRP3 activation and describe an important role in targeting this pathway for the treatment of severe COVID-19.", "title": "Targeting the NLRP3 Inflammasome in Severe COVID-19", "pid": "ehcqey3f", "bm25_score": 215.95265197753906}, {"text": "The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as 'cytokine storm'. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19.", "title": "The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response", "pid": "5f63n7ex", "bm25_score": 215.92269897460938}, {"text": "BACKGROUND: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has become a pandemic. This study addresses the clinical and immunopathological characteristics of severe COVID-19. METHODS: Sixty-nine patients with COVID-19 were classified into severe and nonsevere groups to analyze their clinical and laboratory characteristics. A panel of blood cytokines was quantified over time. Biopsy specimens from 2 deceased cases were obtained for immunopathological, ultrastructural, and in situ hybridization examinations. RESULTS: Circulating cytokines, including IL-8, IL-6, TNF-&#945;, IP10, MCP1, and RANTES, were significantly elevated in patients with severe COVID-19. Dynamic IL-6 and IL-8 were associated with disease progression. SARS-CoV-2 was demonstrated to infect type II and type I pneumocytes and endothelial cells, leading to severe lung damage through cell pyroptosis and apoptosis. In severe cases, lymphopenia, neutrophilia, depletion of CD4+ and CD8+ T lymphocytes, and massive macrophage and neutrophil infiltrates were observed in both blood and lung tissues. CONCLUSIONS: A panel of circulating cytokines could be used to predict disease deterioration and inform clinical interventions. Severe pulmonary damage was predominantly attributed to both cytopathy caused by SARS-CoV-2 and immunopathologic damage. Strategies that prohibit pulmonary recruitment and overactivation of inflammatory cells by suppressing cytokine storm might improve the outcomes of patients with severe COVID-19.", "title": "Clinical and pathological investigation of patients with severe COVID-19", "pid": "n1z5bnqj", "bm25_score": 215.9202880859375}, {"text": "The novel coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is sorely testing health care systems and economies around the world and is rightly considered as the major health emergency in a century. Despite the course of the disease appearing to be mild in many cases, a significant proportion of symptomatic patients develop pneumonia requiring hospitalisation or progress to manifest respiratory complications leading to intensive care treatment. Potential interventions for SARS-CoV2-associated pneumonia are being tested, some of which holding promise, but as of today none of these has yet demonstrated outstanding efficacy in treating COVID-19. In this article, we discuss fresh perspectives and insights into the potential role of immune dysregulation in COVID-19 as well as similarities with systemic inflammatory response in sepsis and the rationale for exploring novel treatment options affecting host immune response.", "title": "The unleashing of the immune system in COVID-19 and sepsis: the calm before the storm?", "pid": "5ycxh1sq", "bm25_score": 215.88882446289062}, {"text": "The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses like SARS-CoV and MERS-CoV, which are established to cause lower respiratory tract infection. The viral infection can be fatal as the disease advances to pneumonia followed by acute respiratory distress syndrome (ARDS). Increasingly higher cytokine concentration on account of over-stimulated immune response against the virus, or the ‘cytokine storm’, is the reason behind the manifestation of lethal clinical symptoms. In this article, we discuss the immune pathogenesis of cytokine storm and its relation with SARS-CoV2/COVID-19 risk factors. People with underlying risk factors are more susceptible to fatal complications of COVID-19 infection leading to poor clinical outcome. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 to a Cytokine Super Cyclone. We also overviewed antiviral immune response provided by BCG vaccine involving the IL-1β, IL-6 and TNF-α secretion via ‘trained monocytes’, which confers early protection against SARS-CoV2.", "title": "Cytokine Storm in COVID-19 patients transforms to a Cytokine Super Cyclone in patients with risk factors", "pid": "6dq6gm27", "bm25_score": 215.88742065429688}, {"text": "The 2019 coronavirus disease (COVID-19) pandemic caused by the virus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has created an unprecedented global crisis for the infrastructure sectors, including economic, political, healthcare, education, and research systems. Although over 90% of infected individuals are asymptomatic or manifest noncritical symptoms and will recover from the infection, those individuals presenting with critical symptoms are in urgent need of effective treatment options. Emerging data related to mechanism of severity and potential therapies for patients presenting with severe symptoms are scattered and therefore require a comprehensive analysis to focus research on developing effective therapeutics. A critical literature review suggests that the severity of SARS-CoV-2 infection is associated with dysregulation of inflammatory immune responses, which in turn inhibits the development of protective immunity to the infection. Therefore, the use of therapeutics that modulate inflammation without compromising the adaptive immune response could be the most effective therapeutic strategy.", "title": "COVID-19 as an Acute Inflammatory Disease.", "pid": "70s35cip", "bm25_score": 215.88467407226562}, {"text": "The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as ‘cytokine storm’. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19.", "title": "The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response", "pid": "gn34m0hb", "bm25_score": 215.86984252929688}, {"text": "Viral sepsis is rare, and its real incidence is not known. SARS-CoV-2 infection causes the release of a significant amount of pro-inflammatory cytokines that aggravates interstitial pneumonia and evolves in viral sepsis with prominent hypercoagulability. We believe it is useful and advisable to establish early immunomodulator therapy and the prophylaxis anticoagulant therapy should be rethought.", "title": "Thromboinflammatory response in SARS-CoV-2 sepsis.", "pid": "ulyp33j1", "bm25_score": 215.8671875}, {"text": "INTRODUCTION: There have been recent mounting concerns regarding multiple reports stating a significantly elevated relative-risk of COVID-19 mortality amongst the Black and Minority Ethnic (BAME) population. An urgent national enquiry investigating the possible reasons for this phenomenon has been issued in the UK. Inflammation is at the forefront of COVID-19 research as disease severity appears to correlate with pro-inflammatory cytokine dysregulation. This narrative review aims to shed light on the novel, pathophysiological role of inflammation in contributing towards the increased COVID-19 mortality risk amongst the BAME population. METHODS: Searches in PubMed, Medline, Scopus, medRxiv and Google Scholar were performed to identify articles published in English from inception to 18th June 2020. These databases were searched using keywords including: 'COVID-19' or 'Black and Minority Ethnic' or 'Inflammation'. A narrative review was synthesized using these included articles. RESULTS: We suggest a novel pathophysiological mechanism by which acute inflammation from COVID-19 may augment existing chronic inflammation, in order to potentiate a 'cytokine storm' and thus the more severe disease phenotype observed in the BAME population. Obesity, insulin resistance, cardiovascular disease, psychological stress, chronic infections and genetic predispositions are all relevant factors which may be contributing to elevated chronic systemic inflammation amongst the BAME population. CONCLUSION: Overall, this review provides early insights and directions for ongoing research regarding the pathophysiological mechanisms that may explain the severe COVID-19 disease phenotype observed amongst the BAME population. We suggest 'personalization' of chronic disease management, which can be used with other interventions, in order to tackle this.", "title": "COVID-19 and ethnicity: A novel pathophysiological role for inflammation", "pid": "y2lg48m0", "bm25_score": 215.85842895507812}, {"text": "INTRODUCTION: The cytokine release syndrome (CRS) of COVID-19 is associated with the development of critical illness requiring multi-organ support. Further research is required to halt progression of multi-organ injury induced by hyper-inflammation. AREAS COVERED: PubMed/MEDLINETM databases were accessed between May 9th-June 9th, 2020, to review the latest perspectives on the treatment and pathogenesis of CRS. EXPERT OPINION: Over-activity of chemotaxis triggers a macrophage activation syndrome (MAS) resulting in the release of pro-inflammatory cytokines. IL-6 and TNF- &#945; are at the forefront of hyper-inflammation. The inflammatory cascade induces endothelial activation and capillary leak, leading to circulatory collapse and shock. As endothelial dysfunction persists, there is activation of the clotting cascade and microvascular obstruction. Continued endothelial activation results in multi-organ failure, regardless of pulmonary tissue damage. We propose that targeting the endothelium may interrupt this cycle. Immuno-modulating therapies have been suggested, however, further data is necessary to confirm that they do not jeopardize adaptive immunity. Inhibition of IL-6 and the Janus Kinase, signal transducer and activator of transcription proteins pathway (JAK/STAT), are favorable targets. Remote ischemic conditioning (RIC) reduces the inflammation of sepsis in animal models and should be considered as a low risk intervention, in combination with cardiovascular protection.", "title": "The cytokine storm of COVID-19: a spotlight on prevention and protection", "pid": "rvqxohiq", "bm25_score": 215.85768127441406}, {"text": "AIM: Coronavirus disease 2019 (COVID-19) is a novel highly contagious infection caused by SARS-CoV-2, which has been became a global public health challenge. The pathogenesis of this virus is not yet clearly understood, but there is evidence of a hyper-inflammatory immune response in critically ill patients, which leads to acute respiratory distress syndrome (ARDS) and multi-organ failure. MATERIAL AND METHODS: A literature review was performed to identify relevant articles on COVID-19 published up to April 30, 2020. The search resulted in 361 total articles. After reviewing the titles and abstracts for inclusion, some irrelevant papers were excluded. Additional relevant articles were identified from a review of citations referenced. KEY FINDINGS: SARS-CoV-2, directly and indirectly, affects the immune system and avoids being eliminated in early stages. On the other hand, the secretion of inflammatory cytokines creates critical conditions that lead to multi-organ failure. SIGNIFICANCE: The immune system which is affected by the virus tries to respond via a cytokine storm and hyperinflammation, which itself leads to further multi-organ damage and even death.", "title": "The immune system and COVID-19: Friend or foe?", "pid": "d44coxr1", "bm25_score": 215.85543823242188}, {"text": "Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.", "title": "The pathogenesis and treatment of the `Cytokine Storm' in COVID-19", "pid": "iaatjew2", "bm25_score": 215.85467529296875}, {"text": "Severe acute respiratory syndrome (SARS) caused by a novel human coronavirus (CoV), designated SARS-CoV, is a highly contagious respiratory disease with the lungs as a major target. Although the exact mechanism of SARS-CoV pathogenesis remains unknown, an intense, ill-regulated local inflammatory response has been suggested as partially responsible for the devastating lung pathology. We investigated the interaction of SARS-CoV with human macrophages (Mphi) and dendritic cells (DC), two key innate immune cells of the host immune system, by focusing on their susceptibility to viral infection and subsequent responses (e.g., phenotypic maturation, T cell-priming activity, phagocytosis, and cytokine production). We found neither cell to be permissive for SARS-CoV replication. However, incubation of Mphi and DC with live, but not gamma irradiation-inactivated, viruses appeared to better sustain their viability. Also, exposure to infectious SARS-CoV led to the phenotypic and functional maturation of DC, with regard to MHC class II and costimulatory molecule expression, T cell-stimulatory capacity, and cytokine production, respectively. Cytokine production was also observed for Mphi, which were refractory to cell surface phenotypic changes. Strikingly, live SARS-CoV could further prime cell types to respond to a suboptimal dose of bacterial LPS (100 ng/ml), resulting in massive release of IL-6 and IL-12. However, the endocytic capacity (e.g., Ag capture) of Mphi was significantly compromised upon exposure to infectious SARS-CoV. This study is the first demonstration that although SARS-CoV does not productively infect human Mphi or DC, it appears to exert differential effects on Mphi and DC maturation and functions, which might contribute to SARS pathogenesis.", "title": "Severe acute respiratory syndrome and the innate immune responses: modulation of effector cell function without productive infection.", "pid": "pveldpqy", "bm25_score": 215.85458374023438}, {"text": "COVID-19 caused by a novel agent SARS-CoV-2 progressed to a pandemic condition and resulted in a major public health concern worldwide, leading to social and economic issues at the same time. The pathogenesis of COVID-19 starts with the bonding of the virus to ACE-2 receptors expressed in many tissues, and the triggered excessive immune response plays a critical role in the course of the disease. The cytokine storm that occurs upon excessive production of pro-inflammatory cytokines is considered responsible for the severe progression of the disease and the organ damage. However, the accurate pathophysiological mechanism of the disease, which progresses with various clinical presentations, is still substantially unknown. While various studies have been conducted on the effect of genetic polymorphism on the course and severity of the disease, the presence of a significant effect has not been proven yet. The clinical course of the disease is variable, with clinical representation ranging from 81% mild course to 14% severe course along with 5% critical course in patients. Asymptomatic course is considered to be higher than expected, although its frequency is not known exactly. Older adults and those with comorbidities are exposed to a more severe disease course. The disease progress with various symptoms, such as fever, cough, dyspnea, malaise, myalgia, taste and smell dysfunctions, diarrhea, and headache. A range of complications (Acute Respiratory Distress Syndrome, thromboembolic conditions, arrhythmia and cardiac events, secondary infections) could be seen during the course of the disease. Varied laboratory tests are vital to determine the severity and prognosis of the disease, along with the condition and exposure of the affected systems during the course of COVID-19.", "title": "COVID-19: Pathogenesis, Genetic Polymorphism, Clinical Features and Laboratory Findings.", "pid": "ot5v8n0c", "bm25_score": 215.8367919921875}, {"text": "Patients with COVID-19 who require ICU admission might have the cytokine storm. It is a state of out-of-control release of a variety of inflammatory cytokines. The molecular mechanism of the cytokine storm has not been explored extensively yet. The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. Four molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine overproduction are addressed in this work. The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components. The molecular clarification of these axes will elucidate an array of therapeutic strategies to confront the cytokine storm in order to prevent and treat COVID-19 associated acute respiratory distress syndrome.", "title": "COVID-19 cytokine storm: The anger of inflammation", "pid": "s82qv18v", "bm25_score": 215.83535766601562}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS-COv-2) is the etiologic agent of the 2019 coronavirus disease (COVID19). The majority of infected people presents flu like symptoms and among them 15-20% develops a severe interstitial pneumonitis (IP) that may eventually evolve in acute respiratory distress syndrome (ARDS). IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes. The virus is recognized by the \"pattern recognition receptors\" (PRR) of the immune cells that release cytokines activating more immune cells that produce a large number of pro-inflammatory cytokines, tissue factors and vasoactive peptides. Affected patients might develop the \"cytokine storm syndrome,\" a fulminant and fatal hypercytokinaemia with multiorgan failure. In patients infected by SARS-COv-2 increase in T-helper 2 (TH2) cytokines (IL-4 and IL10) are reported in addition to the T-helper 1 (TH1) cytokines (IL1B, IFNγ, IP10, and MCP1) previously detected in other coronavirus infections. Cytokines and other molecules involved in immune response and inflammation are conceivable therapeutic targets for IP and ARDS, improving symptoms and decreasing intensive care unit admissions. To this aim off label drugs may be used taking into consideration the window timing for immunosuppressive drugs in virus infected patients. Some off label therapeutic options and preclinical evidence drugs are herein considered.", "title": "Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs", "pid": "f640gmgs", "bm25_score": 215.83363342285156}, {"text": "RATIONALE Coronavirus disease 2019 (COVID-19) is a global threat to health. Its inflammatory characteristics are incompletely understood. OBJECTIVES To define the cytokine profile of COVID-19, and to identify evidence of immunometabolic alterations in those with severe illness. METHODS Levels of interleukin (IL)-1β, IL-6, IL-8, IL-10 and soluble TNF receptor 1 (sTNFR1) were assessed in plasma from healthy volunteers, hospitalized-but-stable COVID-19 patients (COVIDstable), COVID-19 patients requiring intensive care unit (ICU) admission (COVIDICU) and individuals with severe community-acquired pneumonia requiring ICU support (CAPICU). Immunometabolic markers were measured in circulating neutrophils from patients with severe COVID-19. The acute phase response of alpha-1 antitrypsin (AAT) to COVID-19 was also evaluated. MAIN RESULTS IL-1β, IL-6, IL-8 and sTNFR1 were all increased in patients with COVID-19. COVIDICU patients could be clearly differentiated from COVIDstable, and demonstrated higher levels of IL-1β, IL-6 and sTNFR1 - but lower IL-10 - than CAPICU. COVID-19 neutrophils displayed altered immunometabolism, with increased cytosolic PKM2, phosphorylated PKM2, HIF-1α and lactate. The production and sialylation of AAT increased in COVID-19, but this anti-inflammatory response was overwhelmed in severe illness, with the IL-6:AAT ratio markedly higher in patients requiring ICU admission (P<0.0001). In critically unwell COVID-19 patients, increases in IL-6:AAT predicted prolonged ICU stay and mortality, while improvement in IL-6:AAT was associated with clinical resolution (P<0.0001). CONCLUSIONS The COVID-19 cytokinemia is distinct from that of other types of pneumonia leading to organ failure and ICU need. Neutrophils undergo immunometabolic reprogramming in severe COVID-19 illness. Cytokine ratios may predict outcomes in this population. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).", "title": "Characterization of the Inflammatory Response to Severe COVID-19 Illness.", "pid": "ic45wuzg", "bm25_score": 215.8252716064453}, {"text": "SARS-CoV-2 infection, named COVID-19, can lead to a dysregulated immune response and abnormal coagulation responsible for a viral sepsis. In this review, we specify physiopathological mechanisms of each phase of COVID-19 - viral, immune and pro-thrombotic - notably because they involve different treatment. Finally, we specify the physiopathological mechanisms of organ injury.", "title": "COVID-19 : physiopathologie d'une maladie à plusieurs visages./ [COVID-19: Pathogenesis of a multi-faceted disease]", "pid": "goordy3i", "bm25_score": 215.8171844482422}, {"text": "Coronavirus disease-2019 (COVID-19) is caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was recently declared as a pandemic by the World Health Organization. In its severe form, the disease is characterized by acute respiratory distress syndrome, and there are no targeted intervention strategies to treat or prevent it. The immune response is thought to both contribute to the pathogenesis of disease and provide protection during its resolution. Thus, understanding the immune response to SARS-CoV-2 is of the utmost importance for developing and testing vaccines and therapeutics. In this review, we discuss the earliest knowledge and hypotheses of the mechanisms of immune pathology in the lung during acute infection as well at the later stages of disease resolution, recovery, and immune memory formation.", "title": "Early Insights into Immune Responses during COVID-19.", "pid": "1mhxy9hh", "bm25_score": 215.80612182617188}, {"text": "This paper presents an evidence-based strategy for improving clinical outcomes in COVID-19. Recommendations are based on the phases of the disease, because optimal interventions for one phase may not be appropriate for a different phase. The four phases addressed are: Prevention, Infection, Inflammation and Recovery. Underlying this phased approach is recognition of emerging evidence for two different components of pathophysiology, early infection and late stage severe complications. These two aspects of the disease suggest two different patterns of clinical emphasis that seem on the surface to be not entirely concordant. We describe the application of therapeutic strategies and appropriate tactics that address four main stages of disease progression for COVID-19. Emerging evidence in COVID-19 suggests that the SARS-CoV-2 virus may both evade the innate immune response and kill macrophages. Delayed innate immune response and a depleted population of macrophages can theoretically result in a blunted antigen presentation, delaying and diminishing activation of the adaptive immune response. Thus, one clinical strategy involves supporting patient innate and adaptive immune responses early in the time course of illness, with the goal of improving the timeliness, readiness, and robustness of both the innate and adaptive immune responses. At the other end of the disease pathology spectrum, risk of fatality in COVID-19 is driven by excessive and persistent upregulation of inflammatory mechanisms associated with cytokine storm. Thus, the second clinical strategy is to prevent or mitigate excessive inflammatory response to prevent the cytokine storm associated with high mortality risk. Clinical support for immune system pathogen clearance mechanisms involves obligate activation of immune response components that are inherently inflammatory. This puts the goals of the first clinical strategy (immune activation) potentially at odds with the goals of the second strategy(mitigation of proinflammatory effects). This creates a need for discernment about the time course of the illness and with that, understanding of which components of an overall strategy to apply at each phase of the time course of the illness. We review evidence from early observational studies and the existing literature on both outcomes and mechanisms of disease, to inform a phased approach to support the patient at risk for infection, with infection, with escalating inflammation during infection, and at risk of negative sequelae as they move into recovery.", "title": "Evidence Supporting a Phased Immuno-physiological Approach to COVID-19 From Prevention Through Recovery.", "pid": "quweeq9e", "bm25_score": 215.80068969726562}, {"text": "As of April 20, 2020, over time, the COVID-19 pandemic has resulted in 157 970 deaths out of 2 319 066 confirmed cases, at a Case Fatality Rate of ~6.8%. With the pandemic rapidly spreading, and health delivery systems being overwhelmed, it is imperative that safe and effective pharmacotherapeutic strategies are rapidly explored to improve survival. In this paper, we use established and emerging evidence to propose a testable hypothesis that, a vicious positive feedback loop of des-Arg(9)-bradykinin- and bradykinin-mediated inflammation → injury → inflammation, likely precipitates life threatening respiratory complications in COVID-19. Through our hypothesis, we make the prediction that the FDA-approved molecule, icatibant, might be able to interrupt this feedback loop and, thereby, improve the clinical outcomes. This hypothesis could lead to basic, translational, and clinical studies aimed at reducing COVID-19 morbidity and mortality.", "title": "A hypothesized role for dysregulated bradykinin signaling in COVID-19 respiratory complications", "pid": "ztvquckn", "bm25_score": 215.79698181152344}, {"text": "The inflammatory response to severe acute respiratory syndrome-related coronavirus 2 infection has a direct impact on the clinical outcomes of coronavirus disease 2019 patients. Of the many innate immune pathways that are engaged by severe acute respiratory syndrome-related coronavirus 2, we highlight the importance of the inflammasome pathway. We discuss available pharmaceutical agents that target a critical component of inflammasome activation, signaling leading to cellular pyroptosis, and the downstream cytokines as a promising target for the treatment of severe coronavirus disease 2019-associated diseases.", "title": "Inflammasomes and Pyroptosis as Therapeutic Targets for COVID-19.", "pid": "2h2w9yi4", "bm25_score": 215.79684448242188}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS-COv-2) is the etiologic agent of the 2019 coronavirus disease (COVID19). The majority of infected people presents flu like symptoms and among them 15–20% develops a severe interstitial pneumonitis (IP) that may eventually evolve in acute respiratory distress syndrome (ARDS). IP is caused by the viral glycoprotein spike (S) binding to the angiotensin converting enzyme 2 (ACE2) expressed on the surface of alveolar pneumocytes. The virus is recognized by the “pattern recognition receptors” (PRR) of the immune cells that release cytokines activating more immune cells that produce a large number of pro-inflammatory cytokines, tissue factors and vasoactive peptides. Affected patients might develop the “cytokine storm syndrome,” a fulminant and fatal hypercytokinaemia with multiorgan failure. In patients infected by SARS-COv-2 increase in T-helper 2 (TH2) cytokines (IL-4 and IL10) are reported in addition to the T-helper 1 (TH1) cytokines (IL1B, IFNγ, IP10, and MCP1) previously detected in other coronavirus infections. Cytokines and other molecules involved in immune response and inflammation are conceivable therapeutic targets for IP and ARDS, improving symptoms and decreasing intensive care unit admissions. To this aim off label drugs may be used taking into consideration the window timing for immunosuppressive drugs in virus infected patients. Some off label therapeutic options and preclinical evidence drugs are herein considered.", "title": "Fighting the Host Reaction to SARS-COv-2 in Critically Ill Patients: The Possible Contribution of Off-Label Drugs", "pid": "6zwkfzab", "bm25_score": 215.7917022705078}, {"text": "Influenza A virus (IAV) infects the respiratory tract in humans and causes significant morbidity and mortality worldwide each year. Aggressive inflammation, known as a cytokine storm, is thought to cause most of the damage in the lungs during IAV infection. Dysfunctional coagulation is a common complication in pathogenic influenza, manifested by lung endothelial activation, vascular leak, disseminated intravascular coagulation and pulmonary microembolism. Importantly, emerging evidence shows that an uncontrolled coagulation system, including both the cellular (endothelial cells and platelets) and protein (coagulation factors, anticoagulants and fibrinolysis proteases) components, contributes to the pathogenesis of influenza by augmenting viral replication and immune pathogenesis. In this review, we focus on the underlying mechanisms of the dysfunctional coagulatory response in the pathogenesis of IAV.", "title": "Aberrant coagulation causes a hyper-inflammatory response in severe influenza pneumonia", "pid": "1ib0n0yu", "bm25_score": 215.7882843017578}, {"text": "Summary Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.", "title": "The pathogenesis and treatment of the `Cytokine Storm' in COVID-19", "pid": "fqlv35vo", "bm25_score": 215.78692626953125}, {"text": "The recent COVID-19 pandemic has had a significant impact on our lives and has rapidly expanded to reach more than 4 million cases worldwide by May 2020. These cases are characterized by extreme variability, from a mild or asymptomatic form lasting for a few days up to severe forms of interstitial pneumonia that may require ventilatory therapy and can lead to patient death.Several hypotheses have been drawn up to understand the role of the interaction between the infectious agent and the immune system in the development of the disease and the most severe forms; the role of the cytokine storm seems important.Innate immunity, as one of the first elements of guest interaction with different infectious agents, could play an important role in the development of the cytokine storm and be responsible for boosting more severe forms. Therefore, it seems important to study also this important arm of the immune system to adequately understand the pathogenesis of the disease. Research on this topic is also needed to develop therapeutic strategies for treatment of this disease.", "title": "COVID 19: a clue from innate immunity", "pid": "911ozh90", "bm25_score": 215.78094482421875}, {"text": "The recent COVID-19 pandemic has had a significant impact on our lives and has rapidly expanded to reach more than 4 million cases worldwide by May 2020. These cases are characterized by extreme variability, from a mild or asymptomatic form lasting for a few days up to severe forms of interstitial pneumonia that may require ventilatory therapy and can lead to patient death. Several hypotheses have been drawn up to understand the role of the interaction between the infectious agent and the immune system in the development of the disease and the most severe forms; the role of the cytokine storm seems important. Innate immunity, as one of the first elements of guest interaction with different infectious agents, could play an important role in the development of the cytokine storm and be responsible for boosting more severe forms. Therefore, it seems important to study also this important arm of the immune system to adequately understand the pathogenesis of the disease. Research on this topic is also needed to develop therapeutic strategies for treatment of this disease.", "title": "COVID 19: a clue from innate immunity", "pid": "n21y5kps", "bm25_score": 215.78094482421875}, {"text": "INTRODUCTION The cytokine release syndrome (CRS) of COVID-19 is associated with the development of critical illness requiring multi-organ support. Further research is required to halt progression of multi-organ injury induced by hyper-inflammation. AREAS COVERED PubMed/MEDLINETM databases were accessed between May 9th-June 9th, 2020, to review the latest perspectives on the treatment and pathogenesis of CRS. EXPERT OPINION Over-activity of chemotaxis triggers a macrophage activation syndrome (MAS) resulting in the release of pro-inflammatory cytokines. IL-6 and TNF- α are at the forefront of hyper-inflammation. The inflammatory cascade induces endothelial activation and capillary leak, leading to circulatory collapse and shock. As endothelial dysfunction persists, there is activation of the clotting cascade and microvascular obstruction. Continued endothelial activation results in multi-organ failure, regardless of pulmonary tissue damage. We propose that targeting the endothelium may interrupt this cycle. Immuno-modulating therapies have been suggested, however, further data is necessary to confirm that they do not jeopardize adaptive immunity. Inhibition of IL-6 and the Janus Kinase, signal transducer and activator of transcription proteins pathway (JAK/STAT), are favorable targets. Remote ischemic conditioning (RIC) reduces the inflammation of sepsis in animal models and should be considered as a low risk intervention, in combination with cardiovascular protection.", "title": "The cytokine storm of COVID-19: a spotlight on prevention and protection.", "pid": "gf519r3l", "bm25_score": 215.77734375}, {"text": "COVID-19 is an infectious disease characterized by several important systemic problems such as severe pneumonia. One of mechanisms responsible of these systemic problems is the release of pro-inflammatory cytokines, such as interleukin (IL)-1beta and IL-6(Conti et al., 2020). The binding of virus to TRL (Toll Like Receptor) can determine the release of pro-IL-1beta with successive activation and production of active mature IL-1beta, responsible of lung inflammation, fever and fibrosis(Conti et al., 2020). The interstitial pneumonia is linked to an over-production of IL-6. Based on this principle, several researchers started the use of an anti-arthritis drug, tocilizumab, for its anti-IL-6 action.", "title": "New intriguing possibility for prevention of coronavirus pneumonitis: Natural purified polyphenols", "pid": "z9c9r3xw", "bm25_score": 215.77713012695312}, {"text": "COVID-19 is an infectious disease caused by 2019-nCoV and characterizes as an atypical pneumonia. Since 2019-nCoV is a newly emerging virus, the pathogenesis of COVID-19 is not well known. Most patients had a self-limited course, and some became severe even death. In this review, the authors compared two coronavirus outbreaks during the past two decades: the SARS-CoV and 2019-nCoV. Among the biological nature of the pathogens, viral receptor distribution on the human cells, and the pathological findings in the targeted organs and clinical features of the patients with the diseases, found similarities and differences between the two diseases. Due to the shared receptor ACE2 and the pathological similarities of the SARS-CoV and 2019-nCoV diseases. They proposed a pathogenesis model for COVID-19. Like the SARS-CoV disease, COVID-19 is a systematic disease and targets the lungs, vasculatures, and the immune system. The basic pathogenesis involves two interlinked processes: a severe lung inflammation and immune deficiency, both of which are related to an inappropriate immune response and over-production of cytokines. Thus, treatment approaches should include antiviral and anti-proinflammatory cytokines, anti-infectious and life support therapies, especially in patients with severe diseases.", "title": "[From SARS to COVID-19: pathogens, receptor, pathogenesis and principles of the treatment].", "pid": "qpwu24e8", "bm25_score": 215.7716827392578}, {"text": "Clinical manifestations of COVID-19 vary from asymptomatic virus shedding, non-specific pharyngitis, to pneumonia with silent hypoxia and respiratory failure. Dendritic cells and macrophages are sentinel cells for innate and adaptive immunity that affect the pathogenesis of SARS and MERS. However, the interplay between SARS-CoV-2 and these cell types remains unknown. Herein, we investigated the infection and host response of monocyte-derived dendritic cells (moDCs) and macrophages (MDMs) infected by SARS-CoV-2. We demonstrated that moDCs and MDMs were permissive to SARS-CoV-2 infection and protein expression but did not support productive virus replication. Importantly, SARS-CoV-2 launched an attenuated interferon response in both cell types. Additionally, SARS-CoV-2 triggered significant pro-inflammatory cytokine/chemokine expression in MDMs but not in moDCs. Further investigations suggested that this attenuated immune response to SARS-CoV-2 in moDCs was associated with viral antagonism of STAT1 phosphorylation. These findings on pathogenesis may explain the mild and insidious course of COVID-19 till late deterioration.", "title": "Attenuated interferon and pro-inflammatory response in SARS-CoV-2-infected human dendritic cells is associated with viral antagonism of STAT1 phosphorylation", "pid": "fwtohhe2", "bm25_score": 215.77001953125}, {"text": "As the outbreak of the new coronavirus (SARS-CoV-2) infection is spreading globally, great effort is being made to understand the disease pathogenesis and host factors that predispose to disease progression in an attempt to find a window of opportunity for intervention. In addition to the direct cytopathic effect of the virus, the host hyper-inflammatory response has emerged as a key factor in determining disease severity and mortality. Accumulating clinical observations raised hypotheses to explain why some patients develop more severe disease while others only manifest mild or no symptoms. So far, Covid-19 management remains mainly supportive. However, many researches are underway to clarify the role of antiviral and immunomodulating drugs in changing morbidity and mortality in patients who become severely ill. This review summarizes the current state of knowledge on the interaction between SARS-CoV-2 and the host immune system and discusses recent findings on proposed pharmacologic treatments.", "title": "Recent Insight into SARS-CoV2 Immunopathology and Rationale for Potential Treatment and Preventive Strategies in COVID-19", "pid": "rso3ryl1", "bm25_score": 215.7611083984375}, {"text": "Coronaviruses including severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2, also known as 2019-nCoV especially in China) replicate and divide in host cell. During this they are partly hidden from the innate immune responses although inflammatory consequences of viral replication still occur. We propose that anti-inflammatory antiviral prostaglandins may not only restrict viral replication but can also prevent inflammatory responses in the lungs and other vital organs that are known to be part of the immuno-pathogenesis of coronavirus disease-19 (COVID-19). The combination of anti-inflammatory antiviral prostaglandins with interferons may lead to the clearance of viruses inside the growth-restricted infected cells. However, further experimental studies and clinical trials should be conducted to evaluate the safety and efficacy of these possible therapies.", "title": "Immuno-pathogenesis of nCOVID-19 and a possible host-directed therapy including anti-inflammatory and anti-viral prostaglandin (PG J(2)) for effective treatment and reduce the death toll", "pid": "1hebq65a", "bm25_score": 215.7605438232422}, {"text": "The beginning of 2020 has seen the emergence of COVID-19, an outbreak caused by a novel coronavirus, SARS-CoV-2, an important pathogen for humans. There is an urgent need to better understand this new virus and to develop ways to control its spread. In Iran, the first case of the COVID-19 was reported after spread from China and other countries. Fever, cough, and fatigue were the most common symptoms of this virus. In worldwide, the incubation period of COVID-19 was 3 to 7 days and approximately 80% of infections are mild or asymptomatic, 15% are severe, requiring oxygen, and 5% are critical infections, requiring ventilation. To mount an antiviral response, the innate immune system recognizes molecular structures that are produced by the invasion of the virus. COVID-19 infection induces IgG antibodies against N protein that can be detected by serum as early as day 4 after the onset of disease and with most patients seroconverting by day 14. Laboratory evidence of clinical patients showed that a specific T-cell response against SARS-CoV-2 is important for the recognition and killing of infected cells, particularly in the lungs of infected individuals. At present, there is no specific antiviral therapy for COVID-19 and the main treatments are supportive. In this review, we investigated the innate and acquired immune responses in patients who recovered from COVID-19, which could inform the design of prophylactic vaccines and immunotherapy for the future.", "title": "Immune responses and pathogenesis of SARS-CoV-2 during an outbreak in Iran: Comparison with SARS and MERS", "pid": "3nnlkbph", "bm25_score": 215.76002502441406}, {"text": "BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. SUMMARY: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. KEY MESSAGES: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.", "title": "Weathering the Cytokine Storm in COVID-19: Therapeutic Implications", "pid": "lnltoj1n", "bm25_score": 215.7534637451172}, {"text": "BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. SUMMARY: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. Key Messages: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.", "title": "Weathering the Cytokine Storm in COVID-19: Therapeutic Implications", "pid": "re7ar8b1", "bm25_score": 215.7534637451172}, {"text": "COVID-19 is an infectious disease caused by 2019-nCoV and characterizes as an atypical pneumonia. Since 2019-nCoV is a newly emerging virus, the pathogenesis of COVID-19 is not well known. Most patients had a self-limited course, and some became severe even death. In this review, the authors compared two coronavirus outbreaks during the past two decades: the SARS-CoV and 2019-nCoV. Among the biological nature of the pathogens, viral receptor distribution on the human cells, and the pathological findings in the targeted organs and clinical features of the patients with the diseases, found similarities and differences between the two diseases had been found. Due to the shared receptor ACE2 and the pathological similarities of the SARS-CoV and 2019-nCoV diseases,authors proposed a pathogenesis model for COVID-19. Like the SARS-CoV disease, COVID-19 is a systematic disease and targets the lungs, vasculatures, and the immune system. The basic pathogenesis involves two interlinked processes: a severe lung inflammation and immune deficiency, both of which were related to an inappropriate immune response and over-production of cytokines. Thus, treatment approaches should include antiviral and anti-proinflammatory cytokines, anti-infectious and life support therapies, especially in patients with severe diseases.", "title": "[From SARS to COVID-19: pathogens, receptor, pathogenesis and principles of the treatment]", "pid": "a290vxor", "bm25_score": 215.75306701660156}, {"text": "The first case of human transmission of SARS-CoV-2 was reported in China in December 2019. A few months later, this viral infection had spread worldwide and became a pandemic. The disease caused by SARS-CoV-2, termed COVID-19, is multifactorial and associated with both specific antiviral as well as inflammatory responses, the extent of which may determine why some individuals are asymptomatic while others develop serious complications. Here we review possible life-threating immune events that can occur during disease progression to uncover key factors behind COVID-19 severity and provide suggestions for interventions with repurposed drugs in well-controlled and randomized clinical trials. These drugs include therapeutics with potential to inhibit SARS-CoV-2 entry into host cells such as serine protease inhibitors of the cellular protease TMPS2 and drugs targeting the renin-angiotensin system; antivirals with potential to block SARS-CoV-2 replication or factors that could boost the antiviral response; monoclonal antibodies targeting pro-inflammatory cytokines that drive the hyperinflammatory response during COVID-19 progression toward the severe stage and therapeutics that could ameliorate the function of the lungs. Furthermore, in order to help make more informed decisions on the timing of the intervention with the drugs listed in this review, we have grouped these therapeutics according to the stage of COVID-19 progression that we considered most appropriate for their mechanism of action.", "title": "Lessons Learned to Date on COVID-19 Hyperinflammatory Syndrome: Considerations for Interventions to Mitigate SARS-CoV-2 Viral Infection and Detrimental Hyperinflammation", "pid": "2qugltxu", "bm25_score": 215.7434844970703}, {"text": "COVID-19 caused by a novel agent SARS-CoV-2 progressed to a pandemic condition and resulted in a major public health concern worldwide, leading to social and economic issues at the same time. The pathogenesis of COVID-19 starts with the bonding of the virus to ACE2 receptors expressed in many tissues, and the triggered excessive immune response plays a critical role in the course of the disease. The cytokine storm that occurs upon excessive production of pro-inflammatory cytokines is considered responsible for the severe progression of the disease and the organ damage. However, the accurate pathophysiological mechanism of the disease, which progresses with various clinical presentations, is still substantially unknown. While various studies have been conducted on the effect of genetic polymorphism on the course and severity of the disease, the presence of a significant effect has not been proven yet. The clinical course of the disease is variable, with clinical representation ranging from 81% mild course to 14% severe course along with 5% critical course in patients. Asymptomatic course is considered to be higher than expected, although its frequency is not known exactly. Older adults and those with comorbidities are exposed to a more severe disease course. The disease progress with various symptoms, such as fever, cough, dyspnea, malaise, myalgia, taste and smell dysfunctions, diarrhea, and headache. A range of complications (acute respiratory distress syndrome, thromboembolic conditions, arrhythmia and cardiac events, secondary infections) could be seen during the course of the disease. Varied laboratory tests are vital to determine these verity and prognosis of the disease, along with the condition and exposure of the affected systems during thecourse of COVID-19.", "title": "COVID-19: pathogenesis, genetic polymorphism, clinical features and laboratory findings", "pid": "6hzlbpxg", "bm25_score": 215.74061584472656}, {"text": "Avian influenza A (H5N1) and severe acute respiratory syndrome (SARS) coronavirus are infections that cause a severe viral pneumonia leading to acute respiratory dysfunction syndrome and carry a high case-fatality rate. We have investigated innate immune responses to both viruses using primary human macrophages and respiratory epithelial cells as in vitro models. In contrast to human influenza A H1NI viruses, the H5N1 viruses hyper-induce cytokines (tumour necrosis factor [TNF]alpha, interferon beta) and chemokines (IP10, MIP1alpha, MCP) in in vitro cultures of primary human macrophages. A similar differential effect is observed in primary human bronchial epithelial cells and in type 2 pneumocytes although TNFalpha is not induced in respiratory epithelial cells. The cell signalling pathways responsible for this differential effect remain to be explored. Preliminary data suggest that such differential signalling involves p38 MAP kinase rather than NF-kappaB. SARS coronavirus infection of primary human macrophages is associated with a strong induction of chemokines without an associated type 1 interferon response. These observations may be relevant in disease pathogenesis.", "title": "Pathogenesis of avian flu H5N1 and SARS.", "pid": "ta6dfiu2", "bm25_score": 215.73385620117188}, {"text": "The novel coronavirus disease (COVID-19) pandemic is placing significant strains on health systems, scientific communities, essential public services, and economies all over the world. In this context, the world´s scientific biomedical establishment is unleashing an unprecedented response to the COVID-19 pandemic. This is a battle against time, considering the thousands of human lives are lost every day. In this commentary, based on a very recent research report, we intend to highlight how a new mechanism describing the RAGE transactivation produced by Ang II-mediated ATR1 activation can run continuously and thus, reinforcing a sustained inflammation in lungs, due to the SARS-Cov-2-mediated imbalance of the ACE/And II/ATR1 pathway.", "title": "SARS-CoV-2-mediated inflammatory response in lungs: should we look at RAGE?", "pid": "mlxpv16t", "bm25_score": 215.7311553955078}, {"text": "The pandemia of coronavirus disease 2019 (COVID-19) has caused more than 355,000 confirmed deaths worldwide. However, publications on postmortem findings are scarce. We present the pulmonary findings in four cases of fatal COVID-19 with a spectrum of lung pathology reflecting disease course and duration, invasive therapies, and laboratory features. Early disease is characterized by neutrophilic, exudative capillaritis with microthrombosis and high levels of IL-1beta and IL-6. Later stages are associated with diffuse alveolar damage and ongoing intravascular thrombosis in small to medium-sized pulmonary vessels, occasionally with areas of infarction equivalents, accompanied by laboratory features of disseminated intravascular coagulation. In late stages, organizing pneumonia with extensive intra-alveolar proliferation of fibroblasts and marked metaplasia of alveolar epithelium can be observed. Viral RNA is encountered in the lung, with virus particles in endothelial cells and pneumocytes. In many patients, multi-organ failure with severe liver damage sets in finally, possibly as consequence of an early-onset pro-inflammatory cytokine storm and/or thrombotic microangiopathy.", "title": "The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation", "pid": "vx5cszxg", "bm25_score": 215.72499084472656}, {"text": "Abstract Severe COVID-19 associated pneumonia patients may exhibit features of systemic hyper-inflammation designated under the umbrella term of macrophage activation syndrome (MAS) or cytokine storm, also known as secondary haemophagocytic lymphohistocytosis (sHLH). This is distinct from HLH associated with immunodeficiency states termed primary HLH -with radically different therapy strategies in both situations. COVID-19 infection with MAS typically occurs in subjects with adult respiratory distress syndrome (ARDS) and historically, non-survival in ARDS was linked to sustained IL-6 and IL-1 elevation. We provide a model for the classification of MAS to stratify the MAS-like presentation in COVID-19 pneumonia and explore the complexities of discerning ARDS from MAS. We discuss the potential impact of timing of anti-cytokine therapy on viral clearance and the impact of such therapy on intra-pulmonary macrophage activation and emergent pulmonary vascular disease.", "title": "The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease", "pid": "34slyg9x", "bm25_score": 215.72181701660156}]}
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We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.", "title": "Cytokine Storm in COVID19: A Neural Hypothesis.", "pid": "e58nciq3", "bm25_score": 220.503662109375}, {"text": "Cytokine storm in COVID-19 is characterized by an excessive inflammatory response to SARS-CoV-2 that is caused by a dysregulated immune system of the host. We are proposing a new hypothesis that SARS-CoV-2 mediated inflammation of nucleus tractus solitarius (NTS) may be responsible for the cytokine storm in COVID 19. The inflamed NTS may result in a dysregulated cholinergic anti-inflammatory pathway and hypothalamic-pituitary-adrenal axis.", "title": "Cytokine Storm in COVID19: A Neural Hypothesis", "pid": "ynrvowoc", "bm25_score": 220.42666625976562}, {"text": "Corona Virus Disease 2019 (COVID-19) has seriously affected the treatment of patients and social stability. In the later stage of disease, some COVID-19 patients may develop into acute respiratory distress syndrome or even multiple organ failure. However, one of the most important mechanism underlying the deterioration of disease is cytokine storm. At present, some therapies such as interleukin-6 antibody blocker, stem cell therapy, and transfusion of convalescent plasma have been applied to counteract the cytokine storm and have made some progress. This article reviews the influences of cytokine storm syndrome on the COVID-19 and the corresponding immunotherapies to resist cytokine storm.", "title": "[Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies].", "pid": "urr5iuy2", "bm25_score": 220.36160278320312}, {"text": "Corona Virus Disease 2019 (COVID-19) has seriously affected the treatment of patients and social stability. In the later stage of disease, some COVID-19 patients may develop into acute respiratory distress syndrome or even multiple organ failure. However, one of the most important mechanism underlying the deterioration of disease is cytokine storm. At present, some therapies such as interleukin-6 antibody blocker, stem cell therapy, and transfusion of convalescent plasma have been applied to counteract the cytokine storm and have made some progress. This article reviews the influences of cytokine storm syndrome on the COVID-19 and the corresponding immunotherapies to resist cytokine storm.", "title": "[Advances in the research of cytokine storm mechanism induced by Corona Virus Disease 2019 and the corresponding immunotherapies]", "pid": "3d04p4xp", "bm25_score": 220.1986541748047}, {"text": "A novel coronavirus disease 2019 (COVID-19) triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is currently spreading globally, causing severe pneumonia and acute lung injury in many patients. Even worse, severe respiratory may develop into acute respiratory distress syndrome and multiple organ dysfunction syndrome in COVID-19. The cytokine storm caused by immune over-activation due to virus infection may be an important cause of death in the late period of progress, but the pathogenesis of cytokine storm is still unclear. This article reviews the mechanisms of SARS-CoV-2-induced cytokine storm in detail based on the current discovered researches, and put forward some valuable medication ideas for the targeted cytokines drug researches and treatment. The goal of this work will be helpful for reducing excessive immune response.", "title": "Cytokine Storm Induced by SARS-CoV-2", "pid": "fozglfc8", "bm25_score": 219.85659790039062}, {"text": "Coronavirus disease 2019 (COVID-19) has seriously affected the safety of patients and social stability. Some COVID-19 patients in the later stage of disease may develop into acute respiratory distress syndrome or even multiple organ failure. However, one of the most important mechanisms underlying the deterioration of disease is cytokine storm. At present, some therapies such as interleukin-6 antibody blocker, stem cell therapy, and transfusion of convalescent plasma have been applied to counteract the cytokine storm with some progresses being achieved. This article reviews the influences of cytokine storm syndrome on the COVID-19 and the corresponding immunotherapies to resist cytokine storm.", "title": "[Advances in the research of mechanism and related immunotherapy on the cytokine storm induced by coronavirus disease 2019]", "pid": "zukc3lvq", "bm25_score": 219.80072021484375}, {"text": "Patients with COVID-19 who require ICU admission might have the cytokine storm. It is a state of out-of-control release of a variety of inflammatory cytokines. The molecular mechanism of the cytokine storm has not been explored extensively yet. The attachment of SARS-CoV-2 spike glycoprotein with angiotensin-converting enzyme 2 (ACE2), as its cellular receptor, triggers complex molecular events that leads to hyperinflammation. Four molecular axes that may be involved in SARS-CoV-2 driven inflammatory cytokine overproduction are addressed in this work. The virus-mediated down-regulation of ACE2 causes a burst of inflammatory cytokine release through dysregulation of the renin-angiotensin-aldosterone system (ACE/angiotensin II/AT1R axis), attenuation of Mas receptor (ACE2/MasR axis), increased activation of [des-Arg9]-bradykinin (ACE2/bradykinin B1R/DABK axis), and activation of the complement system including C5a and C5b-9 components. The molecular clarification of these axes will elucidate an array of therapeutic strategies to confront the cytokine storm in order to prevent and treat COVID-19 associated acute respiratory distress syndrome.", "title": "COVID-19 cytokine storm: The anger of inflammation", "pid": "s82qv18v", "bm25_score": 219.72314453125}, {"text": "Coronavirus disease 2019 (COVID-19), caused by the virus designated as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread widely throughout the world. Despite the strict global outbreak management and quarantine measures that have been implemented, the incidence of COVID-19 continues to rise, resulting in more than 290,000 deaths and representing an extremely serious threat to human life and health. The clinical symptoms of the affected patients are heterogeneous, ranging from mild upper respiratory symptoms to severe pneumonitis and even acute respiratory distress syndrome (ARDS) or death. Systemic immune over activation due to SARS-CoV-2 infection causes the cytokine storm, which is especially noteworthy in severely ill patients with COVID-19. Pieces of evidence from current studies have shown that the cytokine storm may be an important factor in disease progression, even leading to multiple organ failure and death. This review provides an overview of the knowledge on the COVID-19 epidemiological profile, the molecular mechanisms of the SARS-CoV-2-induced cytokine storm and immune responses, the pathophysiological changes that occur during infection, the main antiviral compounds used in treatment strategies and the potential drugs for targeting cytokines, this information is presented to provide valuable guidance for further studies and for a therapeutic reduction of this excessive immune response.", "title": "Cytokine storm induced by SARS-CoV-2", "pid": "bxfyse59", "bm25_score": 219.7069091796875}, {"text": "INTRODUCTION: The cytokine release syndrome (CRS) of COVID-19 is associated with the development of critical illness requiring multi-organ support. Further research is required to halt progression of multi-organ injury induced by hyper-inflammation. AREAS COVERED: PubMed/MEDLINETM databases were accessed between May 9th-June 9th, 2020, to review the latest perspectives on the treatment and pathogenesis of CRS. EXPERT OPINION: Over-activity of chemotaxis triggers a macrophage activation syndrome (MAS) resulting in the release of pro-inflammatory cytokines. IL-6 and TNF- &#945; are at the forefront of hyper-inflammation. The inflammatory cascade induces endothelial activation and capillary leak, leading to circulatory collapse and shock. As endothelial dysfunction persists, there is activation of the clotting cascade and microvascular obstruction. Continued endothelial activation results in multi-organ failure, regardless of pulmonary tissue damage. We propose that targeting the endothelium may interrupt this cycle. Immuno-modulating therapies have been suggested, however, further data is necessary to confirm that they do not jeopardize adaptive immunity. Inhibition of IL-6 and the Janus Kinase, signal transducer and activator of transcription proteins pathway (JAK/STAT), are favorable targets. Remote ischemic conditioning (RIC) reduces the inflammation of sepsis in animal models and should be considered as a low risk intervention, in combination with cardiovascular protection.", "title": "The cytokine storm of COVID-19: a spotlight on prevention and protection", "pid": "rvqxohiq", "bm25_score": 219.6323699951172}, {"text": "Coronavirus disease 2019 (COVID-19), which began in Wuhan, China in December 2019 has caused a large global pandemic and poses a serious threat to public health. More than four million cases of COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have been confirmed as of May 11, 2020. SARS-CoV-2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID-19 severity and is also a crucial cause of death from COVID-19. In the absence of antivirals and vaccines for COVID-19, there is an urgent need to understand the cytokine storm in COVID-19. Here, we have reviewed the current understanding of the features of SARS-CoV-2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID-19. Additionally, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID-19. This article is protected by copyright. All rights reserved.", "title": "The cytokine storm and COVID-19", "pid": "hqzkzupi", "bm25_score": 219.46109008789062}, {"text": "Summary Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.", "title": "The pathogenesis and treatment of the `Cytokine Storm' in COVID-19", "pid": "fqlv35vo", "bm25_score": 219.46038818359375}, {"text": "Cytokine storm is an excessive immune response to external stimuli. The pathogenesis of the cytokine storm is complex. The disease progresses rapidly, and the mortality is high. Certain evidence shows that, during the coronavirus disease 2019 (COVID-19) epidemic, the severe deterioration of some patients has been closely related to the cytokine storm in their bodies. This article reviews the occurrence mechanism and treatment strategies of the COVID-19 virus-induced inflammatory storm in attempt to provide valuable medication guidance for clinical treatment.", "title": "The pathogenesis and treatment of the `Cytokine Storm' in COVID-19", "pid": "iaatjew2", "bm25_score": 219.38888549804688}, {"text": "INTRODUCTION The cytokine release syndrome (CRS) of COVID-19 is associated with the development of critical illness requiring multi-organ support. Further research is required to halt progression of multi-organ injury induced by hyper-inflammation. AREAS COVERED PubMed/MEDLINETM databases were accessed between May 9th-June 9th, 2020, to review the latest perspectives on the treatment and pathogenesis of CRS. EXPERT OPINION Over-activity of chemotaxis triggers a macrophage activation syndrome (MAS) resulting in the release of pro-inflammatory cytokines. IL-6 and TNF- α are at the forefront of hyper-inflammation. The inflammatory cascade induces endothelial activation and capillary leak, leading to circulatory collapse and shock. As endothelial dysfunction persists, there is activation of the clotting cascade and microvascular obstruction. Continued endothelial activation results in multi-organ failure, regardless of pulmonary tissue damage. We propose that targeting the endothelium may interrupt this cycle. Immuno-modulating therapies have been suggested, however, further data is necessary to confirm that they do not jeopardize adaptive immunity. Inhibition of IL-6 and the Janus Kinase, signal transducer and activator of transcription proteins pathway (JAK/STAT), are favorable targets. Remote ischemic conditioning (RIC) reduces the inflammation of sepsis in animal models and should be considered as a low risk intervention, in combination with cardiovascular protection.", "title": "The cytokine storm of COVID-19: a spotlight on prevention and protection.", "pid": "gf519r3l", "bm25_score": 219.36257934570312}, {"text": "Coronavirus disease-2019 (COVID-19) severity appears to parallel the host immune response, with a subset of patients developing COVID-19 cytokine storm syndrome (CSS).(1) Serum inflammatory cytokines are elevated in COVID-19,(2-5) and interleukin (IL)-6 appears to play a central role in COVID-19 related CSS.(6-8) Based on the success of IL-6 receptor blockade for chimeric antigen receptor T-cell therapy associated cytokine release syndrome (CAR T-cell CRS), similar strategies using tocilizumab are being investigated in COVID-19.", "title": "Amelioration of COVID-19 related cytokine storm syndrome: Parallels to chimeric antigen receptor-T cell cytokine release syndrome", "pid": "jxsj3lg6", "bm25_score": 219.33213806152344}, {"text": "Recent advances in the pathophysiologic understanding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has indicated that patients with severe coronavirus disease 2019 (COVID-19) might experience cytokine release syndrome (CRS), characterized by increased interleukin (IL)-6, IL-2, IL-7, IL-10, etc. Therefore, the treatment of cytokine storm has been proposed as a critical part of rescuing severe COVID-19. Several of the cytokines involved in COVID-19 employ a distinct intracellular signaling pathway mediated by Janus kinases (JAKs). JAK inhibition, therefore, presents an attractive therapeutic strategy for CRS, which is a common cause of adverse clinical outcomes in COVID-19. Below, we review the possibilities and challenges of targeting the pathway in COVID-19.", "title": "Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19", "pid": "9f6fxd94", "bm25_score": 219.28155517578125}, {"text": "Since December 2019, a viral pneumonia, named coronavirus disease 2019 (COVID-19), from Wuhan, China, has swept the world. Although the case fatality rate is not high, the number of people infected is large and there is still a large number of patients dying. With the collation and publication of more and more clinical data, a large number of data suggest that there are mild or severe cytokine storms in severe patients, which is an important cause of death. Therefore, treatment of the cytokine storm has become an important part of rescuing severe COVID-19 patients. Interleukin-6 (IL-6) plays an important role in cytokine release syndrome. If it is possible to block the signal transduction pathway of IL-6, it is expected to become a new method for the treatment of severe COVID-19 patients. Tocilizumab is an IL-6 receptor (IL-6R) blocker that can effectively block the IL-6 signal transduction pathway and thus is likely to become an effective drug for patients with severe COVID-19.", "title": "Cytokine release syndrome in severe COVID-19: interleukin-6 receptor antagonist tocilizumab may be the key to reduce mortality", "pid": "rcl425pz", "bm25_score": 219.18746948242188}, {"text": "Recent advances in the pathophysiologic understanding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has indicated that patients with severe COVID-19 might experience cytokine release syndrome (CRS), characterized by increased interleukin (IL)-6, IL-2, IL-7, IL-10, etc. Therefore, the treatment of cytokine storm has been proposed as a critical part of rescuing severe COVID-19. Several of the cytokines involved in COVID-19 employ a distinct intracellular signaling pathway mediated by Janus kinases (JAKs). JAK inhibition, therefore, presents an attractive therapeutic strategy for CRS, which is a common cause of adverse clinical outcomes in COVID-19. Below, we review the possibilities and challenges of targeting the pathway in COVID-19.", "title": "Targeting JAK-STAT Signaling to Control Cytokine Release Syndrome in COVID-19", "pid": "xb4ld4tr", "bm25_score": 219.04833984375}, {"text": "In 2019-2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called \"cytokine storm\" an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account.", "title": "The cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system", "pid": "9ch0wti7", "bm25_score": 219.00619506835938}, {"text": "", "title": "Cytokine storm syndrome in severe COVID-19", "pid": "m6kxxio1", "bm25_score": 218.98585510253906}, {"text": "In 2019-2020 a new coronavirus named SARS-CoV-2 was identified as the causative agent of a several acute respiratory infection named COVID-19, which is causing a worldwide pandemic. There are still many unresolved questions regarding the pathogenesis of this disease and especially the reasons underlying the extremely different clinical course, ranging from asymptomatic forms to severe manifestations, including the Acute Respiratory Distress Syndrome (ARDS). SARS-CoV-2 showed phylogenetic similarities to both SARS-CoV and MERS-CoV viruses, and some of the clinical features are shared between COVID-19 and previously identified beta-coronavirus infections. Available evidence indicate that the so called “cytokine storm” an uncontrolled over-production of soluble markers of inflammation which, in turn, sustain an aberrant systemic inflammatory response, is a major responsible for the occurrence of ARDS. Chemokines are low molecular weight proteins with powerful chemoattractant activity which play a role in the immune cell recruitment during inflammation. This review will be aimed at providing an overview of the current knowledge on the involvement of the chemokine/chemokine-receptor system in the cytokine storm related to SARS-CoV-2 infection. Basic and clinical evidences obtained from previous SARS and MERS epidemics and available data from COVID-19 will be taken into account.", "title": "The Cytokine storm in COVID-19: An overview of the involvement of the chemokine/chemokine-receptor system", "pid": "ex9nh1yi", "bm25_score": 218.95516967773438}, {"text": "Cytokine storm defines a dysregulation of and an excessively exaggerated immune response most often accompanying selected viral infections and several autoimmune diseases. Newly emerging and re-emerging infections of the respiratory tract, especially influenza, SARS, and hantavirus post considerable medical problems. Their morbidities and mortalities are often a direct result of cytokine storm. This chapter visits primarily influenza virus infection and resultant cytokine storm. It provides the compelling evidence that illuminates cytokine storm in influenza pathogenesis and the clear findings that cytokine storm is chemically tractable by therapy directed toward sphingosine-1-phosphate receptor (S1PR) modulation, specifically S1P1R agonist therapy. The mechanism(s) of how S1P1R signaling works and the pathways involved are subjects of this review.", "title": "Cytokine Storm Plays a Direct Role in the Morbidity and Mortality from Influenza Virus Infection and is Chemically Treatable with a Single Sphingosine-1-Phosphate Agonist Molecule", "pid": "hrsnr60j", "bm25_score": 218.8107452392578}, {"text": "The lung is a key target of the cytokine storm that can be triggered by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), responsible for the widespread clinical syndrome known as coronavirus disease 2019 (COVID-19). Indeed, in some patients, SARS-CoV-2 promotes a dysfunctional immune response that dysregulates the cytokine secretory pattern. Hypercytokinemia underlies the hyperinflammatory state leading to injury of alveolar epithelial cells and vascular endothelial cells, as well as to lung infiltration sustained by neutrophils and macrophages. Within such a pathogenic context, interleukin-6 (IL-6) and other cytokines/chemokines play a pivotal pro-inflammatory role. Therefore, cytokines and their receptors, as well as cytokine-dependent intracellular signalling pathways can be targeted by potential therapies aimed to relieve the heavy burden of cytokine storm. In particular, the anti-IL-6-receptor monoclonal antibody tocilizumab is emerging as one of the most promising pharmacologic treatments. The reviews of this paper are available via the supplemental material section.", "title": "Lung under attack by COVID-19-induced cytokine storm: pathogenic mechanisms and therapeutic implications", "pid": "o9xh6bqz", "bm25_score": 218.78329467773438}, {"text": "The seventh human coronavirus SARS-CoV2 belongs to the cluster of extremely pathogenic coronaviruses like SARS-CoV and MERS-CoV, which are established to cause lower respiratory tract infection. The viral infection can be fatal as the disease advances to pneumonia followed by acute respiratory distress syndrome (ARDS). Increasingly higher cytokine concentration on account of over-stimulated immune response against the virus, or the ‘cytokine storm’, is the reason behind the manifestation of lethal clinical symptoms. In this article, we discuss the immune pathogenesis of cytokine storm and its relation with SARS-CoV2/COVID-19 risk factors. People with underlying risk factors are more susceptible to fatal complications of COVID-19 infection leading to poor clinical outcome. The increased pro-inflammatory immune status in patients with risk factors (diabetes, hypertension, cardiovascular disease, COPD) exacerbates the Cytokine-storm of COVID-19 to a Cytokine Super Cyclone. We also overviewed antiviral immune response provided by BCG vaccine involving the IL-1β, IL-6 and TNF-α secretion via ‘trained monocytes’, which confers early protection against SARS-CoV2.", "title": "Cytokine Storm in COVID-19 patients transforms to a Cytokine Super Cyclone in patients with risk factors", "pid": "6dq6gm27", "bm25_score": 218.76528930664062}, {"text": "Coronavirus disease 2019 (COVID‐19), which began in Wuhan, China in December 2019 has caused a large global pandemic and poses a serious threat to public health. More than four million cases of COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), have been confirmed as of May 11, 2020. SARS‐CoV‐2 is a highly pathogenic and transmissible coronavirus that primarily spreads through respiratory droplets and close contact. A growing body of clinical data suggests that a cytokine storm is associated with COVID‐19 severity and is also a crucial cause of death from COVID‐19. In the absence of antivirals and vaccines for COVID‐19, there is an urgent need to understand the cytokine storm in COVID‐19. Here, we have reviewed the current understanding of the features of SARS‐CoV‐2 and the pathological features, pathophysiological mechanisms, and treatments of the cytokine storm induced by COVID‐19. Additionally, we suggest that the identification and treatment of the cytokine storm are important components for rescuing patients with severe COVID‐19. This article is protected by copyright. All rights reserved.", "title": "The cytokine storm and COVID‐19", "pid": "rvrgcugn", "bm25_score": 218.74624633789062}, {"text": "COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-&#945; agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.", "title": "Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment", "pid": "57qod8v1", "bm25_score": 218.71873474121094}, {"text": "COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called \"cytokine storm\" induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.", "title": "The COVID-19 Cytokine Storm; What We Know So Far", "pid": "ete5n5pw", "bm25_score": 218.7141876220703}, {"text": "COVID-19 is a rapidly spreading global threat that has been declared as a pandemic by the WHO. COVID-19 is transmitted via droplets or direct contact and infects the respiratory tract resulting in pneumonia in most of the cases and acute respiratory distress syndrome (ARDS) in about 15 % of the cases. Mortality in COVID-19 patients has been linked to the presence of the so-called “cytokine storm” induced by the virus. Excessive production of proinflammatory cytokines leads to ARDS aggravation and widespread tissue damage resulting in multi-organ failure and death. Targeting cytokines during the management of COVID-19 patients could improve survival rates and reduce mortality.", "title": "The COVID-19 Cytokine Storm; What We Know So Far", "pid": "ne1qvf5g", "bm25_score": 218.6929168701172}, {"text": "A subset of patients with severe COVID-19 develop profound inflammation and multi-organ dysfunction consistent with a \"Cytokine Storm Syndrome\" (CSS). In this review we compare the clinical features, diagnosis, and pathogenesis of COVID-CSS with other hematological CSS, namely secondary hemophagocytic lymphohistiocytosis (sHLH), idiopathic multicentric Castleman disease (iMCD), and CAR-T cell therapy associated Cytokine Release Syndrome (CRS). Novel therapeutics targeting cytokines or inhibiting cell signaling pathways have now become the mainstay of treatment in these CSS. We review the evidence for cytokine blockade and attenuation in these known CSS as well as the emerging literature and clinical trials pertaining to COVID-CSS. Established markers of inflammation as well as cytokine levels are compared and contrasted between these four entities in order to establish a foundation for future diagnostic criteria of COVID-CSS.", "title": "Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes", "pid": "2b6l1c0n", "bm25_score": 218.59402465820312}, {"text": "A subset of patients with severe COVID-19 develop profound inflammation and multi-organ dysfunction consistent with a “Cytokine Storm Syndrome” (CSS). In this review we compare the clinical features, diagnosis, and pathogenesis of COVID-CSS with other hematological CSS, namely secondary hemophagocytic lymphohistiocytosis (sHLH), idiopathic multicentric Castleman disease (iMCD), and CAR-T cell therapy associated Cytokine Release Syndrome (CRS). Novel therapeutics targeting cytokines or inhibiting cell signaling pathways have now become the mainstay of treatment in these CSS. We review the evidence for cytokine blockade and attenuation in these known CSS as well as the emerging literature and clinical trials pertaining to COVID-CSS. Established markers of inflammation as well as cytokine levels are compared and contrasted between these four entities in order to establish a foundation for future diagnostic criteria of COVID-CSS.", "title": "Weathering the COVID-19 storm: Lessons from hematologic cytokine syndromes", "pid": "9321dl89", "bm25_score": 218.56500244140625}, {"text": "Abstract Corona Virus Disease 2019 (COVID-19) pandemic is rapidly spreading all over the world. Excessive immune responses trigger life-threatening cytokine release syndrome (CRS) which can result in overproduction of pro-inflammatory cytokines including tumor necrosis factor alpha (TNFα), interleukin-6 (IL-6), and IL-1β with different pro-inflammatory roles. Anecdotal evidence suggests that the modulation of systemic immune responses may have a potential role in the treatment of patients with COVID-19. Given the importance of the issue and the lack of therapeutic treatment or vaccine; anti-cytokine therapy such as IL-6, TNFα and IL-1 antagonists have been suggested for the alleviation of hyper-inflammation status in these patients. In this mini-review, we addressed the inflammatory pathways of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its relationship with the host cytokine storm. Furthermore, the proposed therapeutic options to reverse hyper-inflammation in infected patients were mentioned.", "title": "Targeting Cytokine Storm to Manage Patients with COVID-19: A Mini-Review", "pid": "cv8r9pbl", "bm25_score": 218.52076721191406}, {"text": "COVID-19 infection has a heterogenous disease course; it may be asymptomatic or causes only mild symptoms in the majority of the cases, while immunologic complications such as macrophage activation syndrome also known as secondary hemophagocytic lymphohistiocytosis, resulting in cytokine storm syndrome and acute respiratory distress syndrome, may also occur in some patients. According to current literature, impairment of SARS-CoV-2 clearance due to genetic and viral features, lower levels of interferons, increased neutrophil extracellular traps, and increased pyroptosis and probable other unknown mechanisms create a background for severe disease course complicated by macrophage activation syndrome and cytokine storm. Various genetic mutations may also constitute a risk factor for severe disease course and occurrence of cytokine storm in COVID-19. Once, immunologic complications like cytokine storm occur, anti-viral treatment alone is not enough and should be combined with appropriate anti-inflammatory treatment. Anti-rheumatic drugs, which are tried for managing immunologic complications of COVID-19 infection, will also be discussed including chloroquine, hydroxychloroquine, JAK inhibitors, IL-6 inhibitors, IL-1 inhibitors, anti-TNF-α agents, corticosteroids, intravenous immunoglobulin (IVIG), and colchicine. Early recognition and appropriate treatment of immunologic complications will decrease the morbidity and mortality in COVID-19 infection, which requires the collaboration of infectious disease, lung, and intensive care unit specialists with other experts such as immunologists, rheumatologists, and hematologists.", "title": "Cytokine storm in COVID-19: pathogenesis and overview of anti-inflammatory agents used in treatment", "pid": "r3a3xr8b", "bm25_score": 218.49119567871094}, {"text": "The pandemic caused by SARS-COV2 Virus/COVID-19, which was initially reported in China in December 2019, has become a major global health concern. COVID-19 can manifest with cytokine storm - an exaggerated systemic inflammatory phenomenon due to over-production of proinflammatory cytokines by immune cells that results in diffuse inflammatory lung disease and acute respiratory distress syndrome. It may be complicated by septic shock and subsequent multi-organ failure. Based on the most recently published evidence, this article will review and discuss comprehensive information on its clinical manifestations, laboratory tests, potential therapeutics, and prevention guidelines.", "title": "2019 Novel Coronavirus Pandemic: What Do We Know?", "pid": "k3w39apy", "bm25_score": 218.44747924804688}, {"text": "Cytokine storm is a life-threatening complication of Covid-19 infection. Excessive cytokines are the products of hyperactive immune inflammatory response mounted by the host against the virus. There is no agreed treatment for cytokine storm. Three therapeutic agents with proven immune-modulatory properties in regular use in a wide range of inflammatory disorders (high dose intravenous immunoglobulin, Rituximab and thalidomide) are proposed for the treatment of cytokine storm. Safety and efficacy of the proposed treatment should be assessed by randomised controlled clinical trials. The use of the proposed treatment is expected to reduce the mortality rate and alter the overall management of the pandemic.", "title": "Alternative management of Covid-19 infection", "pid": "1hfnv35j", "bm25_score": 218.40589904785156}, {"text": "Abstract Presently, we need more therapeutic molecules for this COVID-19 outbreak. The severity and mortality of the disease is associated with a high level of release of cytokine in the patients which is known as CRS (cytokine release syndrome) or cytokine storm syndrome. IL-6 is a type of pro-inflammatory cytokine which release in the severe COVID-19 patients. This cytokine initiates CRS the JAK-STAT pathway. Tocilizumab, a humanized monoclonal antibody, is designed to bind both mIL-6R (membrane bound receptor for IL-6) and sIL-6R (soluble receptor for IL-6) and inhibit the JAK-STAT signaling pathway. It finally stops the cytokine storm syndrome. However, we need to understand that how tocilizumab is bound with mIL-6R or sIL-6R. Similarly, we also need to understand more about the real molecular mechanism of activity of tocilizumab.", "title": "Tocilizumab: A Therapeutic Option for the Treatment of Cytokine Storm Syndrome in COVID-19", "pid": "5c9f4m2f", "bm25_score": 218.33822631835938}, {"text": "Coronavirus disease‐2019 (COVID‐19) severity appears to parallel the host immune response, with a subset of patients developing COVID‐19 cytokine storm syndrome (CSS).(1) Serum inflammatory cytokines are elevated in COVID‐19,(2–5) and interleukin (IL)‐6 appears to play a central role in COVID‐19 related CSS.(6–8) Based on the success of IL‐6 receptor blockade for chimeric antigen receptor T‐cell therapy associated cytokine release syndrome (CAR T‐cell CRS), similar strategies using tocilizumab are being investigated in COVID‐19.", "title": "Amelioration of COVID‐19 related cytokine storm syndrome: Parallels to chimeric antigen receptor‐T cell cytokine release syndrome", "pid": "i757oxb6", "bm25_score": 218.3365478515625}, {"text": "Patients with novel corona virus infection (COVID-19) can develop acute respiratory failure secondary to acute respiratory distress syndrome. Cytokine storm is suggested as one of underlying mechanisms for the rapid clinical decline. Immunocompromised patients and cancer patients are at particular risk for poor outcomes due to COVID-19 infection. This case report describes the presentation and clinical course of a cancer survivor who became critically ill and required mechanical ventilation. The patient was treated with hydroxychloroquine, azithromycin, and ceftriaxone; however, he remained febrile, hypoxemic, continued to require full mechanical ventilator support and his chest X-ray showed increased bilateral infiltrates. The patient was treated with tocilizumab, after which he improved and was successfully extubated. This report illustrates a possible role of tocilizumab in management of cytokine storm in critically ill patients with COVID-19 infection.", "title": "Weather the Cytokine Storm: A Report of Successful Management of a Colon Cancer Survivor and a Critically Ill Patient with COVID-19", "pid": "a8jt6rth", "bm25_score": 218.33627319335938}, {"text": "Clinical evidence indicates that the fatal outcome observed with severe acute respiratory syndrome-coronavirus-2 infection often results from alveolar injury that impedes airway capacity and multi-organ failure-both of which are associated with the hyperproduction of cytokines, also known as a cytokine storm or cytokine release syndrome. Clinical reports show that both mild and severe forms of disease result in changes in circulating leukocyte subsets and cytokine secretion, particularly IL-6, IL-1ß, IL-10, TNF, GM-CSF, IP-10 (IFN-induced protein 10), IL-17, MCP-3, and IL-1ra. Not surprising, therapies that target the immune response and curtail the cytokine storm in coronavirus 2019 (COVID-19) patients have become a focus of recent clinical trials. Here we review reports on leukocyte and cytokine data associated with COVID-19 disease in 3939 patients in China and describe emerging data on immunopathology. With an emphasis on immune modulation, we also look at ongoing clinical studies aimed at blocking proinflammatory cytokines; transfer of immunosuppressive mesenchymal stem cells; use of convalescent plasma transfusion; as well as immunoregulatory therapy and traditional Chinese medicine regimes. In examining leukocyte and cytokine activity in COVID-19, we focus in particular on how these levels are altered as the disease progresses (neutrophil NETosis, macrophage, T cell response, etc.) and proposed consequences to organ pathology (coagulopathy, etc.). Viral and host interactions are described to gain further insight into leukocyte biology and how dysregulated cytokine responses lead to disease and/or organ damage. By better understanding the mechanisms that drive the intensity of a cytokine storm, we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.", "title": "Cytokine storm and leukocyte changes in mild versus severe SARS-CoV-2 infection: Review of 3939 COVID-19 patients in China and emerging pathogenesis and therapy concepts", "pid": "nmdko4nl", "bm25_score": 218.31491088867188}, {"text": "Abstract Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.", "title": "Cytokine storm intervention in the early stages of COVID-19 pneumonia", "pid": "5bmdzgla", "bm25_score": 218.30409240722656}, {"text": "Abstract Severe COVID-19 associated pneumonia patients may exhibit features of systemic hyper-inflammation designated under the umbrella term of macrophage activation syndrome (MAS) or cytokine storm, also known as secondary haemophagocytic lymphohistocytosis (sHLH). This is distinct from HLH associated with immunodeficiency states termed primary HLH -with radically different therapy strategies in both situations. COVID-19 infection with MAS typically occurs in subjects with adult respiratory distress syndrome (ARDS) and historically, non-survival in ARDS was linked to sustained IL-6 and IL-1 elevation. We provide a model for the classification of MAS to stratify the MAS-like presentation in COVID-19 pneumonia and explore the complexities of discerning ARDS from MAS. We discuss the potential impact of timing of anti-cytokine therapy on viral clearance and the impact of such therapy on intra-pulmonary macrophage activation and emergent pulmonary vascular disease.", "title": "The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease", "pid": "34slyg9x", "bm25_score": 218.30137634277344}, {"text": "Abstract Coronavirus Disease 2019 (COVID-19) was first identified in China at the end of 2019. Acute respiratory distress syndrome (ARDS) represents the most common and serious complication of COVID-19. Cytokine storms are a pathophysiological feature of COVID-19 and play an important role in distinguishing hyper-inflammatory subphenotypes of ARDS. Accordingly, in this review, we focus on hyper-inflammatory host responses in ARDS that play a critical role in the differentiated development of COVID-19. Furthermore, we discuss inflammation-related indicators that have the potential to identify hyper-inflammatory subphenotypes of COVID-19, especially for those with a high risk of ARDS. Finally, we explore the possibility of improving the quality of monitoring and treatment of COVID-19 patients and in reducing the incidence of critical illness and mortality via better distinguishing hyper- and hypo-inflammatory subphenotypes of COVID-19.", "title": "Coronavirus Disease 2019 (COVID-19): Cytokine Storms, Hyper-Inflammatory Phenotypes, and Acute Respiratory Distress Syndrome", "pid": "c5co9cfq", "bm25_score": 218.3004150390625}, {"text": "BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. SUMMARY: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. Key Messages: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.", "title": "Weathering the Cytokine Storm in COVID-19: Therapeutic Implications", "pid": "re7ar8b1", "bm25_score": 218.2726287841797}, {"text": "BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recently emerged in Wuhan, Hubei-China, as responsible for the coronavirus disease 2019 (COVID-19) and then spread rapidly worldwide. While most individuals remain asymptomatic or develop only mild symptoms, approximately 5% develop severe forms of COVID-19 characterized by acute respiratory distress syndrome (ARDS) and multiple-organ failure (MOF) that usually require intensive-care support and often yield a poor prognosis. SUMMARY: The pathophysiology of COVID-19 is far from being completely understood, and the lack of effective treatments leads to a sense of urgency to develop new therapeutic strategies based on pathophysiological assumptions. The exaggerated cytokine release in response to viral infection, a condition known as cytokine release syndrome (CRS) or cytokine storm, is emerging as the mechanism leading to ARDS and MOF in COVID-19, thus endorsing the hypothesis that properly timed anti-inflammatory therapeutic strategies could improve patients' clinical outcomes and prognosis. KEY MESSAGES: The objective of this article is to explore and comment on the potential role of the promising immunomodulatory therapies using pharmacological and nonpharmacological approaches to overcome the dysregulated proinflammatory response in COVID-19.", "title": "Weathering the Cytokine Storm in COVID-19: Therapeutic Implications", "pid": "lnltoj1n", "bm25_score": 218.2726287841797}, {"text": "Clinical intervention in patients with corona virus disease 2019 (COVID-19) has demonstrated a strong upregulation of cytokine production in patients who are critically ill with SARS-CoV2-induced pneumonia. In a retrospective study of 41 patients with COVID-19, most patients with SARS-CoV-2 infection developed mild symptoms, whereas some patients later developed aggravated disease symptoms, and eventually passed away because of multiple organ dysfunction syndrome (MODS), as a consequence of a severe cytokine storm. Guidelines for the diagnosis and treatment of SARS-CoV-2 infected pneumonia were first published January 30th, 2020; these guidelines recommended for the first time that cytokine monitoring should be applied in severely ill patients to reduce pneumonia related mortality. The cytokine storm observed in COVID-19 illness is also an important component of mortality in other viral diseases, including SARS, MERS and influenza. In view of the severe morbidity and mortality of COVID-19 pneumonia, we review the current understanding of treatment of human coronavirus infections from the perspective of a dysregulated cytokine and immune response.", "title": "Cytokine storm intervention in the early stages of COVID-19 pneumonia", "pid": "8a0tmn90", "bm25_score": 218.2438201904297}, {"text": "Knowledge about the pathobiology of SARS-COV-2 as it interacts with immune defenses is limited. SARS-COV-2 is spread by droplets that come into contact with mucous membranes. COVID-19 is characterized by 3 stages: asymptomatic-paucisymptomatic incubation, nonsevere symptomatic illness for 80% of those infected, and severe respiratory illness. A syndrome characterized by hypercytokinemic inflammation referred to as a \"cytokine storm\" can occur in patients with advanced disease. Effective antiviral agents that can prevent viral infection in exposed individuals are needed.", "title": "Cytokine storm and the prospects for immunotherapy with COVID-19", "pid": "dd836h0r", "bm25_score": 218.19102478027344}, {"text": "Corona Virus Disease 2019(COVID-19)-affected patients with severe immune abnormalities have a risk of cytokine release syndrome. The definition, prevention, and treatment of symptoms of cytokine release syndrome in critically ill patients with COVID-19 are important problems. This was a single-center case series of 11 COVID-19 patients with acute respiratory distress syndrome (ARDS) from The First Affiliated Hospital of Guangzhou Medical University in China from January 26, 2020 to February 18, 2020. The termination date of follow-up was February 19, 2020. In this single-center analysis of 11 critically ill patients with COVID-19, 8 patients were determined to have characteristics of cytokine release syndrome (CRS), including pulmonary inflammation, fever, and dysfunction of non-pulmonary organs; an increase of- Interleukin-6 (IL-6) in peripheral blood was the highest risk factor and an early indicator of CRS in COVID-19.", "title": "The Definition and Risks of Cytokine Release Syndrome in 11 COVID-19-Affected Critically Ill Patients with Pneumonia: Analysis of Disease Characteristics", "pid": "6vywryyn", "bm25_score": 218.14356994628906}, {"text": "The elevated circulating levels of cytokines associated with a variety of infectious and immune-mediated conditions are frequently termed a cytokine storm. Here, we explain the protective functions of cytokines in “ideal” responses; the multi-factorial origins that can drive these responses to become pathological; and how this ultimately leads to vascular damage, immunopathology, and worsening clinical outcomes.", "title": "Cytokine Storms: Understanding COVID-19", "pid": "i3doh4k4", "bm25_score": 218.13623046875}, {"text": "The elevated circulating levels of cytokines associated with a variety of infectious and immune-mediated conditions are frequently termed a cytokine storm. Here, we explain the protective functions of cytokines in \"ideal\" responses; the multi-factorial origins that can drive these responses to become pathological; and how this ultimately leads to vascular damage, immunopathology, and worsening clinical outcomes.", "title": "Cytokine Storms: Understanding COVID-19", "pid": "xetcmhkz", "bm25_score": 218.11346435546875}, {"text": "Severe COVID-19 associated pneumonia patients may exhibit features of systemic hyper-inflammation designated under the umbrella term of macrophage activation syndrome (MAS) or cytokine storm, also known as secondary haemophagocytic lymphohistocytosis (sHLH). This is distinct from HLH associated with immunodeficiency states termed primary HLH -with radically different therapy strategies in both situations. COVID-19 infection with MAS typically occurs in subjects with adult respiratory distress syndrome (ARDS) and historically, non-survival in ARDS was linked to sustained IL-6 and IL-1 elevation. We provide a model for the classification of MAS to stratify the MAS-like presentation in COVID-19 pneumonia and explore the complexities of discerning ARDS from MAS. We discuss the potential impact of timing of anti-cytokine therapy on viral clearance and the impact of such therapy on intra-pulmonary macrophage activation and emergent pulmonary vascular disease.", "title": "The Role of Cytokines including Interleukin-6 in COVID-19 induced Pneumonia and Macrophage Activation Syndrome-Like Disease", "pid": "yfoipwuv", "bm25_score": 218.1072998046875}, {"text": "Abstract Since December 2019, a viral pneumonia (COVID-19) from Wuhan, China has swept the world. Although the case fatality rate is not high, the number of people infected is large, and there are still a large number of patients dying. With the collation and publication of more and more clinical data, a large number of data suggest that there are mild or severe cytokine storms in severe patients, which is also an important cause of death. Therefore, the treatment of cytokine storm has become an important part of rescuing severe patients. Interleukin-6 (IL-6) plays an important role in cytokine release syndrome (CRS). If it can block the signal transduction pathway of IL-6, it is expected to become a new method for the treatment of severe patients. Tocilizumab is a blocker of IL-6R, which can effectively block IL-6 signal transduction pathway. So, tocilizumab is likely to become an effective drug for patients with severe COVID-19.", "title": "The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality", "pid": "vx9vqr1k", "bm25_score": 218.08505249023438}, {"text": "The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: \"mild\",symbolized as a \"drizzle\" of cytokines, severe as a \"storm\", and critical as a \"hurricane\". In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a \"cytokine-release syndrome\", SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.", "title": "The amount of cytokine-release defines different shades of Sars-Cov2 infection.", "pid": "5rc9x979", "bm25_score": 218.07456970214844}, {"text": "Knowledge about the pathobiology of SARS-COV-2 as it interacts with immune defenses is limited. SARS-COV-2 is spread by droplets that come into contact with mucous membranes. COVID-19 is characterized by 3 stages: asymptomatic-paucisymptomatic incubation, nonsevere symptomatic illness for 80% of those infected, and severe respiratory illness. A syndrome characterized by hypercytokinemic inflammation referred to as a \"cytokine storm\" can occur in patients with advanced disease. Effective antiviral agents that can prevent viral infection in exposed individuals are needed.", "title": "Cytokine storm and the prospects for immunotherapy with COVID-19.", "pid": "2skjqwis", "bm25_score": 218.06546020507812}, {"text": "Since the outbreak of 2019-nCoV, the epidemic has developed rapidly and the situation is grim. LANCET figured out that the 2019-nCoV is closely related to &quot;cytokine storm&quot;. &quot;Cytokine storm&quot; is an excessive immune response of the body to external stimuli such as viruses and bacteria. As the virus attacking the body, it stimulates the secretion of a large number of inflammatory factors: interleukin(IL), interferon(IFN), C-X-C motif chemokine(CXCL) and so on, which lead to cytokine cascade reaction. With the exudation of inflammatory factors, cytokines increase abnormally in tissues and organs, interfering with the immune system, causing excessive immune response of the body, resulting in diffuse damage of lung cells, pulmonary fibrosis, and multiple organ damage, even death. Arachidonic acid(AA) metabolic pathway is principally used to synthesize inflammatory cytokines, such as monocyte chemotactic protein 1(MCP-1), tumor necrosis factor(TNF), IL, IFN, etc., which is closely related to the occurrence, development and regression of inflammation. Therefore, the inhibition of AA metabolism pathway is benefit for inhibiting the release of inflammatory factors in the body and alleviating the &quot;cytokine storm&quot;. Based on the pharmacophore models of the targets on AA metabolic pathway, the traditional Chinese medicine database 2009(TCMD 2009) was screened. The potential herbs were ranked by the number of hit molecules, which were scored by pharmacophore fit value. In the end, we obtained the potential active prescriptions on &quot;cytokine storm&quot; according to the potential herbs in the &quot;National novel coronavirus pneumonia diagnosis and treatment plan(trial version sixth)&quot;. The results showed that the hit components with the inhibitory effect on AA were magnolignan â , lonicerin and physcion-8-O-ß-D-glucopy-ranoside, which mostly extracted from Magnoliae Officinalis Cortex, Zingiberis Rhizoma Recens, Lonicerae Japonicae Flos, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Ginseng Radix et Rhizoma, Arctii Fructus, Dryopteridis Crassirhizomatis Rhizoma, Paeoniaeradix Rubra, Dioscoreae Rhizoma. Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway, Huoxiang Zhengqi Capsules, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, Qingfei Paidu Decoction, Xuebijing Injection, Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines. This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus.", "title": "[Study on treatment of \"cytokine storm\" by anti-2019-nCoV prescriptions based on arachidonic acid metabolic pathway]", "pid": "r5xyuweg", "bm25_score": 217.9705047607422}, {"text": "Interleukin 1 (IL-1) is a potential target of therapy in COVID-19 during the severe respiratory-inflammatory phase (\"cytokine release syndrome\"), when pulmonary macrophages are hyperactivated, releasing IL-1 and other cytokines. Preliminary evidence indicates that anakinra and canakinumab, drugs that block the action of IL-1 and have a good safety profile, improve the outcomes of patients with COVID-19 cytokine release syndrome. Results from large, randomized clinical trials are pending.", "title": "Cytokine release syndrome and the prospects for immunotherapy with COVID-19. Part 2: The role of interleukin 1", "pid": "fbq8yraw", "bm25_score": 217.9462432861328}, {"text": "Interleukin 1 (IL-1) is a potential target of therapy in COVID-19 during the severe respiratory-inflammatory phase (\"cytokine release syndrome\"), when pulmonary macrophages are hyperactivated, releasing IL-1 and other cytokines. Preliminary evidence indicates that anakinra and canakinumab, drugs that block the action of IL-1 and have a good safety profile, improve the outcomes of patients with COVID-19 cytokine release syndrome. Results from large, randomized clinical trials are pending.", "title": "Cytokine release syndrome and the prospects for immunotherapy with COVID-19. Part 2: The role of interleukin 1.", "pid": "ia028j7d", "bm25_score": 217.9267120361328}, {"text": "For some patients with SARS-CoV-2, the worst clinical damage is not caused by the virus itself, but by an overactive inflammatory state In fact, in some people the immune system goes into overdrive and launches a large-scale assault on the tissue known as cytokine storm This excessive inflammatory/immune reaction can damage tissue and eventually kill people Evidence shows that blocking such cytokine storms can be effective and trials are under way to test drugs that act by reducing cytokine response, such as tocilizumab and sarilumab which bind interleukin 6 (IL-6), or anakinra which is the interleukin 1 receptor antagonist (IL-1) However, other drugs that block the cytokine cascade can also be considered In this article we describe the scientific and molecular motivation for the use of drugs that act by modulating the hyperactive inflammatory system in severe patients suffering from SARS-CoV-2, considering in particular an old drug that has been in use for many years for other therapeutic indications such as colchicine, and that could be favorable to its use, with low cost and good tolerability", "title": "Cytokine storm and colchicine potential role in fighting SARS-CoV-2 pneumonia", "pid": "ihhs7btc", "bm25_score": 217.8906707763672}, {"text": "The recent outbreak of coronavirus disease (COVID 19), spreading from China all around the world in early 2020, has led scientists to investigate the immuno-mediated mechanisms underlying the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) infection. Depending on the amount of cytokines released as the result of the immunological activation induced by SARS-CoV2, three major clinical phenotypes can be identified: \"mild\",symbolized as a \"drizzle\" of cytokines, severe as a \"storm\", and critical as a \"hurricane\". In patients with mild symptoms, the release of pro-inflammatory cytokines is balanced to obtain a defense response against the virus which is often self-limiting and overcomes without tissue damage. In severe phenotype, resembling a \"cytokine-release syndrome\", SARS-CoV2 causes the lysis of the immune-mediators leading to a cytokine storm able to induce lung epithelium damage and acute respiratory distress syndrome. In critical patients, the immune response may become uncontrolled, thus the cytokine burst resembles a form of secondary hemophagocytic lymphohistiocytosis which may result in a multi organ failure. In addition to the standard of care, an immune-modulatory therapy tailored to each one of the different phenotypes should be used in order to prevent or reduce the release of cytokines responsible for organ damage and disease progression.", "title": "The amount of cytokine-release defines different shades of Sars-Cov2 infection", "pid": "vt56yqel", "bm25_score": 217.86825561523438}, {"text": "The cytokine storm has captured the attention of the public and the scientific community alike, and while the general notion of an excessive or uncontrolled release of proinflammatory cytokines is well known, the concept of a cytokine storm and the biological consequences of cytokine overproduction are not clearly defined. Cytokine storms are associated with a wide variety of infectious and noninfectious diseases. The term was popularized largely in the context of avian H5N1 influenza virus infection, bringing the term into popular media. In this review, we focus on the cytokine storm in the context of virus infection, and we highlight how high-throughput genomic methods are revealing the importance of the kinetics of cytokine gene expression and the remarkable degree of redundancy and overlap in cytokine signaling. We also address evidence for and against the role of the cytokine storm in the pathology of clinical and infectious disease and discuss why it has been so difficult to use knowledge of the cytokine storm and immunomodulatory therapies to improve the clinical outcomes for patients with severe acute infections.", "title": "Into the eye of the cytokine storm.", "pid": "44babp7t", "bm25_score": 217.85797119140625}, {"text": "", "title": "Cytokine release syndrome in severe COVID-19", "pid": "pdn4x9ss", "bm25_score": 217.83865356445312}, {"text": "", "title": "COVID-19: consider cytokine storm syndromes and immunosuppression", "pid": "4bfve7dl", "bm25_score": 217.80535888671875}, {"text": "Coronavirus disease 2019 pandemic caused by severe acute respiratory syndrome-coronavirus-2 is a worldwide public health emergency that will have a lasting generational impact in terms of mortality and economic devastation. Social distancing to prevent viral transmission and supportive care of infected patients are the main interventions now available. This global health crisis therefore merits innovative therapies. Cytokine release syndrome mediated by interleukin-6 is a critical driver of coronavirus disease 2019 mortality. Herein, we review and discuss key immunologic effects of direct interleukin-6 blockade, downstream nonselective Janus kinase inhibition, and selective Janus kinase 2 suppression to treat coronavirus disease 2019–related cytokine release syndrome. We provide evidence that selective targeting of interleukin-6 or Janus kinase 2 is well informed by existing data. This contrasts with broad, nonselective blockade of Janus kinase-mediated signaling, which would inhibit both deleterious and beneficial cytokines, as well as critical host antiviral immunity.", "title": "Less Can Be More When Targeting Interleukin-6-Mediated Cytokine Release Syndrome in Coronavirus Disease 2019", "pid": "wwgeiphc", "bm25_score": 217.77554321289062}, {"text": "COVID-19 is a global pandemic that emerged from Wuhan, China. Besides pneumonia and acute respiratory distress syndrome, the disease leads to multisystem involvement in the form of myocarditis, arrhythmias, cardiac arrest, gastrointestinal symptoms, hypoxemic brain injury, acute liver and renal function impairment. There are also reports of cutaneous lesions in form of urticarial and maculopapular rashes, chilblain like fingers and toes (covid feet), livedoid vasculopathy and chicken-pox like or varicelliform vesicles. Clinically, many of these skin lesions are likely secondary to occlusion of small to medium blood vessels due to microthrombi formation or due to viral laden antigen-antibody immune complexes; and same explanation may hold true for possible hypoxemic injury simultaneously occurring in other vital organs like lungs, heart, brain and kidneys. The histopathology, immunoflorescence and RT-PCR analysis of skin biopsies can provide useful insights for ascertaining the pathogenesis of this complex viral syndrome. Apparently, it is interplay of disarmed cellular immunity and over-activated humoral immunity that culminates in end-organ changes. The morbidity and mortality can be significantly reduced by upgrading the cellular immunity and downgrading the humoral response; along with prevention of hypoxemic and reperfusion injuries by using antivirals, immunomodulators, antioxidants, anti-platelets and anticoagulants in judicious and phased manner. This article is protected by copyright. All rights reserved.", "title": "Unraveling the mystery of Covid-19 Cytokine storm: From skin to organ systems", "pid": "ve83421h", "bm25_score": 217.7408447265625}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronaviridae that causes respiratory disorders. After infection, large amounts of inflammatory cytokines are secreted, known as the cytokine storm. These cytokines can cause pulmonary damage induced by inflammation resulting in acute respiratory distress syndrome (ARDS), and even death. One of the therapeutic approaches for treatment of ARDS is a mesenchymal stem cell (MSC). MSCs suppress inflammation and reduce lung injury through their immunomodulatory properties. MSCs also have the potential to prevent apoptosis of the lung cells and regenerate them. But our suggestion is using MSCs-derived exosomes. Because these exosomes apply the same immunomodulatory and tissue repair effects of MSCs and they don't have problems associated to cell maintenance and injections. For investigation the hypothesis, MSCs should be isolated from tissues and characterized. Then, the exosomes should be isolated from the supernatants and characterized. These exosomes should be injected into a transgenic animal for COVID-19. In the final section, lung function assessment, histological examination, micro-CT, differential leukocyte, viral load analysis, cytokine assay, and CRP level analysis can be investigated. COVID-19 treatment is currently focused on supportive therapies and no vaccine has been developed for it. So, numerous researches are needed to find potential therapies. Since the pathogenesis of this disease was identified in previous studies and can cause lung injury with ARDS, investigation of the therapeutic approaches that can suppress inflammation, cytokine storm and ARDS can be helpful in finding a novel therapeutic approach for this disease.", "title": "Hypothesis for the management and treatment of the COVID-19-induced acute respiratory distress syndrome and lung injury using mesenchymal stem cell-derived exosomes", "pid": "kdudslre", "bm25_score": 217.6997528076172}, {"text": "Poor outcomes in COVID-19 correlate with clinical and laboratory features of cytokine storm syndrome. Broad screening for cytokine storm and early, targeted antiinflammatory therapy may prevent immunopathology and could help conserve limited health care resources. While studies are ongoing, extrapolating from clinical experience in cytokine storm syndromes may benefit the multidisciplinary teams caring for patients with severe COVID-19.", "title": "On the Alert for Cytokine Storm: Immunopathology in COVID-19", "pid": "6io0zd0z", "bm25_score": 217.69204711914062}, {"text": "During pathogenic influenza virus infection, robust cytokine production (cytokine storm), excessive inflammatory infiltrates, and virus-induced tissue destruction all contribute to morbidity and mortality. Earlier we reported that modulation of sphingosine-1-phosphate-1 receptor (S1P1R) signaling provided a chemically tractable approach for the effective blunting of cytokine storm, leading to the improvement of clinical and survival outcomes. Here, we show that S1P1R agonist treatment suppresses global cytokine amplification. Importantly, S1P1R agonist treatment was able to blunt cytokine/chemokine production and innate immune cell recruitment in the lung independently of endosomal and cytosolic innate sensing pathways. S1P1R signaling suppression of cytokine amplification was independent of multiple innate signaling adaptor pathways for myeloid differentiation primary response gene 88 (MyD88) and IFN-β promoter stimulator-1 signaling, indicating a common pathway inhibition of cytokine storm. We identify the MyD88 adaptor molecule as responsible for the majority of cytokine amplification observed following influenza virus challenge.", "title": "Mapping the innate signaling cascade essential for cytokine storm during influenza virus infection.", "pid": "5gcd4tom", "bm25_score": 217.63755798339844}, {"text": "Abstract The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. Here, we discuss the pathogenesis of severe acute respiratory syndrome (SARS)-induced CRS, compare the CRS in COVID-19 with that in SARS and Middle East respiratory syndrome (MERS), and summarize the existing therapies for CRS. We propose to utilize interleukin-6 (IL-6) blockade to manage COVID-19-induced CRS and discuss several factors that should be taken into consideration for its clinical application.", "title": "Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?", "pid": "6gwnhkn4", "bm25_score": 217.62648010253906}, {"text": "The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. Here, we discuss the pathogenesis of severe acute respiratory syndrome (SARS)-induced CRS, compare the CRS in COVID-19 with that in SARS and Middle East respiratory syndrome (MERS), and summarize the existing therapies for CRS. We propose to utilize interleukin-6 (IL-6) blockade to manage COVID-19-induced CRS and discuss several factors that should be taken into consideration for its clinical application.", "title": "Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?", "pid": "uzfpv5rd", "bm25_score": 217.6209716796875}, {"text": "Since the outbreak of 2019-nCoV, the epidemic has developed rapidly and the situation is grim. LANCET figured out that the 2019-nCoV is closely related to \"cytokine storm\". \"Cytokine storm\" is an excessive immune response of the body to external stimuli such as viruses and bacteria. As the virus attacking the body, it stimulates the secretion of a large number of inflammatory factors: interleukin(IL), interferon(IFN), C-X-C motif chemokine(CXCL) and so on, which lead to cytokine cascade reaction. With the exudation of inflammatory factors, cytokines increase abnormally in tissues and organs, interfering with the immune system, causing excessive immune response of the body, resulting in diffuse damage of lung cells, pulmonary fibrosis, and multiple organ damage, even death. Arachidonic acid(AA) metabolic pathway is principally used to synthesize inflammatory cytokines, such as monocyte chemotactic protein 1(MCP-1), tumor necrosis factor(TNF), IL, IFN, etc., which is closely related to the occurrence, development and regression of inflammation. Therefore, the inhibition of AA metabolism pathway is benefit for inhibiting the release of inflammatory factors in the body and alleviating the \"cytokine storm\". Based on the pharmacophore models of the targets on AA metabolic pathway, the traditional Chinese medicine database 2009(TCMD 2009) was screened. The potential herbs were ranked by the number of hit molecules, which were scored by pharmacophore fit value. In the end, we obtained the potential active prescriptions on \"cytokine storm\" according to the potential herbs in the \"National novel coronavirus pneumonia diagnosis and treatment plan(trial version sixth)\". The results showed that the hit components with the inhibitory effect on AA were magnolignan Ⅰ, lonicerin and physcion-8-O-β-D-glucopy-ranoside, which mostly extracted from Magnoliae Officinalis Cortex, Zingiberis Rhizoma Recens, Lonicerae Japonicae Flos, Rhei Radix et Rhizoma, Salviae Miltiorrhizae Radix et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Ginseng Radix et Rhizoma, Arctii Fructus, Dryopteridis Crassirhizomatis Rhizoma, Paeoniaeradix Rubra, Dioscoreae Rhizoma. Finally the anti-2019-nCoV prescriptions were analyzed to obtain the potential active prescriptions on AA metabolic pathway, Huoxiang Zhengqi Capsules, Jinhua Qinggan Granules, Lianhua Qingwen Capsules, Qingfei Paidu Decoction, Xuebijing Injection, Reduning Injection and Tanreqing Injection were found that may prevent 2019-nCoV via regulate cytokines. This study intends to provide reference for clinical use of traditional Chinese medicine to resist new coronavirus.", "title": "[Study on treatment of \"cytokine storm\" by anti-2019-nCoV prescriptions based on arachidonic acid metabolic pathway].", "pid": "2plg8f0u", "bm25_score": 217.6187744140625}, {"text": "On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient's clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk.", "title": "Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity", "pid": "uoyy6ckq", "bm25_score": 217.6053466796875}, {"text": "The pandemic caused by SARS-COV2 Virus/COVID-19, which was initially reported in China in December 2019, has become a major global health concern COVID-19 can manifest with cytokine storm - an exaggerated systemic inflammatory phenomenon due to over-production of proinflammatory cytokines by immune cells that results in diffuse inflammatory lung disease and acute respiratory distress syndrome It may be complicated by septic shock and subsequent multi-organ failure Based on the most recently published evidence, this article will review and discuss comprehensive information on its clinical manifestations, laboratory tests, potential therapeutics, and prevention guidelines", "title": "2019 Novel Coronavirus Pandemic: What Do We Know?", "pid": "8lnb2tnz", "bm25_score": 217.60374450683594}, {"text": "SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this \"cytokine storm\" and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (&#945;7nAchR). Nicotine, an exogenous &#945;7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients.", "title": "Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm", "pid": "8o5juhgc", "bm25_score": 217.58969116210938}, {"text": "In December 2019, a novel coronavirus pneumonia, coronavirus disease 2019 (COVID‐19), caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) was reported in Wuhan, China. A hyperinflammatory immune response, or cytokine release syndrome (CRS) is observed in critically unwell patients with SARS‐CoV‐2 globally. Severe lymphopenia, hyperactivated pro‐inflammatory T cells(1) and decreased regulatory T cells(2) are seen in these critically ill patients, suggesting dysregulated immune responses.", "title": "Interleukin‐6 Blockade Treatment for COVID‐19 associated Cytokine Release Syndrome in a Patient with Poorly Controlled Chronic Myeloid Leukaemia", "pid": "vz2bpkyk", "bm25_score": 217.57827758789062}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronaviridae that causes respiratory disorders. After infection, large amounts of inflammatory cytokines are secreted, known as the cytokine storm. These cytokines can cause pulmonary damage induced by inflammation resulting in acute respiratory distress syndrome (ARDS), and even death. One of the therapeutic approaches for treatment of ARDS is a mesenchymal stem cell (MSC). MSCs suppress inflammation and reduce lung injury through their immunomodulatory properties. MSCs also have the potential to prevent apoptosis of the lung cells and regenerate them. But our suggestion is using MSCs-derived exosomes. Because these exosomes apply the same immunomodulatory and tissue repair effects of MSCs and they don’t have problems associated to cell maintenance and injections. For investigation the hypothesis, MSCs should be isolated from tissues and characterized. Then, the exosomes should be isolated from the supernatants and characterized. These exosomes should be injected into a transgenic animal for COVID-19. In the final section, lung function assessment, histological examination, micro-CT, differential leukocyte, viral load analysis, cytokine assay, and CRP level analysis can be investigated. COVID-19 treatment is currently focused on supportive therapies and no vaccine has not been developed for it, so, numerous research studies are needed to find potential. Since the pathogenesis of this disease was identified in previous studies and can cause lung injury with ARDS, so, investigation of the therapeutic approaches that can suppress inflammation, cytokine storm and ARDS can be helpful in finding a novel therapeutic approach for this disease.", "title": "Hypothesis for the management and treatment of the COVID-19-induced acute respiratory distress syndrome and lung injury using mesenchymal stem cell-derived exosomes", "pid": "2m9nchys", "bm25_score": 217.57286071777344}, {"text": "", "title": "Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists", "pid": "xr0wx0fu", "bm25_score": 217.57070922851562}, {"text": "Sars-CoV-2 complications include pneumonia and acute respiratory distress syndrome (ARDS), which require intensive care unit admission. These conditions have rapidly overwhelmed healthcare systems, with detrimental effects on the quality of care and increased mortality. Social isolation strategies have been implemented worldwide with the aim of reducing hospital pressure. Among therapeutic strategies, the use of immunomodulating drugs, to improve prognosis, seems promising. Particularly, since pneumonia and ARDS are associated with a cytokine storm, drugs belonging to therapeutic classes as anti-IL-6, anti-TNF, and JAK inhibitors are currently studied. In this article, we discuss the potential advantages of the most promising pharmacological approaches.", "title": "Exploring pharmacological approaches for managing cytokine storm associated with pneumonia and acute respiratory distress syndrome in COVID-19 patients", "pid": "z9tio4wd", "bm25_score": 217.56964111328125}, {"text": "The pandemic coronavirus infectious disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is rapidly spreading across the globe. In this issue of the JCI, Chen and colleagues compared the clinical and immunological characteristics between moderate and severe COVID-19. The authors found that respiratory distress on admission is associated with unfavorable outcomes. Increased cytokine levels (IL-6, IL-10, and TNF-&#945;), lymphopenia (in CD4+ and CD8+ T cells), and decreased IFN-γ expression in CD4+ T cells are associated with severe COVID-19. Overall, this study characterized the cytokine storm in severe COVID-19 and provides insights into immune therapeutics and vaccine design.", "title": "SARS-CoV-2: a storm is raging", "pid": "539d5v41", "bm25_score": 217.54917907714844}, {"text": "", "title": "Understanding the cytokine storm during COVID-19: Contribution of preexisting chronic inflammation.", "pid": "jb1zbxlv", "bm25_score": 217.546630859375}, {"text": "", "title": "[Novel coronavirus infection (COVID-19) and cytokine storms - treatment options based on inflammatory processes]", "pid": "7mzszjh6", "bm25_score": 217.54046630859375}, {"text": "The outbreak of the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for coronavirus disease 2019 (COVID-19) has developed into an unprecedented global pandemic. Clinical investigations in patients with COVID-19 has shown a strong upregulation of cytokine and interferon production in SARS-CoV2- induced pneumonia, with an associated cytokine storm syndrome. Thus, the identification of existing approved therapies with proven safety profiles to treat hyperinflammation is a critical unmet need in order to reduce COVI-19 associated mortality. To date, no specific therapeutic drugs or vaccines are available to treat COVID-19 patients. This review evaluates several options that have been proposed to control SARS-CoV2 hyperinflammation and cytokine storm, eincluding antiviral drugs, vaccines, small-molecules, monoclonal antibodies, oligonucleotides, peptides, and interferons (IFNs).", "title": "COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons", "pid": "y4kohxgy", "bm25_score": 217.5345916748047}, {"text": "Severe influenza remains unusual in its virulence for humans. Complications or ultimately death arising from these infections are often associated with hyperinduction of proinflammatory cytokine production, which is also known as ‘cytokine storm'. For this disease, it has been proposed that immunomodulatory therapy may improve the outcome, with or without the combination of antiviral agents. Here, we review the current literature on how various effectors of the immune system initiate the cytokine storm and exacerbate pathological damage in hosts. We also review some of the current immunomodulatory strategies for the treatment of cytokine storms in severe influenza, including corticosteroids, peroxisome proliferator-activated receptor agonists, sphingosine-1-phosphate receptor 1 agonists, cyclooxygenase-2 inhibitors, antioxidants, anti-tumour-necrosis factor therapy, intravenous immunoglobulin therapy, statins, arbidol, herbs, and other potential therapeutic strategies.", "title": "The cytokine storm of severe influenza and development of immunomodulatory therapy", "pid": "ndth5zne", "bm25_score": 217.53089904785156}, {"text": "SARS-CoV-2 is a new coronavirus that has caused a worldwide pandemic. It causes severe acute respiratory syndrome (COVID-19), which is fatal in many cases, and is characterized by a cytokine release syndrome (CRS). Great efforts are currently being made to block the signal transduction pathway of pro-inflammatory cytokines in order to control this “cytokine storm” and rescue severely affected patients. Consequently, possible treatments for cytokine-mediated hyperinflammation, preferably within approved safe therapies, are urgently being researched to reduce rising mortality. One approach to inhibit proinflammatory cytokine release is to activate the cholinergic anti-inflammatory pathway through nicotinic acetylcholine receptors (α7nAchR). Nicotine, an exogenous α7nAchR agonist, is clinically used in ulcerative colitis to counteract inflammation. We have found epidemiological evidence, based on recent clinical SARS-CoV-2 studies in China, that suggest that smokers are statistically less likely to be hospitalized. In conclusion, our hypothesis proposes that nicotine could constitute a novel potential CRS therapy in severe SARS-CoV-2 patients.", "title": "Cytokine Release Syndrome (CRS) and Nicotine in COVID-19 Patients: Trying to Calm the Storm", "pid": "i8y1kwul", "bm25_score": 217.49700927734375}, {"text": "", "title": "Is a \"Cytokine Storm\" Relevant to COVID-19?", "pid": "jrsp0yef", "bm25_score": 217.48208618164062}, {"text": "The term cytokine storm syndromes describes conditions characterised by a life-threatening, fulminant hypercytokinaemia with high mortality. Cytokine storm syndromes can be genetic or a secondary complication of autoimmune or autoinflammatory disorders, infections, and haematological malignancies. These syndromes represent a key area of interface between rheumatology and general medicine. Rheumatologists often lead in management, in view of their experience using intensive immunosuppressive regimens and managing cytokine storm syndromes in the context of rheumatic disorders or infection (known as secondary haemophagocytic lymphohistiocytosis or macrophage activation syndrome [sHLH/MAS]). Interleukin (IL)-1 is pivotal in hyperinflammation. Anakinra, a recombinant humanised IL-1 receptor antagonist, is licenced at a dose of 100 mg once daily by subcutaneous injection for rheumatoid arthritis, systemic juvenile idiopathic arthritis, adult-onset Still's disease, and cryopyrin-associated periodic syndromes. In cytokine storm syndromes, the subcutaneous route is often problematic, as absorption can be unreliable in patients with critical illness, and multiple injections are needed to achieve the high doses required. As a result, intravenous anakinra is used in clinical practice for sHLH/MAS, despite this being an off-licence indication and route of administration. Among 46 patients admitted to our three international, tertiary centres for sHLH/MAS and treated with anakinra over 12 months, the intravenous route of delivery was used in 18 (39%) patients. In this Viewpoint, we describe current challenges in the management of cytokine storm syndromes and review the pharmacokinetic and safety profile of intravenous anakinra. There is accumulating evidence to support the rationale for, and safety of, intravenous anakinra as a first-line treatment in patients with sHLH/MAS. Intravenous anakinra has important clinical relevance when high doses of drug are required or if patients have subcutaneous oedema, severe thrombocytopenia, or neurological involvement. Cross-speciality management and collaboration, with the generation of international, multi-centre registries and biobanks, are needed to better understand the aetiopathogenesis and improve the poor prognosis of cytokine storm syndromes.", "title": "Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome", "pid": "q521ofrq", "bm25_score": 217.4716796875}, {"text": "On 7 January 2020, researchers isolated and sequenced in China from patients with severe pneumonitis a novel coronavirus, then called SARS-CoV-2, which rapidly spread worldwide, becoming a global health emergency. Typical manifestations consist of flu-like symptoms such as fever, cough, fatigue, and dyspnea. However, in about 20% of patients, the infection progresses to severe interstitial pneumonia and can induce an uncontrolled host-immune response, leading to a life-threatening condition called cytokine release syndrome (CRS). CRS represents an emergency scenario of a frequent challenge, which is the complex and interwoven link between infections and autoimmunity. Indeed, treatment of CRS involves the use of both antivirals to control the underlying infection and immunosuppressive agents to dampen the aberrant pro-inflammatory response of the host. Several trials, evaluating the safety and effectiveness of immunosuppressants commonly used in rheumatic diseases, are ongoing in patients with COVID-19 and CRS, some of which are achieving promising results. However, such a use should follow a multidisciplinary approach, be accompanied by close monitoring, be tailored to patient’s clinical and serological features, and be initiated at the right time to reach the best results. Autoimmune patients receiving immunosuppressants could be prone to SARS-CoV-2 infections; however, suspension of the ongoing therapy is contraindicated to avoid disease flares and a consequent increase in the infection risk.", "title": "Cytokine Release Syndrome in COVID-19 Patients, A New Scenario for an Old Concern: The Fragile Balance between Infections and Autoimmunity", "pid": "5pv7kw6i", "bm25_score": 217.47064208984375}, {"text": "COVID-19 leads to mortality of several patients and the cytokine storm is reportedly critical in the patients. To reduce the cytokine storm, we would like to propose the interleukin (IL) 6 receptor (IL-6R) antagonist therapy for the COVID-19 patients. Two humanized monoclonal antibodies are in clinical trial following IL-6R antagonist therapies namely tocilizumab and sarilumab. However, researchers and physicians should look for more IL-6R antagonists for the therapy of cytokine storm syndrome severe acute respiratory syndrome coronavirus 2 infected persons to enhance the therapeutic options for cytokine storm.", "title": "COVID-19: Consider IL-6 receptor antagonist for the therapy of cytokine storm syndrome in SARS-CoV-2 infected patients", "pid": "wbk2q4aj", "bm25_score": 217.47003173828125}, {"text": "Knowledge about the pathobiology of SARS-CoV-2 as it interacts with immune defenses is limited. SARS-CoV-2 is spread by droplets that come into contact with mucous membranes. COVID-19 is characterized by 2 or 3 stages: most patients who recover experience 2 stages of illness commencing with an asymptomatic or paucisymptomatic incubation period, followed by a nonsevere symptomatic illness lasting for several weeks, occurring in about 80% of those infected. In the remainder, a third phase marked by a severe respiratory illness, often accompanied by multisystem dysfunction, coagulopathy, and shock is observed. This phase of the illness is characterized by hypercytokinemic inflammation and is often referred to as \"cytokine storm.\" While the immunopathogenesis remains unclear, prospects of treating this severe phase of the illness with immunotherapy are evolving, with some treatments showing promise.", "title": "Cytokine storm and the prospects for immunotherapy with COVID-19", "pid": "be38b41o", "bm25_score": 217.45660400390625}, {"text": "COVID-19 is a global pandemic that emerged from Wuhan, China. Besides pneumonia and acute respiratory distress syndrome, the disease leads to multisystem involvement in the form of myocarditis, arrhythmias, cardiac arrest, gastrointestinal symptoms, hypoxemic brain injury, acute liver, and renal function impairment. There are also reports of cutaneous lesions in form of urticarial and maculopapular rashes, chilblain like fingers and toes (covid feet), livedoid vasculopathy, and chicken-pox like or varicelliform vesicles. Clinically, many of these skin lesions are likely secondary to occlusion of small to medium blood vessels due to microthrombi formation or due to viral laden antigen-antibody immune complexes; and same explanation may hold true for possible hypoxemic injury simultaneously occurring in other vital organs like lungs, heart, brain, and kidneys. The histopathology, immunoflorescence and RT-PCR analysis of skin biopsies can provide useful insights for ascertaining the pathogenesis of this complex viral syndrome. Apparently, it is interplay of disarmed cellular immunity and over-activated humoral immunity that culminates in end-organ changes. The morbidity and mortality can be significantly reduced by upgrading the cellular immunity and downgrading the humoral response; along with prevention of hypoxemic and reperfusion injuries by using antivirals, immunomodulators, antioxidants, anti-platelets, and anticoagulants in judicious and phased manner.", "title": "Unraveling the mystery of Covid-19 cytokine storm: From skin to organ systems", "pid": "zbkukpdc", "bm25_score": 217.45556640625}, {"text": "Coronavirus Disease 2019 (COVID-19) has sparked a global pandemic, affecting more than 4 million people worldwide. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause acute lung injury (ALI) and even acute respiratory distress syndrome (ARDS); with a fatality of 7.0 %. Accumulating evidence suggested that the progression of COVID-19 is associated with lymphopenia and excessive inflammation, and a subset of severe cases might exhibit cytokine storm triggered by secondary hemophagocytic lymphohistiocytosis (sHLH). Furthermore, secondary bacterial infection may contribute to the exacerbation of COVID-19. We recommend using both IL-10 and IL-6 as the indicators of cytokine storm, and monitoring the elevation of procalcitonin (PCT) as an alert for initiating antibacterial agents. Understanding the dynamic progression of SARS-CoV-2 infection is crucial to determine an effective treatment strategy to reduce the rising mortality of this global pandemic.", "title": "Biochemical indicators of coronavirus disease 2019 exacerbation and the clinical implications", "pid": "j25rvp1i", "bm25_score": 217.43775939941406}, {"text": "Summary The term cytokine storm syndromes describes conditions characterised by a life-threatening, fulminant hypercytokinaemia with high mortality. Cytokine storm syndromes can be genetic or a secondary complication of autoimmune or autoinflammatory disorders, infections, and haematological malignancies. These syndromes represent a key area of interface between rheumatology and general medicine. Rheumatologists often lead in management, in view of their experience using intensive immunosuppressive regimens and managing cytokine storm syndromes in the context of rheumatic disorders or infection (known as secondary haemophagocytic lymphohistiocytosis or macrophage activation syndrome [sHLH/MAS]). Interleukin (IL)-1 is pivotal in hyperinflammation. Anakinra, a recombinant humanised IL-1 receptor antagonist, is licenced at a dose of 100 mg once daily by subcutaneous injection for rheumatoid arthritis, systemic juvenile idiopathic arthritis, adult-onset Still's disease, and cryopyrin-associated periodic syndromes. In cytokine storm syndromes, the subcutaneous route is often problematic, as absorption can be unreliable in patients with critical illness, and multiple injections are needed to achieve the high doses required. As a result, intravenous anakinra is used in clinical practice for sHLH/MAS, despite this being an off-licence indication and route of administration. Among 46 patients admitted to our three international, tertiary centres for sHLH/MAS and treated with anakinra over 12 months, the intravenous route of delivery was used in 18 (39%) patients. In this Viewpoint, we describe current challenges in the management of cytokine storm syndromes and review the pharmacokinetic and safety profile of intravenous anakinra. There is accumulating evidence to support the rationale for, and safety of, intravenous anakinra as a first-line treatment in patients with sHLH/MAS. Intravenous anakinra has important clinical relevance when high doses of drug are required or if patients have subcutaneous oedema, severe thrombocytopenia, or neurological involvement. Cross-speciality management and collaboration, with the generation of international, multi-centre registries and biobanks, are needed to better understand the aetiopathogenesis and improve the poor prognosis of cytokine storm syndromes.", "title": "Silencing the cytokine storm: the use of intravenous anakinra in haemophagocytic lymphohistiocytosis or macrophage activation syndrome", "pid": "h4tnz9x4", "bm25_score": 217.43374633789062}, {"text": "", "title": "Cyclosporine therapy in cytokine storm due to coronavirus disease 2019 (COVID-19)", "pid": "20ak2zsy", "bm25_score": 217.42819213867188}, {"text": "Clinical evidence indicates that the fatal outcome observed with severe acute respiratory syndrome‐coronavirus‐2 infection often results from alveolar injury that impedes airway capacity and multi‐organ failure—both of which are associated with the hyperproduction of cytokines, also known as a cytokine storm or cytokine release syndrome. Clinical reports show that both mild and severe forms of disease result in changes in circulating leukocyte subsets and cytokine secretion, particularly IL‐6, IL‐1β, IL‐10, TNF, GM‐CSF, IP‐10 (IFN‐induced protein 10), IL‐17, MCP‐3, and IL‐1ra. Not surprising, therapies that target the immune response and curtail the cytokine storm in coronavirus 2019 (COVID‐19) patients have become a focus of recent clinical trials. Here we review reports on leukocyte and cytokine data associated with COVID‐19 disease in 3939 patients in China and describe emerging data on immunopathology. With an emphasis on immune modulation, we also look at ongoing clinical studies aimed at blocking proinflammatory cytokines; transfer of immunosuppressive mesenchymal stem cells; use of convalescent plasma transfusion; as well as immunoregulatory therapy and traditional Chinese medicine regimes. In examining leukocyte and cytokine activity in COVID‐19, we focus in particular on how these levels are altered as the disease progresses (neutrophil NETosis, macrophage, T cell response, etc.) and proposed consequences to organ pathology (coagulopathy, etc.). Viral and host interactions are described to gain further insight into leukocyte biology and how dysregulated cytokine responses lead to disease and/or organ damage. By better understanding the mechanisms that drive the intensity of a cytokine storm, we can tailor treatment strategies at specific disease stages and improve our response to this worldwide public health threat.", "title": "Cytokine storm and leukocyte changes in mild versus severe SARS‐CoV‐2 infection: Review of 3939 COVID‐19 patients in China and emerging pathogenesis and therapy concepts", "pid": "r4vobu5w", "bm25_score": 217.39187622070312}, {"text": "Poor outcomes in COVID‐19 correlate with clinical and laboratory features of cytokine storm syndrome. Broad screening for cytokine storm and early, targeted antiinflammatory therapy may prevent immunopathology and could help conserve limited health care resources. While studies are ongoing, extrapolating from clinical experience in cytokine storm syndromes may benefit the multidisciplinary teams caring for patients with severe COVID‐19.", "title": "On the Alert for Cytokine Storm: Immunopathology in COVID‐19", "pid": "y26r9g3m", "bm25_score": 217.39027404785156}, {"text": "", "title": "Understanding the cytokine storm during COVID-19: Contribution of preexisting chronic inflammation", "pid": "lp5rftyk", "bm25_score": 217.3893585205078}, {"text": "The coronavirus disease-19 (COVID-19) has spread over many countries and regions since the end of 2019, becoming the most severe public health event at present. Most of the critical cases developed multiple organ dysfunction, including acute kidney injury (AKI). Cytokine storm syndrome (CSS) may complicate the process of severe COVID-19 patients. This manuscript reviews the different aspects of blood purification in critically ill patients with AKI and increased inflammatory factors, and examines its potential role in severe COVID-19 treatment. Continuous renal replacement therapy (CRRT) has been practiced in many sepsis patients with AKI. Still, the timing and dosing need further robust evidence. In addition to the traditional CRRT, the high-throughput membrane with adsorption function and cytokine adsorption column are two representatives of recently emerging novel membrane technologies. Their potential in removing inflammatory factors and other toxins prospects for the treatment of severe COVID-19.", "title": "Is there a role for blood purification therapies targeting cytokine storm syndrome in critically severe COVID-19 patients?", "pid": "cabnh61m", "bm25_score": 217.3654022216797}, {"text": "Since December 2019, a novel coronavirus pneumonia (COVID-19) has broken out in Wuhan, China and spread rapidly. Recent studies have found that ⁓ 15.7% of patients develop severe pneumonia, and cytokine storm is an important factor leading to rapid disease progression. Currently, there are no specific drugs for COVID-19 and the cytokine storm it causes. IL-6 is one of the key cytokines involved in infection-induced cytokine storm. Tocilizumab, which is the IL-6 receptor antagonist, has been approved by the US FDA for the treatment of cytokine release syndrome (CRS), is expected to treat cytokine storm caused by COVID-19 and is now in clinical trials. In this paper, we will elaborate the role of cytokine storm in COVID-19, the mechanism of tocilizumab on cytokine storm and the key points of pharmaceutical care based on the actual clinical application for COVID-19 in our hospital, the latest research reports, clinical trial progress of tocilizumab, drug instruction from the US FDA, and “Diagnosis and Treatment Plan of Novel Coronavirus Pneumonia (seventh trial edition)” in China, so as to provide reference for the treatment of COVID-19.", "title": "Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia", "pid": "nqprluto", "bm25_score": 217.3553466796875}, {"text": "", "title": "Brief annotations on cytokine release syndrome and interleukin-6 therapeutic blockage in SARS-CoV-2/COVID-19.", "pid": "4qs9hq9y", "bm25_score": 217.32843017578125}, {"text": "The outbreak of Corona Virus Disease 2019 (COVID-19) has spread to more than 70 countries worldwide and there was a higher mortality in those who developed serious illness.Cytokine storm syndrome is an important pathophysiological basis for COVID-19 patients developing into severe or critical conditions. It was indicated in the diagnosis and treatment scheme, by the National Health Commission of the People's Republic of China, that blood purifications such as plasma exchange, plasma adsorption, hemoperfusion, hemofiltration and plasmafiltration could be considered for use in the critical patients with cytokine storm syndrome. This expert consensus, proposed by the Chinese Society of Nephrology and the Nephrology Committee of Chinese Research Hospital Association, is to guide and standardize the clinical application of blood purifications in the treatment of severe or critical patients with COVID-19.", "title": "[Expert consensus on Corona Virus Disease 2019 with special blood purification technology].", "pid": "jqtoundb", "bm25_score": 217.3223876953125}, {"text": "The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as 'cytokine storm'. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19.", "title": "The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response", "pid": "5f63n7ex", "bm25_score": 217.30076599121094}, {"text": "Since December 2019, a novel coronavirus pneumonia (COVID-19) has broken out in Wuhan, China and spread rapidly. Recent studies have found that ⁓ 15.7% of patients develop severe pneumonia, and cytokine storm is an important factor leading to rapid disease progression. Currently, there are no specific drugs for COVID-19 and the cytokine storm it causes. IL-6 is one of the key cytokines involved in infection-induced cytokine storm. Tocilizumab, which is the IL-6 receptor antagonist, has been approved by the US FDA for the treatment of cytokine release syndrome (CRS), is expected to treat cytokine storm caused by COVID-19 and is now in clinical trials. In this paper, we will elaborate the role of cytokine storm in COVID-19, the mechanism of tocilizumab on cytokine storm and the key points of pharmaceutical care based on the actual clinical application for COVID-19 in our hospital, the latest research reports, clinical trial progress of tocilizumab, drug instruction from the US FDA, and \"Diagnosis and Treatment Plan of Novel Coronavirus Pneumonia (seventh trial edition)\" in China, so as to provide reference for the treatment of COVID-19.", "title": "Rational Use of Tocilizumab in the Treatment of Novel Coronavirus Pneumonia", "pid": "yaov2osz", "bm25_score": 217.28834533691406}, {"text": "The pandemic caused by the novel coronavirus SARS-CoV-2 has placed an unprecedented burden on healthcare systems around the world. In patients who experience severe disease, acute respiratory distress is often accompanied by a pathological immune reaction, sometimes referred to as ‘cytokine storm’. One hallmark feature of the profound inflammatory state seen in patients with COVID-19 who succumb to pneumonia and hypoxia is marked elevation of serum cytokines, especially interferon gamma, tumor necrosis factor alpha, interleukin 17 (IL-17), interleukin 8 (IL-8) and interleukin 6 (IL-6). Initial experience from the outbreaks in Italy, China and the USA has anecdotally demonstrated improved outcomes for critically ill patients with COVID-19 with the administration of cytokine-modulatory therapies, especially anti-IL-6 agents. Although ongoing trials are investigating anti-IL-6 therapies, access to these therapies is a concern, especially as the numbers of cases worldwide continue to climb. An immunology-informed approach may help identify alternative agents to modulate the pathological inflammation seen in patients with COVID-19. Drawing on extensive experience administering these and other immune-modulating therapies, the Society for Immunotherapy of Cancer offers this perspective on potential alternatives to anti-IL-6 that may also warrant consideration for management of the systemic inflammatory response and pulmonary compromise that can be seen in patients with severe COVID-19.", "title": "The Society for Immunotherapy of Cancer perspective on regulation of interleukin-6 signaling in COVID-19-related systemic inflammatory response", "pid": "gn34m0hb", "bm25_score": 217.27984619140625}, {"text": "", "title": "THE “PERFECT CYTOKINE STORM” OF COVID-19", "pid": "tqjmg3qb", "bm25_score": 217.2564697265625}]}
{"idx": 39, "qid": "40", "q_text": "What are the observed mutations in the SARS-CoV-2 genome and how often do the mutations occur?", "qrels": {"02bwyi1w": 2, "02cfyuf4": 2, "02o93wlh": 2, "65uifxid": 1, "038xu4hq": 0, "03agubzq": 1, "04bi0d50": 1, "06e3vxu9": 0, "06vlesc7": 0, "084o1dmp": 0, "08b0g46x": 1, "08ds967z": 0, "09ots6oj": 0, "09r8xd0u": 2, "09ubsq2k": 0, "0c7tf0np": 0, "0c8vnvx9": 0, "0chuwvg6": 1, "0d9hzmyk": 2, "0frnuhut": 1, "0gier0lu": 0, "exvvms1j": 0, "0gmtnkbh": 2, "0hldozml": 2, "0hxan9rw": 2, "0iq9s94n": 0, "0kgyc97m": 0, "0kxo3a4q": 2, "0nh58odf": 2, "0nmwbpns": 0, "0plznmwi": 0, "0rk2dw4e": 0, "m5yaeqc9": 2, "0s7oq0uv": 2, "0vnpodgu": 2, "hbvqezb0": 0, "0xruezf2": 2, "0ydpwdpz": 1, "10kgcx23": 0, "127c5bve": 2, "13h5aigg": 0, "13ir5xc5": 0, "13ir7swr": 1, "13tc3loo": 2, "146matzr": 0, "14pgap3r": 2, "16lkzgtq": 2, "1a4l1beo": 0, "1bvsn9e8": 0, "1evug4fr": 2, "1ewi3dka": 0, "1fhja82a": 0, "1fxrmuzl": 2, "1gsy43a0": 2, "1h1hwbos": 2, "1iq1j47x": 2, "1iqg0efn": 2, 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unique opportunity to study the introduction and evolution of a pathogen into a completely naïve human population. We identified and analysed the amino acid mutations that gained prominence worldwide in the early months of the pandemic. Eight mutations have been identified along the viral genome, mostly located in conserved segments of the structural proteins and showing low variability among coronavirus, which indicated that they might have a functional impact. At the moment of writing this paper, these mutations present a varied success in the SARS-CoV-2 virus population; ranging from a change in the spike protein that becomes absolutely prevalent, two mutations in the nucleocapsid protein showing frequencies around 25%, to a mutation in the matrix protein that nearly fades out after reaching a frequency of 20%.", "title": "SARS-CoV-2 amino acid substitutions widely spread in the human population are mainly located in highly conserved segments of the structural proteins", "pid": "0hldozml", "bm25_score": 220.1210479736328}, {"text": "The COVID-19 pandemic has spread across the globe at an alarming rate in the last four months. However, unlike any of the previous global outbreaks the availability of hundreds of SARS-CoV-2 sequences provides us with a unique opportunity to understand viral evolution in real time. We analysed 480 full-length (>29000 nt) sequences from the 1575 SARS-CoV-2 sequences available and identified 37 single-nucleotide substitutions occurring in >1% of the genomes. Majority of the substitutions were C to T or G to A. We identify C/Gs with an upstream TTT trinucleotide motif as hotspots for mutations in the SARS-CoV-2 genome. Interestingly, two of the 37 substitutions occur within highly conserved secondary structures in the 5’ and 3’ untranslated regions that are critical for the virus life cycle. Furthermore, clustering analysis revealed unique geographical distribution of SARS-CoV-2 variants defined by their mutation profile. Of note, we observed several co-occurring mutations that almost never occur individually. We define 3 mutually exclusive lineages (A1, B1 and C1) of SARS-CoV-2 which account for about three quarters of the genomes analysed. We identify lineage-defining leading mutations in the SARS-CoV-2 genome which precede the occurrence of sub-lineage defining trailing mutations. The identification of mutually exclusive lineage-defining mutations with geographically restricted patterns of distribution has potential implications for diagnosis, pathogenesis and vaccine design. Our work provides novel insights on the temporal evolution of SARS-CoV-2.", "title": "Mutation landscape of SARS-CoV-2 reveals three mutually exclusive clusters of leading and trailing single nucleotide substitutions", "pid": "miujzgtd", "bm25_score": 220.0101318359375}, {"text": "OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has been rapidly spreading worldwide. Although the causal relationship among mutations and the features of SARS-CoV-2 such as rapid transmission, pathogenicity, and tropism, remains unclear, our results of genomic mutations in SARS-CoV-2 may help to interpret the interaction between genomic characterization in SARS-CoV-2 and infectivity with the host. METHODS: A total of 4,254 genomic sequences of SARS-CoV-2 were collected from the Global Initiative on Sharing all Influenza Data (GISAID). Multiple sequence alignment for phylogenetic analysis and comparative genomic approach for mutation analysis were conducted using Molecular Evolutionary Genetics Analysis (MEGA), and an in-house program based on Perl language, respectively. RESULTS: Phylogenetic analysis of SARS-CoV-2 strains indicated that there were 3 major clades including S, V, and G, and 2 subclades (G.1 and G.2). There were 767 types of synonymous and 1,352 types of non-synonymous mutation. ORF1a, ORF1b, S, and N genes were detected at high frequency, whereas ORF7b and E genes exhibited low frequency. In the receptor-binding domain (RBD) of the S gene, 11 non-synonymous mutations were observed in the region adjacent to the angiotensin converting enzyme 2 (ACE2) binding site. CONCLUSION: It has been reported that the rapid infectivity and transmission of SARS-CoV-2 associated with host receptor affinity are derived from several mutations in its genes. Without these genetic mutations to enhance evolutionary adaptation, species recognition, host receptor affinity, and pathogenicity, it would not survive. It is expected that our results could provide an important clue in understanding the genomic characteristics of SARS-CoV-2.", "title": "Genome-Wide Identification and Characterization of Point Mutations in the SARS-CoV-2 Genome", "pid": "shn7vx3d", "bm25_score": 219.8558349609375}, {"text": "Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive repository. Up until March 27, 2020, we downloaded 53 illumina datasets, mostly from China, USA (Washington DC) and Australia (Victoria). Of 30 high quality datasets, 27 datasets (90%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA sequencing samples. Sequencing samples from USA in GenBank present this signature with 50% allele frequencies among samples. Australian mutation signatures were more diverse than USA samples, but still, clonal events were found in those samples. Mutations in the helicase and orf1a coding regions from SARS-CoV-2 were predominant, among others, suggesting that these proteins are prone to evolve by natural selection. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.", "title": "Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions", "pid": "gfwqog3x", "bm25_score": 219.84002685546875}, {"text": "The pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure. Here, we analyzed mutation patterns in 34 human SARS-CoV-2 isolates and a closely related RaTG13 isolated from Rhinolophus affinis (a horseshoe bat). We also evaluated the CpG dinucleotide contents in SARS-CoV-2 and other human and animal coronavirus genomes. Out of 1136 single nucleotide variations (~4% divergence) between human SARS-CoV-2 and bat RaTG13, 682 (60%) can be attributed to C>U and U>C substitutions, far exceeding other types of substitutions. An accumulation of C>U mutations was also observed in SARS-CoV2 variants that arose within the human population. Globally, the C>U substitutions increased the frequency of codons for hydrophobic amino acids in SARS-CoV-2 peptides, while U>C substitutions decreased it. In contrast to most other coronaviruses, both SARS-CoV-2 and RaTG13 exhibited CpG depletion in their genomes. The data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus. We hypothesize that the high frequency C>U transitions reflect virus adaptation processes in their hosts, and that SARS-CoV-2 could have been evolving for a relatively long period in humans following the transfer from animals before spreading worldwide.", "title": "Mutation Patterns of Human SARS-CoV-2 and Bat RaTG13 Coronavirus Genomes Are Strongly Biased Towards C>U Transitions, Indicating Rapid Evolution in Their Hosts", "pid": "k4l759k2", "bm25_score": 219.81219482421875}, {"text": "Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), which was first reported in Wuhan, China in November 2019 has developed into a pandemic since March 2020, causing substantial human casualties and economic losses. Studies on SARS-CoV-2 are being carried out at an unprecedented rate to tackle this threat. Genomics studies, in particular, are indispensable to elucidate the dynamic nature of the RNA genome of SARS-CoV-2. RNA viruses are marked by their unique ability to undergo high rates of mutation in their genome, much more frequently than their hosts, which diversifies their strengths qualifying them to elude host immune response and amplify drug resistance. In this study, we sequenced and analyzed the genomic information of the SARS-CoV-2 isolates from two infected Indian patients and explored the possible implications of point mutations in its biology. In addition to multiple point mutations, we found a remarkable similarity between relatively common mutations of 36-nucleotide deletion in ORF8 of SARS-CoV-2. Our results corroborate with the earlier reported 29-nucleotide deletion in SARS, which was frequent during the early stage of human-to-human transmission. The results will be useful to understand the biology of SARS-CoV-2 and itsattenuation for vaccine development.", "title": "Identification of unique mutations in SARS-CoV-2 strains isolated from India suggests its attenuated pathotype", "pid": "fujejfwb", "bm25_score": 219.80845642089844}, {"text": "In order to explore nonsynonymous mutations and deletions in the spike (S) protein of SARS-CoV-2, we comprehensively analyzed 35,750 complete S protein gene sequences from across six continents and five climate zones around the world, as documented in the GISAID database as of June 24th, 2020. Through a custom Python-based pipeline for analyzing mutations, we identified 27,801 (77.77 % of spike sequences) mutated strains compared to Wuhan-Hu-1 strain. 84.40% of these strains had only single amino-acid (aa) substitution mutations, but an outlier strain from Bosnia and Herzegovina (EPI_ISL_463893) was found to possess six aa substitutions. The D614G variant of the major G clade was found to be predominant across circulating strains in all climates. We also identified 988 unique aa substitution mutations distributed across 660 positions within the spike protein, with eleven sites showing high variability – these sites had four types of aa variations at each position. Besides, 17 in-frame deletions at four major regions (three in N-terminal domain and one just downstream of the RBD) may have possible impact on attenuation. Moreover, the mutational frequency differed significantly (p= 0.003, Kruskal–Wallis test) among the SARS-CoV-2 strains worldwide. This study presents a fast and accurate pipeline for identifying nonsynonymous mutations and deletions from large dataset for any particular protein coding sequence and presents this S protein data as representative analysis. By using separate multi-sequence alignment with MAFFT, removing ambiguous sequences and in-frame stop codons, and utilizing pairwise alignment, this method can derive nonsynonymus mutations (Reference:Position:Strain). We believe this will aid in the surveillance of any proteins encoded by SARS-CoV-2, and will prove to be crucial in tracking the ever-increasing variation of many other divergent RNA viruses in the future.", "title": "Comprehensive annotations of the mutational spectra of SARS-CoV-2 spike protein: a fast and accurate pipeline", "pid": "1iqg0efn", "bm25_score": 219.77410888671875}, {"text": "Here we aim to describe early mutational events across samples from publicly available SARS-CoV-2 sequences from the sequence read archive and GenBank repositories. Up until 27 March 2020, we downloaded 50 illumina datasets, mostly from China, USA (WA State) and Australia (VIC). A total of 30 datasets (60%) contain at least a single founder mutation and most of the variants are missense (over 63%). Five-point mutations with clonal (founder) effect were found in USA next-generation sequencing samples. Sequencing samples from North America in GenBank (22 April 2020) present this signature with up to 39% allele frequencies among samples (n = 1,359). Australian variant signatures were more diverse than USA samples, but still, clonal events were found in these samples. Mutations in the helicase, encoded by the ORF1ab gene in SARS-CoV-2 were predominant, among others, suggesting that these regions are actively evolving. Finally, we firmly urge that primer sets for diagnosis be carefully designed, since rapidly occurring variants would affect the performance of the reverse transcribed quantitative PCR (RT-qPCR) based viral testing.", "title": "Insights on early mutational events in SARS-CoV-2 virus reveal founder effects across geographical regions", "pid": "0xruezf2", "bm25_score": 219.76771545410156}, {"text": "The pandemic caused by the spread of SARS-CoV-2 has led to considerable interest in its evolutionary origin and genome structure. Here, we analyzed mutation patterns in 34 human SARS-CoV-2 isolates and a closely related RaTG13 isolated from Rhinolophus affinis (a horseshoe bat). We also evaluated the CpG dinucleotide contents in SARS-CoV-2 and other human and animal coronavirus genomes. Out of 1136 single nucleotide variations (~4% divergence) between human SARS-CoV-2 and bat RaTG13, 682 (60%) can be attributed to C>U and U>C substitutions, far exceeding other types of substitutions. An accumulation of C>U mutations was also observed in SARS-CoV2 variants that arose within the human population. Globally, the C>U substitutions increased the frequency of codons for hydrophobic amino acids in SARS-CoV-2 peptides, while U>C substitutions decreased it. In contrast to most other coronaviruses, both SARS-CoV-2 and RaTG13 exhibited CpG depletion in their genomes. The data suggest that C-to-U conversion mediated by C deamination played a significant role in the evolution of the SARS-CoV-2 coronavirus. We hypothesize that the high frequency C>U transitions reflect virus adaptation processes in their hosts, and that SARS-CoV-2 could have been evolving for a relatively long period in humans following the transfer from animals before spreading worldwide.", "title": "Mutation Patterns of Human SARS-CoV-2 and Bat RaTG13 Coronavirus Genomes Are Strongly Biased Towards C>U Transitions, Indicating Rapid Evolution in Their Hosts.", "pid": "ox7xetlq", "bm25_score": 219.602783203125}, {"text": "The recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has the capability of gaining rapid mutations as the virus spreads. Whole-genome sequencing data offers a wide range of opportunities to study mutation dynamics. The advantage of an increasing amount of whole-genome sequence data of SARS-CoV-2 intrigued us to explore the mutation profile across the genome, to check the genome diversity, and to investigate the implications of those mutations in protein stability and viral transmission. We have identified frequently mutated residues by aligning ~660 SARS-CoV-2 genomes and validated in 10,000 datasets available in GISAID Nextstrain. We further evaluated the potential of these frequently mutated residues in protein structure stability of spike glycoprotein and their possible functional consequences in other proteins. Among the 11 genes, surface glycoprotein, nucleocapsid, ORF1ab, and ORF8 showed frequent mutations, while envelop, membrane, ORF6, ORF7a and ORF7b showed conservation in terms of amino acid substitutions. Combined analysis with the frequently mutated residues identified 20 viral variants, among which 12 specific combinations comprised more than 97% of the isolates considered for the analysis. Some of the mutations across different proteins showed co-occurrences, suggesting their structural and/or functional interaction among different SARS-COV-2 proteins, and their involvement in adaptability and viral transmission. Analysis of protein structure stability of surface glycoprotein mutants indicated the viability of specific variants and are more prone to be temporally and spatially distributed across the globe. A similar empirical analysis of other proteins indicated the existence of important functional implications of several variants. Identification of frequently mutated variants among COVID-19 patients might be useful for better clinical management, contact tracing, and containment of the disease.", "title": "Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission", "pid": "q86nga34", "bm25_score": 219.56695556640625}, {"text": "The recent pandemic of SARS-CoV-2 infection has affected more than 3.0 million people worldwide with more than 200 thousand reported deaths. The SARS-CoV-2 genome has a capability of gaining rapid mutations as the virus spreads. Whole genome sequencing data offers a wide range of opportunities to study the mutation dynamics. The advantage of increasing amount of whole genome sequence data of SARS-CoV-2 intrigued us to explore the mutation profile across the genome, to check the genome diversity and to investigate the implications of those mutations in protein stability and viral transmission. Four proteins, surface glycoprotein, nucleocapsid, ORF1ab and ORF8 showed frequent mutations, while envelop, membrane, ORF6 and ORF7a proteins showed conservation in terms of amino acid substitutions. Some of the mutations across different proteins showed co-occurrence, suggesting their functional cooperation in stability, transmission and adaptability. Combined analysis with the frequently mutated residues identified 20 viral variants, among which 12 specific combinations comprised more than 97% of the isolates considered for the analysis. Analysis of protein structure stability of surface glycoprotein mutants indicated viability of specific variants and are more prone to be temporally and spatially distributed across the globe. Similar empirical analysis of other proteins indicated existence of important functional implications of several variants. Analysis of co-occurred mutants indicated their structural and/or functional interaction among different SARS-COV-2 proteins. Identification of frequently mutated variants among COVID-19 patients might be useful for better clinical management, contact tracing and containment of the disease.", "title": "Characterizations of SARS-CoV-2 mutational profile, spike protein stability and viral transmission", "pid": "86byq11c", "bm25_score": 219.5137176513672}, {"text": "BACKGROUND: SARS-CoV-2 is a new coronavirus that has spread globally, infecting more than 150000 people, and being declared pandemic by the WHO. We provide here bio-informatic, evolutionary analysis of 351 available sequences of its genome with the aim of mapping genome structural variations and the patterns of selection. METHODS: A Maximum likelihood tree has been built and selective pressure has been investigated in order to find any mutation developed during the SARS-CoV-2 epidemic that could potentially affect clinical evolution of the infection. FINDING: We have found in more recent isolates the presence of two mutations affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures. INTERPRETATION: One of the two mutations, likely developed within the genome during virus spread, could affect virus intracellular survival. Genome follow-up of SARS-CoV-2 spread is urgently needed in order to identify mutations that could significantly modify virus pathogenicity.", "title": "Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy", "pid": "su5tlg3l", "bm25_score": 219.34356689453125}, {"text": "• Mutation studies hits cause for the superior infectious rate of SARS-CoV-2. • SARS-CoV-2 is evolving rapidly with number of mutations and SNPs. • Mutations were found in the ACE2 binding region of SARS-CoV-2 spike glycoprotein. • ORF1ab, ORF8 and spike glycoprotein regions of SARS-CoV-2 are highly mutated. • Overwhelming mutations or SNPs of SARS-CoV-2 alerts drug treatment options.", "title": "Overwhelming Mutations or SNPs of SARS-CoV-2: A Point of Caution", "pid": "sd0ah7k5", "bm25_score": 219.27285766601562}, {"text": "SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 5 2020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.", "title": "Emergence of genomic diversity and recurrent mutations in SARS-CoV-2", "pid": "msggi1p2", "bm25_score": 219.2036590576172}, {"text": "The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2 permissive host cells, we identified twelve separate target sequences in the SARS-CoV-2 genome; eight of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host could be constrained by host miRNA defence. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineered viral attenuation and antigen presentation.", "title": "Implications of SARS-CoV-2 mutations for genomic RNA structure and host microRNA targeting", "pid": "4e3cn50u", "bm25_score": 219.168212890625}, {"text": "Abstract SARS-CoV-2 is a SARS-like coronavirus of likely zoonotic origin first identified in December 2019 in Wuhan, the capital of China's Hubei province. The virus has since spread globally, resulting in the currently ongoing COVID-19 pandemic. The first whole genome sequence was published on January 52,020, and thousands of genomes have been sequenced since this date. This resource allows unprecedented insights into the past demography of SARS-CoV-2 but also monitoring of how the virus is adapting to its novel human host, providing information to direct drug and vaccine design. We curated a dataset of 7666 public genome assemblies and analysed the emergence of genomic diversity over time. Our results are in line with previous estimates and point to all sequences sharing a common ancestor towards the end of 2019, supporting this as the period when SARS-CoV-2 jumped into its human host. Due to extensive transmission, the genetic diversity of the virus in several countries recapitulates a large fraction of its worldwide genetic diversity. We identify regions of the SARS-CoV-2 genome that have remained largely invariant to date, and others that have already accumulated diversity. By focusing on mutations which have emerged independently multiple times (homoplasies), we identify 198 filtered recurrent mutations in the SARS-CoV-2 genome. Nearly 80% of the recurrent mutations produced non-synonymous changes at the protein level, suggesting possible ongoing adaptation of SARS-CoV-2. Three sites in Orf1ab in the regions encoding Nsp6, Nsp11, Nsp13, and one in the Spike protein are characterised by a particularly large number of recurrent mutations (>15 events) which may signpost convergent evolution and are of particular interest in the context of adaptation of SARS-CoV-2 to the human host. We additionally provide an interactive user-friendly web-application to query the alignment of the 7666 SARS-CoV-2 genomes.", "title": "Emergence of genomic diversity and recurrent mutations in SARS-CoV-2", "pid": "bsypo08l", "bm25_score": 219.14947509765625}, {"text": "A novel pathogen, named SARS-CoV-2, has caused an unprecedented worldwide pandemic in the first half of 2020. As the SARS-CoV-2 genome sequences have become available, one of the important focus of scientists has become tracking variations in the viral genome. In this study, 30366 SARS-CoV-2 isolate genomes were aligned using the software developed by our group (ODOTool) and 11 variations in SARS-CoV-2 genome over 10% of whole isolates were discussed. Results indicated that, frequency rates of these 11 variations change between 3.56%–88.44 % and these rates differ greatly depending on the continents they have been reported. Despite some variations being in low frequency rate in some continents, C14408T and A23403G variations on Nsp12 and S protein, respectively, observed to be the most prominent variations all over the world, in general, and both cause missense mutations. It is also notable that most of isolates carry C14408T and A23403 variations simultaneously and also nearly all isolates carrying the G25563T variation on ORF3a, also carry C14408T and A23403 variations, although their location distributions are not similar. All these data should be considered towards development of vaccine and antiviral treatment strategies as well as tracing diversity of virus in all over the world.", "title": "An updated analysis of variations in SARS-CoV-2 genome", "pid": "od3c25qg", "bm25_score": 219.14559936523438}, {"text": "Abstract Background SARS-CoV-2 is a new coronavirus that has spread globally, infecting more than 150000 people, and being declared pandemic by the WHO. We provide here bio-informatic, evolutionary analysis of 351 available sequences of its genome with the aim of mapping genome structural variations and the patterns of selection. Methods A Maximum likelihood tree has been built and selective pressure has been investigated in order to find any mutation developed during the SARS-CoV-2 epidemic that could potentially affect clinical evolution of the infection. Finding We have found in more recent isolates the presence of two mutations affecting the Non-Structural Protein 6 (NSP6) and the Open Reding Frame10 (ORF 10) adjacent regions. Amino acidic change stability analysis suggests both mutations could confer lower stability of the protein structures. Interpretation One of the two mutations, likely developed within the genome during virus spread, could affect virus intracellular survival. Genome follow-up of SARS-CoV-2 spread is urgently needed in order to identify mutations that could significantly modify virus pathogenicity.", "title": "Evolutionary analysis of SARS-CoV-2: how mutation of Non-Structural Protein 6 (NSP6) could affect viral autophagy", "pid": "tldg8c94", "bm25_score": 219.0531463623047}, {"text": "The morbidity of SARS-CoV-2 (COVID-19) is reaching 3 Million landmark causing and a serious public health concern globally and it is enigmatic how several antiviral and antibody treatments were not effective in the different period across the globe. With the drastic increasing number of positive cases around the world WHO raised the importance in the assessment of the risk of spread and understanding genetic modifications that could have occurred in the SARS-CoV-2. Using all available deep sequencing data of complete genome from all over the world (NCBI repository), we identified several hundreds of point mutations or SNPs in SARS-CoV-2 all across the genome. This could be the cause for the constant change and differed virulence with an increase in mortality and morbidity. Among the 12 different countries (one sequence from each country) with complete genome sequencing data, we noted the 47 key point mutations or SNPs located along the entire genome that might have impact in the virulence and response to different antivirals against SARS-CoV-2. In this regard, key viral proteins of spike glycoprotein, Nsp1, RdRp and the ORF8 region got heavily mutated within these 3 months via person-to-person passage. We also discuss what could be the possible cause of this rapid mutation in the SARS-CoV-2.", "title": "Overwhelming mutations or SNPs of SARS-CoV-2: A point of caution", "pid": "j8sg5n5g", "bm25_score": 219.04391479492188}, {"text": "The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2-permissive host cells, we identified ten separate target sequences in the SARS-CoV-2 genome; three of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host is constrained by host miRNA defences. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineering conditional attenuation to vaccine development, as well as providing a better understanding of viral tropism and pathogenesis.", "title": "Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting", "pid": "eri92ki6", "bm25_score": 219.0093231201172}, {"text": "A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.", "title": "Genomic characterization of a novel SARS-CoV-2", "pid": "mp3196kj", "bm25_score": 219.00811767578125}, {"text": "Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S(2) domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in S(D) domain) and G1124V (in S(2) subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird’s eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12038-020-00046-1) contains supplementary material, which is available to authorized users.", "title": "Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility", "pid": "6dsx7pey", "bm25_score": 219.00244140625}, {"text": "Direct massively parallel sequencing of SARS-CoV-2 genome was undertaken from nasopharyngeal and oropharyngeal swab samples of infected individuals in Eastern India. Seven of the isolates belonged to the A2a clade, while one belonged to the B4 clade. Specific mutations, characteristic of the A2a clade, were also detected, which included the P323L in RNA-dependent RNA polymerase and D614G in the Spike glycoprotein. Further, our data revealed emergence of novel subclones harbouring nonsynonymous mutations, viz. G1124V in Spike (S) protein, R203K, and G204R in the nucleocapsid (N) protein. The N protein mutations reside in the SR-rich region involved in viral capsid formation and the S protein mutation is in the S2 domain, which is involved in triggering viral fusion with the host cell membrane. Interesting correlation was observed between these mutations and travel or contact history of COVID-19 positive cases. Consequent alterations of miRNA binding and structure were also predicted for these mutations. More importantly, the possible implications of mutation D614G (in SD domain) and G1124V (in S2 subunit) on the structural stability of S protein have also been discussed. Results report for the first time a bird's eye view on the accumulation of mutations in SARS-CoV-2 genome in Eastern India.", "title": "Mutations in SARS-CoV-2 viral RNA identified in Eastern India: Possible implications for the ongoing outbreak in India and impact on viral structure and host susceptibility.", "pid": "02cfyuf4", "bm25_score": 219.00022888183594}, {"text": "We first conducted time-series analysis of mono- and dinucleotide composition for over 10,000 SARS-CoV-2 genomes, as well as over 1500 Zaire ebolavirus genomes, and found clear time-series changes in the compositions on a monthly basis, which should reflect viral adaptations for efficient growth in human cells. We next developed a sequence alignment free method that extensively searches for advantageous mutations and rank them in an increase level for their intrapopulation frequency. Time-series analysis of occurrences of oligonucleotides of diverse lengths for SARS-CoV-2 genomes revealed seven distinctive mutations that rapidly expanded their intrapopulation frequency and are thought to be candidates of advantageous mutations for the efficient growth in human cells.", "title": "Time-series analyses of directional sequence changes in SARS-CoV-2 genomes and an efficient search method for advantageous mutations for growth in human cells", "pid": "0d9hzmyk", "bm25_score": 218.99525451660156}, {"text": "Abstract A new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with human to human transmission and extreme human sickness has been as of late announced from the city of Wuhan in China. Our objectives were to mutation analysis between recently reported genomes at various times and locations and to characterize the genomic structure of SARS-CoV-2 using bioinformatics programs. Information on the variation of viruses is of considerable medical and biological impacts on the prevention, diagnosis, and therapy of infectious diseases. To understand the genomic structure and variations of the SARS-CoV-2. The study analyzed 95 SARS-CoV-2 complete genome sequences available in GenBank, National MicrobiologyData Center (NMDC) and NGDC Genome Warehouse from December-2019 until 05 of April-2020. The genomic signature analysis demonstrates that a strong association between the time of sample collection, location of sample and accumulation of genetic diversity. We found 116 mutations, the three most common mutations were 8782C>T in ORF1ab gene, 28144T>C in ORF8 gene and 29095C>T in the N gene. The mutations might affect the severity and spread of the SARS-CoV-2. The finding heavily supports an intense requirement for additional prompt, inclusive investigations that combine genomic detail, epidemiological information and graph records of the clinical features of patients with COVID-19.", "title": "Genomic characterization of a novel SARS-CoV-2", "pid": "vjfquvlu", "bm25_score": 218.9290771484375}, {"text": "The SARS-CoV-2 virus is a recently-emerged zoonotic pathogen already well adapted to transmission and replication in humans. Although the mutation rate is limited, recently introduced mutations in SARS-CoV-2 have the potential to alter viral fitness. In addition to amino acid changes, mutations could affect RNA secondary structure critical to viral life cycle, or interfere with sequences targeted by host miRNAs. We have analysed subsets of genomes from SARS-CoV-2 isolates from around the globe and show that several mutations introduce changes in Watson-Crick pairing, with resultant changes in predicted secondary structure. Filtering to targets matching miRNAs expressed in SARS-CoV-2-permissive host cells, we identified ten separate target sequences in the SARS-CoV-2 genome; three of these targets have been lost through conserved mutations. A genomic site targeted by the highly abundant miR-197-5p, overexpressed in patients with cardiovascular disease, is lost by a conserved mutation. Our results are compatible with a model that SARS-CoV-2 replication within the human host is constrained by host miRNA defences. The impact of these and further mutations on secondary structures, miRNA targets or potential splice sites offers a new context in which to view future SARS-CoV-2 evolution, and a potential platform for engineering conditional attenuation to vaccine development, as well as providing a better understanding of viral tropism and pathogenesis.", "title": "Implications of SARS-CoV-2 Mutations for Genomic RNA Structure and Host microRNA Targeting.", "pid": "8cex7qi4", "bm25_score": 218.87481689453125}, {"text": "The COVID-19 pandemic is the most important public health threat in recent history. Here we study how its causal agent, SARS-CoV-2, has diversified genetically since its first emergence in December 2019. We have created a pipeline combining both phylogenetic and structural analysis to identify possible human-adaptation related mutations in a data set consisting of 4,894 SARS-CoV-2 complete genome sequences. Although the phylogenetic diversity of SARS-CoV-2 is low, the whole genome phylogenetic tree can be divided into five clusters/clades based on the tree topology and clustering of specific mutations, but its branches exhibit low genetic distance and bootstrap support values. We also identified 11 residues that are high-frequency substitutions, with four of them currently showing some signal for potential positive selection. These fast-evolving sites are in the non-structural proteins nsp2, nsp5 (3CL-protease), nsp6, nsp12 (polymerase) and nsp13 (helicase), in accessory proteins (ORF3a, ORF8) and in the structural proteins N and S. Temporal and spatial analysis of these potentially adaptive mutations revealed that the incidence of some of these sites was declining after having reached an (often local) peak, whereas the frequency of other sites is continually increasing and now exhibit a worldwide distribution. Structural analysis revealed that the mutations are located on the surface of the proteins that modulate biochemical properties. We speculate that this improves binding to cellular proteins and hence represents fine-tuning of adaptation to human cells. Our study has implications for the design of biochemical and clinical experiments to assess whether important properties of SARS-CoV-2 have changed during the epidemic.", "title": "Snapshot of the evolution and mutation patterns of SARS-CoV-2", "pid": "5od0tegt", "bm25_score": 218.86087036132812}, {"text": "Four signature groups of single-nucleotide variants (SNVs) were identified using two-way clustering method in about twenty thousand high quality and high coverage SARS-CoV-2 complete genome sequences. Some frequently occurred SNVs predominate but are mutually exclusively presented in patients from different countries and areas. These major SNV signatures exhibited distinguished evolution patterns overtime. Although it was rare, our data indicated possible cross-infections with multiple groups of SNVs existed simultaneously in some patients, suggesting infections from different SARS-CoV-2 clades or potential re-combination of SARS-CoV-2 sequences. Interestingly nucleotide substitutions among SARS-CoV-2 genomes tend to occur at the sites where one bat RaTG13 coronavirus sequences differ from Wuhan-Hu-1 genome, indicating the tolerance of mutations on those sites or suggesting that major viral strains might exist between Wuhan-Hu-1 and RaTG13 coronavirus.", "title": "Distinct genetic spectrums and evolution patterns of SARS-CoV-2", "pid": "xly61tfw", "bm25_score": 218.82644653320312}, {"text": "In late December 2019, an emerging viral infection COVID-19 was identified in Wuhan, China, and became a global pandemic. Characterization of the genetic variants of SARS-CoV-2 is crucial in following and evaluating it spread across countries. In this study, we collected and analyzed 3,067 SARS-CoV-2 genomes isolated from 55 countries during the first three months after the onset of this virus. Using comparative genomics analysis, we traced the profiles of the whole-genome mutations and compared the frequency of each mutation in the studied population. The accumulation of mutations during the epidemic period with their geographic locations was also monitored. The results showed 782 variant sites, of which 512 (65.47%) had a non-synonymous effect. Frequencies of mutated alleles revealed the presence of 38 recurrent non-synonymous mutations, including ten hotspot mutations with a prevalence higher than 0.10 in this population and distributed in six SARS-CoV-2 genes. The distribution of these recurrent mutations on the world map revealed certain genotypes specific to the geographic location. We also found co-occurring mutations resulting in the presence of several haplotypes. Moreover, evolution over time has shown a mechanism of mutation co-accumulation which might affect the severity and spread of the SARS-CoV-2. On the other hand, analysis of the selective pressure revealed the presence of negatively selected residues that could be taken into considerations as therapeutic targets We have also created an inclusive unified database (http://genoma.ma/covid-19/) that lists all of the genetic variants of the SARS-CoV-2 genomes found in this study with phylogeographic analysis around the world.", "title": "Large scale genomic analysis of 3067 SARS-CoV-2 genomes reveals a clonal geo-distribution and a rich genetic variations of hotspots mutations", "pid": "5mh3ds6y", "bm25_score": 218.81378173828125}, {"text": "The sudden outbreak of the severe acute respiratory syndrome-coronavirus (SARS-CoV-2) has spread globally with more than 1,300,000 patients diagnosed and a death toll of 70,000. Current genomic survey data suggest that single nucleotide variants (SNVs) are abundant. However, no mutation has been directly linked with functional changes in viral pathogenicity. Here we report functional characterizations of 11 patient-derived viral isolates, all of which have at least one mutation. Importantly, these viral isolates show significant variation in cytopathic effects and viral load, up to 270-fold differences, when infecting Vero-E6 cells. We observed intrapersonal variation and 6 different mutations in the spike glycoprotein (S protein), including 2 different SNVs that led to the same missense mutation. Therefore, we provide direct evidence that the SARS-CoV-2 has acquired mutations capable of substantially changing its pathogenicity.", "title": "Patient-derived mutations impact pathogenicity of SARS-CoV-2", "pid": "3eu9umx5", "bm25_score": 218.78982543945312}, {"text": "AIM Recently, more SARS-CoV virus genome sequences are released to the GenBank database. The aim of this study is to reveal the evolution forces of SARS-CoV virus by analyzing the nucleotide mutations in these sequences. METHODS We obtained 20 SARS-CoV virus genome sequences from NCBI database, and calculated the ratio of non-synonymous nucleotide substitution per non-synonymous site (Ka) and synonymous nucleotide substitution per synonymous site (Ks) for SARS-CoV virus genes. RESULTS The Ka/Ks ratios for replicase polyprotein ORF1a, ORF1b, and spike protein gene are 1.09 (P=0.6501), 0.38 (P=0.0074), 0.65 (P=0.0685) respectively. CONCLUSION SARS-CoV virus replicase polyprotein ORF1b is undergoing negative selection; negative selection force is also probably operating on spike protein gene. These results provide basis for future developing a new drug and vaccine against SARS.", "title": "Mutation analysis of 20 SARS virus genome sequences: evidence for negative selection in replicase ORF1b and spike gene.", "pid": "8r5wopu9", "bm25_score": 218.74859619140625}, {"text": "In Morocco two waves of SARS-CoV-2 infections have been recorded. The first one occurred from March 02, 2020 with infections mostly imported from Europe and the second one dominated by local infections. At the time of writing, the genetic diversity of Moroccan isolates of SARS-CoV-2 has not yet been reported. The present study aimed to analyze first the genomic variation of the twenty-eight Moroccan strains of SARS-CoV-2 isolated from March 03, 2020 to May 15, 2020, to compare their distributions with twelve other viral genomes from North Africa as well as to identify their possible sources. Our finding revealed 61 mutations in the Moroccan genomes of SARS-CoV-2 compared to the reference sequence Wuhan-Hu-1/2019, of them 23 (37.7%) were present in two or more genomes. Focusing on non-synonymous mutations, 29 (47.54%) were distributed in five genes (ORF1ab, spike, membrane, nucleocapsid and ORF3a) with variable frequencies. The non-structural protein coding regions nsp3-Multi domain and nsp12-RdRp of the ORF1ab gene harbored more mutations, with six for each. The comparison of genetic variants of fourty North African strains revealed that two non-synonymous mutations D614G (in spike) and Q57H (in ORF3a) were common in four countries (Morocco, Tunisia, Algeria and Egypt), with a prevalence of 92.5% (n = 37) and 42.5% (n = 17), respectively, of the total genomes. Phylogenetic analysis showed that the Moroccan and Tunisian SARS-CoV-2 strains were closely related to those from different origins (Asia, Europe, North and South America) and distributed in different distinct subclades. This could indicate different sources of infection with no specific strain dominating yet in in these countries. These results have the potential to lead to new comprehensive investigations combining genomic data, epidemiological information and the clinical characteristics of patients with SARS-CoV-2.", "title": "Genetic analysis of SARS-CoV-2 strains collected from North Africa: viral origins and mutational spectrum", "pid": "8871aifz", "bm25_score": 218.74119567871094}, {"text": "BACKGROUND: SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. METHODS: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann-Whitney and Fisher-Exact tests were used to assess statistical significance. RESULTS: We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2-5], otherwise they have a median of 1 mutation [range: 0-3] (p value < 0.001). CONCLUSIONS: These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.", "title": "Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant", "pid": "16lkzgtq", "bm25_score": 218.71115112304688}, {"text": "Objectives To reveal epidemic trend and possible origins of SARS-CoV-2 by exploring its evolution and molecular characteristics based on a large number of genomes since it has infected millions of people and spread quickly all over the world. Methods Various evolution analysis methods were employed. Results The estimated Ka/Ks ratio of SARS-CoV-2 is 1.008 or 1.094 based on 622 or 3624 SARS-CoV-2 genomes, and the time to the most recent common ancestor (tMRCA) was inferred in late September 2019. Further 9 key specific sites of highly linkage and four major haplotypes H1, H2, H3 and H4 were found. The Ka/Ks, detected population size and development trends of each major haplotype showed H3 and H4 subgroups were going through a purify evolution and almost disappeared after detection, indicating H3 and H4 might have existed for a long time, while H1 and H2 subgroups were going through a near neutral or neutral evolution and globally increased with time. Notably the frequency of H1 was generally high in Europe and correlated to death rate (r>0.37). Conclusions In this study, the evolution and molecular characteristics of more than 16000 genomic sequences provided a new perspective for revealing epidemiology of SARS-CoV-2.", "title": "Comprehensive evolution and molecular characteristics of a large number of SARS-CoV-2 genomes revealed its epidemic trend and possible origins", "pid": "npcu4wq1", "bm25_score": 218.646728515625}, {"text": "The novel coronavirus SARS-CoV-2 (2019-nCoV) is a member of the family coronaviridae and contains a single-stranded RNA genome with positive-polarity. To reveal the evolution mechanism of SARS-CoV-2 genome, we performed comprehensive genomic analysis with newly sequenced SARS-CoV-2 strains and 20 closely related coronavirus strains. Among 98 nucleotide mutations at 93 sites of the genome among different SARS-CoV-2 strains, 58 of them caused amino acid change, indicating a result of neutral evolution. However, the ratio of nucleotide substitutions to amino acid substitutions of spike gene (9.07) between SARS-CoV-2 WIV04 and Bat-SARSr-CoV RaTG13 was extensively higher than those from comparisons between other coronaviruses (range 1.29 - 4.81). The elevated synonymous mutations between SARS-CoV-2 and RaTG13, suggesting they underwent stronger purifying selection. Moreover, their nucleotide substitutions are enriched with T:C transition, which is consistent with the mutation signature caused by deactivity of RNA 3’-to-5’ exoribonuclease (ExoN). The codon usage was similar between SARS-CoV-2 and other strains in beta-coronavirus lineage B, suggesting it had small impact on the mutation pattern. In comparison of SARS-CoV-2 WIV04 with Bat-SARSr-CoV RaTG13, the ratios of non-synonymous to synonymous substitution rates (dN/dS) was the lowest among all performed comparisons, reconfirming the evolution of SARS-CoV-2 under stringent selective pressure. Moreover, some sites of spike protein might be subjected to positive selection. Therefore, our results will help understanding the evolutionary mechanisms contribute to viral pathogenicity and its adaptation with hosts.", "title": "Comparative genomic analysis revealed specific mutation pattern between human coronavirus SARS-CoV-2 and Bat-SARSr-CoV RaTG13", "pid": "3h1o0oz3", "bm25_score": 218.61817932128906}, {"text": "COVID-A9 is an infection disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid expansion worldwide. In this study we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 using 22 virus genome sequences reported by three different laboratories in Morocco till the date 07/06/2020 as well as (40366) virus genomes from all around the world. The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations of which 30 were missense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred one time in our sequences with no record in other sequence worldwide. These mutations should be investigated to figure out their potential effects on all around the world virulence. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses pertaining to clade 20A, 9 to clade 20B and 2 to clade 20C. This finding suggest that the epidemic spread in Morocco did not show a predominant SARS-CoV-2 route. For multiple and unrelated introductions of SARS-CoV-2 into Morocco via different routes have occurred, giving rise to the diversity of virus genomes in the country. Furthermore, very likely, the SARS-CoV-2 virus circulated in cryptic way in Morocco starting from the fifteen January before the discovering of the first case the second of March.", "title": "Genetic Diversity and Genomic Epidemiology of SARS-COV-2 in Morocco", "pid": "zb1pzdd0", "bm25_score": 218.6014404296875}, {"text": "Monitoring the mutation dynamics of SARS-CoV-2 is critical for the development of effective approaches to contain the pathogen. By analyzing 106 SARS-CoV-2 and 39 SARS genome sequences, we provided direct genetic evidence that SARS-CoV-2 has a much lower mutation rate than SARS. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. The discrepant phylogenies for the spike protein and its receptor binding domain proved a previously reported structural rearrangement prior to the emergence of SARS-CoV-2. Despite that we found the spike glycoprotein of SARS-CoV-2 is particularly more conserved, we identified a mutation that leads to weaker receptor binding capability, which concerns a SARS-CoV-2 sample collected on 27th January 2020 from India. This represents the first report of a significant SARS-CoV-2 mutant, and raises the alarm that the ongoing vaccine development may become futile in future epidemic if more mutations were identified. Highlights Based on the currently available genome sequence data, we proved that SARS-COV-2 genome has a much lower mutation rate and genetic diversity than SARS during the 2002-2003 outbreak. The spike (S) protein encoding gene of SARS-COV-2 is found relatively more conserved than other protein-encoding genes, which is a good indication for the ongoing antiviral drug and vaccine development. Minimum Evolution phylogeny analysis revealed the putative original status of SARS-CoV-2 and the early-stage spread history. We confirmed a previously reported rearrangement in the S protein arrangement of SARS-COV-2, and propose that this rearrangement should have occurred between human SARS-CoV and a bat SARS-CoV, at a time point much earlier before SARS-COV-2 transmission to human. We provided first evidence that a mutated SARS-COV-2 with reduced human ACE2 receptor binding affinity have emerged in India based on a sample collected on 27th January 2020.", "title": "Analysis of the mutation dynamics of SARS-CoV-2 reveals the spread history and emergence of RBD mutant with lower ACE2 binding affinity", "pid": "t8q99tlq", "bm25_score": 218.58807373046875}, {"text": "We sequenced four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Malaysia during the second wave of infection and found unique mutations which suggest local evolution. Circulating Malaysian strains represent introductions from different countries, particularly during the first wave of infection. Genome sequencing is important for understanding local epidemiology.", "title": "Complete Genome Sequences of SARS-CoV-2 Strains Detected in Malaysia", "pid": "8r6u3e3i", "bm25_score": 218.57269287109375}, {"text": "The iconic “red crown” of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is made of its spike (S) glycoprotein. The S protein is the Trojan horse of coronaviruses, mediating their entry into the host cells. While SARS-CoV-2 was becoming a global threat, scientists have been accumulating data on the virus at an impressive pace, both in terms of genomic sequences and of three-dimensional structures. On April 21st, the GISAID resource had collected 10,823 SARS-CoV-2 genomic sequences. We extracted from them all the complete S protein sequences and identified point mutations thereof. Six mutations were located on a 14-residue segment (929-943) in the “fusion core” of the heptad repeat 1 (HR1). Our modeling in the pre- and post-fusion S protein conformations revealed, for three of them, the loss of interactions stabilizing the post-fusion assembly. On May 29th, the SARS-CoV-2 genomic sequences in GISAID were 34,805. An analysis of the occurrences of the HR1 mutations in this updated dataset revealed a significant increase for the S929I and S939F mutations and a dramatic increase for the D936Y mutation, which was particularly widespread in Sweden and Wales/England. We notice that this is also the mutation causing the loss of a strong inter-monomer interaction, the D936-R1185 salt bridge, thus clearly weakening the post-fusion assembly.", "title": "D936Y and Other Mutations in the Fusion Core of the SARS-Cov-2 Spike Protein Heptad Repeat 1 Undermine the Post-Fusion Assembly", "pid": "iihgc5nr", "bm25_score": 218.5697021484375}, {"text": "Starting around December 2019, an epidemic of pneumonia, which was named COVID-19 by the World Health Organization, broke out in Wuhan, China, and is spreading throughout the world. A new coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by the Coronavirus Study Group of the International Committee on Taxonomy of Viruses was soon found to be the cause. At present, the sensitivity of clinical nucleic acid detection is limited, and it is still unclear whether it is related to genetic variation. In this study, we retrieved 95 full-length genomic sequences of SARAS-CoV-2 strains from the National Center for Biotechnology Information and GISAID databases, established the reference sequence by conducting multiple sequence alignment and phylogenetic analyses, and analyzed sequence variations along the SARS-CoV-2 genome. The homology among all viral strains was generally high, among them, 99.99% (99.91%-100%) at the nucleotide level and 99.99% (99.79%-100%) at the amino acid level. Although overall variation in open-reading frame (ORF) regions is low, 13 variation sites in 1a, 1b, S, 3a, M, 8, and N regions were identified, among which positions nt28144 in ORF 8 and nt8782 in ORF 1a showed mutation rate of 30.53% (29/95) and 29.47% (28/95), respectively. These findings suggested that there may be selective mutations in SARS-COV-2, and it is necessary to avoid certain regions when designing primers and probes. Establishment of the reference sequence for SARS-CoV-2 could benefit not only biological study of this virus but also diagnosis, clinical monitoring and intervention of SARS-CoV-2 infection in the future.", "title": "The establishment of reference sequence for SARS-CoV-2 and variation analysis", "pid": "g1zxlaer", "bm25_score": 218.56365966796875}, {"text": "Italy is the first western country suffering heavy severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and disease impact after coronavirus disease-2019 pandemia started in China. Even though the presence of mutations on spike glycoprotein and nucleocapsid in Italian isolates has been reported, the potential impact of these mutations on viral transmission has not been evaluated. We have compared SARS-CoV-2 genome sequences from Italian patients with virus sequences from Chinese patients. We focussed upon three nonsynonymous mutations of genes coding for S(one) and N (two) viral proteins present in Italian isolates and absent in Chinese ones, using various bioinformatics tools. Amino acid analysis and changes in three-dimensional protein structure suggests the mutations reduce protein stability and, particularly for S1 mutation, the enhanced torsional ability of the molecule could favor virus binding to cell receptor(s). This theoretical interpretation awaits experimental and clinical confirmation.", "title": "Evidence for mutations in SARS-CoV-2 Italian isolates potentially affecting virus transmission", "pid": "4z6wcmxq", "bm25_score": 218.55633544921875}, {"text": "We have developed an analysis pipeline to facilitate real-time mutation tracking in SARS-CoV-2, focusing initially on the Spike (S) protein because it mediates infection of human cells and is the target of most vaccine strategies and antibody-based therapeutics. To date we have identified thirteen mutations in Spike that are accumulating. Mutations are considered in a broader phylogenetic context, geographically, and over time, to provide an early warning system to reveal mutations that may confer selective advantages in transmission or resistance to interventions. Each one is evaluated for evidence of positive selection, and the implications of the mutation are explored through structural modeling. The mutation Spike D614G is of urgent concern; it began spreading in Europe in early February, and when introduced to new regions it rapidly becomes the dominant form. Also, we present evidence of recombination between locally circulating strains, indicative of multiple strain infections. These finding have important implications for SARS-CoV-2 transmission, pathogenesis and immune interventions.", "title": "Spike mutation pipeline reveals the emergence of a more transmissible form of SARS-CoV-2", "pid": "4hmecfi0", "bm25_score": 218.53363037109375}, {"text": "The newly identified SARS-CoV-2 has now been reported from around 183 countries with more than a million confirmed human cases including more than 68000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins have gotten substantial attention recently. Spike glycoprotein is widely considered as a possible target to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment tools. In this study, 483 unique variations have been identified among the genomes including 25 non-synonymous mutations and one deletion in the spike protein of SARS-CoV-2. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction with receptor molecules. In addition, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on our findings, potential inhibitors can be designed and tested targeting these proposed sites of variation.", "title": "Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: a computational biology approach", "pid": "vf32wxkx", "bm25_score": 218.53012084960938}, {"text": "In the epidemic evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the issues of mutation, origin, typing and the effect of mutation on molecular detection remain to be unrevealed. In order to identify the evolutionary relationship of SARS-CoV-2 and evaluate the detection efficiency of primers that are currently used in different countries, we retrieved genomic sequences of 373 SARS-CoV-2 strains from multiple databases and performed genome-wide variation analysis. According to the nucleotide C28144T variation, the SARS-CoV-2 can be divided into group A (117 strains) and group B (256 strains). The spike protein gene (S gene) coding region 1841 (total 23403) A1841G, formed a B1 subgroup (40 strains) in group B, of which 30 strains were from European and American countries in March (especially Washington, USA). These mutations are likely to be influenced by the environment or the immunization selection pressure of different populations. Although the mutation is not in the receptor binding region (RBD) and alkaline cleavage region, it may also affect the ability of transmission and pathogenicity; however, the significance is not yet clear. As the ratio of A / B strains in the epidemic months showed an increasing trend (0.35: 1 in January, 0.62: 1 in February and 0.76: 1 in March), it seems that the transmissibility of group A strains becomes stronger with time. Based on the variation of 11 nucleotide sites during the epidemic process, it is speculated that the Washington strain is more like an ancestor type, and the Wuhan strain is the offspring of the group A virus strain. By comparing the detection capabilities of primers in different countries, the SARS-CoV-2 nucleotide variation may only affect molecular detection of very few strains. The differences in the transmissibility, pathogenicity and clinical manifestations of different types of strains require further investigations.", "title": "Genome-wide variations of SARS-CoV-2 infer evolution relationship and transmission route", "pid": "blqzi69t", "bm25_score": 218.49734497070312}, {"text": "COVID-19 is a newly communicable disease with a catastrophe outbreak that affects all over the world. We retrieved about 8,781 nucleotide fragments and complete genomes of SARS-CoV-2 reported from sixty-four countries. The CoV-2 reference genome was obtained from the National Genomics Data Center (NGDC), GISAID, and NCBI Genbank. All the sequences were aligned against reference genomes using Clustal Omega and variants were called using in-house built Python script. We intend to establish a user-friendly online resource to visualize the variants in the viral genome along with the Primer Infopedia. After analyzing and filtering the data globally, it was made available to the public. The detail of data available to the public includes mutations from 5688 SARS-CoV-2 sequences curated from 91 regions. This database incorporated 39920 mutations over 3990 unique positions. According to the translational impact, these mutations include 11829 synonymous mutations including 681 synonymous frameshifts and 21701 nonsynonymous mutations including 10 nonsynonymous frameshifts. Development of SARS-CoV-2 mutation genome browsers is a fundamental step obliging towards the virus surveillance, viral detection, and development of vaccine and therapeutic drugs. The SARS-COV-2 mutation browser is available at http://covid-19.dnageography.com.", "title": "COVID-19 Variants Database: A repository for Human SARS-CoV-2 Polymorphism Data", "pid": "r0gr0bhl", "bm25_score": 218.4795684814453}, {"text": "The COVID-19 pandemic is caused by the coronavirus SARS-CoV-2, which jumped into the human population in late 2019 from a currently uncharacterised reservoir. Due to this extremely recent association with humans, SARS-CoV-2 may not yet be fully adapted to its human host. This has led to speculations that some lineages of SARS-CoV-2 may be evolving towards higher transmissibility. The most plausible candidate mutations under putative natural selection are those which have emerged repeatedly and independently (homoplasies). Here, we formally test whether any of the recurrent mutations that have been observed in SARS-CoV-2 to date are significantly associated with increased viral transmission. To do so, we developed a phylogenetic index to quantify the relative number of descendants in sister clades with and without a specific allele. We apply this index to a carefully curated set of recurrent mutations identified within a dataset of over 23,000 SARS-CoV-2 genomes isolated from patients worldwide. We do not identify a single recurrent mutation in this set convincingly associated with increased viral transmission. Instead, recurrent SARS-CoV-2 mutations currently in circulation appear to be evolutionary neutral. Recurrent mutations also seem primarily induced by the human immune system via host RNA editing, rather than being signatures of adaption to the novel human host. We find no evidence at this stage for the emergence of more transmissible lineages of SARS-CoV-2 due to recurrent mutations.", "title": "No evidence for increased transmissibility from recurrent mutations in SARS-CoV-2", "pid": "a51vkiei", "bm25_score": 218.4390869140625}, {"text": "SARS-CoV-2 caused a global pandemic in early 2020 and has resulted in more than 8,000,000 infections as well as 430,000 deaths in the world so far. Four structural proteins, envelope (E), membrane (M), nucleocapsid (N) and spike (S) glycoprotein, play a key role in controlling the entry into human cells and virion assembly of SARS-CoV-2. However, how these genes evolve during its human to human transmission is largely unknown. In this study, we screened and analyzed roughly 3090 SARS-CoV-2 isolates from GenBank database. The distribution of the four gene alleles is determined:16 for E, 40 for M, 131 for N and 173 for S genes. Phylogenetic analysis shows that global SARS-CoV-2 isolates can be clustered into three to four major clades based on the protein sequences of these genes. Intragenic recombination event isn’t detected among different alleles. However, purifying selection has conducted on the evolution of these genes. By analyzing full genomic sequences of these alleles using codon-substitution models (M8, M3 and M2a) and likelihood ratio tests (LRTs) of codeML package, it reveals that codon 614 of S glycoprotein has subjected to strong positive selection pressure and a persistent D614G mutation is identified. The definitive positive selection of D614G mutation is further confirmed by internal fixed effects likelihood (IFEL) and Evolutionary Fingerprinting methods implemented in Hyphy package. In addition, another potential positive selection site at codon 5 in the signal sequence of the S protein is also identified. The allele containing D614G mutation has undergone significant expansion during SARS-CoV-2 global pandemic, implying a better adaptability of isolates with the mutation. However, L5F allele expansion is relatively restricted. The D614G mutation is located at the subdomain 2 (SD2) of C-terminal portion (CTP) of the S1 subunit. Protein structural modeling shows that the D614G mutation may cause the disruption of salt bridge among S protein monomers increase their flexibility, and in turn promote receptor binding domain (RBD) opening, virus attachment and entry into host cells. Located at the signal sequence of S protein as it is, L5F mutation may facilitate the protein folding, assembly, and secretion of the virus. This is the first evidence of positive Darwinian selection in the spike gene of SARS-CoV-2, which contributes to a better understanding of the adaptive mechanism of this virus and help to provide insights for developing novel therapeutic approaches as well as effective vaccines by targeting on mutation sites.", "title": "Molecular Evolution of SARS-CoV-2 Structural Genes: Evidence of Positive Selection in Spike Glycoprotein", "pid": "jj0n81s9", "bm25_score": 218.42701721191406}, {"text": "Human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is most closely related, by average genetic distance, to two coronaviruses isolated from bats, RaTG13 and RmYN02. However, there is a segment of high amino acid similarity between human SARS-CoV-2 and a pangolin isolated strain, GD410721, in the receptor binding domain (RBD) of the spike protein, a pattern that can be caused by either recombination or by convergent amino acid evolution driven by natural selection. We perform a detailed analysis of the synonymous divergence, which is less likely to be affected by selection than amino acid divergence, between human SARS-CoV-2 and related strains. We show that the synonymous divergence between the bat derived viruses and SARS-CoV-2 is larger than between GD410721 and SARS-CoV-2 in the RBD, providing strong additional support for the recombination hypothesis. However, the synonymous divergence between pangolin strain and SARS-CoV-2 is also relatively high, which is not consistent with a recent recombination between them, instead it suggests a recombination into RaTG13. We also find a 14-fold increase in the dN/dS ratio from the lineage leading to SARS-CoV-2 to the strains of the current pandemic, suggesting that the vast majority of non-synonymous mutations currently segregating within the human strains have a negative impact on viral fitness. Finally, we estimate that the time to the most recent common ancestor of SARS-CoV-2 and RaTG13 or RmYN02 based on synonymous divergence, is 51.71 years (95% C.I., 28.11-75.31) and 37.02 years (95% C.I., 18.19-55.85), respectively.", "title": "Synonymous mutations and the molecular evolution of SARS-Cov-2 origins", "pid": "z11exbyu", "bm25_score": 218.41696166992188}, {"text": "BACKGROUND: SARS-CoV-2 is a RNA coronavirus responsible for the pandemic of the Severe Acute Respiratory Syndrome (COVID-19). RNA viruses are characterized by a high mutation rate, up to a million times higher than that of their hosts. Virus mutagenic capability depends upon several factors, including the fidelity of viral enzymes that replicate nucleic acids, as SARS-CoV-2 RNA dependent RNA polymerase (RdRp). Mutation rate drives viral evolution and genome variability, thereby enabling viruses to escape host immunity and to develop drug resistance. METHODS: We analyzed 220 genomic sequences from the GISAID database derived from patients infected by SARS-CoV-2 worldwide from December 2019 to mid-March 2020. SARS-CoV-2 reference genome was obtained from the GenBank database. Genomes alignment was performed using Clustal Omega. Mann–Whitney and Fisher-Exact tests were used to assess statistical significance. RESULTS: We characterized 8 novel recurrent mutations of SARS-CoV-2, located at positions 1397, 2891, 14408, 17746, 17857, 18060, 23403 and 28881. Mutations in 2891, 3036, 14408, 23403 and 28881 positions are predominantly observed in Europe, whereas those located at positions 17746, 17857 and 18060 are exclusively present in North America. We noticed for the first time a silent mutation in RdRp gene in England (UK) on February 9th, 2020 while a different mutation in RdRp changing its amino acid composition emerged on February 20th, 2020 in Italy (Lombardy). Viruses with RdRp mutation have a median of 3 point mutations [range: 2–5], otherwise they have a median of 1 mutation [range: 0–3] (p value < 0.001). CONCLUSIONS: These findings suggest that the virus is evolving and European, North American and Asian strains might coexist, each of them characterized by a different mutation pattern. The contribution of the mutated RdRp to this phenomenon needs to be investigated. To date, several drugs targeting RdRp enzymes are being employed for SARS-CoV-2 infection treatment. Some of them have a predicted binding moiety in a SARS-CoV-2 RdRp hydrophobic cleft, which is adjacent to the 14408 mutation we identified. Consequently, it is important to study and characterize SARS-CoV-2 RdRp mutation in order to assess possible drug-resistance viral phenotypes. It is also important to recognize whether the presence of some mutations might correlate with different SARS-CoV-2 mortality rates.", "title": "Emerging SARS-CoV-2 mutation hot spots include a novel RNA-dependent-RNA polymerase variant", "pid": "ow2aijmj", "bm25_score": 218.41433715820312}, {"text": "The novel human coronavirus (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic worldwide. The increasing sequencing data have shown abundant single nucleotide variations in SARS-CoV-2 genome. However, it is difficult to quickly analyze genomic variation and screen key mutations of SARS-CoV-2. In this study, we developed a visual program, named BioAider, for quick and convenient sequence annotation and mutation analysis on multiple genome-sequencing data. Using BioAider, we conducted a comprehensive genome variation analysis on 3,240 sequences of SARS-CoV-2 genome. Herein, we detected 14 substitution hotspots within SARS-CoV-2 genome, including 10 non-synonymous and 4 synonymous ones. Among these hotspots, NSP13-Y541C was predicted to be a crucial substitution which might affect the unwinding activity of NSP13, a key protein for viral replication. Besides, we also found 3 groups of potentially linked substitution hotspots which were worth further study. In particular, we discovered a SR-rich region (aa 184-204) on the N protein of SARS-CoV-2 distinct from SARS-CoV, indicating more complex replication mechanism and unique N-M interaction of SARS-CoV-2. Interestingly, the quantity of SRXX repeat fragments in the SR-rich region well reflected the evolutionary relationship among SARS-CoV-2 and SARS-CoV-2 related animal coronaviruses, providing further evidence of its animal origin. Overall, we developed an efficient tool for rapid identification of mutations, identified substitution hotspots in SARS-CoV-2 genomes, and detected a distinctive polymorphism SR-rich region in N protein. This tool and the detected hotspots could facilitate the viral genomic study and may contribute for screening antiviral target sites.", "title": "Characterization of the substitution hotspots in SARS-CoV-2 genome using BioAider and detection of a SR-rich region in N protein providing further evidence of its animal origin", "pid": "hib30ct6", "bm25_score": 218.40841674804688}, {"text": "The COVID-19 pandemic is the most significant public health issue in recent history. Its causal agent, SARS-CoV-2, has evolved rapidly since its first emergence in December 2019. Mutations in the viral genome have critical impacts on the adaptation of viral strains to the local environment, and may alter the characteristics of viral transmission, disease manifestation, and the efficacy of treatment and vaccination. Using the complete sequences of 1,932 SARS-CoV-2 genomes, we examined the genomic, geographic and temporal distributions of aged, new, and frequent mutations of SARS-CoV-2, and identified six phylogenetic clusters of the strains, which also exhibit a geographic preference in different continents. Mutations in the form of single nucleotide variations (SNVs) provide a direct interpretation for the six phylogenetic clusters. Linkage disequilibrium, haplotype structure, evolutionary process, global distribution of mutations unveiled a sketch of the mutational history. Additionally, we found a positive correlation between the average mutation count and case fatality, and this correlation had strengthened with time, suggesting an important role of SNVs on disease outcomes. This study suggests that SNVs may become an important consideration in virus detection, clinical treatment, drug design, and vaccine development to avoid target shifting, and that continued isolation and sequencing is a crucial component in the fight against this pandemic. Significance Statement Mutation is the driving force of evolution for viruses like SARS-CoV-2, the causal agent of COVID-19. In this study, we discovered that the genome of SARS-CoV-2 is changing rapidly from the originally isolated form. These mutations have been spreading around the world and caused more than 2.5 million of infected cases and 170 thousands of deaths. We found that fourteen frequent mutations identified in this study can characterize the six main clusters of SARS-CoV-2 strains. In addition, we found the mutation burden is positively correlated with the fatality of COVID-19 patients. Understanding mutations in the SARS-CoV-2 genome will provide useful insight for the design of treatment and vaccination.", "title": "Genomic, geographic and temporal distributions of SARS-CoV-2 mutations", "pid": "1vhxcbx7", "bm25_score": 218.3904266357422}, {"text": "The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared on March 11, 2020 by the World Health Organization. As of the 31st of May, 2020, there have been more than 6 million COVID-19 cases diagnosed worldwide and over 370,000 deaths, according to Johns Hopkins. Thousands of SARS-CoV-2 strains have been sequenced to date, providing a valuable opportunity to investigate the evolution of the virus on a global scale. We performed a phylogenetic analysis of over 1,225 SARS-CoV-2 genomes spanning from late December 2019 to mid-March 2020. We identified a missense mutation, D614G, in the spike protein of SARS-CoV-2, which has emerged as a predominant clade in Europe (954 of 1,449 (66%) sequences) and is spreading worldwide (1,237 of 2,795 (44%) sequences). Molecular dating analysis estimated the emergence of this clade around mid-to-late January (10 - 25 January) 2020. We also applied structural bioinformatics to assess D614G potential impact on the virulence and epidemiology of SARS-CoV-2. In silico analyses on the spike protein structure suggests that the mutation is most likely neutral to protein function as it relates to its interaction with the human ACE2 receptor. The lack of clinical metadata available prevented our investigation of association between viral clade and disease severity phenotype. Future work that can leverage clinical outcome data with both viral and human genomic diversity is needed to monitor the pandemic.", "title": "Evolutionary and structural analyses of SARS-CoV-2 D614G spike protein mutation now documented worldwide", "pid": "zu46bdpu", "bm25_score": 218.37686157226562}, {"text": "The mutation pattern of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is constantly changing with the places of transmission, but the reason remains to be revealed. Here, we presented the study that comprehensively analyzed the potential selective pressure of immune system restriction, which can drive mutations in circulating SARS-CoV-2 isolates. The results showed that the most common mutation sites of SARS-CoV-2 proteins were located on the non-structural protein ORF1ab and the structural protein Spike. Further analysis revealed mutations in cross-reactive epitopes between SARS-CoV-2 and seasonal coronavirus may help SARS-CoV-2 to escape cellular immunity under the long-term and large-scale community transmission. Meanwhile, the mutations on Spike protein may enhance the ability of SARS-CoV-2 to enter the host cells and escape the recognition of B-cell immunity. This study will increase the understanding of the evolutionary direction and warn about the potential immune escape ability of SARS-CoV-2, which may provide important guidance for the potential vaccine design.", "title": "Antigenic evolution on global scale reveals potential natural selection of SARS-CoV-2 by pre-existing cross-reactive T cell immunity", "pid": "yop76n7z", "bm25_score": 218.37205505371094}, {"text": "A novel coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing COVID-19 pandemic. In this study, we performed a comprehensive epidemiological and genomic analysis of SARS-CoV-2 genomes from ten patients in Shaoxing, a mid-sized city outside of the epicenter Hubei province, China, during the early stage of the outbreak (late January to early February, 2020). We obtained viral genomes with > 99% coverage and a mean depth of 296X demonstrating that viral genomic analysis is feasible via metagenomics sequencing directly on nasopharyngeal samples with SARS-CoV-2 Real-time PCR Ct values less than 28. We found that a cluster of 4 patients with travel history to Hubei shared the exact same virus with patients from Wuhan, Taiwan, Belgium and Australia, highlighting how quickly this virus spread to the globe. The virus from another cluster of husband and wife without travel history but with a sick contact of a confirmed case from another city outside of Hubei accumulated significantly more mutations (9 SNPs vs average 4 SNPs), suggesting a complex and dynamic nature of this outbreak. We also found 70% patients in this study had the S genotype, consistent with an early study showing a higher prevalence of S genotype out of Hubei than that inside Hubei. We calculated an average mutation rate of 1.37x10-3 nucleotide substitution per site per year, which is similar to that of other coronaviruses. Our findings add to the growing knowledge of the epidemiological and genomic characteristics of SARS-CoV-2 that are important for guiding outbreak containment and vaccine development. The moderate mutation rate of this virus also lends hope that development of an effective, long-lasting vaccine may be possible.", "title": "Epidemiological and Genomic Analysis of SARS-CoV-2 in Ten Patients from a Mid-sized City outside of Hubei, China", "pid": "m9k6upe4", "bm25_score": 218.35302734375}, {"text": "The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected, 12 variations were located at the N-terminal domain and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin converting enzyme-2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "title": "Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach", "pid": "w5ytp1q7", "bm25_score": 218.34820556640625}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic virus that has caused the global COVID-19 pandemic. Tracing the evolution and transmission of the virus is crucial to respond to and control the pandemic through appropriate intervention strategies. This paper reports and analyses genomic mutations in the coding regions of SARS-CoV-2 and their probable protein secondary structure and solvent accessibility changes, which are predicted using deep learning models. Prediction results suggest that mutation D614G in the virus spike protein, which has attracted much attention from researchers, is unlikely to make changes in protein secondary structure and relative solvent accessibility. Based on 6,324 viral genome sequences, we create a spreadsheet dataset of point mutations that can facilitate the investigation of SARS-CoV-2 in many perspectives, especially in tracing the evolution and worldwide spread of the virus. Our analysis results also show that coding genes E, M, ORF6, ORF7a, ORF7b and ORF10 are most stable, potentially suitable to be targeted for vaccine and drug development.", "title": "Genomic Mutations and Changes in Protein Secondary Structure and Solvent Accessibility of SARS-CoV-2 (COVID-19 Virus)", "pid": "o9oxchq6", "bm25_score": 218.34359741210938}, {"text": "In the NCBI database, as on June 6, 2020, total number of available complete genome sequences of SARS-CoV2 across the world is 3617. The envelope protein of SARS-CoV2 possesses several non-synonymous mutations over the transmembrane domain and (C)-terminus in 15 (0.414%) genomes among 3617 available SARS-CoV2 genomes. More precisely, it is to be mentioned that 10(0.386%) out of 2588 genomes from the USA, 3(0.806%) from Asia, 1 (0.348%) from Europe and 1 (0.274%) from Oceania contain the missense mutations over the envelope proteins of SARS-CoV2 genomes. The C-terminus motif DLLV has been changed to DFLV and YLLV in the proteins QJR88103 (Australia: Victoria) and QKI36831 (China: Guangzhou) respectively, which might affect the binding of this motif with the host protein PALS1.", "title": "SARS-CoV2 envelope protein: Non-synonymous mutations and its consequences", "pid": "phl6ibbv", "bm25_score": 218.3404541015625}, {"text": "The newly identified SARS-CoV-2 has now been reported from around 185 countries with more than a million confirmed human cases including more than 120,000 deaths. The genomes of SARS-COV-2 strains isolated from different parts of the world are now available and the unique features of constituent genes and proteins need to be explored to understand the biology of the virus. Spike glycoprotein is one of the major targets to be explored because of its role during the entry of coronaviruses into host cells. We analyzed 320 whole-genome sequences and 320 spike protein sequences of SARS-CoV-2 using multiple sequence alignment. In this study, 483 unique variations have been identified among the genomes of SARS-CoV-2 including 25 nonsynonymous mutations and one deletion in the spike (S) protein. Among the 26 variations detected in S, 12 variations were located at the N-terminal domain (NTD) and 6 variations at the receptor-binding domain (RBD) which might alter the interaction of S protein with the host receptor angiotensin-converting enzyme 2 (ACE2). Besides, 22 amino acid insertions were identified in the spike protein of SARS-CoV-2 in comparison with that of SARS-CoV. Phylogenetic analyses of spike protein revealed that Bat coronavirus have a close evolutionary relationship with circulating SARS-CoV-2. The genetic variation analysis data presented in this study can help a better understanding of SARS-CoV-2 pathogenesis. Based on results reported herein, potential inhibitors against S protein can be designed by considering these variations and their impact on protein structure.", "title": "Exploring the genomic and proteomic variations of SARS-CoV-2 spike glycoprotein: A computational biology approach", "pid": "c5fygzvz", "bm25_score": 218.3345947265625}, {"text": "The effect of the rapid accumulation of non-synonymous mutations on the pathogenesis of SARS-CoV-2 is not yet known. To predict the impact of non-synonymous mutations and polyproline regions identified in ORF3a on the formation of B-cell epitopes and their role in evading the immune response, nucleotide and protein sequences of 537 available SARS-CoV-2 genomes were analyzed for the presence of non-synonymous mutations and polyproline regions. Mutations were correlated with changes in epitope formation. A total of 19 different non-synonymous amino acids substitutions were detected in ORF3a among 537 SARS-CoV-2 strains. G251V was the most common and identified in 9.9% (n=53) of the strains and was predicted to lead to the loss of a B-cell like epitope in ORF3a. Polyproline regions were detected in two strains (EPI_ISL_410486, France and EPI_ISL_407079, Finland) and affected epitopes formation. The accumulation of non-synonymous mutations and detected polyproline regions in ORF3a of SARS-CoV-2 could be driving the evasion of the host immune response thus favoring viral spread. Rapid mutations accumulating in ORF3a should be closely monitored throughout the COVID-19 pandemic. Importance At the surge of the COVID-19 pandemic and after three months of the identification of SARS-CoV-2 as the disease-causing pathogen, nucleic acid changes due to host-pathogen interactions are insightful into the evolution of this virus. In this paper, we have identified a set of non-synonymous mutations in ORF3a and predicted their impact on B-cell like epitope formation. The accumulation of non-synonymous mutations in ORF3a could be driving protein changes that mediate immune evasion and favoring viral spread.", "title": "SARS-CoV-2 and ORF3a: Non-Synonymous Mutations and Polyproline Regions", "pid": "tylwbnpl", "bm25_score": 218.3085479736328}, {"text": "The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has caused an unprecedented pandemic. Since the first sequenced whole-genome of SARS-CoV-2 on January 2020, the identification of its genetic variants has become crucial in tracking and evaluating their spread across the globe. In this study, we compared 15,259 SARS-CoV-2 genomes isolated from 60 countries since the outbreak of this novel coronavirus with the first sequenced genome in Wuhan to quantify the evolutionary divergence of SARS-CoV-2. Thus, we compared the codon usage patterns, every two weeks, of 13 of SARS-CoV-2 genes encoding for the membrane protein (M), envelope (E), spike surface glycoprotein (S), nucleoprotein (N), non-structural 3C-like proteinase (3CLpro), ssRNA-binding protein (RBP), 2’-O-ribose methyltransferase (OMT), endoRNase (RNase), helicase, RNA-dependent RNA polymerase (RdRp), Nsp7, Nsp8, and exonuclease ExoN. As a general rule, we find that SARS-CoV-2 genome tends to diverge over time by accumulating mutations on its genome and, specifically, on the coding sequences for proteins N and S. Interestingly, different patterns of codon usage were observed among these genes. Genes S, Nsp7, NSp8, tend to use a norrower set of synonymous codons that are better optimized to the human host. Conversely, genes E and M consistently use a broader set of synonymous codons, which does not vary with respect to the reference genome. We identified key SARS-CoV-2 genes (S, N, ExoN, RNase, RdRp, Nsp7 and Nsp8) suggested to be causally implicated in the virus adaptation to the human host.", "title": "Temporal evolution and adaptation of SARS-COV 2 codon usage", "pid": "xh41koro", "bm25_score": 218.3072509765625}, {"text": "Abstract The SARS-CoV-2 virus is being intensively studied, particularly, its evolution in the increasingly available sequences between countries/continents with classical phylogenetic tree representation. More recently, certain protein mutations are correlated with specific functional impacts. Our clinical data from patients suggest different clinical symptoms between European countries. Among others, SARS-CoV-2 mutations could explain these disparities. Our analyses point out an association of diverse mutations, including co-evolving ones, in a few SARS-CoV-2 proteins, with specific countries. We therefore suggest combining clinical information from patients and the determination of the associated SARS-CoV-2 genome to better understand the specific symptoms.", "title": "SARS-CoV-2: virus mutations in specific European populations", "pid": "y5th0mrf", "bm25_score": 218.24960327148438}, {"text": "The set of mutations observed at the outset of the SARS-CoV-2 pandemic may illuminate how the virus will adapt to humans as it continues to spread. Viruses are expected to quickly acquire beneficial mutations upon jumping to a new host species. Advantageous nucleotide substitutions can be identified by their parallel occurrence in multiple independent lineages and are likely to result in changes to protein sequences. Here we show that SARS-CoV-2 is acquiring mutations more slowly than expected for neutral evolution, suggesting purifying selection is the dominant mode of evolution during the initial phase of the pandemic. However, several parallel mutations arose in multiple independent lineages and may provide a fitness advantage over the ancestral genome. We propose plausible reasons for several of the most frequent mutations. The absence of mutations in other genome regions suggests essential components of SARS-CoV-2 that could be the target of drug development. Overall this study provides genomic insights into how SARS-CoV-2 has adapted and will continue to adapt to humans. SUMMARY In this study we sought signals of evolution to identify how the SARS-CoV-2 genome has adapted at the outset of the COVID-19 pandemic. We find that the genome is largely undergoing purifying selection that maintains its ancestral sequence. However, we identified multiple positions on the genome that appear to confer an adaptive advantage based on their repeated evolution in independent lineages. This information indicates how SARS-CoV-2 will evolve as it diversifies in an increasing number of hosts.", "title": "SARS-CoV-2 genome evolution exposes early human adaptations", "pid": "ttbur07i", "bm25_score": 218.23983764648438}, {"text": "OBJECTIVE To determine the sequence of S2 gene of SARS-associated coronavirus (SARS-CoV) GD322 and analyze the phyletic evolution of S2 gene. METHOD S2 gene fragment was amplified from SARS-CoV GD322 genome with RT-PCR and ligated to pGEM-T vector for sequence analysis after transformation of the plasmid into E. coli DH5a. The variability of S2 genes and S2 proteins from 12 strains isolated in the early, intermediate and advanced stages of the SARS outbreak were analyzed and the phylogenetic tree was constructed with Lasergene, Clustal X, DNAman and Treeview. T cell antigen epitopes of S2 protein were predicted on the basis of Internet database. RESULT With the epidemic spread of SARS-CoV, the S2 genes of the virus tended to become stable. Homology of S2 genes of SARS-CoV isolated in advanced stage of the outbreak reached 99.9%. Prediction of T cell antigen epitope showed that mutation at the 57th amino acid effected T cell antigen epitope. CONCLUSION S2 gene of GD322 SARS-CoV is relatively stable during the epidemic spread of the virus, and mutation at the 57th amino acids of S2 protein may affect the T cell antigen epitope.", "title": "[Variability analysis of S2 gene of SARS-CoV].", "pid": "8ozjpov2", "bm25_score": 218.23355102539062}, {"text": "The Coronavirus disease 19 (COVID-19) pandemic has been ongoing since its onset in late November 2019 in Wuhan, China. To date, the SARS-CoV-2 virus has infected more than 8 million people worldwide and killed over 5% of them. Efforts are being made all over the world to control the spread of the disease and most importantly to develop a vaccine. Understanding the genetic evolution of the virus, its geographic characteristics and stability is particularly important for developing a universal vaccine covering all circulating strains of SARS-CoV-2 and for predicting its efficacy. In this perspective, we analyzed the sequences of 30,983 complete genomes from 80 countries located in six geographical zones (Africa, Asia, Europe, North & South America, and Oceania) isolated from December 24, 2019 to May 13, 2020, and compared them to the reference genome. Our in-depth analysis revealed the presence of 3,206 variant sites compared to the reference Wuhan-Hu-1 genome, with a distribution that is largely uniform over all continents. Remarkably, a low frequency of recurrent mutations was observed; only 182 mutations (5.67%) had a prevalence greater than 1%. Nevertheless, fourteen hotspot mutations (> 10%) were identified at different locations, seven at the ORF1ab gene (in regions coding for nsp2, nsp3, nsp6, nsp12, nsp13, nsp14 and nsp15), three in the nucleocapsid protein, one in the spike protein, one in orf3a, and one in orf8. Moreover, 35 non-synonymous mutations were identified in the receptor-binding domain (RBD) of the spike protein with a low prevalence (<1%) across all genomes, of which only four could potentially enhance the binding of the SARS-CoV-2 spike protein to the human receptor ACE2. These results along with the phylogenetic analysis demonstrate that the virus does not have a significant divergence at the protein level compared to the reference both among and within different geographical areas. Unlike the influenza virus or HIV viruses, the slow rate of mutation of SARS-CoV-2 makes the potential of developing an effective global vaccine very likely.", "title": "Genomic diversity and hotspot mutations in 30,983 SARS-CoV-2 genomes: moving toward a universal vaccine for the “confined virus”?", "pid": "xbn5ov9s", "bm25_score": 218.22454833984375}, {"text": "The genome comparison of inter-species and intra-species can give us much information about the origin and evolution of viruses. There are 137 mutation sites in the 17 genomes of SARS-CoV,and the mutation rate is about 8.04 x 10(-3) substitution/site/year. The distribution of the segregating sites is not steady,the most variable region appears in S1 protein,and the nucleotide sequence of RNA-dependent RNA polymerase has very few mutation sites. The substitution bias of nucleotide acids and amino acids indicates the non-random drift products. The comparison of genome structures of SARS-CoV and other coronaviruses shows that SARS-CoV and IBV share the same genome structure. Phylogenetic analyses of conserved genes of coronaviruses indicate that SARS-CoV is a new branch of coronaviruses and appears more close to the group II coronaviruses. Interestingly,SARS-CoV shares some different features with different groups of coronaviruses. Additional analyses show that the first ORFs between S and E genes of some coronaviruses are transmembrane proteins and share the common motif,indicating the possible common ancestor. From the host distribution of different groups of coronaviruses and the phylogeny of s2m,we can deduce that avian is the probable natural host of SARS-CoV.", "title": "[The genome comparison of SARS-CoV and other coronaviruses].", "pid": "6loaq8pq", "bm25_score": 218.223388671875}, {"text": "Abstract In the NCBI database, as on June 6, 2020, total number of available complete genome sequences of SARS-CoV2 across the world is 3617. The envelope protein of SARS-CoV2 possesses several non-synonymous mutations over the transmembrane domain and (C)-terminus in 15 (0.414%) genomes among 3617 available SARS-CoV2 genomes. More precisely, it is to be mentioned that 10(0.386%) out of 2588 genomes from the USA, 3(0.806%) from Asia, 1 (0.348%) from Europe and 1 (0.274%) from Oceania contain the missense mutations over the envelope proteins of SARS-CoV2 genomes. The C-terminus motif DLLV has been changed to DFLV and YLLV in the proteins QJR88103 (Australia: Victoria) and QKI36831 (China: Guangzhou) respectively, which might affect the binding of this motif with the host protein PALS1.", "title": "SARS-CoV2 envelope protein: Non-synonymous mutations and its consequences", "pid": "gnrnsxej", "bm25_score": 218.223388671875}, {"text": "Severe acute respiratory syndrome (SARS) caused by SARS-associated coronavirus (SARS-CoV) is a fatal disease. Prevention of future outbreaks is essential and requires understanding pathogenesis and evolution of the virus. We have isolated a SARS-CoV in China and analyzed 47 SARS-CoV genomes with the aims to reveal the evolution trends of the virus and provide insights into understanding pathogenesis and SARS epidemic. Specimen from a SARS patient was inoculated into cell culture. The presence of SARS-CoV was determined by RT-PCR and confirmed by electron microscopy. Virus was isolated followed by the determination of its genome sequences, which were then analyzed by comparing with other 46 SARS-CoV genomes. Genetic mutations with potential implications to pathogenesis and the epidemic were characterized. This viral genome consists of 29,728 nucleotides with overall organization in agreement with that of published isolates. A total of 348 positions were mutated on 47 viral genomes. Among them 22 had mutations in more than three genomes. Hot spots of nucleotide variations and unique trends of mutations were identified on the viral genomes. Mutation rates were different from gene to gene and were correlated well with periodical or geographic characteristics of the epidemic.", "title": "Isolation of Virus from a SARS Patient and Genome-wide Analysis of Genetic Mutations Related to Pathogenesis and Epidemiology from 47 SARS-CoV Isolates", "pid": "fwdpzv85", "bm25_score": 218.19119262695312}, {"text": "The wave of COVID-19 is a big threat to the human population. Presently, the world is going through different phases of lock down in order to stop this wave of pandemic; India being no exception. We have also started the lock down on 23rd March 2020. In this current situation, apart from social distancing only a vaccine can be the proper solution to serve the population of human being. Thus it is important for all the nations to perform the genome-wide analysis in order to identify the genetic variation in Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) so that proper vaccine can be designed. This fast motivated us to analyze publicly available 566 Indian complete or near complete SARS-CoV-2 genomes to find the mutation points as substitution, deletion and insertion. In this regard, we have performed the multiple sequence alignment in presence of reference sequence from NCBI. After the alignment, a consensus sequence is build to analyze each genome in order to identify the mutation points. As a consequence, we have found 933 substitutions, 2449 deletions and 2 insertions, in total 3384 unique mutation points, in 566 genomes across 29.9 K bp. Further, it has been classified into three groups as 100 clusters of mutations (mostly deletions), 1609 point mutations as substitution, deletion and insertion and 64 SNPs. These outcomes are visualized using BioCircos and bar plots as well as plotting entropy value of each genomic location. Moreover, phylogenetic analysis has also been performed to see the evolution of SARS-CoV-2 virus in India. It also shows the wide variation in tree which indeed vivid in genomic analysis. Finally, these SNPs can be the useful target for virus classification, designing and defining the effective dose of vaccine for the heterogeneous population.", "title": "Genome-wide analysis of Indian SARS-CoV-2 genomes for the identification of genetic mutation and SNP", "pid": "lt0uo7q3", "bm25_score": 218.1880645751953}, {"text": "Background The origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still a debatable topic. The association of the virus spread from the market is supported by the close relation of genome sequences of environmental surface samples with virus samples from earliest patients by phylogenetic analysis. Objectives To have an insight into the SARS-CoV-2 genome sequences reported from India for better understanding on their epidemiology and virulence. Methods Genome sequences of Indian isolates of SARS-CoV-2 were analyzed to understand their phylogeny and divergence with respect to other isolates reported from other countries. Amino acid sequences of individual open reading frames (ORFs) from SARS-CoV-2 Indian isolates were aligned with sequences of isolates reported from other countries to identify the mutations occurred in Indian isolates. Results Our analysis suggests that Indian SARS-CoV-2 isolates are closely related to isolates reported from other parts of the world. Most ORFs are highly conserved; mutations were also detected in some ORFs. We found that most isolates reported from India have key mutations at 614th position of the S protein and 84th position of the ORF 8, which has been reported to be associated with high virulence and high transmission rate. Conclusion An attempt was made to understand the SARS-CoV-2 virus reported from India. SARS-CoV-2 reported from India was closely similar to other SARS-CoV-2 reported from other parts of the world, which suggests that vaccines and other therapeutic methods generated from other countries might work well in India. In addition, available sequence data suggest that majority of Indian isolates are capable of high transmission and virulence.", "title": "Genome analysis of SARS-CoV-2 isolates occurring in India: Present scenario.", "pid": "bcx51aci", "bm25_score": 218.18800354003906}, {"text": "COVID-19, caused by the novel SARS-CoV-2 virus, started in China in late 2019, and soon became a global pandemic. With the help of thousands of viral genome sequences that have been accumulating, it has become possible to track the evolution of viral genome over time as it spread across the world. An important question that still needs to be answered is whether any of the common mutations affect the viral properties, and therefore the disease characteristics. Therefore, we sought to understand the effects of mutations in RNA-dependent RNA polymerase (RdRp), particularly the common 14408C>T mutation, on mutation rate and viral spread. By focusing on mutations in the slowly evolving M or E genes, we aimed to minimize the effects of selective pressure. Our results indicate that 14408C>T mutation increases the mutation rate, while the third-most common RdRp mutation, 15324C>T, has the opposite effect. It is possible that 14408C>T mutation may have contributed to the dominance of its co-mutations in Europe and elsewhere.", "title": "RdRp mutations are associated with SARS-CoV-2 genome evolution", "pid": "i09lh5i6", "bm25_score": 218.18740844726562}, {"text": "Impact of mutations on the evolution of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) are needed for ongoing global efforts to track and trace the current pandemic, in order to enact effective prevention and treatment options. SARS-Co-V-2 viral genomes were detected and sequenced from 18 Romanian patients suffering from coronavirus disease-2019. Viral Spike S glycoprotein sequences were used to generate model structures and assess the role of mutations on protein stability. We integrated the phylogenetic tree within the available European SARS-Co-V-2 genomic sequences. We further provide an epidemiological overview of the pre-existing conditions that are lethal in relevant Romanian patients. Non-synonymous mutations in the viral Spike glycoprotein relating to infectivity are constructed in models of protein structures. Continuing search to limit and treat SARS-CoV-2 benefit from our contribution in delineating the viral Spike glycoprotein mutations, as well as from assessment of their role on protein stability or complex formation with human receptor angiotensin-converting enzyme 2. Our results help implement and extend worldwide genomic surveillance of coronavirus disease-2019.", "title": "Whole-Genome Sequences of the Severe Acute Respiratory Syndrome Coronavirus-2 obtained from Romanian patients between March and June of 2020", "pid": "uhru7rn8", "bm25_score": 218.1599884033203}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which first occurred in Wuhan (China) in December of 2019, causes a severe acute respiratory illness with a high mortality rate, and has spread around the world. To gain an understanding of the evolution of the newly emerging SARS-CoV-2, we herein analyzed the codon usage pattern of SARS-CoV-2. For this purpose, we compared the codon usage of SARS-CoV-2 with that of other viruses belonging to the subfamily of Orthocoronavirinae. We found that SARS-CoV-2 has a high AU content that strongly influences its codon usage, which appears to be better adapted to the human host. We also studied the evolutionary pressures that influence the codon usage of five conserved coronavirus genes encoding the viral replicase, spike, envelope, membrane and nucleocapsid proteins. We found different patterns of both mutational bias and natural selection that affect the codon usage of these genes. Moreover, we show here that the two integral membrane proteins (matrix and envelope) tend to evolve slowly by accumulating nucleotide mutations on their corresponding genes. Conversely, genes encoding nucleocapsid (N), viral replicase and spike proteins (S), although they are regarded as are important targets for the development of vaccines and antiviral drugs, tend to evolve faster in comparison to the two genes mentioned above. Overall, our results suggest that the higher divergence observed for the latter three genes could represent a significant barrier in the development of antiviral therapeutics against SARS-CoV-2.", "title": "Codon Usage and Phenotypic Divergences of SARS-CoV-2 Genes", "pid": "wrqpb5qa", "bm25_score": 218.15823364257812}, {"text": "During the current outbreak of COVID-19, research labs around the globe submit sequences of the local SARS-CoV-2 genomes to the GISAID database to provide a comprehensive analysis of the variability and spread of the virus during the outbreak. We explored the variations in the submitted genomes and found a significant number of variants that can be seen only in one submission (singletons). While it is not completely clear whether these variants are erroneous or not, these variants show lower transition/transversion ratio. These singleton variants may influence the estimations of the viral mutation rate and tree topology. We suggest that genomes with multiple singletons even marked as high-covered should be considered with caution. We also provide a simple script for checking variant frequency against the database before submission.", "title": "Quality control of low-frequency variants in SARS-CoV-2 genomes", "pid": "lkdkdque", "bm25_score": 218.1304931640625}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectivity is a major concern in coronavirus disease 2019 (COVID-19) prevention and economic reopening. However, rigorous determination of SARS-COV-2 infectivity is essentially impossible owing to its continuous evolution with over 13752 single nucleotide polymorphisms (SNP) variants in six different subtypes. We develop an advanced machine learning algorithm based on the algebraic topology to quantitatively evaluate the binding affinity changes of SARS-CoV-2 spike glycoprotein (S protein) and host angiotensin-converting enzyme 2 (ACE2) receptor following the mutations. Based on mutation-induced binding affinity changes, we reveal that five out of six SARS-CoV-2 subtypes have become either moderately or slightly more infectious, while one subtype has weakened its infectivity. We find that SARS-CoV-2 is slightly more infectious than SARS-CoV according to computed S protein-ACE2 binding affinity changes. Based on a systematic evaluation of all possible 3686 future mutations on the S protein receptor-binding domain (RBD), we show that most likely future mutations will make SARS-CoV-2 more infectious. Combining sequence alignment, probability analysis, and binding affinity calculation, we predict that a few residues on the receptor-binding motif (RBM), i.e., 452, 489, 500, 501, and 505, have very high chances to mutate into significantly more infectious COVID-19 strains.", "title": "Mutations strengthened SARS-CoV-2 infectivity", "pid": "8s8gezpz", "bm25_score": 218.12118530273438}, {"text": "COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.", "title": "Genetic diversity and evolution of SARS-CoV-2", "pid": "can1e8ro", "bm25_score": 218.12022399902344}, {"text": "Humanity has seen numerous pandemics during its course of evolution. The list includes many such as measles, Ebola, SARS, MERS, etc. Latest edition to this pandemic list is COVID-19, caused by the novel coronavirus, SARS-CoV-2. As of 4th July 2020, COVID-19 has affected over 10 million people from 170+ countries, and 5,28,364 deaths. Genomic technologies have enabled us to understand the genomic constitution of the pathogens, their virulence, evolution, rate of mutations, etc. To date, more than 60,000 virus genomes have been deposited in the public depositories like GISAID and NCBI. While we are writing this, India is the 3rd most-affected country with COVID-19 with 0.6 million cases, and >18000 deaths. Gujarat is the fourth highest affected state with 5.44 percent death rate compared to national average of 2.8 percent. Here, 361 SARS-CoV-2 genomes from across Gujarat have been sequenced and analyzed in order to understand its phylogenetic distribution and variants against global and national sequences. Further, variants were analyzed from diseased and recovered patients from Gujarat and the World to understand its role in pathogenesis. From missense mutations, found from Gujarat SARS-CoV-2 genomes, C28854T, deleterious mutation in nucleocapsid (N) gene was found to be significantly associated with mortality in patients. The other significant deleterious variant found in diseased patients from Gujarat and the world is G25563T, which is located in Orf3a and has a potential role in viral pathogenesis. SARS-CoV-2 genomes from Gujarat are forming distinct cluster under GH clade of GISAID.", "title": "Genomic variations in SARS-CoV-2 genomes from Gujarat: Underlying role of variants in disease epidemiology", "pid": "wgtatr8v", "bm25_score": 218.113037109375}, {"text": "Since the first recorded case of the SARS-CoV-2, it has acquired several mutations in its genome while spreading throughout the globe. However, apart from some changes in protein coding, functional importance of these mutations in disease pathophysiology are still largely unknown. In this study, we investigated the significance of these mutations both from the host’s and virus’s perspective by analyzing the host miRNA binding and virus’s internal ribosome entry site (IRES), respectively. Strikingly, we observed that due to the acquired mutations, host miRNAs bind differently compared to the reference; where few of the miRNAs lost and few gained the binding affinity for targeting the viral genome. Moreover, functional enrichment analysis suggests that targets of both of these gained and lost miRNAs might be involved in various host immune signaling pathways. Also, we sought to shed some insights on the impacts of mutations on the IRES structure of SARS-CoV-2. Remarkably, we detected that three particular mutations in the IRES can disrupt its secondary structure which can further make the virus less functional. These results could be valuable in exploring the functional importance of the mutations of SARS-CoV-2 and could provide novel insights into the differences observed different parts of the world.", "title": "SARS-CoV-2 mutations altering regulatory properties: deciphering host’s and virus’s perspectives", "pid": "6f1y5hhv", "bm25_score": 218.09182739257812}, {"text": "Given the higher mortality rate and widespread phenomenon of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV-2) within the United States (US) population, understanding the mutational pattern of SARS CoV-2 has global implications for detection and therapy to prevent further escalation. Los Angeles has become an epicenter of the SARS-CoV-2 pandemic in the US. Efforts to contain the spread of SARS-CoV-2 require identifying its genetic and geographic variation and understanding the drivers of these differences. For the first time, we report genetic characterization of SARS-CoV-2 genome isolates in the Los Angeles population using targeted next generation sequencing (NGS). Samples collected at Cedars Sinai Medical Center were collected from patients with confirmed SARS-CoV-2 infection. We identified and diagnosed 192 patients by our in-house qPCR assay. In this population, the highest frequency variants were in known mutations in the 5'UTR, AA193 protein, RdRp and the spike glycoprotein. SARS-CoV-2 transmission within the local community was tracked by integrating mutation data with patient postal codes with two predominant community spread clusters being identified. Notably, significant viral genomic diversity was identified. Less than 10 percent of the Los Angeles community samples resembled published mutational profiles of SARS-CoV-2 genomes from China, while >50 percent of the isolates shared closely similarities to those from New York State. Based on these findings we conclude SARS-CoV-2 was likely introduced into the Los Angeles community predominantly from New York State but also via multiple other independent transmission routes including but not limited to Washington State and China.", "title": "Analysis of SARS-CoV-2 Genomes from Southern California Reveals Community Transmission Pathways in the Early Stage of the US COVID-19 Pandemic", "pid": "h3ftgzqz", "bm25_score": 218.055419921875}, {"text": "The causative agent of the coronavirus disease 2019 (COVID-19) pandemic, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is steadily mutating during continuous transmission among humans. Such mutations can occur in the spike (S) protein that binds to the angiotensin-converting enzyme-2 (ACE2) receptor and is cleaved by transmembrane protease serine 2 (TMPRSS2). However, whether S mutations affect SARS-CoV-2 infectivity remains unknown. Here, we show that naturally occurring S mutations can reduce or enhance cell entry via ACE2 and TMPRSS2. A SARS-CoV-2 S-pseudotyped lentivirus exhibits substantially lower entry than SARS-CoV S. Among S variants, the D614G mutant shows the highest cell entry, as supported by structural observations. Nevertheless, the D614G mutant remains susceptible to neutralization by antisera against prototypic viruses. Taken together, these data indicate that the D614G mutation enhances viral infectivity while maintaining neutralization susceptibility.", "title": "Naturally mutated spike proteins of SARS-CoV-2 variants show differential levels of cell entry", "pid": "9m3lc4y8", "bm25_score": 218.03643798828125}, {"text": "Four clinical isolates of SARS coronavirus were serially passaged in two primate cell lines (FRhK4 and Vero E6). Viral genetic sequences encoding for structural proteins and open reading frames 6–8 were determined in the original clinical specimen, the initial virus isolate (passage 0) and at passages 5, 10, and 15. After 15 passages, a total of 15 different mutations were identified and 12 of them were non‐synonymous mutations. Seven of these mutations were recurrent mutation and all located at the spike, membrane, and Orf 8a protein encoding sequences. Mutations in the membrane protein and a deletion in ORF 6–8 were already observed in passage 0, suggesting these amino acid substitutions are important in the adaptation of the virus isolate in primate cell culture. A mutation in the spike gene (residue 24079) appeared to be unique to adaptation in FRhK4 cells. It is important to be aware of cell culture associated mutations when interpreting data on molecular evolution of SARS coronavirus. J. Med. Virol. 76:435–440, 2005. © 2005 Wiley‐Liss, Inc.", "title": "Recurrent mutations associated with isolation and passage of SARS coronavirus in cells from non‐human primates", "pid": "yqfx56y5", "bm25_score": 218.02511596679688}, {"text": "Control of the ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic requires accurate laboratory testing to identify infected individuals, while also clearing essential staff to continue work. At the current time a number of RT-PCR tests have been developed to identify SARS-CoV-2, targeting multiple regions in the viral genome. In comparison to other RNA viruses the mutation rate of SARS-CoV-2 is moderate, however given the large number of transmission chains it is prudent to monitor circulating viruses for mutations that might compromise these tests. Here we report the identification of a C-to-T transition at position 26340 of the SARS-CoV-2 genome which is associated with failure of the cobas(R) SARS-CoV-2 E-gene assay. This variant was detected in four health care workers from the same team. Whole genome sequencing of SARS-CoV-2 showed all four to carry genetically identical viruses. Examination of viral genomes deposited on GISAID showed this mutation has arisen independently on three occasions. This work highlights the necessity of monitoring SARS-CoV-2 for the emergence of SNPs which might adversely affect the RT-PCRs used in diagnostics. Additionally, it argues that two regions in the SARS-CoV-2 should be targeted in RT-PCRs to avoid false negatives.", "title": "Failure of the cobas(R) SARS-CoV-2 (Roche) E-gene assay is associated with a C-to-T transition at position 26340 of the SARS-CoV-2 genome", "pid": "vd62r8qu", "bm25_score": 218.0222930908203}, {"text": "The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has motivated an intensive analysis of its molecular epidemiology following its worldwide spread. To understand the early evolutionary events following its emergence, a data set of 985 complete SARS-CoV-2 sequences was assembled. Variants showed a mean of 5.5 to 9.5 nucleotide differences from each other, consistent with a midrange coronavirus substitution rate of 3 × 10(−4) substitutions/site/year. Almost one-half of sequence changes were C→U transitions, with an 8-fold base frequency normalized directional asymmetry between C→U and U→C substitutions. Elevated ratios were observed in other recently emerged coronaviruses (SARS-CoV, Middle East respiratory syndrome [MERS]-CoV), and decreasing ratios were observed in other human coronaviruses (HCoV-NL63, -OC43, -229E, and -HKU1) proportionate to their increasing divergence. C→U transitions underpinned almost one-half of the amino acid differences between SARS-CoV-2 variants and occurred preferentially in both 5′ U/A and 3′ U/A flanking sequence contexts comparable to favored motifs of human APOBEC3 proteins. Marked base asymmetries observed in nonpandemic human coronaviruses (U ≫ A > G ≫ C) and low G+C contents may represent long-term effects of prolonged C→U hypermutation in their hosts. The evidence that much of sequence change in SARS-CoV-2 and other coronaviruses may be driven by a host APOBEC-like editing process has profound implications for understanding their short- and long-term evolution. Repeated cycles of mutation and reversion in favored mutational hot spots and the widespread occurrence of amino acid changes with no adaptive value for the virus represent a quite different paradigm of virus sequence change from neutral and Darwinian evolutionary frameworks and are not incorporated by standard models used in molecular epidemiology investigations. IMPORTANCE The wealth of accurately curated sequence data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its long genome, and its low substitution rate provides a relatively blank canvas with which to investigate effects of mutational and editing processes imposed by the host cell. The finding that a large proportion of sequence change in SARS-CoV-2 in the initial months of the pandemic comprised C→U mutations in a host APOBEC-like context provides evidence for a potent host-driven antiviral editing mechanism against coronaviruses more often associated with antiretroviral defense. In evolutionary terms, the contribution of biased, convergent, and context-dependent mutations to sequence change in SARS-CoV-2 is substantial, and these processes are not incorporated by standard models used in molecular epidemiology investigations.", "title": "Rampant C→U Hypermutation in the Genomes of SARS-CoV-2 and Other Coronaviruses: Causes and Consequences for Their Short- and Long-Term Evolutionary Trajectories", "pid": "jw6kh8os", "bm25_score": 218.01731872558594}, {"text": "Background This is a comprehensive analysis of 46 Indian SARS-CoV-2 genome sequences available from the NCBI and GISAID repository during early 2020. Evolutionary dynamics, gene-specific phylogeny and emergence of the novel co-evolving mutations in nine structural and non-structural genes among circulating SARS-CoV-2 strains in ten states of India have been assessed. Materials and methods 46 SARS-CoV-2 nucleotide sequences submitted from India were downloaded from the GISAID (39/46) or from NCBI (7/46) database. Phylogenetic study and analyses of mutation were based on the nine structural and non-structural genes of SARS-CoV-2 strains. Secondary structure of RdRP/NSP12 protein was predicted with respect to the novel A97V mutation. Results Phylogenetic analyses revealed the evolution of “genome-type clusters” and adaptive selection of “L” type SARS-CoV-2 strains with genetic closeness to the bat SARS-like coronaviruses than pangolin or MERS-CoVs. With regards to the novel co-evolving mutations, 2 groups are seen to circulate in India at present: the “major group” (52.2%) and the “minor group” (30.4%), harboring four and five co-existing mutations, respectively. The “major group” mutations fall in the A2a clade. All the minor group mutations, except 11083G>T (L37F, NSP6) were unique to the Indian isolates. Conclusion The study highlights rapidly evolving SARS-CoV-2 virus and co-circulation of multiple clades and sub-clades, driving this pandemic worldwide. This comprehensive study is a potential resource for monitoring the novel mutations in the viral genome, changes in viral pathogenesis, for designing vaccines and other therapeutics.", "title": "The novel Coronavirus enigma: Phylogeny and mutation analyses of SARS-CoV-2 viruses circulating in India during early 2020", "pid": "915srotp", "bm25_score": 218.01275634765625}, {"text": "The SARS-CoV-2 spike (S) protein, the viral mediator for binding and entry into the host cell, has sparked great interest as a target for vaccine development and treatments with neutralizing antibodies. Initial data suggest that the virus has low mutation rates, but its large genome could facilitate recombination, insertions, and deletions, as has been described in other coronaviruses. Here, we deep-sequenced the complete SARS-CoV-2 S gene from 18 patients (10 with mild and 8 with severe COVID-19), and found that the virus accumulates deletions upstream and very close to the S1/S2 cleavage site, generating a frameshift with appearance of a stop codon. These deletions were found in a small percentage of the viral quasispecies (2.2%) in samples from all the mild and only half the severe COVID-19 patients. Our results suggest that the virus may generate free S1 protein released to the circulation. We propose that natural selection has favored a “Don’t burn down the house” strategy, in which free S1 protein may compete with viral particles for the ACE2 receptor, thus reducing the severity of the infection and tissue damage without losing transmission capability.", "title": "Naturally occurring SARS-CoV-2 gene deletions close to the spike S1/S2 cleavage site in the viral quasispecies of COVID19 patients", "pid": "d0tg9i90", "bm25_score": 218.00729370117188}, {"text": "The spread of SARS-CoV-2 since December 2019 has become a pandemic and impacted many aspects of human society. Here, we analyzed genetic variation of SARS-CoV-2 and its related coronavirus and found the evidence of intergenomic recombination. After correction for mutational bias, analysis of 137 SARS-CoV-2 genomes as of 2/23/2020 revealed the excess of low frequency mutations on both synonymous and nonsynonymous sites which is consistent with recent origin of the virus. In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China was two time higher than those derived from the rest of the world. In addition, in network analysis, haplotypes collected from Wuhan city were at interior and have more mutational connections, both of which are consistent with the observation that the outbreak of cov-19 was originated from China. SUMMARY In contrast to adaptive evolution previously reported for SARS-CoV in its brief epidemic, our analysis of SARS-CoV-2 genomes shows signs of relaxation of selection. The sequence similarity of the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression. Therefore, SARS-CoV-2 might have cryptically circulated within humans for years before being recently noticed. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and reveal critical steps required for effective spreading. Two mutations, 84S in orf8 protein and 251V in orf3 protein, occurred coincidentally with human intervention. The 84S first appeared on 1/5/2020 and reached a plateau around 1/23/2020, the lockdown of Wuhan. 251V emerged on 1/21/2020 and rapidly increased its frequency. Thus, the roles of these mutations on infectivity need to be elucidated.", "title": "The origin and underlying driving forces of the SARS-CoV-2 outbreak", "pid": "bawgldfi", "bm25_score": 218.00714111328125}, {"text": "A previously unknown coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been shown to cause coronavirus disease 2019 (COVID-19) pandemic. The first case of COVID-19 in Turkey has been declared in March 11th, 2020 and from there on, more than 150,000 people in the country have been diagnosed with the disease. In this study, 62 viral sequences from Turkey, which have been uploaded to GISAID database, were analyzed by means of their nucleotide substitutions in comparison to the reference SARS-CoV-2 genome from Wuhan. Our results indicate that the viral isolates from Turkey harbor some common mutations with the viral strains from Europe, Oceania, North America and Asia. When the mutations were evaluated, C3037T, C14408T and A23403G were found to be the most common nucleotide substitutions among the viral isolates in Turkey, which are mostly seen as linked mutations and are part of a haplotype observed high in Europe.", "title": "Identification of the nucleotide substitutions in 62 SARS-CoV-2 sequences from Turkey", "pid": "34ojrsc4", "bm25_score": 217.9827880859375}, {"text": "Abstract COVID-19 is a viral respiratory illness caused by a new coronavirus called SARS-CoV-2. The World Health Organization declared the SARS-CoV-2 outbreak a global public health emergency. We performed genetic analyses of eighty-six complete or near-complete genomes of SARS-CoV-2 and revealed many mutations and deletions on coding and non-coding regions. These observations provided evidence of the genetic diversity and rapid evolution of this novel coronavirus.", "title": "Genetic diversity and evolution of SARS-CoV-2", "pid": "0nh58odf", "bm25_score": 217.9712677001953}, {"text": "AIM: The COVID-19 pandemic is caused by infection with the SARS-CoV-2 virus. The major mutation detected to date in the SARS-CoV-2 viral envelope spike protein, which is responsible for virus attachment to the host and is also the main target for host antibodies, is a mutation of an aspartate (D) at position 614 found frequently in Chinese strains to a glycine (G). We sought to infer health impact of this mutation. RESULT: Increased case fatality rate correlated strongly with the proportion of viruses bearing G614 on a country by country basis. The amino acid at position 614 occurs at an internal protein interface of the viral spike, and the presence of G at this position was calculated to destabilise a specific conformation of the viral spike, within which the key host receptor binding site is more accessible. CONCLUSION: These results imply that G614 is a more pathogenic strain of SARS-CoV-2, which may influence vaccine design. The prevalence of this form of the virus should also be included in epidemiologic models predicting the COVID-19 health burden and fatality over time in specific regions. Physicians should be aware of this characteristic of the virus to anticipate the clinical course of infection.", "title": "SARS-CoV-2 viral spike G614 mutation exhibits higher case fatality rate", "pid": "273ppceg", "bm25_score": 217.96524047851562}, {"text": "Monitoring the mutation dynamics of human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is critical in understanding its infectivity, virulence and pathogenicity for development of a vaccine. In an \"age of mobility\", the pandemic highlights the importance and vulnerability of regionalisation and labour market interdependence in Southeast Asia. We intend to characterise the genetic variability of viral populations within the region to provide preliminary information for regional surveillance in the future. By analysing 142 complete genomes from South East Asian (SEA) countries, we identified three central variants distinguished by nucleotide and amino acid changes.", "title": "An overview of the genetic variations of the SARS-CoV-2 genomes isolated in Southeast Asian countries.", "pid": "zf3moii7", "bm25_score": 217.94723510742188}, {"text": "Recent days have seen growing evidence of cancer's susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of the effect of genomic differences on the virus' entrance genes in lung cancer. Genetic confirmation of the hypotheses regarding gene expression and mutation pattern of target genes, including angiotensin-converting enzyme-2 (ACE2), transmembrane serine protease 2 (TMPRSS2), basigin (CD147/BSG) and paired basic amino acid cleaving enzyme (FURIN/PCSK3), as well as correlation analysis, was done in relation to lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC) using in silico analysis. Not only were gene expression and mutation patterns detected, but also there were correlation and survival analysis between ACE2 and other target genes expression levels. The total genetic anomaly carrying rate of target genes, including ACE2, TMPRSS2, CD147/BSG, and FURIN/PCSK3, was determined as 8.1% and 21 mutations were detected, with 7 of these mutations having pathogenic features. p.H34N on the RBD binding residues for SARS-CoV-2 was determined in our LUAD patient group. According to gene expression analysis results, though the TMPRSS2 level was statistically significantly decreased in the LUSC patient group compared to healthy control, the ACE2 level was determined to be high in LUAD and LUSC groups. There were no meaningful differences in the expression of CD147 and FURIN genes. The challenge for today is building the assessment of genomic susceptibility to COVID-19 in lung cancer, requiring detailed experimental laboratory studies, in addition to in silico analyses, as a way of assessing the mechanism of novel virus invasion that can be used in the development of effective SARS-CoV-2 therapy.", "title": "Structural variations and expression profiles of the SARS-CoV-2 host invasion genes in lung cancer", "pid": "89umkl6m", "bm25_score": 217.94552612304688}, {"text": "The current global pandemic COVID-19, caused by SARS-CoV-2, has resulted in millions of infections worldwide in a few months. Global efforts to tackle this situation have produced a tremendous body of genomic data, which can be used for tracing transmission routes, characterization of isolates, and monitoring variants with potential for unusual virulence. Several groups have analyzed these genomes using different approaches. However, as new data become available, the research community needs a pipeline to perform a set of routine analyses, that can quickly incorporate new genome sequences and update the analysis reports. We developed a programmatic tool, CoVa, with this objective. It is a fast, accurate and user-friendly utility to perform a variety of genome analyses on hundreds of SARS-CoV-2 sequences. Using CoVa, we define a modified sequence typing nomenclature and identify sites under positive selection. Further analysis identified some peptides and sites showing geographical patterns of selection. Specifically, we show differences in sequence type distribution between sequences from India and those from the rest of the world. We also show that several sites show signatures of positive selection uniquely in sequences from India. Preliminary evolutionary analysis, using features that will be incorporated into CoVa in the near future, show a mutation rate of 7.4 × 10−4 substitutions/site/year, confirm a temporal signal with a November 2019 origin of SARS-CoV-2, and a heterogeneity in the geographical distribution of Indian samples.", "title": "SARS-CoV-2 sequence typing, evolution and signatures of selection using CoVa, a Python-based command-line utility", "pid": "w8vs7s28", "bm25_score": 217.9370880126953}, {"text": "BACKGROUND SARS-CoV is the causative agent of severe acute respiratory syndrome (SARS) which has been associated with outbreaks of SARS in Guangdong, Hong Kong and Beijing of China, and other regions worldwide. SARS-CoV from human has shown some variations but its origin is still unknown. The genotyping and phylogeny of SARS-CoV were analyzed and reported in this paper. METHODS Full or partial genomes of 44 SARS-CoV strains were collected from GenBank. The genotype, single nucleotide polymorphism and phylogeny of these SARS-CoV strains were analyzed by molecular biological, bioinformatic and epidemiological methods. RESULTS There were 188 point mutations in the 33 virus full genomes with the counts of mutation mounting to 297. Further analysis was carried out among 36 of 188 loci with more than two times of mutation. All the 36 mutation loci occurred in coding sequences and 22 loci were non-synonymous. The gene mutation rates of replicase 1AB, S2 domain of spike glycoprotein and nucleocapsid protein were lower (0.079% - 0.103%). There were 4 mutation loci in S1 domain of spike glycoprotein. The gene mutation rate of ORF10 was the highest (3.333%) with 4 mutation loci in this small domain (120 bp) and 3 of 4 loci related to deletion mutation. By bioinformatics processing and analysis, the nucleotides at 7 loci of genome (T:T:A:G:T:C:T/C:G:G:A:C:T:C) can classify SARS-CoV into two types. Therefore a novel definition is put forward that according to these 7 loci of mutation, 40 strains of SARS-CoV in GenBank can be grouped into two genotypes, T:T:A:G:T:C:T and C:G:G:A:C:T:C, and named as SARS-CoV Yexin genotype and Xiaohong genotype. The two genotypes can be further divided into some sub-genotypes. These genotypes can also be approved by phylogenetic tree of three levels of 44 loci of mutation, spike glycoprotein gene and complete genome sequence. Compared to various strains among SARS-CoV Yexin genotype and Xiaohong genotype, GD01 strain of Yexin genotype is more closely related to SARS-CoV like-virus from animals. CONCLUSION The results mentioned above suggest that SARS-CoV is responding to host immunological pressures and experiencing variation which provide clues, information and evidence of molecular biology for the clinical pathology, vaccine developing and epidemic investigation.", "title": "Molecular biological analysis of genotyping and phylogeny of severe acute respiratory syndrome associated coronavirus.", "pid": "3n37dlt4", "bm25_score": 217.9311981201172}, {"text": "To dissect the mechanisms underlying the observed inflation of variants in SARS-CoV-2 genome, we present the largest up-to-date analysis of intra-host genomic diversity, which reveals that the majority of samples present a complex sublineage architecture, due to the interplay between host-related mutational processes and transmission dynamics. Strikingly, the deconvolution of the entire set of intra-host variants reveals the existence of mutually exclusive viral mutational signatures, which prove that distinct hosts differently respond to SARS-CoV-2 infections. In particular, two signatures are likely ruled by APOBEC and Reactive Oxygen Species (ROS), which induce hypermutation in a significant number of samples, and appear to be affected by severe purifying selection. Conversely, several mutations linked to low-rate mutational processes appear to transit to clonality in the population, eventually leading to the definition of new viral genotypes and to an increase of overall genomic diversity. Finally, we demonstrate that a high number of variants are observed in samples associated to independent lineages, likely due to signature-related mutational hotspots or to positive selection.", "title": "Mutational Signatures and Heterogeneous Host Response Revealed Via Large-Scale Characterization of SARS-COV-2 Genomic Diversity", "pid": "7se14455", "bm25_score": 217.9293670654297}, {"text": "Background: The origin of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is still a debatable topic. The association of the virus spread from the market is supported by the close relation of genome sequences of environmental surface samples with virus samples from earliest patients by phylogenetic analysis. Objectives: To have an insight into the SARS-CoV-2 genome sequences reported from India for better understanding on their epidemiology and virulence. Methods: Genome sequences of Indian isolates of SARS-CoV-2 were analyzed to understand their phylogeny and divergence with respect to other isolates reported from other countries. Amino acid sequences of individual open reading frames (ORFs) from SARS-CoV-2 Indian isolates were aligned with sequences of isolates reported from other countries to identify the mutations occurred in Indian isolates. Results: Our analysis suggests that Indian SARS-CoV-2 isolates are closely related to isolates reported from other parts of the world. Most ORFs are highly conserved; mutations were also detected in some ORFs. We found that most isolates reported from India have key mutations at 614th position of the S protein and 84th position of the ORF 8, which has been reported to be associated with high virulence and high transmission rate. Conclusion: An attempt was made to understand the SARS-CoV-2 virus reported from India. SARS-CoV-2 reported from India was closely similar to other SARS-CoV-2 reported from other parts of the world, which suggests that vaccines and other therapeutic methods generated from other countries might work well in India. In addition, available sequence data suggest that majority of Indian isolates are capable of high transmission and virulence.", "title": "Genome analysis of SARS-CoV-2 isolates occurring in India: Present scenario", "pid": "2nvk7glh", "bm25_score": 217.92596435546875}, {"text": "The emerging global infectious COVID-19 disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. To understand the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. This study presents an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The single-nucleotide polymorphism (SNP) genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. The proposed method serves an effective tool for monitoring and tracking the epidemic of pathogenic viruses in their global and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.", "title": "Genotyping coronavirus SARS-CoV-2: methods and implications", "pid": "leyqhma0", "bm25_score": 217.925537109375}, {"text": "The recent emergence of a novel coronavirus (SARS-CoV-2) is causing a severe global health threat characterized by severe acute respiratory syndrome (Covid-19). At the moment, there is no specific treatment for this disease, and vaccines are still under development. The structural protein Spike is essential for virus infection and has been used as the main target for vaccine and serological diagnosis test development. We analysed 2363 sequences of the Spike protein from SARS-CoV-2 isolates and identified variability in 44 amino acid residues and their worldwide distribution in all continents. We used the three-dimensional structure of the homo-trimer model to predict conformational epitopes of B-cell, and sequence of Spike protein Wuhan-Hu-1 to predict linear epitopes of T-Cytotoxic and T-Helper cells. We identified 45 epitopes with amino acid variations. Finally, we showed the distribution of mutations within the epitopes. Our findings can help researches to identify more efficient strategies for the development of vaccines, therapies, and serological diagnostic tests based on the Spike protein of Sars-Cov-2.", "title": "SARS-CoV-2 mutations and where to find them: An in silico perspective of structural changes and antigenicity of the Spike protein", "pid": "srgi9jc6", "bm25_score": 217.9248046875}, {"text": "The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has motivated an intensive analysis of its molecular epidemiology following its worldwide spread. To understand the early evolutionary events following its emergence, a data set of 985 complete SARS-CoV-2 sequences was assembled. Variants showed a mean of 5.5 to 9.5 nucleotide differences from each other, consistent with a midrange coronavirus substitution rate of 3 × 10-4 substitutions/site/year. Almost one-half of sequence changes were C→U transitions, with an 8-fold base frequency normalized directional asymmetry between C→U and U→C substitutions. Elevated ratios were observed in other recently emerged coronaviruses (SARS-CoV, Middle East respiratory syndrome [MERS]-CoV), and decreasing ratios were observed in other human coronaviruses (HCoV-NL63, -OC43, -229E, and -HKU1) proportionate to their increasing divergence. C→U transitions underpinned almost one-half of the amino acid differences between SARS-CoV-2 variants and occurred preferentially in both 5' U/A and 3' U/A flanking sequence contexts comparable to favored motifs of human APOBEC3 proteins. Marked base asymmetries observed in nonpandemic human coronaviruses (U ≫ A > G ≫ C) and low G+C contents may represent long-term effects of prolonged C→U hypermutation in their hosts. The evidence that much of sequence change in SARS-CoV-2 and other coronaviruses may be driven by a host APOBEC-like editing process has profound implications for understanding their short- and long-term evolution. Repeated cycles of mutation and reversion in favored mutational hot spots and the widespread occurrence of amino acid changes with no adaptive value for the virus represent a quite different paradigm of virus sequence change from neutral and Darwinian evolutionary frameworks and are not incorporated by standard models used in molecular epidemiology investigations.IMPORTANCE The wealth of accurately curated sequence data for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its long genome, and its low substitution rate provides a relatively blank canvas with which to investigate effects of mutational and editing processes imposed by the host cell. The finding that a large proportion of sequence change in SARS-CoV-2 in the initial months of the pandemic comprised C→U mutations in a host APOBEC-like context provides evidence for a potent host-driven antiviral editing mechanism against coronaviruses more often associated with antiretroviral defense. In evolutionary terms, the contribution of biased, convergent, and context-dependent mutations to sequence change in SARS-CoV-2 is substantial, and these processes are not incorporated by standard models used in molecular epidemiology investigations.", "title": "Rampant C→U Hypermutation in the Genomes of SARS-CoV-2 and Other Coronaviruses: Causes and Consequences for Their Short- and Long-Term Evolutionary Trajectories", "pid": "14pgap3r", "bm25_score": 217.91880798339844}, {"text": "The emerging global infectious COVID-19 coronavirus disease by novel Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) presents critical threats to global public health and the economy since it was identified in late December 2019 in China. The virus has gone through various pathways of evolution. For understanding the evolution and transmission of SARS-CoV-2, genotyping of virus isolates is of great importance. We present an accurate method for effectively genotyping SARS-CoV-2 viruses using complete genomes. The method employs the multiple sequence alignments of the genome isolates with the SARS-CoV-2 reference genome. The SNP genotypes are then measured by Jaccard distances to track the relationship of virus isolates. The genotyping analysis of SARS-CoV-2 isolates from the globe reveals that specific multiple mutations are the predominated mutation type during the current epidemic. Our method serves a promising tool for monitoring and tracking the epidemic of pathogenic viruses in their gradual and local genetic variations. The genotyping analysis shows that the genes encoding the S proteins and RNA polymerase, RNA primase, and nucleoprotein, undergo frequent mutations. These mutations are critical for vaccine development in disease control.", "title": "Genotyping coronavirus SARS-CoV-2: methods and implications", "pid": "ulygq434", "bm25_score": 217.90365600585938}, {"text": "Abstract Focused efforts by several international laboratories have resulted in the sequencing of the genome of the causative agent of severe acute respiratory syndrome (SARS), novel coronavirus SARS-CoV, in record time. Using cumulative skew diagrams, I found that mutational patterns in the SARS-CoV genome were strikingly different from other coronaviruses in terms of mutation rates, although they were in general agreement with the model of the coronavirus lifecycle. These findings might be relevant for the development of sequence-based diagnostics and the design of agents to treat SARS.", "title": "Mutational patterns correlate with genome organization in SARS and other coronaviruses", "pid": "g68g6xxu", "bm25_score": 217.9027557373047}, {"text": "OBJECTIVE: To analyze the evolution and variation of SARS-CoV-2 during the epidemic starting at the end of 2019. METHODS: We downloaded the full-length genome sequence of SARS-CoV-2 from the databases of GISAID and NCBI. Using the software for bioinformatics including MEGA-X, BEAST, and TempEst, we constructed the genomic evolution tree, inferred the time evolution signal of the virus, calculated the tMRCA time of the virus and analyzed the selection pressure of the virus during evolution. RESULTS: The phylogenetic tree showed that SARS-CoV-2 belonged to the Sarbecovirus subgenus of ß Coronavirus genus together with bat coronavirus BetaCoV/bat/Yunnan/RaTG13/2013, bat-SL-CoVZC45, bat-SL-CoVZXC21 and SARS-CoV. The genomic sequences of SARS-CoV-2 isolated from the ongoing epidemic showed a weak time evolution signal with an average tMRCA time of 73 days (95% CI: 38.9-119.3 days). No positive time evolution signal was found between SARS-CoV-2 and BetaCoV/bat/Yunnan/RaTG13/2013, but the former virus had a strong positive temporal evolution relationship with bat-SL-CoVZC45 and SARS-CoV. The major cause for mutations of SARS-CoV-2 was the pressure of purification selection during the epidemic. CONCLUSIONS: SARS-CoV-2 may have emerged as early as November, 2019, originating most likely from bat-associated coronavirus. This finding may provide evidence for tracing the sources and evolution of the virus.", "title": "[Analysis of variation and evolution of SARS-CoV-2 genome]", "pid": "fofy6whl", "bm25_score": 217.8962860107422}]}
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significant changes have occurred in the United States as the infection spread reached and passed its exponential phase. A stringent analysis of COVID-19 epidemiologic data requires time and would generally be expected to happen with significant delay after the exponential phase of the disease is over and when the focus of the health care system is diverted away from crisis management. Although much has been said about high-risk groups and the vulnerability of the elderly and patients with underlying comorbidities, the impact of race on the susceptibility of ethnic minorities living in indigent communities has not been discussed in detail worldwide and specifically in the United States. There are currently some data on disparities between African American and Caucasian populations for COVID-19 infection and mortality. While health care authorities are reorganizing resources and infrastructure to provide care for symptomatic COVID-19 patients, they should not shy away from protecting the general public as a whole and specifically the most vulnerable members of society, such as the elderly, ethnic minorities, and people with underlying comorbidities.", "title": "Why African Americans Are a Potential Target for COVID-19 Infection in the United States", "pid": "wwucpqin", "bm25_score": 220.20620727539062}, {"text": "The mental health consequences of the COVID-19 pandemic are particularly relevant in African-American communities because African-Americans have been disproportionately impacted by the disease, yet they are traditionally less engaged in mental health treatment compared with other racial groups. Using the state of Michigan as an example, we describe the social and psychological consequences of the pandemic on African-American communities in the United States, highlighting community members' concerns about contracting the disease, fears of racial bias in testing and treatment, experiences of sustained grief and loss, and retraumatization of already-traumatized communities. Furthermore, we describe the multilevel, community-wide approaches that have been used thus far to mitigate adverse mental health outcomes within our local African-American communities. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Social and psychological consequences of the COVID-19 pandemic in African-American communities: Lessons from Michigan.", "pid": "zdmoifko", "bm25_score": 220.14157104492188}, {"text": "The mental health consequences of the COVID-19 pandemic are particularly relevant in African-American communities because African-Americans have been disproportionately impacted by the disease, yet they are traditionally less engaged in mental health treatment compared with other racial groups. Using the state of Michigan as an example, we describe the social and psychological consequences of the pandemic on African-American communities in the United States, highlighting community members' concerns about contracting the disease, fears of racial bias in testing and treatment, experiences of sustained grief and loss, and retraumatization of already-traumatized communities. Furthermore, we describe the multilevel, community-wide approaches that have been used thus far to mitigate adverse mental health outcomes within our local African-American communities. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Social and psychological consequences of the COVID-19 pandemic in African-American communities: Lessons from Michigan", "pid": "423uero3", "bm25_score": 220.07443237304688}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected over 1.5 million individuals and led to over 91, 000 deaths in the United States (US) alone as of May 20th, 2020. Minority populations, however, continue to be a high-risk population to contract the SARS-CoV-2 infection. While socioeconomic inequality may help to explain why minority ethnic populations are contracting the SARS-CoV-2 in larger proportions, the reason for elevated mortality rates in African Americans is still unknown. African Americans are less likely than whites to utilize high-quality hospitals, ambulatory care services, and regular primary care providers; this is most likely a result of barriers to accessing high quality treatment, as African Americans have substantially higher uninsured rates. However, previous reports have shown that regardless of insurance status, African Americans are more likely to be directed toward lower quality treatment plans compared to their white counterparts, and that physicians carry implicit biases that negatively impact treatment regimens for these minority populations. While income, education, and access to healthcare should be revised in due time, in the short term physicians should do everything possible to learn about implicit biases that may exist in healthcare, as the first step to minimize implicit biases is to recognize that they exist.", "title": "Coronavirus Disease Health Care Delivery Impact on African Americans", "pid": "7k4reog4", "bm25_score": 219.868896484375}, {"text": "Socio-economic disparities quite often have a central role in the unfolding of large-scale catastrophic events. One of the most concerning aspects of the ongoing COVID-19 pandemics is that it disproportionately affects people from Black and African American backgrounds creating an unexpected infection gap. Interestingly, the abnormal impact on these ethnic groups seem to be almost uncorrelated with other risk factors, including co-morbidity, poverty, level of education, access to healthcare, residential segregation, and response to cures. A proposed explanation for the observed incidence gap is that people from African American backgrounds are more often employed in low-income service jobs, and are thus more exposed to infection through face-to-face contacts, but the lack of direct data has not allowed to draw strong conclusions in this sense so far. Here we introduce the concept of dynamic segregation, that is the extent to which a given group of people is internally clustered or exposed to other groups, as a result of mobility and commuting habits. By analysing census and mobility data on more than 120 major US cities, we found that the dynamic segregation of African American communities is significantly associated with the weekly excess COVID-19 incidence and mortality in those communities. The results confirm that knowing where people commute to, rather than where they live, is much more relevant for disease modelling.", "title": "Disproportionate incidence of COVID-19 in African Americans correlates with dynamic segregation", "pid": "3lkahro8", "bm25_score": 219.58856201171875}, {"text": "Generations of nurses to come, now called heroes in the media, will have challenges in providing care for persons during this global pandemic. COVID-19 has impacted all demographics, regardless of race, gender, or socioeconomic class globally. African Americans have experienced a disproportionate number of deaths related to COVID-19 in the New Orleans and surrounding Metropolitan areas. According to the Louisiana Department of Health (2020), fifty-seven percent (57.40%) of the deaths in Louisiana related to COVID-19 have been African American (Black) and fifty-five percent (55.2%) have been males as of May 11, 2020. Social determinants of health are the conditions in which people age and the conditions they are born, grow, age and work. These conditions include neighborhoods, schools, and places of employment. These circumstances are shaped by the distribution of money, power, and resources at global, national, and local levels (World Health Organization, 2020). Years later the same community that comprised \"pre-and post-Katrina\" are now facing this pandemic.", "title": "COVID-19: A Closer Lens", "pid": "peys32ve", "bm25_score": 219.49664306640625}, {"text": "IMPORTANCE: The novel Coronavirus Disease 2019 (COVID-19), declared a pandemic in March 2020, may present with disproportionately higher rates in underrepresented racial/ethnic minority populations in the United States, including African American communities who have traditionally been over-represented in negative health outcomes. STUDY OBJECTIVE: To understand the impact of the density of African American communities (defined as the percentage of African Americans in a county) on COVID-19 prevalence and death rate within the three most populous counties in each U.S. state and territory (n=152). Design: An ecological study using linear regression was employed for the study. SETTING: The top three most populous counties of each U.S. state and territory were included in analyses for a final sample size of n=152 counties. PARTICIPANTS: Confirmed COVID-19 cases and deaths that were accumulated between January 22, 2020 and April 12, 2020 in each of the three most populous counties in each U.S. state and territory were included. MAIN OUTCOME MEASURES: Linear regression was used to determine the association between African American density and COVID-19 prevalence (defined as the percentage of cases for the county population), and death rate (defined as number of deaths per 100,000 population). The models were adjusted for median age and poverty. RESULTS: There was a direct association between African American density and COVID-19 prevalence; COVID-19 prevalence increased 5% for every 1% increase in county AA density (p<.01). There was also an association between county AA density and COVID-19 deaths, such; the death rate increased 2 per 100,000 for every percentage increase in county AA density (p=.02). CONCLUSION: These study findings indicate that communities with a high African American density have been disproportionately burdened with COVID-19. Further study is needed to indicate if this burden is related to environmental factors or individual factors such as types of employment or comorbidities that members of these community have.", "title": "The impact of COVID-19 on African American communities in the United States", "pid": "80w0wu9e", "bm25_score": 219.4770965576172}, {"text": "Generations of nurses to come, now called heroes in the media, will have challenges in providing care for persons during this global pandemic. COVID-19 has impacted all demographics, regardless of race, gender, or socioeconomic class globally. African Americans have experienced a disproportionate number of deaths related to COVID-19 in the New Orleans and surrounding Metropolitan areas. According to the Louisiana Department of Health (2020), fifty-seven percent (57.40%) of the deaths in Louisiana related to COVID-19 have been African American (Black) and fifty-five percent (55.2%) have been males as of May 11, 2020. Social determinants of health are the conditions in which people age and the conditions they are born, grow, age and work. These conditions include neighborhoods, schools, and places of employment. These circumstances are shaped by the distribution of money, power, and resources at global, national, and local levels (World Health Organization, 2020). Years later the same community that comprised \"pre-and post-Katrina\" are now facing this pandemic.", "title": "COVID-19: A Closer Lens.", "pid": "b7x39b3m", "bm25_score": 219.44114685058594}, {"text": "The COVID-19 pandemic has unveiled unsettling disparities in the outcome of the disease among African Americans. These disparities are not new, but are rooted in structural inequities that must be addressed to adequately care for communities of color. We describe the historical context of these structural inequities, their impact on the progression of COVID-19 in the African American (Black) community, and suggest a multifaceted approach to addressing these healthcare disparities. Of note, terminology from survey data cited for this article varied from Blacks, African Americans or both; for consistency, we use African Americans throughout.", "title": "Racial Disparity of Coronavirus Disease 2019 (COVID-19) in African American Communities", "pid": "bgpep5lc", "bm25_score": 219.25942993164062}, {"text": "", "title": "COVID-19 Is Disproportionately High in African Americans. This Will Come as No Surprise", "pid": "ujlsdpzf", "bm25_score": 219.01441955566406}, {"text": "The COVID-19 pandemic has disproportionately affected racial and ethnic minority groups, with high rates of death in African American, Native American, and LatinX communities. While the mechanisms of these disparities are being investigated, they can be conceived as arising from biomedical factors as well as social determinants of health. Minority groups are disproportionately affected by chronic medical conditions and lower access to healthcare that may portend worse COVID-19 outcomes. Furthermore, minority communities are more likely to experience living and working conditions that predispose them to worse outcomes. Underpinning these disparities are long-standing structural and societal factors that the COVID-19 pandemic has exposed. Clinicians can partner with patients and communities to reduce the short-term impact of COVID-19 disparities while advocating for structural change.", "title": "The Disproportionate Impact of COVID-19 on Racial and Ethnic Minorities in the United States", "pid": "u7s67aug", "bm25_score": 218.96243286132812}, {"text": "Emerging statistics demonstrate that COVID‐19 disproportionately affects African Americans. The effects of COVID‐19 for this population are inextricably linked to areas of systemic oppression and disenfranchisement, which are further exacerbated by COVID‐19: (1) healthcare inequality; (2) segregation, overall health, and food insecurity; (3) underrepresentation in government and the medical profession; and (4) inequalities in participatory democracy and public engagement. Following a discussion of these issues, this article shares early and preliminary lessons and strategies on how public administration scholars and practitioners can lead in crafting equitable responses to this global pandemic to uplift the African American community. This article is protected by copyright. All rights reserved.", "title": "Social Equity and COVID‐19: The Case of African Americans", "pid": "yq7enzvm", "bm25_score": 218.94354248046875}, {"text": "", "title": "COVID-19 and African Americans.", "pid": "fs983x5g", "bm25_score": 218.91116333007812}, {"text": "Although the current COVID-19 crisis is felt globally, at the local level, COVID-19 has disproportionately affected poor, highly segregated African American communities in Chicago. To understand the emerging pattern of racial inequality in the effects of COVID-19, we examined the relative burden of social vulnerability and health risk factors. We found significant spatial clusters of social vulnerability and risk factors, both of which are significantly associated with the increased COVID-19-related death rate. We also found that a higher percentage of African Americans was associated with increased levels of social vulnerability and risk factors. In addition, the proportion of African American residents has an independent effect on the COVID-19 death rate. We argue that existing inequity is often highlighted in emergency conditions. The disproportionate effects of COVID-19 in African American communities are a reflection of racial inequality and social exclusion that existed before the COVID-19 crisis.", "title": "Social Vulnerability and Racial Inequality in COVID-19 Deaths in Chicago.", "pid": "gn8uwuca", "bm25_score": 218.75111389160156}, {"text": "To date, 110,000+ people in the United States have died from the COVID-19 pandemic. In this paper, the authors will discuss COVID-19 relative to Black people and their overrepresentation among those who are infected and died from the disease. Their dying, death, and grief experiences are explored through a cultural and spiritual lens. The physical distancing, social isolation, misinformation, and restrictive burials and cremations now elicited by this unprecedented pandemic have had diminished familial, cultural, emotional, and economic impacts on the Black community. Implications for public health and Black peoples' involvement in the political process are also addressed.", "title": "Six feet apart or six feet under: The impact of COVID-19 on the Black community.", "pid": "phcd8b4m", "bm25_score": 218.6770782470703}, {"text": "Mental health clinicians and researchers must be prepared to address the unique needs of Black Americans who have been disproportionately affected by the COVID-19 pandemic. Race-conscious and culturally competent interventions that consider factors such as discrimination, distrust of health care providers, and historical and racial trauma as well as protective factors including social support and culturally sanctioned coping strategies are needed. Research to accurately assess and design treatments for the mental health consequences of COVID-19 among Black Americans is warranted. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Mental health ramifications of the COVID-19 pandemic for Black Americans: Clinical and research recommendations", "pid": "ef494his", "bm25_score": 218.62106323242188}, {"text": "African Americans and Latinos are overrepresented among cases of and deaths from COVID-19 nationally and in many of the U.S. regions hardest hit by the pandemic. The editorialist discusses lessons that we should have learned from prior experiences and strategies to reduce observed disparities.", "title": "This Time Must Be Different: Disparities During the COVID-19 Pandemic", "pid": "fsid4a39", "bm25_score": 218.5851593017578}, {"text": "Mental health clinicians and researchers must be prepared to address the unique needs of Black Americans who have been disproportionately affected by the COVID-19 pandemic. Race-conscious and culturally competent interventions that consider factors such as discrimination, distrust of health care providers, and historical and racial trauma as well as protective factors including social support and culturally sanctioned coping strategies are needed. Research to accurately assess and design treatments for the mental health consequences of COVID-19 among Black Americans is warranted. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Mental health ramifications of the COVID-19 pandemic for Black Americans: Clinical and research recommendations.", "pid": "4q97416a", "bm25_score": 218.58145141601562}, {"text": "Although the current COVID-19 crisis is felt globally, at the local level, COVID-19 has disproportionately affected poor, highly segregated African American communities in Chicago. To understand the emerging pattern of racial inequality in the effects of COVID-19, we examined the relative burden of social vulnerability and health risk factors. We found significant spatial clusters of social vulnerability and risk factors, both of which are significantly associated with the increased COVID-19-related death rate. We also found that a higher percentage of African Americans was associated with increased levels of social vulnerability and risk factors. In addition, the proportion of African American residents has an independent effect on the COVID-19 death rate. We argue that existing inequity is often highlighted in emergency conditions. The disproportionate effects of COVID-19 in African American communities are a reflection of racial inequality and social exclusion that existed before the COVID-19 crisis.", "title": "Social Vulnerability and Racial Inequality in COVID-19 Deaths in Chicago", "pid": "aa9zegjr", "bm25_score": 218.55557250976562}, {"text": "", "title": "COVID-19 and African Americans", "pid": "97mg41jl", "bm25_score": 218.53250122070312}, {"text": "COVID-19 has had disproportionate contagion and fatality in Black, Latino, and Native American communities and among the poor in the United States. Toxic stress resulting from racial and social inequities have been magnified during the pandemic, with implications for poor physical and mental health and socioeconomic outcomes. It is imperative that our country focus and invest in addressing health inequities and work across sectors to build self-efficacy and long-term capacity within communities and systems of care serving the most disenfranchised, now and in the aftermath of the COVID-19 epidemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Inequity and the disproportionate impact of COVID-19 on communities of color in the United States: The need for a trauma-informed social justice response.", "pid": "q7telkky", "bm25_score": 218.47354125976562}, {"text": "", "title": "COVID-19 is Out of Proportion in African Americans. This Will Come as No Surprise…", "pid": "cv3op3bb", "bm25_score": 218.417236328125}, {"text": "", "title": "Community Outreach Panel Explores and Addresses Higher Rates of COVID-19–Related Deaths in the African American Population", "pid": "4vsfl62z", "bm25_score": 218.37216186523438}, {"text": "BACKGROUND: Cardiovascular disease related mortality is the leading cause of death in the United States, with hypertension being the most prevalent and potent risk factor. For decades hypertension has disproportionately affected African Americans, who also have a higher burden of associated comorbidities including diabetes and heart failure. METHODS: Current literature including guideline reports and newer studies on hypertension in African Americans in PubMed were reviewed. We also reviewed newer publications on the relationship between COVID-19 and cardiovascular disease. FINDINGS: While APOL1 has been theorized in the epidemiology of hypertension, the increased prevalence and associated risks are primarily due to environmental and lifestyle factors. These factors include poor diet, adverse lifestyle, and social determinants. Hypertension control can be achieved by lifestyle modifications such as low sodium diet, weight loss, and adequate physical activity. When lifestyle modifications alone do not adequately control hypertension, a common occurrence among African Americans who suffer with greater prevalence of resistant hypertension, pharmacological intervention is indicated. The efficacy of renal denervation, and the use of sodium-glucose cotransporter 2 and aminopeptidase A inhibitors, have been studied for treatment of resistant hypertension. Furthermore, the recent COVID-19 crisis has been particularly devastating among African Americans who demonstrate increased incidence and poorer health outcomes related to the disease. CONCLUSION: The disparities in outcomes, which are largely attributable to a greater prevalence of comorbidities such as hypertension and obesity, in addition to adverse environmental and socioeconomic factors, highlight the necessity of specialized clinical approaches and programs for African Americans to address longstanding barriers to equitable care.", "title": "Contemporary and Future Concepts on Hypertension in African Americans: COVID-19 and Beyond", "pid": "cn2j9ih4", "bm25_score": 218.300048828125}, {"text": "As the city of Detroit raids itself of deaths by shifting from homicides, COVID-19 infection continues to harrow the city with more deaths. From March 19 to May 15, more Detroiters died in 2 months than were killed in 2 years of city homicides. African Americans or Blacks (highest-risk phenotypes) developing COVID-19 infection are more likely to die disproportionately. The confluence of diabetes, hypertension, cardiovascular disease, and the higher prevalence of obesity among Blacks have provided the needed environment for viruses like COVID-19 to thrive and cause serious infections. The purpose of this study is to connect mortality rates from COVID-19 infection to increasing obesity trends among African Americans within the city of Detroit. Statistical analyses were conducted using SPSS ver. 23. Results showed that the highest mortality rates among African Americans occurred more in the obese individuals infected with COVID-19 in the city of Detroit. Out of 1930 deaths from COVID-19 infections, 733 deaths were due to obesity alone in patients without reported comorbid conditions like diabetes, hypertension, and cardiovascular disease. Mortality rate for both male and female African Americans amounted to a total of 11.9%. Thirty-eight percent of reported COVID-19-infected African Americans were obese. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s42399-020-00385-y) contains supplementary material, which is available to authorized users.", "title": "Higher Obesity Trends Among African Americans Are Associated with Increased Mortality in Infected COVID-19 Patients Within the City of Detroit", "pid": "753klfdp", "bm25_score": 218.27684020996094}, {"text": "COVID-19 has had disproportionate contagion and fatality in Black, Latino, and Native American communities and among the poor in the United States. Toxic stress resulting from racial and social inequities have been magnified during the pandemic, with implications for poor physical and mental health and socioeconomic outcomes. It is imperative that our country focus and invest in addressing health inequities and work across sectors to build self-efficacy and long-term capacity within communities and systems of care serving the most disenfranchised, now and in the aftermath of the COVID-19 epidemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Inequity and the disproportionate impact of COVID-19 on communities of color in the United States: The need for a trauma-informed social justice response", "pid": "81crwncn", "bm25_score": 218.26434326171875}, {"text": "To date, 110,000+ people in the United States have died from the COVID-19 pandemic. In this paper, the authors will discuss COVID-19 relative to Black people and their overrepresentation among those who are infected and died from the disease. Their dying, death, and grief experiences are explored through a cultural and spiritual lens. The physical distancing, social isolation, misinformation, and restrictive burials and cremations now elicited by this unprecedented pandemic have had diminished familial, cultural, emotional, and economic impacts on the Black community. Implications for public health and Black peoples' involvement in the political process are also addressed.", "title": "Six feet apart or six feet under: The impact of COVID-19 on the Black community", "pid": "i2b9py8e", "bm25_score": 218.207275390625}, {"text": "", "title": "The Disproportionate Impact of COVID-19 on Racial and Ethnic Minorities in the United States.", "pid": "i6a26q3j", "bm25_score": 218.15797424316406}, {"text": "", "title": "COVID-19 Among African Americans: From Preliminary Epidemiological Surveillance Data to Public Health Action", "pid": "l10g2cy0", "bm25_score": 218.1056671142578}, {"text": "", "title": "Covid-19: Black people and other minorities are hardest hit in US.", "pid": "8w38bob3", "bm25_score": 218.0911102294922}, {"text": "A series of 15-min videos were produced to provide resources to pastors in African-American communities to aid them in conveying accurate public and mental health information about COVID-19. Video presenters included trusted experts in public and mental health and pastors with considerable experience responding to the needs of the African-American community during the COVID-19 pandemic. Four culturally specific core themes to consider when providing care to African Americans who are at increased risk during the pandemic were identified: ritual disruption, negative reactions for not following public health guidelines, trauma, and culture and trust. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "A culturally specific mental health and spirituality approach for African Americans facing the COVID-19 pandemic.", "pid": "juzi9th6", "bm25_score": 218.08676147460938}, {"text": "African Americans are overrepresented among reported coronavirus disease 2019 (COVID-19) cases and deaths. There are a multitude of factors that may explain the African American disparity in COVID-19 outcomes, including higher rates of comorbidities. While individual-level factors predictably contribute to disparate COVID-19 outcomes, systematic and structural factors have not yet been reported. It stands to reason that implicit biases may fuel the racial disparity in COVID-19 outcomes. To address this racial disparity, we must apply a health equity lens and disaggregate data explicitly for African Americans, as well as other populations at risk for biased treatment in the health-care system.", "title": "Are Clinicians Contributing to Excess African American COVID-19 Deaths? Unbeknownst to Them, They May Be", "pid": "1lw5vbu9", "bm25_score": 218.0281982421875}, {"text": "The sudden and rapid advancement of the novel Coronavirus (COVID-19) pandemic has led to an unanticipated and unprecedented global crisis. Since its emergence in the United States, there is increasing discussion surrounding the impact of the virus among vulnerable populations. Older adults, young children, and persons with chronic medical or mental health conditions, persons with disabilities, pregnant women, immunocompromised persons and those who are institutionalized or homeless are considered most vulnerable to death and lost quality of life (World Health Organization, 2020).", "title": "COVID‐19: Shedding light on racial and health inequities in the USA", "pid": "4prhmi8f", "bm25_score": 218.00015258789062}, {"text": "", "title": "COVID-19 Among African Americans: From Preliminary Epidemiological Surveillance Data to Public Health Action.", "pid": "ybkuoivn", "bm25_score": 217.99700927734375}, {"text": "", "title": "The Disproportionate Impact of COVID-19 on Racial and Ethnic Minorities in the United States", "pid": "ey1sqch4", "bm25_score": 217.9315185546875}, {"text": "Initial surveillance data suggests a disproportionately high number of deaths among Black patients with COVID-19. However, high-risk comorbidities are often over-represented in the Black population, and understanding whether the disparity is entirely secondary to them is essential. We performed a retrospective cohort study using real-time analysis of electronic medical records (EMR) of patients from multiple healthcare organizations in the United States. Our results showed that Black patients with COVID-19 have a significantly higher risk of mortality, hospitalization, and invasive mechanical ventilation compared to White patients. The incremental risk of poor outcomes in Blacks persists despite accounting for a higher prevalence of comorbidities. This may point to the disparities in socioeconomic determinants of health affecting Blacks and the need for an improvement in the care of this vulnerable population.", "title": "Comorbidities and Disparities in Outcomes of COVID-19 Among African American and White Patients", "pid": "cuo7qdkj", "bm25_score": 217.92710876464844}, {"text": "A series of 15-min videos were produced to provide resources to pastors in African-American communities to aid them in conveying accurate public and mental health information about COVID-19. Video presenters included trusted experts in public and mental health and pastors with considerable experience responding to the needs of the African-American community during the COVID-19 pandemic. Four culturally specific core themes to consider when providing care to African Americans who are at increased risk during the pandemic were identified: ritual disruption, negative reactions for not following public health guidelines, trauma, and culture and trust. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "A culturally specific mental health and spirituality approach for African Americans facing the COVID-19 pandemic", "pid": "5c6nwrdo", "bm25_score": 217.875}, {"text": "Background African American have been severely affected by COVID-19 noted with the rising mortality rates within the African American community. Health disparities, health inequities and issues with systemic health access are some of the pre-existing issues African American were subjected to within the southern states in the United States. Second, social distancing is a critical non-pharmacological intervention to reduce the spread of COVID-19. However, social distancing was not practical and presented a challenge within the African American community, specifically, in the southern states. Objective This article assesses the effect of COVID-19 on African American in the southern states. Methodology This short communication queried the publicly available Department of Health statistics on COVID-19 related mortality and underlying health conditions in four southern states (Alabama [AL], Georgia [GA], Louisiana [LA] and Mississippi [MS]) with a high proportion of African American residents. Second, unacast COVID-19 toolkit was used to derive a social distancing (SD) grade for any given state, based on three different metrics: (i) percent change in average distance travelled (ii) percent change in non-essential visits and (iii) decrease in human encounters (compared to national baseline). Results Across the four states, on average, as many as 54% of COVID-19 related deaths are in the African American community, although this minority group comprises only 32% of the population cumulatively. This article finds that all four southern states received a social distancing grade of F. COVID-19 have demonstrated that adverse outcomes are higher in individuals with underlying health conditions such as diabetes, cardiovascular diseases, or pre-existing pulmonary compromise. Conclusion Recognizing that there is a great need for African American representation or diversity in the health workforce would be able to better address the health disparities. In addition, the lack of diversity in the healthcare system causes the morbidity and mortality rates to increase in the African American communities because it is not able to address its primary obligations within the African American communities in the southern states during COVID-19 pandemic. These primary obligations are to restore, protect, improve health and to suppress health disparities and inequalities of COVID-19 within in the African American communities. Keywords: COVID-19; African American; Mortality", "title": "Disproportionate COVID-19 Related Mortality Amongst African Americans in Four Southern States in the United States", "pid": "8yvu9xhw", "bm25_score": 217.8031005859375}, {"text": "The Coronavirus disease 2019 (COVID-19) pandemic has significantly impacted and devastated the world. As the infection spreads, the projected mortality and economic devastation are unprecedented. In particular, racial and ethnic minorities may be at a particular disadvantage as many already assume the status of a marginalized group. Black Americans have a long-standing history of disadvantage and are in a vulnerable position to experience the impact of this crisis and the myth of Black immunity to COVID-19 is detrimental to promoting and maintaining preventative measures. We are the first to present the earliest available data in the peer-reviewed literature on the racial and ethnic distribution of COVID-19-confirmed cases and fatalities in the state of Connecticut. We also seek to explode the myth of Black immunity to the virus. Finally, we call for a National Commission on COVID-19 Racial and Ethnic Health Disparities to further explore and respond to the unique challenges that the crisis presents for Black and Brown communities.", "title": "The COVID-19 Pandemic: a Call to Action to Identify and Address Racial and Ethnic Disparities", "pid": "orz4be90", "bm25_score": 217.7335205078125}, {"text": "", "title": "Covid-19: Black people and other minorities are hardest hit in US", "pid": "hpzykj2r", "bm25_score": 217.70501708984375}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic has brought to light significant health inequities that have existed in our society for decades. Blacks, Hispanics, Native Americans, and immigrants are the populations most likely to experience disparities related to burden of disease, health care, and health outcomes. Increasingly, national and state statistics on COVID-19 report disproportionately higher mortality rates in blacks. There has never been a more pressing time for us to enact progressive and far-reaching changes in social, economic, and political policies that will shape programs aimed at improving the health of all people living in the United States.", "title": "COVID-19 and the Widening Gap in Health Inequity.", "pid": "sza8r2e1", "bm25_score": 217.6949920654297}, {"text": "The Black and Latino populations have experienced a disproportionate burden of COVID-19 morbidity and mortality, reflecting persistent structural inequalities that increase risk of exposure to COVID-19 and risk of death for those infected. According to the National Center for Health Statistics, as of July 4, 2020, deaths to Black and Latino individuals comprised 23% and 17%, respectively, of the approximately 115,000 COVID-19 deaths. COVID-19 mortality is likely to result in a larger decline in life expectancy during 2020 than the US has experienced for decades as well as a particularly large reduction for Black and Latino individuals. We estimate life expectancy at birth and at age 65 for 2020, by race and ethnicity, using four scenarios of deaths-one in which the COVID-19 pandemic had not occurred and three including COVID-19 mortality projections produced by the Institute for Health Metrics and Evaluation. Our most likely estimate indicates a reduction in life expectancy at birth greater than 1.5 years for both the Black and Latino populations, which is one year larger than the reduction for whites. This would imply that the Black-white gap would increase by 30%, from 3.6 to 4.7 years, thereby eliminating progress made in reducing this differential since 2008 and reversing an overall trend of steeper mortality declines among the Black population since the early 1990s. Latinos, who have consistently experienced lower mortality than whites (a phenomenon known as the Latino or Hispanic paradox), would see their survival advantage decline by 36%, equivalent to its magnitude in 2006.", "title": "Impact of COVID-19 on 2020 US life expectancy for the Black and Latino populations", "pid": "bjvg2ivr", "bm25_score": 217.6431427001953}, {"text": "We are colleagues and friends working together in busy emergency departments in Washington DC. As Black physicians working in urban America, we do not find the recent deluge of news reports chronicling the disproportionate effect that the coronavirus disease (COVID-19) pandemic is having on the disenfranchised and minority populations in our country shocking. We have long been witness to and are in a constant state of alarm over the legal, medical, educational, social and economic inequities faced by the most vulnerable residents of this country.", "title": "For us, COVID-19 is personal", "pid": "2djys8ky", "bm25_score": 217.62396240234375}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic has brought to light significant health inequities that have existed in our society for decades. Blacks, Hispanics, Native Americans, and immigrants are the populations most likely to experience disparities related to burden of disease, health care, and health outcomes. Increasingly, national and state statistics on COVID-19 report disproportionately higher mortality rates in blacks. There has never been a more pressing time for us to enact progressive and far-reaching changes in social, economic, and political policies that will shape programs aimed at improving the health of all people living in the United States.", "title": "COVID-19 and the Widening Gap in Health Inequity", "pid": "3omm8wkv", "bm25_score": 217.56613159179688}, {"text": "PURPOSE: Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. METHODS: Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. RESULTS: Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. CONCLUSIONS: Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.", "title": "Assessing Differential Impacts of COVID-19 on Black Communities", "pid": "kr86wlax", "bm25_score": 217.52720642089844}, {"text": "Purpose: Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. Methods: Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. Results: Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. Conclusions: Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.", "title": "Assessing Differential Impacts of COVID-19 on Black Communities", "pid": "dl3vkqas", "bm25_score": 217.52720642089844}, {"text": "Purpose Given incomplete data reporting by race, we used data on COVID-19 cases and deaths in US counties to describe racial disparities in COVID-19 disease and death and associated determinants. Methods Using publicly available data (accessed April 13, 2020), predictors of COVID-19 cases and deaths were compared between disproportionately (>13%) black and all other (<13% black) counties. Rate ratios were calculated and population attributable fractions (PAF) were estimated using COVID-19 cases and deaths via zero-inflated negative binomial regression model. National maps with county-level data and an interactive scatterplot of COVID-19 cases were generated. Results Nearly ninety-seven percent of disproportionately black counties (656/677) reported a case and 49% (330/677) reported a death versus 81% (1987/2,465) and 28% (684/ 2465), respectively, for all other counties. Counties with higher proportions of black people have higher prevalence of comorbidities and greater air pollution. Counties with higher proportions of black residents had more COVID-19 diagnoses (RR 1.24, 95% CI 1.17-1.33) and deaths (RR 1.18, 95% CI 1.00-1.40), after adjusting for county-level characteristics such as age, poverty, comorbidities, and epidemic duration. COVID-19 deaths were higher in disproportionally black rural and small metro counties. The PAF of COVID-19 diagnosis due to lack of health insurance was 3.3% for counties with <13% black residents and 4.2% for counties with >13% black residents. Conclusions Nearly twenty-two percent of US counties are disproportionately black and they accounted for 52% of COVID-19 diagnoses and 58% of COVID-19 deaths nationally. County-level comparisons can both inform COVID-19 responses and identify epidemic hot spots. Social conditions, structural racism, and other factors elevate risk for COVID-19 diagnoses and deaths in black communities.", "title": "Assessing Differential Impacts of COVID-19 on Black Communities", "pid": "p5owyivo", "bm25_score": 217.48468017578125}, {"text": "As reporting of COVID‐19 at the US state level has become more granular, many states have reported a higher proportion of deaths among African‐Americans. In our study, we assessed state level data on race, population density, age, obesity rates, insurance data, GDP, per capita healthcare resources (hospital‐beds/ventilators per‐capita), median household income and high‐school graduation rates. We report a higher death rate among states with a greater proportion of African‐American residents despite adjusting for case rates and state‐level factors. To the best of our knowledge this is the first study looking at state level data (from across the US) and mortality with COVID‐19. This article is protected by copyright. All rights reserved.", "title": "Differences in race and other state‐level characteristics and associations with mortality from COVID‐19 infection", "pid": "rxgnrrx8", "bm25_score": 217.41009521484375}, {"text": "The Coronavirus disease 2019 (COVID-19) pandemic has affected African American populations disproportionately in regards to both morbidity and mortality. A multitude of factors likely account for this discrepancy. Gene expression represents the interaction of genetics and environment. To elucidate whether levels of expression of genes implicated in COVID-19 vary in African Americans as compared to European Americans, we re-mine The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) RNA-Seq data. Multiple genes integral to infection, inflammation and immunity are differentially regulated across the two populations. Most notably, F8A2 and F8A3, which encode the HAP40 protein that mediates early endosome movement in Huntington’s Disease, are more highly expressed by up to 24-fold in African Americans. Such differences in gene expression can establish prognostic signatures and have critical implications for precision treatment of diseases such as COVID-19. We advocate routine inclusion of information such as postal code, education level, and profession (as a proxies for socioeconomic condition) and race in the metadata about each individual sampled for sequencing studies. This relatively simple change would enable large-scale data-driven approaches to dissect relationships among race, socio-economic factors, and disease.", "title": "Differential expression of COVID-19-related genes in European Americans and African Americans", "pid": "miayce9l", "bm25_score": 217.4088134765625}, {"text": "Introduction: Racial and ethnic minorities have shouldered a disproportioned burden of coronavirus disease 2019 (COVID-19) infection to date in the US, but data on the various drivers of these disparities is limited. Objectives: To describe the characteristics and outcomes of COVID-19 patients and explore factors associated with hospitalization risk by race. Methods: Case series of 448 consecutive patients with confirmed COVID-19 seen at Kaiser Permanente Georgia (KPGA), an integrated health care system serving the Atlanta metropolitan area, from March 3 to May 12, 2020. KPGA members with laboratory-confirmed COVID-19. Multivariable analyses for hospitalization risk also included an additional 3489 persons under investigation (PUI) with suspected infection. COVID-19 treatment and outcomes, underlying comorbidities and quality of care management metrics, socio-demographic and other individual and community-level social determinants of health (SDOH) indicators. Results: Of 448 COVID-19 positive members, 68,3% was non-Hispanic Black (n=306), 18% non-Hispanic White (n=81) and 13,7% Other race (n=61). Median age was 54 [IQR 43-63) years. Overall, 224 patients were hospitalized, median age 60 (50-69) years. Black race was a significant factor in the Confirmed + PUI, female and male models (ORs from 1.98 to 2.19). Obesity was associated with higher hospitalization odds in the confirmed, confirmed + PUI, Black and male models (ORs from 1.78 to 2.77). Chronic disease control metrics (diabetes, hypertension, hyperlipidemia) were associated with lower odds of hospitalization ranging from 48% to 35% in the confirmed + PUI and Black models. Self-reported physical inactivity was associated with 50% higher hospitalization odds in the Black and Female models. Residence in the Northeast region of Atlanta was associated with lower hospitalization odds in the Confirmed + PUI, White and female models (ORs from 0.22 to 0.64) Conclusions: We found that non-Hispanic Black KPGA members had a disproportionately higher risk of infection and, after adjusting for covariates, twice the risk of hospitalization compared to other race groups. We found no significant differences in clinical outcomes or mortality across race/ethnicity groups. In addition to age, sex and comorbidity burden, pre-pandemic self-reported exercise, metrics on quality of care and control of underlying cardio-metabolic diseases, and location of residence in Atlanta were significantly associated with hospitalization risk by race groups. Beyond well-known physiologic and clinical factors, individual and community-level social indicators and health behaviors must be considered as interventions designed to reduce COVID-19 disparities and the systemic effects of racism are implemented.", "title": "Clinical, Behavioral and Social Factors Associated with Racial Disparities in Hospitalized and Ambulatory COVID-19 Patients from an Integrated Health Care System in Georgia", "pid": "ix2cbs4j", "bm25_score": 217.30374145507812}, {"text": "", "title": "Being African American and Rural: A Double Jeopardy From COVID-19", "pid": "cme34stj", "bm25_score": 217.27728271484375}, {"text": "BACKGROUND: Recent news reports state that racial minority groups, such as African-Americans, are experiencing a greater COVID-19 burden, as measured by confirmed cases and deaths. Limited racial data is available on a national level. METHODS: We conducted the first nationwide analysis to examine COVID-19 and race on a county level. We obtained datasets on COVID-19 cases and deaths, and racial population totals, by US county. We examined if correlations exist between the racial percentages and percentages of confirmed COVID-19 cases and deaths by county. RESULTS: A positive correlation existed between percentages of African-Americans living in a county and who have COVID-19 (r = 0.254, P < 0.0001), who have died from COVID-19 (r = 0.268, P < 0.0001), and case mortality (r = 0.055, P = 0.003). Positive correlations also existed between percentages of Asian-Americans living in counties and these factors. Negative correlations existed between percentages of Whites living in counties and these factors. CONCLUSIONS: A weak, albeit very significant, positive relationship exists between the percentage of African-Americans living in a county and the percentage of COVID-19 confirmed cases, confirmed deaths and case mortality in the county. This is in support of many city and statewide analyses, and we urge for targeted resources towards work that further examine these racial associations.", "title": "Racial demographics and COVID-19 confirmed cases and deaths: a correlational analysis of 2886 US counties", "pid": "ne552y3i", "bm25_score": 217.265380859375}, {"text": "International and national crises often highlight inequalities in the labor market that disproportionately affect individuals from marginalized backgrounds. The COVID-19 pandemic, and the resulting changes in society due to social distancing measures, has showcased inequities in access to decent work and experiences of discrimination resulting in many of the vulnerable populations in the United States experiencing a much harsher impact on economic and work-related factors. The purpose of this essay is to describe how the COVID-19 pandemic may differentially affect workers of color, individuals from low-income backgrounds, and women in complex ways. First, this essay will discuss disproportionate representation of workers from low-income and racial/ethnic minority backgrounds in sectors most affected by COVID-19. Second, it will discuss the lack of decent work for low-income workers who perform \"essential\" tasks. Third, this essay will highlight economic and work-related implications of increased discrimination Asian Americans are experiencing in society. Finally, role conflict and stress for women who are managing additional unpaid work, including caretaking responsibilities, while needing to continue to engage in paid work will be examined. A research agenda will be set forth throughout the essay, calling for vocational psychologists to engage in research that fully examines how the COVID-19 pandemic is affecting vulnerable communities.", "title": "The impact of the COVID-19 pandemic on marginalized populations in the United States: A research agenda", "pid": "yvnjspsc", "bm25_score": 217.17657470703125}, {"text": "BACKGROUND: Recent news reports state that racial minority groups, such as African–Americans, are experiencing a greater COVID-19 burden, as measured by confirmed cases and deaths. Limited racial data is available on a national level. METHODS: We conducted the first nationwide analysis to examine COVID-19 and race on a county level. We obtained datasets on COVID-19 cases and deaths, and racial population totals, by US county. We examined if correlations exist between the racial percentages and percentages of confirmed COVID-19 cases and deaths by county. RESULTS: A positive correlation existed between percentages of African–Americans living in a county and who have COVID-19 (r = 0.254, P < 0.0001), who have died from COVID-19 (r = 0.268, P < 0.0001), and case mortality (r = 0.055, P = 0.003). Positive correlations also existed between percentages of Asian–Americans living in counties and these factors. Negative correlations existed between percentages of Whites living in counties and these factors. CONCLUSIONS: A weak, albeit very significant, positive relationship exists between the percentage of African–Americans living in a county and the percentage of COVID-19 confirmed cases, confirmed deaths and case mortality in the county. This is in support of many city and statewide analyses, and we urge for targeted resources towards work that further examine these racial associations.", "title": "Racial demographics and COVID-19 confirmed cases and deaths: a correlational analysis of 2886 US counties", "pid": "58ye9c5a", "bm25_score": 217.16934204101562}, {"text": "Abstract Background: There is preliminary evidence of racial and social-economic disparities in the population infected by and dying from COVID-19. The goal of this study is to report the associations of COVID-19 with respect to race, health and economic inequality in the United States. Methods: We performed a cross-sectional study of the associations between infection and mortality rate of COVID-19 and demographic, socioeconomic and mobility variables from 369 counties (total population: 102,178,117 [median: 73,447, IQR: 30,761-256,098]) from the seven most affected states (Michigan, New York, New Jersey, Pennsylvania, California, Louisiana, Massachusetts). Findings: The risk factors for infection and mortality are different. Our analysis shows that counties with more diverse demographics, higher population, education, income levels, and lower disability rates were at a higher risk of COVID-19 infection. However, counties with higher disability and poverty rates had a higher death rate. African Americans were more vulnerable to COVID-19 than other ethnic groups (1,981 African American infected cases versus 658 Whites per million). Data on mobility changes corroborate the impact of social distancing. Interpretation: The observed inequality might be due to the workforce of essential services, poverty, and access to care. Counties in more urban areas are probably better equipped at providing care. The lower rate of infection, but a higher death rate in counties with higher poverty and disability could be due to lower levels of mobility, but a higher rate of comorbidities and health care access. Keywords: Healthcare Disparities, Health Status Disparities, Socioeconomic Factors, COVID-19, Economic Inequality, Racial Disparity, United States, Population-Based Analysis.", "title": "Racial, Economic and Health Inequality and COVID-19 Infection in the United States", "pid": "alrf67ep", "bm25_score": 217.13720703125}, {"text": "The high numbers of COVID-19 infections and deaths, economic difficulties, uncertainty about the future, as well as the approaches needed to contain the spread of the virus are all playing critical roles in the short and long-term social and psychological impact of the COVID-19 pandemic. Inequities based on race and socioeconomic status influence the rates of infection and deaths and steps that are needed to achieve recovery. This commentary focuses on similarities and differences after other disasters and efforts being initiated to provide support and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Psychological and social impact of COVID-19.", "pid": "hdy4h13e", "bm25_score": 217.11602783203125}, {"text": "Importance: Data from the coronavirus disease 2019 (COVID-19) pandemic in the US show large differences in hospitalizations and mortality across race and geography. However, there are limited data on health information, beliefs, and behaviors that might indicate different exposure to risk. Objective: To determine the association of sociodemographic characteristics with reported incidence, knowledge, and behavior regarding COVID-19 among US adults. Design, Setting, and Participants: A US national survey study was conducted from March 29 to April 13, 2020, to measure differences in knowledge, beliefs, and behavior about COVID-19. The survey oversampled COVID-19 hotspot areas. The survey was conducted electronically. The criteria for inclusion were age 18 years or older and residence in the US. Data analysis was performed in April 2020. Main Outcomes and Measures: The main outcomes were incidence, knowledge, and behaviors related to COVID-19 as measured by survey response. Results: The survey included 5198 individuals (mean [SD] age, 48 [18] years; 2336 men [45%]; 3759 white [72%], 830 [16%] African American, and 609 [12%] Hispanic). The largest differences in COVID-19-related knowledge and behaviors were associated with race/ethnicity, sex, and age, with African American participants, men, and people younger than 55 years showing less knowledge than other groups. African American respondents were 3.5 percentage points (95% CI, 1.5 to 5.5 percentage points; P = .001) more likely than white respondents to report being infected with COVID-19, as were men compared with women (3.2 percentage points; 95% CI, 2.0 to 4.4 percentage points; P < .001). Knowing someone who tested positive for COVID-19 was more common among African American respondents (7.2 percentage points; 95% CI, 3.4 to 10.9 percentage points; P < .001), people younger than 30 years (11.6 percentage points; 95% CI, 7.5 to 15.7 percentage points; P < .001), and people with higher incomes (coefficient on earning &#8805;$100 000, 12.3 percentage points; 95% CI, 8.7 to 15.8 percentage points; P < .001). Knowledge of potential fomite spread was lower among African American respondents (-9.4 percentage points; 95% CI, -13.1 to -5.7 percentage points; P < .001), Hispanic respondents (-4.8 percentage points; 95% CI, -8.9 to -0.77 percentage points; P = .02), and people younger than 30 years (-10.3 percentage points; 95% CI, -14.1 to -6.5 percentage points; P < .001). Similar gaps were found with respect to knowledge of COVID-19 symptoms and preventive behaviors. Conclusions and Relevance: In this survey study of US adults, there were gaps in reported incidence of COVID-19 and knowledge regarding its spread and symptoms and social distancing behavior. More effort is needed to increase accurate information and encourage appropriate behaviors among minority communities, men, and younger people.", "title": "Disparities in Coronavirus 2019 Reported Incidence, Knowledge, and Behavior Among US Adults", "pid": "0iy8stse", "bm25_score": 217.11581420898438}, {"text": "We are colleagues and friends working together in busy emergency departments in Washington DC. As Black physicians working in urban America, we do not find the recent deluge of news reports chronicling the disproportionate effect that the coronavirus disease (COVID‐19) pandemic is having on the disenfranchised and minority populations in our country shocking. We have long been witness to and are in a constant state of alarm over the legal, medical, educational, social and economic inequities faced by the most vulnerable residents of this country.", "title": "For us, COVID‐19 is personal", "pid": "13hperkz", "bm25_score": 217.07928466796875}, {"text": "Health inequities have long defined health and the healthcare system in the USA. The clinical and research capacity across the USA is unparalleled, yet compared to other high and even some middle-income countries, the average health indicators of the population remain suboptimal in 2020, a finding at least in part explained by inequity in healthcare access. In this context, COVID-19 has rapidly emerged as a major threat to the public's health. While it was initially thought that severe acute respiratory syndrome coronavirus 2 would be the great equaliser as it would not discriminate, it is clear that COVID-19 incidence and mortality have rapidly reinforced health disparities drawn by historical and contemporary inequities. Here, we synthesise the data highlighting specific risks among particular marginalised and under-resourced communities including those in jails, prisons and detention centers, immigrants and the undocumented, people with disabilities and people experiencing homelessness across the USA. The drivers of these disparities are pervasive structural risks including limited access to preventive services, inability to comply with physical distancing recommendations, underlying health disparities and intersecting stigmas particularly affecting racial and ethnic minorities across the country, including African Americans, Latinx Americans and Native Americans. Advancing the COVID-19 response, saving lives and restarting the economy necessitate rapidly addressing these inequities rather than ignoring and even reinforcing them.", "title": "COVID-19 and the US response: accelerating health inequities", "pid": "n3wbuxnv", "bm25_score": 217.074462890625}, {"text": "BACKGROUND: Many people living with HIV (PLWH) have comorbidities which are risk factors for severe COVID-19 or have exposures that may lead to acquisition of SARS-CoV-2. There are few studies, however, on the demographics, comorbidities, clinical presentation or outcomes of COVID-19 in people with HIV. OBJECTIVE: To evaluate risk factors, clinical manifestations and outcomes in a large cohort of PLWH with COVID-19. METHODS: We systematically identified all PLWH who were diagnosed with COVID-19 at a large hospital from March 3 to April 26, 2020 during an outbreak in Massachusetts. We analyzed each of the cases to extract information including demographics, medical comorbidities, clinical presentation, and illness course after COVID-19 diagnosis. RESULTS: We describe a cohort of 36 PLWH with confirmed COVID-19 and another 11 patients with probable COVID-19. Almost 85% of PLWH with confirmed COVID-19 had a comorbidity associated with severe disease, including obesity, cardiovascular disease, or hypertension. Approximately 77% of PLWH with COVID-19 were non-Hispanic Black or Latinx whereas only 40% of the PLWH in our clinic were Black or Latinx. Nearly half of PLWH with COVID-19 had exposure to congregate settings. In addition to people with confirmed COVID-19, we identified another 11 individuals with probable COVID-19, almost all of whom had negative PCR testing. CONCLUSION: In the largest cohort to date of PLWH and confirmed COVID-19, almost all had a comorbidity associated with severe disease, highlighting the importance of non-HIV risk factors in this population. The racial disparities and frequent link to congregate settings in PLWH and COVID-19 need to be explored urgently.", "title": "Disproportionate burden of COVID-19 among racial minorities and those in congregate settings among a large cohort of people with HIV", "pid": "8c53ne5x", "bm25_score": 217.06622314453125}, {"text": "Abstract International and national crises often highlight inequalities in the labor market that disproportionately affect individuals from marginalized backgrounds. The COVID-19 pandemic, and the resulting changes in society due to social distancing measures, has showcased inequities in access to decent work and experiences of discrimination resulting in many of the vulnerable populations in the United States experiencing a much harsher impact on economic and work-related factors. The purpose of this essay is to describe how the COVID-19 pandemic may differentially affect workers of color, individuals from low-income backgrounds, and women in complex ways. First, this essay will discuss disproportionate representation of workers from low-income and racial/ethnic minority backgrounds in sectors most affected by COVID-19. Second, it will discuss the lack of decent work for low-income workers who perform “essential” tasks. Third, this essay will highlight economic and work-related implications of increased discrimination Asian Americans are experiencing in society. Finally, role conflict and stress for women who are managing additional unpaid work, including caretaking responsibilities, while needing to continue to engage in paid work will be examined. A research agenda will be set forth throughout the essay, calling for vocational psychologists to engage in research that fully examines how the COVID-19 pandemic is affecting vulnerable communities.", "title": "The impact of the COVID-19 pandemic on marginalized populations in the United States: A research agenda", "pid": "lc4q55ei", "bm25_score": 217.05113220214844}, {"text": "Health inequities have long defined health and the healthcare system in the USA. The clinical and research capacity across the USA is unparalleled, yet compared to other high and even some middle-income countries, the average health indicators of the population remain suboptimal in 2020, a finding at least in part explained by inequity in healthcare access. In this context, COVID-19 has rapidly emerged as a major threat to the public’s health. While it was initially thought that severe acute respiratory syndrome coronavirus 2 would be the great equaliser as it would not discriminate, it is clear that COVID-19 incidence and mortality have rapidly reinforced health disparities drawn by historical and contemporary inequities. Here, we synthesise the data highlighting specific risks among particular marginalised and under-resourced communities including those in jails, prisons and detention centers, immigrants and the undocumented, people with disabilities and people experiencing homelessness across the USA. The drivers of these disparities are pervasive structural risks including limited access to preventive services, inability to comply with physical distancing recommendations, underlying health disparities and intersecting stigmas particularly affecting racial and ethnic minorities across the country, including African Americans, Latinx Americans and Native Americans. Advancing the COVID-19 response, saving lives and restarting the economy necessitate rapidly addressing these inequities rather than ignoring and even reinforcing them.", "title": "COVID-19 and the US response: accelerating health inequities", "pid": "0ctlde8w", "bm25_score": 217.03958129882812}, {"text": "BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19-positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19-positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.", "title": "Hospitalization and Mortality among Black Patients and White Patients with Covid-19", "pid": "e76foj38", "bm25_score": 217.00860595703125}, {"text": "Black communities in the United States are bearing the brunt of the COVID-19 pandemic and the underlying conditions that exacerbate its negative consequences. Syndemic theory provides a useful framework for understanding how such interacting epidemics to develop under conditions of health and social disparity. Multiple historical and present-day factors have created the syndemic conditions within which Black Americans experience the lethal force of COVID-19. These factors include racism and its manifestations (e.g., chattel slavery, mortgage redlining, political gerrymandering, lack of Medicaid expansion, employment discrimination, and healthcare provider bias). Improving racial disparities in COVID-19 will require that we implement policies that address structural racism at the root of these disparities.", "title": "Understanding COVID-19 Risks and Vulnerabilities among Black Communities in America: The Lethal Force of Syndemics", "pid": "vs4qb91t", "bm25_score": 217.00405883789062}, {"text": "SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in the United States during January 2020 (1). Since then, >980,000 cases have been reported in the United States, including >55,000 associated deaths as of April 28, 2020 (2). Detailed data on demographic characteristics, underlying medical conditions, and clinical outcomes for persons hospitalized with COVID-19 are needed to inform prevention strategies and community-specific intervention messages. For this report, CDC, the Georgia Department of Public Health, and eight Georgia hospitals (seven in metropolitan Atlanta and one in southern Georgia) summarized medical record-abstracted data for hospitalized adult patients with laboratory-confirmed* COVID-19 who were admitted during March 2020. Among 305 hospitalized patients with COVID-19, 61.6% were aged <65 years, 50.5% were female, and 83.2% with known race/ethnicity were non-Hispanic black (black). Over a quarter of patients (26.2%) did not have conditions thought to put them at higher risk for severe disease, including being aged ≥65 years. The proportion of hospitalized patients who were black was higher than expected based on overall hospital admissions. In an adjusted time-to-event analysis, black patients were not more likely than were nonblack patients to receive invasive mechanical ventilation† (IMV) or to die during hospitalization (hazard ratio [HR] = 0.63; 95% confidence interval [CI] = 0.35-1.13). Given the overrepresentation of black patients within this hospitalized cohort, it is important for public health officials to ensure that prevention activities prioritize communities and racial/ethnic groups most affected by COVID-19. Clinicians and public officials should be aware that all adults, regardless of underlying conditions or age, are at risk for serious illness from COVID-19.", "title": "Characteristics and Clinical Outcomes of Adult Patients Hospitalized with COVID-19 - Georgia, March 2020.", "pid": "vvuaegse", "bm25_score": 217.0016326904297}, {"text": "Importance: Racial disparities in COVID-19 outcomes have been amplified during this pandemic and reports on outcomes in African-American (AA) populations, known to have higher rates of cardiovascular (CV) comorbidities, remain limited. Objective: To examine prevalence of comorbidities, rates of hospitalization and survival, and incidence of CV manifestations of COVID-19 in a predominantly AA population in south metropolitan Chicago. Design, Setting, Participants: This was an observational cohort study of COVID-19 patients encountered from March 16 to April 16, 2020 at the University of Chicago. Deidentified data were obtained from an institutional data warehouse. Group comparisons and logistic regression modeling based on baseline demographics, clinical characteristics, laboratory and diagnostic testing was performed. Exposures: COVID-19 was diagnosed by nasopharyngeal swab testing and clinical management was at the discretion of treating physicians. Main Outcomes and Measures: Primary outcomes were hospitalization and in-hospital mortality, and secondary outcomes included incident CV manifestations of COVID-19 in the context of overall cardiology service utilization. Results: During the 30 day study period, 1008 patients tested positive for COVID-19 and 689 had available encounter data. Of these, 596 (87%) were AA and 356 (52%) were hospitalized, of which 319 (90%) were AA. Age > 60 years, tobacco use, BMI >40 kg/m2, diabetes mellitus (DM), insulin use, hypertension, chronic kidney disease, coronary artery disease (CAD), and atrial fibrillation (AF) were more common in hospitalized patients. Age > 60 years, tobacco use, CAD, and AF were associated with greater risk of in-hospital mortality along with several elevated initial laboratory markers including troponin, NT-proBNP, blood urea nitrogen, and ferritin. Despite this, cardiac manifestations of COVID-19 were uncommon, coincident with a 69% decrease in cardiology service utilization. For hospitalized patients, median length of stay was 6.2 days (3.4-11.9 days) and mortality was 13%. AA patients were more commonly hospitalized, but without increased mortality. Conclusions and Relevance: In this AA-predominant experience from south metropolitan Chicago, CV comorbidities and chronic diseases were highly prevalent and associated with increased hospitalization and mortality. Insulin-requiring DM and CKD emerged as novel predictors for hospitalization. Despite the highest rate of comorbidities reported to date, CV manifestations of COVID-19 and mortality were relatively low. The unexpectedly low rate of mortality merits further study.", "title": "Outcomes and Cardiovascular Comorbidities in a Predominantly African-American Population with COVID-19", "pid": "4f6h7agt", "bm25_score": 216.97679138183594}, {"text": "", "title": "African American children are at higher risk of COVID-19 infection", "pid": "orf50kvt", "bm25_score": 216.9761962890625}, {"text": "", "title": "African-American COVID-19 Mortality: A Sentinel Event", "pid": "vvbepc9g", "bm25_score": 216.97425842285156}, {"text": "Introduction. The population and spatial characteristics of COVID-19 infections are poorly understood, but there is increasing evidence that in addition to individual clinical factors, demographic, socioeconomic and racial characteristics play an important role. Methods. We analyzed positive COVID-19 testing results counts within New York City ZIP Code Tabulation Areas (ZCTA) with Bayesian hierarchical Poisson spatial models using integrated nested Laplace approximations. Results. Spatial clustering accounted for approximately 32% of the variation in the data, with hot spots in all five boroughs. Spatial risk did not correspond precisely to population-based rates of positive tests. The strongest univariate association with positive testing rates was the proportion of residents in a ZIP Code Tabulation Area with Chronic Obstructive Pulmonary Disease (COPD). For every one unit increase in a scaled standardized measure of COPD in a community, there was an approximate 8-fold increase in the risk of a positive COVID-19 test in a ZCTA (Incidence Density Ratio = 8.2, 95% Credible Interval 3.7, 18.3). The next strongest association was with the proportion of Black and African American residents, for which there was a nearly five-fold increase in the risk of a positive COVID-19 test. (IDR = 4.8, 95% Cr I 2.4, 9.7). Increases in the proportion of residents older than 65, housing density and the proportion of residents with heart disease were each associated with an approximate doubling of risk. In a multivariable model including estimates for age, COPD, heart disease, housing density and Black/African American race, the only variables that remained associated with positive COVID-19 testing with a probability greater than chance were the proportion of Black/African American residents and proportion of older persons. Conclusions. The population and spatial patterns of COVID-19 infections differ by race, age, physical environment and health status. Areas with large proportions of Black/African American residents are at markedly higher risk that is not fully explained by characteristics of the environment and pre-existing conditions in the population.", "title": "Blacks/African Americans are 5 Times More Likely to Develop COVID-19: Spatial Modeling of New York City ZIP Code-level Testing Results", "pid": "crqvdk4k", "bm25_score": 216.97254943847656}, {"text": "As the architect of racial disparity, racism shapes the vulnerability of communities. Socially vulnerable communities are less resilient in their ability to respond to and recover from natural and man‐made disasters when compared to resourced communities. This essay argues that racism exposes existing practices and structures in public administration that, along with the effects of COVID‐19, have led to disproportionate infection and death rates of Black people. Using the Centers for Disease Control's Social Vulnerability Index (SVI) authors analyze the ways Black bodies occupy the most vulnerable communities, making them bear the brunt of COVID‐19’s impact. Findings suggest that existing disparities exacerbate COVID‐19 outcomes for Black people. Targeted universalism is offered as an administrative framework to meet the needs of all people impacted by COVID‐19. This article is protected by copyright. All rights reserved.", "title": "Social Vulnerability and Equity: The Disproportionate Impact of COVID‐19", "pid": "gbqacbvl", "bm25_score": 216.97003173828125}, {"text": "Abstract The 2019 coronavirus disease is a serious public health emergency, with serious adverse implications for populations, healthcare systems, and economies globally. Recently, concerns have been raised about possible association between ethnicity, incidence and outcomes of COVID-19 arisen from early government data. In this review, we will explore the possible association using both recent COVID-19 studies and studies of previous pandemics. We call for data on ethnicity to be routinely collected by governments, as part of international collaboration, alongside other patient demographics and further research to robustly determine magnitude of association. Moreover, governments must learn from previous pandemics and recommended strategies to mitigate risks on minority ethnicities due to socioeconomic disadvantages.", "title": "COVID-19: Unique public health issues facing Black, Asian and minority ethnic communities", "pid": "ket7ma6o", "bm25_score": 216.9677276611328}, {"text": "", "title": "Increased cardiovascular mortality in African Americans with COVID-19", "pid": "ynvu5sk5", "bm25_score": 216.95822143554688}, {"text": "INTRODUCTION: On March 13, 2020 the WHO declared COVID-19 a pandemic. Shortly after that, it was reported that mortality rates in New York City (NYC), the epicenter of the pandemic in the United States, were found to be significantly higher in African American and Hispanics. The aim of this manuscript is to evaluate the mortality rates in NYC among the different ethnic groups and the different boroughs as it relates to the obesity rates to see whether this issue merits further evaluation. METHODS: COVID-19 data was obtained from the official New York (NY) authorities in relation to total number of cases in the different boroughs of NYC. Age adjusted COVID-19 related mortality rates of the different ethnic groups were also obtained. This data was cross compared to historic community health data on obesity rates previously published and also obesity rates among the different ethnic groups in NYC. RESULTS: The two NYC boroughs that have the highest mortality rates are The Bronx (6%) and Brooklyn (5.4%). Both The Bronx and Brooklyn were also found to have the highest obesity rates 32% and 27% respectively. The two ethnic groups with the highest obesity rates (Hispanics and African Americans) were also found to have the highest age adjusted mortality rates per 100,000 compared to the other ethnic groups (22.8% and 19.8% respectively). CONCLUSION: Hispanics and African Americans in NYC seem to be disproportionately affected by the COVID-19 pandemic because of the higher incidence of mortality rates. Obesity may have played a role in the high incidence of mortality in those ethnic groups.", "title": "Are African American and Hispanics Disproportionately Affected by COVID-19 Because of Higher Obesity Rates?", "pid": "fvkr77sf", "bm25_score": 216.95779418945312}, {"text": "Importance: To cope with the continuing COVID-19 pandemic, state and local health officials need information on the effectiveness of policies aimed at curbing contagion, as well as area-specific socio-demographic characteristics that can portend vulnerability to the disease. Objective: To investigate whether state-imposed stay-at-home orders, African American population in the state, state poverty and other state socio-demographic characteristics, were associated with the state-level incidence of COVID-19 infection. Design, Setting, Participants: State-level, aggregated, publicly available data on positive COVID-19 cases and tests were used. The period considered was March 1st -May 4th. All U.S. states except Washington were included. Outcomes of interest were daily cumulative and daily incremental COVID-19 infection rates. Outcomes were log-transformed. Log-linear regression models with a quadratic time-trend and random intercepts for states were estimated. Covariates included log-transformed test-rates, a binary indicator for stay-at-home, percentage of African American, poverty, percentage elderly, state population and prevalence of selected comorbidities. Binary fixed effects for date each state first started reporting test data were included. Results: Stay-at-home orders were associated with decreases in cumulative ({beta}:-1.23; T-stat: -6.84) and daily ({beta}:-0.46; T-stat: -2.56) infection-rates. Predictive analyses indicated that expected cumulative infection rates would be 3 times higher and expected daily incremental rates about 60% higher in absence of stay-at-home orders. Higher African American population was associated with higher cumulative ({beta}: 0.08; T-stat: 4.01) and daily ({beta}: 0.06; T-stat: 3.50) rates. State poverty rates had mixed results and were not robust to model specifications. There was strong evidence of a quadratic daily trend for cumulative and daily rates. Results were largely robust to alternate specifications. Conclusions: We find evidence that stay-at-home orders, which were widely supported by public-health experts, helped to substantially curb COVID-19 infection-rates. As we move to a phased re-opening, continued precautions advised by public-health experts should be adhered to. Also, a larger African American population is strongly associated with incidence of COVID-19 infection. Policies and resources to help mitigate African American vulnerability to COVID-19 is an urgent public health and social justice issue, especially since the ongoing mass protests against police brutality may further exacerbate COVID-19 contagion in this community.", "title": "Stay-at-Home Orders, African American Population, Poverty and State-level Covid-19 Infections: Are there associations?", "pid": "csujgaae", "bm25_score": 216.94410705566406}, {"text": "Infection by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the viral etiology of the novel coronavirus disease 2019 (COVID‐19), was first reported in Wuhan, China in late 2019. Peculiarly, the virus has not caused significant impact on pediatric populations, unlike other coronaviruses (1). Children comprise only 1.7% of COVID‐19 positive cases in the United States (2). Furthermore, children are noted to have a milder disease course (3, 4). However, much is unknown about the age, gender and race risk factors of COVID‐19 among children. There has been recent evidence suggestive of higher rates of COVID‐19 and related fatality rates in African American adult communities around the United States(5). However, there is limited data, to our knowledge, whether any race or ethnicity group is at higher risk for COVID‐19 infection in children.", "title": "African American children are at higher risk for COVID‐19 infection", "pid": "b5lrwe3i", "bm25_score": 216.9285430908203}, {"text": "COVID-19 has changed our lives and it appears to be especially harmful for some groups more than others. Black and Asian ethnic minorities are at particular risk and have reported greater mortality and intensive care needs. Mental illnesses are more common among Black and ethnic minorities, as are crisis care pathways including compulsory admission. This editorial sets out what might underlie these two phenomena, explaining how societal structures and disadvantage generate and can escalate inequalities in crises.", "title": "Mental health and COVID-19: is the virus racist?", "pid": "aku7m0i5", "bm25_score": 216.8816375732422}, {"text": "The 2019 coronavirus disease is a serious public health emergency, with serious adverse implications for populations, healthcare systems, and economies globally. Recently, concerns have been raised about possible association between ethnicity, incidence and outcomes of COVID-19 arisen from early government data. In this review, we will explore the possible association using both recent COVID-19 studies and studies of previous pandemics. We call for data on ethnicity to be routinely collected by governments, as part of an international collaboration, alongside other patient demographics and further research to robustly determine the magnitude of association. Moreover, governments must learn from previous pandemics and recommended strategies to mitigate risks on minority ethnicities due to socioeconomic disadvantages.", "title": "COVID-19: Unique public health issues facing Black, Asian and minority ethnic communities", "pid": "xzc7bwe3", "bm25_score": 216.8680419921875}, {"text": "", "title": "African American COVID-19 Mortality: A Sentinel Event", "pid": "9keet8ih", "bm25_score": 216.86094665527344}, {"text": "BACKGROUND Many people living with HIV (PLWH) have comorbidities which are risk factors for severe COVID-19 or have exposures that may lead to acquisition of SARS-CoV-2. There are few studies, however, on the demographics, comorbidities, clinical presentation or outcomes of COVID-19 in people with HIV. OBJECTIVE To evaluate risk factors, clinical manifestations and outcomes in a large cohort of PLWH with COVID-19. METHODS We systematically identified all PLWH who were diagnosed with COVID-19 at a large hospital from March 3 to April 26, 2020 during an outbreak in Massachusetts. We analyzed each of the cases to extract information including demographics, medical comorbidities, clinical presentation, and illness course after COVID-19 diagnosis. RESULTS We describe a cohort of 36 PLWH with confirmed COVID-19 and another 11 patients with probable COVID-19. Almost 85% of PLWH with confirmed COVID-19 had a comorbidity associated with severe disease, including obesity, cardiovascular disease, or hypertension. Approximately 77% of PLWH with COVID-19 were non-Hispanic Black or Latinx whereas only 40% of the PLWH in our clinic were Black or Latinx. Nearly half of PLWH with COVID-19 had exposure to congregate settings. In addition to people with confirmed COVID-19, we identified another 11 individuals with probable COVID-19, almost all of whom had negative PCR testing. CONCLUSION In the largest cohort to date of PLWH and confirmed COVID-19, almost all had a comorbidity associated with severe disease, highlighting the importance of non-HIV risk factors in this population. The racial disparities and frequent link to congregate settings in PLWH and COVID-19 need to be explored urgently.", "title": "Disproportionate burden of COVID-19 among racial minorities and those in congregate settings among a large cohort of people with HIV.", "pid": "jnugy88i", "bm25_score": 216.85641479492188}, {"text": "IMPORTANCE: Data from the coronavirus disease 2019 (COVID-19) pandemic in the US show large differences in hospitalizations and mortality across race and geography. However, there are limited data on health information, beliefs, and behaviors that might indicate different exposure to risk. OBJECTIVE: To determine the association of sociodemographic characteristics with reported incidence, knowledge, and behavior regarding COVID-19 among US adults. DESIGN, SETTING, AND PARTICIPANTS: A US national survey study was conducted from March 29 to April 13, 2020, to measure differences in knowledge, beliefs, and behavior about COVID-19. The survey oversampled COVID-19 hotspot areas. The survey was conducted electronically. The criteria for inclusion were age 18 years or older and residence in the US. Data analysis was performed in April 2020. MAIN OUTCOMES AND MEASURES: The main outcomes were incidence, knowledge, and behaviors related to COVID-19 as measured by survey response. RESULTS: The survey included 5198 individuals (mean [SD] age, 48 [18] years; 2336 men [45%]; 3759 white [72%], 830 [16%] African American, and 609 [12%] Hispanic). The largest differences in COVID-19–related knowledge and behaviors were associated with race/ethnicity, sex, and age, with African American participants, men, and people younger than 55 years showing less knowledge than other groups. African American respondents were 3.5 percentage points (95% CI, 1.5 to 5.5 percentage points; P = .001) more likely than white respondents to report being infected with COVID-19, as were men compared with women (3.2 percentage points; 95% CI, 2.0 to 4.4 percentage points; P < .001). Knowing someone who tested positive for COVID-19 was more common among African American respondents (7.2 percentage points; 95% CI, 3.4 to 10.9 percentage points; P < .001), people younger than 30 years (11.6 percentage points; 95% CI, 7.5 to 15.7 percentage points; P < .001), and people with higher incomes (coefficient on earning ≥$100 000, 12.3 percentage points; 95% CI, 8.7 to 15.8 percentage points; P < .001). Knowledge of potential fomite spread was lower among African American respondents (−9.4 percentage points; 95% CI, −13.1 to −5.7 percentage points; P < .001), Hispanic respondents (−4.8 percentage points; 95% CI, −8.9 to −0.77 percentage points; P = .02), and people younger than 30 years (−10.3 percentage points; 95% CI, −14.1 to −6.5 percentage points; P < .001). Similar gaps were found with respect to knowledge of COVID-19 symptoms and preventive behaviors. CONCLUSIONS AND RELEVANCE: In this survey study of US adults, there were gaps in reported incidence of COVID-19 and knowledge regarding its spread and symptoms and social distancing behavior. More effort is needed to increase accurate information and encourage appropriate behaviors among minority communities, men, and younger people.", "title": "Disparities in Coronavirus 2019 Reported Incidence, Knowledge, and Behavior Among US Adults", "pid": "zz299uk5", "bm25_score": 216.84359741210938}, {"text": "The high numbers of COVID-19 infections and deaths, economic difficulties, uncertainty about the future, as well as the approaches needed to contain the spread of the virus are all playing critical roles in the short and long-term social and psychological impact of the COVID-19 pandemic. Inequities based on race and socioeconomic status influence the rates of infection and deaths and steps that are needed to achieve recovery. This commentary focuses on similarities and differences after other disasters and efforts being initiated to provide support and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Psychological and social impact of COVID-19", "pid": "nj2dllu3", "bm25_score": 216.82833862304688}, {"text": "Importance: Despite emerging reports of poor COVID-19 outcomes among African Americans, data on race and ethnic susceptibility to SARS-CoV-2 infection are limited. Objective: To determine socio-demographic factors associated with higher likelihood of SARS-CoV-2 infection. To explore mediating pathways for race disparities in the SARS-CoV-2 pandemic. Design: Cross sectional analysis of COVID-19 Surveillance and Outcomes Registry (CURATOR). Multivariable logistic regression models were fitted to provide likelihood estimates (adjusted Odds Ratios: aOR, 95% confidence intervals: CI) of positive SARS-CoV-2 test. Structural Equation Modeling (SEM) framework was utilized to explore three mediation pathways (low income, high population density, high comorbidity burden) for association between African American race and SARS-CoV-2 infection. Setting: A large healthcare system comprising of one central tertiary care, seven large community hospitals and an expansive ambulatory and emergency care network in the Greater Houston area. Participants: Individuals of all ages, races, ethnicities and sex tested for SARS-CoV-2. Exposure: Socio-demographic (age, sex, race, ethnicity, household income, residence population density) and comorbidity (hypertension, diabetes, obesity, cardiac disease) factors. Main Outcome: Positive reverse transcriptase polymerized chain reaction test for SARS-CoV-2. Results: Among 4,513 tested individuals, 754 (16.7%) tested positive. Overall mean (SD) age was 50.6 (18.9) years, 62% females and 26% were African American. African American race was associated with higher comorbidity burden, lower socio-economic status, and higher population density residence. In the fully adjusted model, African American race (vs. White; aOR, CI: 1.84, 1.49-2.27) and Hispanic ethnicity (vs. non-Hispanic; aOR, CI: 1.70, 1.35-2.14) had a higher likelihood of infection. Older individuals and males were also at a higher risk of SARS-CoV-2 infection. The SEM framework demonstrated a statistically significant (p = 0.008) indirect effect of African American race on SARS-CoV-2 infection mediated via a pathway that included residence in densely populated zip code. Conclusions and Relevance: There is strong evidence of race and ethnic disparities in the SARS-CoV-2 pandemic potentially mediated through unique social determinants of health.", "title": "Racial and Ethnic Disparities in SARS-CoV-2 Pandemic: Analysis of a COVID-19 Observational Registry for a Diverse U.S. Metropolitan Population", "pid": "guvkeog0", "bm25_score": 216.78028869628906}, {"text": "The Coronavirus disease 2019 (COVID-19) pandemic has unveiled the stark racial disparities that are present in United States (US) and other developed countries today. In recent weeks, several states have released demographic data that highlights the disproportionate rate of COVID-19 infections in racial/ethnic minorities1 . These disparities are likely a result of the structural inequities that minorities face due to factors such as racism, neighborhood segregation, income, housing and education inequality, and poor access to medical care.", "title": "Racial Disparities in COVID-19 Deaths Reveal Harsh Truths About Structural Inequality in America.", "pid": "a2kjjsq1", "bm25_score": 216.77938842773438}, {"text": "Social distancing is one of the few tools that the everyman has to combat the Coronavirus disease. However, for those who are subject to racialized stereotypes about work productivity, educational ability, and other assumptions, the choice to socially distance can have many unintended consequences. This article is an appeal to our posterity, inviting a conversation about how we will remember the Coronavirus' impact on our lives. Will we selectively provide compassion for the racial groups we perceive more favorable when this is over? Or will we play favorites when it is time to pick up the pieces? This article provides scenarios and commentary on how social distancing could affect Black American populations - regardless of income or socioeconomic status. It argues that history has not been kind to Black Americans who have bought into mass national causes, and that there is an opportunity here to act differently.", "title": "When Blackness Does Not Fade After a Pandemic: An Appeal to Acknowledge the Unequal Burden of Social Isolation", "pid": "cm78qs4z", "bm25_score": 216.75332641601562}, {"text": "Scant attention has been paid to intersecting vulnerabilities experienced by Black, Latinx, and older adults of color (BLOAC) that increase COVID-19 related risks. Structural inequities have resulted in disproportionate rates of chronic conditions and limited access to care. Media coverage, focused on COVID-19 mortality among institutionalized older adults (OA), has overlooked community-dwelling OA, leaving their unique risks unaddressed in research and intervention efforts. Key vulnerabilities impacting noninstitutionalized BLOAC exacerbating adverse health outcomes during COVID-19 are discussed, and recommendations are given for gerontological social work (GSW) education, training, and practice to meet the needs of BLOAC during the COVID-19 pandemic.", "title": "Social Workers Must Address Intersecting Vulnerabilities among Noninstitutionalized, Black, Latinx, and Older Adults of Color during the COVID-19 Pandemic", "pid": "882rmszp", "bm25_score": 216.71092224121094}, {"text": "Scant attention has been paid to intersecting vulnerabilities experienced by Black, Latinx, and older adults of color (BLOAC) that increase COVID-19 related risks. Structural inequities have resulted in disproportionate rates of chronic conditions and limited access to care. Media coverage, focused on COVID-19 mortality among institutionalized older adults (OA), has overlooked community-dwelling OA, leaving their unique risks unaddressed in research and intervention efforts. Key vulnerabilities impacting noninstitutionalized BLOAC exacerbating adverse health outcomes during COVID-19 are discussed, and recommendations are given for gerontological social work (GSW) education, training, and practice to meet the needs of BLOAC during the COVID-19 pandemic.", "title": "Social Workers Must Address Intersecting Vulnerabilities among Noninstitutionalized, Black, Latinx, and Older Adults of Color during the COVID-19 Pandemic.", "pid": "ivjt0eml", "bm25_score": 216.70751953125}, {"text": "Social distancing is one of the few tools that the everyman has to combat the Coronavirus disease. However, for those who are subject to racialized stereotypes about work productivity, educational ability, and other assumptions, the choice to socially distance can have many unintended consequences. This article is an appeal to our posterity, inviting a conversation about how we will remember the Coronavirus’ impact on our lives. Will we selectively provide compassion for the racial groups we perceive more favorable when this is over? Or will we play favorites when it is time to pick up the pieces? This article provides scenarios and commentary on how social distancing could affect Black American populations – regardless of income or socioeconomic status. It argues that history has not been kind to Black Americans who have bought into mass national causes, and that there is an opportunity here to act differently.", "title": "When Blackness Does Not Fade After a Pandemic: An Appeal to Acknowledge the Unequal Burden of Social Isolation", "pid": "ms5qy9wl", "bm25_score": 216.70538330078125}, {"text": "Importance: Blacks/African-Americans are overrepresented in the number of COVID-19 infections, hospitalizations and deaths. Reasons for this disparity have not been well-characterized but may be due to underlying comorbidities or sociodemographic factors. Objective: To systematically determine patient characteristics associated with racial/ethnic disparities in COVID-19 outcomes. Design: A retrospective cohort study with comparative control groups. Setting: Patients tested for COVID-19 at University of Michigan Medicine from March 10, 2020 to April 22, 2020. Participants: 5,698 tested patients and two sets of comparison groups who were not tested for COVID-19: randomly selected unmatched controls (n = 7,211) and frequency-matched controls by race, age, and sex (n = 13,351). Main Outcomes and Measures: We identified factors associated with testing and testing positive for COVID-19, being hospitalized, requiring intensive care unit (ICU) admission, and mortality (in/out-patient during the time frame). Factors included race/ethnicity, age, smoking, alcohol consumption, healthcare utilization, and residential-level socioeconomic characteristics (SES; i.e., education, unemployment, population density, and poverty rate). Medical comorbidities were defined from the International Classification of Diseases (ICD) codes, and were aggregated into a comorbidity score. Results: Of 5,698 patients, (median age, 47 years; 38% male; mean BMI, 30.1), the majority were non-Hispanic Whites (NHW, 59.2%) and non-Hispanic Black/African-Americans (NHAA, 17.2%). Among 1,119 diagnosed, there were 41.2% NHW and 37.4% NHAA; 44.8% hospitalized, 20.6% admitted to ICU, and 3.8% died. Adjusting for age, sex, and SES, NHAA were 1.66 times more likely to be hospitalized (95% CI, 1.09-2.52; P=.02), 1.52 times more likely to enter ICU (95% CI, 0.92-2.52; P=.10). In addition to older age, male sex and obesity, high population density neighborhood (OR, 1.27 associated with one SD change [95% CI, 1.20-1.76]; P=.02) was associated with hospitalization. Pre-existing kidney disease led to 2.55 times higher risk of hospitalization (95% CI, 1.62-4.02; P<.001) in the overall population and 11.9 times higher mortality risk in NHAA (95% CI, 2.2-64.7, P=.004). Conclusions and Relevance: Pre-existing type II diabetes/kidney diseases and living in high population density areas were associated with high risk for COVID-19 susceptibility and poor prognosis. Association of risk factors with COVID-19 outcomes differed by race. NHAA patients were disproportionately affected by obesity and kidney disease.", "title": "COVID-19 outcomes, risk factors and associations by race: a comprehensive analysis using electronic health records data in Michigan Medicine", "pid": "zxb8zfep", "bm25_score": 216.69334411621094}, {"text": "BACKGROUND: Many reports on coronavirus disease 2019 (Covid-19) have highlighted age- and sex-related differences in health outcomes. More information is needed about racial and ethnic differences in outcomes from Covid-19. METHODS: In this retrospective cohort study, we analyzed data from patients seen within an integrated-delivery health system (Ochsner Health) in Louisiana between March 1 and April 11, 2020, who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, the virus that causes Covid-19) on qualitative polymerase-chain-reaction assay. The Ochsner Health population is 31% black non-Hispanic and 65% white non-Hispanic. The primary outcomes were hospitalization and in-hospital death. RESULTS: A total of 3626 patients tested positive, of whom 145 were excluded (84 had missing data on race or ethnic group, 9 were Hispanic, and 52 were Asian or of another race or ethnic group). Of the 3481 Covid-19–positive patients included in our analyses, 60.0% were female, 70.4% were black non-Hispanic, and 29.6% were white non-Hispanic. Black patients had higher prevalences of obesity, diabetes, hypertension, and chronic kidney disease than white patients. A total of 39.7% of Covid-19–positive patients (1382 patients) were hospitalized, 76.9% of whom were black. In multivariable analyses, black race, increasing age, a higher score on the Charlson Comorbidity Index (indicating a greater burden of illness), public insurance (Medicare or Medicaid), residence in a low-income area, and obesity were associated with increased odds of hospital admission. Among the 326 patients who died from Covid-19, 70.6% were black. In adjusted time-to-event analyses, variables that were associated with higher in-hospital mortality were increasing age and presentation with an elevated respiratory rate; elevated levels of venous lactate, creatinine, or procalcitonin; or low platelet or lymphocyte counts. However, black race was not independently associated with higher mortality (hazard ratio for death vs. white race, 0.89; 95% confidence interval, 0.68 to 1.17). CONCLUSIONS: In a large cohort in Louisiana, 76.9% of the patients who were hospitalized with Covid-19 and 70.6% of those who died were black, whereas blacks comprise only 31% of the Ochsner Health population. Black race was not associated with higher in-hospital mortality than white race, after adjustment for differences in sociodemographic and clinical characteristics on admission.", "title": "Hospitalization and Mortality among Black Patients and White Patients with Covid-19", "pid": "fm8koqjd", "bm25_score": 216.66070556640625}, {"text": "There is an urgent need to measure the impacts of COVID-19 among gay men and other men who have sex with men (MSM). We conducted a cross-sectional survey with a global sample of gay men and other MSM (n = 2732) from April 16, 2020 to May 4, 2020, through a social networking app. We characterized the economic, mental health, HIV prevention and HIV treatment impacts of COVID-19 and the COVID-19 response, and examined whether sub-groups of our study population are disproportionately impacted by COVID-19. Many gay men and other MSM not only reported economic and mental health consequences, but also interruptions to HIV prevention and testing, and HIV care and treatment services. These consequences were significantly greater among people living with HIV, racial/ethnic minorities, immigrants, sex workers, and socio-economically disadvantaged groups. These findings highlight the urgent need to mitigate the negative impacts of COVID-19 among gay men and other MSM.", "title": "Economic, Mental Health, HIV Prevention and HIV Treatment Impacts of COVID-19 and the COVID-19 Response on a Global Sample of Cisgender Gay Men and Other Men Who Have Sex with Men", "pid": "0vcwpr49", "bm25_score": 216.63668823242188}, {"text": "Coronavirus disease 2019 (Covid-19) has devastated global populations and has had a large impact in the United States with the number of infections and deaths growing exponentially. Using a smooth generalized additive model with quasipoisson counts for total infections and deaths, we developed a county-level predictive model that included population demographics, social characteristics, social distancing, and testing data. This model strongly predicted the actual US distribution of Covid-19, accounting for 94.8% of spatial-temporal variation in total infections and 99.3% in Covid-19 related fatalities from March 15, 2020. US counties with higher population density, poverty index, civilian population, and minorities, especially African Americans had a higher number of confirmed infections adjusted for county population. Social distancing measured by the change in the rate of human encounter per km2 relative to pre-covid-19 national average was associated with slower rate of Covid-19 infections, whereas higher testing was associated with higher number of infections. The number of people infected was increasing, however, the rate of increase in new infections was starting to show signs of plateauing starting from the second week of April. Our model projects 2.11 million people to test positive for Covid-19 and 122,951 fatalities by June 1, 2020. Importantly, our model suggests strong social differences in the infections and deaths across US communities, and inequities in areas with larger African American minorities and higher poverty index expected to show higher rates of Covid-19 infections and deaths. Preventive steps including social distancing and community closures have been a cornerstone in stopping the transmission and potentially reducing the spread of the disease. Crucial knowledge of the role of social characteristics in the disease transmission is essential to understand current disease distribution, predict future distribution, and plan additional preventive steps.", "title": "Strong Effects of Population Density and Social Characteristics on Distribution of COVID-19 Infections in the United States", "pid": "6wqxcshu", "bm25_score": 216.59793090820312}, {"text": "The health and economic consequences of COVID-19 will be devastatingly widespread, but the populations that will suffer most are those who have experienced longstanding health disparities. For example, emerging evidence strongly suggests that incidence and case fatality rates are higher among Blacks than Whites.1 Immigrants are among the groups most likely to experience disproportionate effects from COVID-19. Unlike race/ethnicity, however, nativity and citizenship status are not included on the Centers for Disease Control and Prevention's (CDC's) coronavirus case report form,2 so data regarding testing and spread across immigrant groups are likely to remain scarce. Information from other health and social surveys-including data that I present in Table 1-suggest that noncitizens experience barriers to physical distancing that will place them at high risk of contracting COVID-19 and have high levels of disadvantage that leave them vulnerable to its economic effects. I recommend three policy changes to address the high health and economic risk among noncitizens, goals that are in the best interest of public health and the broader economy. (Am J Public Health. Published online ahead of print June 25, 2020: e1-e3. doi:10.2105/AJPH.2020.305792).", "title": "Policy Recommendations to Address High Risk of COVID-19 Among Immigrants.", "pid": "bb8u9nmj", "bm25_score": 216.57479858398438}, {"text": "PURPOSE: Heightened COVID-19 mortality among Black non-Hispanic and Hispanic communities (relative to white non-Hispanic) is well established. This study aims to estimate the relative contributions to fatality disparities in terms of differences in SARS-CoV-2 infections, diagnoses, and disease severity. METHODS: We constructed COVID-19 outcome continua (similar to the HIV care continuum) for white non-Hispanic, Black non-Hispanic, and Hispanic adults in New York State. For each stage in the COVID-19 outcome continua (population, infection experience, diagnosis, hospitalization, fatality), we synthesized the most recent publicly-available data. We described each continuum using overall percentages, fatality rates, and relative changes between stages, with comparisons between race and ethnicity using risk ratios. RESULTS: Estimated per-population COVID-19 fatality rates were 0.03%, 0.18%, and 0.12% for white non-Hispanic, Black non-Hispanic, and Hispanic adults. The 3.48-fold disparity for Hispanic, relative to white, communities was explained by differences in infection-experience, whereas the 5.38-fold disparity for non-Hispanic Black, relative to white, communities was primarily driven by differences in both infection-experience and in the need for hospitalization, given infection. CONCLUSIONS: These findings suggest the most impactful stages upon which to intervene with programs and policies to build COVID-19 health equity.", "title": "Assessing racial and ethnic disparities using a COVID-19 outcomes continuum for New York State", "pid": "k2wojibt", "bm25_score": 216.5721893310547}, {"text": "The SARS-CoV-2, which emerged from East Asia in December 2019, has rapidly evolved into a global pandemic infecting close to 7 million people. The current uncertainties regarding its impact on Africa calls for critical monitoring of the evolution of the pandemic and correlation of factors that influence the burden of the disease. We herein discuss possible implications of SARS-CoV-2 on the African continent.", "title": "Potential implications of SARS-CoV-2 epidemic in Africa: where are we going from now?", "pid": "rsj4eee3", "bm25_score": 216.55975341796875}, {"text": "Redlining is the discriminatory practice whereby institutions avoided investment in certain neighborhoods due to their demographics. Here we explore the lasting impacts of redlining on the spread of COVID-19 in New York City (NYC). Using data available through the Home Mortgage Disclosure Act, we construct a redlining index for each NYC census tract via a multi-level logistical model. We compare this redlining index with the COVID-19 statistics for each NYC Zip Code Tabulation Area. Accurate mappings of the pandemic would aid the identification of the most vulnerable areas and permit the most effective allocation of medical resources, while reducing ethnic health disparities.", "title": "Racial Impact on Infections and Deaths due to COVID-19 in New York City", "pid": "o4o5n9f4", "bm25_score": 216.5242919921875}, {"text": "The health and economic consequences of COVID-19 will be devastatingly widespread, but the populations that will suffer most are those who have experienced longstanding health disparities. For example, emerging evidence strongly suggests that incidence and case fatality rates are higher among Blacks than Whites.1 Immigrants are among the groups most likely to experience disproportionate effects from COVID-19. Unlike race/ethnicity, however, nativity and citizenship status are not included on the Centers for Disease Control and Prevention's (CDC's) coronavirus case report form,2 so data regarding testing and spread across immigrant groups are likely to remain scarce. Information from other health and social surveys-including data that I present in Table 1-suggest that noncitizens experience barriers to physical distancing that will place them at high risk of contracting COVID-19 and have high levels of disadvantage that leave them vulnerable to its economic effects. I recommend three policy changes to address the high health and economic risk among noncitizens, goals that are in the best interest of public health and the broader economy. (Am J Public Health. Published online ahead of print June 25, 2020: e1-e3. doi:10.2105/AJPH.2020.305792).", "title": "Policy Recommendations to Address High Risk of COVID-19 Among Immigrants", "pid": "71rhjy74", "bm25_score": 216.5056610107422}, {"text": "The present commentary offers a timely exploration of the racial trauma experienced by Asian, Black, and Latinx communities as it relates to COVID-19. Instances of individual, cultural, and structural racism and implications for mental health are discussed. Evidence-based strategies are identified for mental health professionals in order to support healing and mitigate the risk of further racial traumas. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "The outbreak that was always here: Racial trauma in the context of COVID-19 and implications for mental health providers.", "pid": "fzaso4xm", "bm25_score": 216.5012664794922}, {"text": "There is an urgent need to measure the impacts of COVID-19 among gay men and other men who have sex with men (MSM). We conducted a cross-sectional survey with a global sample of gay men and other MSM (n = 2732) from April 16, 2020 to May 4, 2020, through a social networking app. We characterized the economic, mental health, HIV prevention and HIV treatment impacts of COVID-19 and the COVID-19 response, and examined whether sub-groups of our study population are disproportionately impacted by COVID-19. Many gay men and other MSM not only reported economic and mental health consequences, but also interruptions to HIV prevention and testing, and HIV care and treatment services. These consequences were significantly greater among people living with HIV, racial/ethnic minorities, immigrants, sex workers, and socio-economically disadvantaged groups. These findings highlight the urgent need to mitigate the negative impacts of COVID-19 among gay men and other MSM. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10461-020-02969-0) contains supplementary material, which is available to authorized users.", "title": "Economic, Mental Health, HIV Prevention and HIV Treatment Impacts of COVID-19 and the COVID-19 Response on a Global Sample of Cisgender Gay Men and Other Men Who Have Sex with Men", "pid": "m6poosn3", "bm25_score": 216.49139404296875}, {"text": "BACKGROUND: Social and health inequities predispose vulnerable populations to adverse morbidity and mortality outcomes of epidemics and pandemics. While racial disparities in cumulative incidence (CmI) and mortality from the influenza pandemics of 1918 and 2009 implicated Blacks with survival disadvantage relative to Whites in the United States, COVID-19 currently indicates comparable disparities. We aimed to: (a) assess COVID-19 CmI by race, (b) determine the Black-White case fatality (CF) and risk differentials, and (c) apply explanatory model for mortality risk differentials. METHODS: COVID-19 data on confirmed cases and deaths by selective states health departments were assessed using a cross-sectional ecologic design. Chi-square was used for CF independence, while binomial regression model for the Black-White risk differentials. RESULTS: The COVID-19 mortality CmI indicated Blacks/AA with 34% of the total mortality in the United States, albeit their 13% population size. The COVID-19 CF was higher among Blacks/AA relative to Whites; Maryland, (2.7% vs. 2.5%), Wisconsin (7.4% vs. 4.8%), Illinois (4.8% vs. 4.2%), Chicago (5.9% vs. 3.2%), Detroit (Michigan), 7.2% and St. John the Baptist Parish (Louisiana), 7.9%. Blacks/AA compared to Whites in Michigan were 15% more likely to die, CmI risk ratio (CmIRR) = 1.15, 95% CI, 1.01-1.32. Blacks/AA relative to Whites in Illinois were 13% more likely to die, CmIRR = 1.13, 95% CI, 0.93-1.39, while Blacks/AA compared to Whites in Wisconsin were 51% more likely to die, CmIRR = 1.51, 95% CI, 1.10-2.10. In Chicago, Blacks/AA were more than twice as likely to die, CmIRR = 2.24, 95% CI, 1.36-3.88. CONCLUSION: Substantial racial/ethnic disparities are observed in COVID-19 CF and mortality with Blacks/AA disproportionately affected across the United States.", "title": "Black-White Risk Differentials in COVID-19 (SARS-COV2) Transmission, Mortality and Case Fatality in the United States: Translational Epidemiologic Perspective and Challenges", "pid": "9cy1jrw9", "bm25_score": 216.48619079589844}, {"text": "", "title": "COVID-19 and Racial/Ethnic Disparities.", "pid": "el6qel8s", "bm25_score": 216.4778289794922}]}
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A lot of COVID-19 infected patients develop acute respiratory distress syndrome (ARDS), which may lead to multiple organ damage. These symptoms are associated with a cytokine storm syndrome. The aim of this letter is to note the 5 crucial points that vitamin D could have protective and therapeutic effects against COVID-19. For that reason, COVID-19 infection-induced multiple organ damage might be prevented by vitamin D.", "title": "Vitamin D can prevent COVID-19 infection-induced multiple organ damage", "pid": "yjx6ejrh", "bm25_score": 220.15823364257812}, {"text": "The outbreak of COVID-19 has created a global public health crisis. Little is known about the protective factors of this infection. Therefore, preventive health measures that can reduce the risk of infection, progression and severity are desperately needed. This review discussed the possible roles of vitamin D in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Moreover, this study determined the correlation of vitamin D levels with COVID-19 cases and deaths in 20 European countries as of 20 May 2020. A significant negative correlation (p = 0.033) has been observed between mean vitamin D levels and COVID-19 cases per one million population in European countries. However, the correlation of vitamin D with COVID-19 deaths of these countries was not significant. Some retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find the correlation when confounding variables are adjusted. Several studies demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections and pneumonia. These include direct inhibition with viral replication or with anti-inflammatory or immunomodulatory ways. In the meta-analysis, vitamin D supplementation has been shown as safe and effective against acute respiratory tract infections. Thus, people who are at higher risk of vitamin D deficiency during this global pandemic should consider taking vitamin D supplements to maintain the circulating 25(OH)D in the optimal levels 75-125 nmol/L. In conclusion, there not enough evidence on the association between vitamin D levels and COVID-19 severity and mortality. Therefore, randomized control trials and cohort studies are necessary to test this hypothesis.", "title": "Role of vitamin D in preventing of COVID-19 infection, progression and severity", "pid": "uz34fjyp", "bm25_score": 220.0542755126953}, {"text": "The outbreak of COVID-19 has created a global public health crisis. Little is known about the protective factors of this infection. Therefore, preventive health measures that can reduce the risk of infection, progression and severity are desperately needed. This review discussed the possible roles of vitamin D in reducing the risk of COVID-19 and other acute respiratory tract infections and severity. Moreover, this study determined the correlation of vitamin D levels with COVID-19 cases and deaths in 20 European countries as of 20 May 2020. A significant negative correlation (p=0.033) has been observed between mean vitamin D levels and COVID-19 cases per one million population in European countries. However, the correlation of vitamin D with COVID-19 deaths of these countries was not significant. Some retrospective studies demonstrated a correlation between vitamin D status and COVID-19 severity and mortality, while other studies did not find the correlation when confounding variables are adjusted. Several studies demonstrated the role of vitamin D in reducing the risk of acute viral respiratory tract infections and pneumonia. These include direct inhibition with viral replication or with anti-inflammatory or immunomodulatory ways. In the meta-analysis, vitamin D supplementation has been shown as safe and effective against acute respiratory tract infections. Thus, people who are at higher risk of vitamin D deficiency during this global pandemic should consider taking vitamin D supplements to maintain the circulating 25(OH)D in the optimal levels (75-125nmol/L). In conclusion, there is not enough evidence on the association between vitamin D levels and COVID-19 severity and mortality. Therefore, randomized control trials and cohort studies are necessary to test this hypothesis.", "title": "Role of vitamin D in preventing of COVID-19 infection, progression and severity", "pid": "8ceblnkz", "bm25_score": 219.9879608154297}, {"text": "Epidemiological data report that several countries with a high prevalence of hypovitaminosis D may have increased susceptibility to complications and mortality due to COVID-19 infection. These reports, however, have limitations given that they derive from observational studies. Nevertheless, while awaiting more robust data, clinicians should treat patients with vitamin D deficiency irrespective of whether or not it has a link with respiratory infections.", "title": "Vitamin D and COVID-19", "pid": "kfrhwsjb", "bm25_score": 219.7352752685547}, {"text": "", "title": "Comments on: The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality", "pid": "fspjo8qy", "bm25_score": 219.6880645751953}, {"text": "The study discusses the possible role of adequate vitamin D status in plasma or serum for preventing acute respiratory infections during the Covid-19 pandemic. Our arguments respond to an article, published in Italy, that describes the high prevalence of hypovitaminosis D in older Italian women and raises the possible preventive and therapeutic role of optimal vitamin D levels. Based on literature review, we highlight the findings regarding the protective role of vitamin D for infectious diseases of the respiratory system. However, randomized controlled trials are currently lacking. Adequate vitamin D status is obtained from sun exposure and foods rich in vitamin D. Studies in Brazil have shown that hypovitaminosis D is quite common in spite of high insolation. Authors recommend ecological, epidemiological and randomized controlled trials studies to verify this hypothesis.", "title": "Does Vitamin D play a role in the management of Covid-19 in Brazil?", "pid": "x4ietehr", "bm25_score": 219.6333465576172}, {"text": "Coronavirus infection is a serious health problem awaiting an effective vaccine and/or antiviral treatment. The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro)coagulation. Based on many preclinical studies and observational data in humans, ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. Several randomized clinical trials using either oral vitamin D or oral Calcifediol (25OHD) are ongoing. Based on a pilot study, oral calcifediol may be the most promising approach. These studies are expected to provide guidelines within a few months.", "title": "Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166", "pid": "cb2j9i53", "bm25_score": 219.62474060058594}, {"text": "Coronavirus infection is a serious health problem awaiting an effective vaccine and/or antiviral treatment. The major complication of coronavirus disease 2019 (COVID-19), the Acute Respiratory Distress syndrome (ARDS), is due to a variety of mechanisms including cytokine storm, dysregulation of the renin-angiotensin system, neutrophil activation and increased (micro)coagulation. Based on many preclinical studies and observational data in humans, ARDS may be aggravated by vitamin D deficiency and tapered down by activation of the vitamin D receptor. Several randomized clinical trials using either oral vitamin D or oral Calcifediol (25OHD) are ongoing. Based on a pilot study, oral calcifediol may be the most promising approach. These studies are expected to provide guidelines within a few months.", "title": "Vitamin D Receptor stimulation to reduce Acute Respiratory Distress Syndrome (ARDS) in patients with Coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166", "pid": "5rfxis6f", "bm25_score": 219.62474060058594}, {"text": "Coronavirus disease (COVID-19) is a major pandemic and now a leading cause of death worldwide. Currently, no drugs/vaccine is available for the treatment of this disease. Future preventions and social distancing are the only ways to prevent this disease from community transmission. Vitamin D is an important micronutrient and has been reported to improve immunity and protect against respiratory illness. This short review highlights the important scientific link between Vit D levels and susceptibility to COVID-19 in patients. This review also discusses recommendations for Vit D dose required for healthy as well as COVID-19 susceptible patients for protection and prevention.", "title": "Vitamin D Levels and COVID-19 Susceptibility: Is there any Correlation?", "pid": "bpfwcssk", "bm25_score": 219.41664123535156}, {"text": "", "title": "Vitamin D Supplementation: A Potential Approach for Coronavirus/COVID-19 Therapeutics?", "pid": "56p8jlua", "bm25_score": 219.38204956054688}, {"text": "", "title": "COVID-19 and vitamin D—Is there a link and an opportunity for intervention?", "pid": "zx767txr", "bm25_score": 219.3320770263672}, {"text": "", "title": "COVID-19 and vitamin D-Is there a link and an opportunity for intervention?", "pid": "0ngg5pef", "bm25_score": 219.2708282470703}, {"text": "", "title": "Perspective: improving vitamin D status in the management of COVID-19", "pid": "gj42zytf", "bm25_score": 219.23411560058594}, {"text": "Coronavirus 2019 disease (COVID-19) mostly adversely affects the elderly, a population at higher risk for low serum 25-hydroxyvitamin D (25(OH)D) levels. In this viewpoint, we highlight the well-known musculoskeletal properties of vitamin D, which are particularly relevant in the context of COVID-19, suggesting further potential benefits through extra-skeletal effects. Maintaining optimal 25(OH)D is crucial to prevent falls, frailty and fractures in elderly patients, with low activity levels due to lockdown, or who are relatively immobilized during hospitalization and after discharge for prolonged periods of time. Hypovitaminosis D is also associated with susceptibility to respiratory infections, admissions to the intensive care unit, and mortality. We underscore the importance of achieving desirable serum 25(OH)D in COVID-19 elderly patients, to ensure beneficial musculoskeletal effects and possibly respiratory effects of vitamin D, in the context of COVID-19.", "title": "The D-side of COVID-19: musculoskeletal benefits of vitamin D and beyond", "pid": "dqqrulyx", "bm25_score": 219.09512329101562}, {"text": "• Vitamin D deficiency is very frequent. • Controlled trials showed that vitamin D decreases acute respiratory infections. • Despite a lack of direct evidence of an effect of vitamin D on COVID-19 infection. • Daily vitamin D supplementation with moderate doses is safe and cheap. • Even a small decrease in COVID-19 infections would easily justify this intervention.", "title": "Vitamin D deficiency and COVID-19 pandemic", "pid": "fe7e60dl", "bm25_score": 219.06878662109375}, {"text": "The severity of coronavirus 2019 infection (COVID-19) is determined by the presence of pneumonia, severe acute respiratory distress syndrome (SARS-CoV-2), myocarditis, microvascular thrombosis and/or cytokine storms, all of which involve underlying inflammation. A principal defence against uncontrolled inflammation, and against viral infection in general, is provided by T regulatory lymphocytes (Tregs). Treg levels have been reported to be low in many COVID-19 patients and can be increased by vitamin D supplementation. Low vitamin D levels have been associated with an increase in inflammatory cytokines and a significantly increased risk of pneumonia and viral upper respiratory tract infections. Vitamin D deficiency is associated with an increase in thrombotic episodes, which are frequently observed in COVID-19. Vitamin D deficiency has been found to occur more frequently in patients with obesity and diabetes. These conditions are reported to carry a higher mortality in COVID-19. If vitamin D does in fact reduce the severity of COVID-19 in regard to pneumonia/ARDS, inflammation, inflammatory cytokines and thrombosis, it is our opinion that supplements would offer a relatively easy option to decrease the impact of the pandemic.", "title": "Does vitamin D deficiency increase the severity of COVID-19?", "pid": "m22h669g", "bm25_score": 219.00494384765625}, {"text": "", "title": "Reply to Jakovac: “COVID-19 and vitamin D—Is there a link and an opportunity for intervention?”", "pid": "xk7s39t5", "bm25_score": 219.00228881835938}, {"text": "", "title": "Vitamin D and COVID-19", "pid": "vjgrq22k", "bm25_score": 218.93478393554688}, {"text": "We thank Kumar et al for their comments on our review article and the letter connected with that by Panarese and Shahini.(1,2) We agree that there is a complicated effect of vitamin D in preventing the severity of COVID‐19, while this mechanism is not exactly the same as that of influenza.", "title": "Letter: does vitamin D have a potential role against COVID‐19? Authors' reply", "pid": "s7pwtw9j", "bm25_score": 218.83815002441406}, {"text": "", "title": "Letter: Covid-19, and vitamin D. Authors' reply", "pid": "qigonwc9", "bm25_score": 218.83734130859375}, {"text": "WHO declared SARS-CoV-2 a global pandemic. The present aim was to propose an hypothesis that there is a potential association between mean levels of vitamin D in various countries with cases and mortality caused by COVID-19. The mean levels of vitamin D for 20 European countries and morbidity and mortality caused by COVID-19 were acquired. Negative correlations between mean levels of vitamin D (average 56 mmol/L, STDEV 10.61) in each country and the number of COVID-19 cases/1 M (mean 295.95, STDEV 298.7, and mortality/1 M (mean 5.96, STDEV 15.13) were observed. Vitamin D levels are severely low in the aging population especially in Spain, Italy and Switzerland. This is also the most vulnerable group of the population in relation to COVID-19. It should be advisable to perform dedicated studies about vitamin D levels in COVID-19 patients with different degrees of disease severity.", "title": "The role of vitamin D in the prevention of coronavirus disease 2019 infection and mortality", "pid": "jak0gx9k", "bm25_score": 218.80621337890625}, {"text": "", "title": "Letter: does vitamin D have a potential role against COVID-19? Authors' reply", "pid": "ay562jqu", "bm25_score": 218.75177001953125}, {"text": "PURPOSE: Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is still under way. In the emergency setting new or available therapies to contrast the spread of COVID-19 are urgently needed. Elderly males, especially those affected by previous diseases or with comorbidities, are more prone to develop interstitial pneumonia that can deteriorate evolving to ARDS (acute respiratory distress syndrome) that require hospitalization in Intensive Care Units (ICUs). Even children and young patients are not spared by SARS-CoV 2 infection, yet they seem to develop a milder form of disease. In this setting the immunomodulatory role of Vitamin D, should be further investigated. METHODS: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. RESULTS: Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and ß-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis. CONCLUSIONS: In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.", "title": "Possible role of vitamin D in Covid-19 infection in pediatric population", "pid": "46aln4tk", "bm25_score": 218.70628356933594}, {"text": "", "title": "Vitamin D and Covid-19: A Note of Caution.", "pid": "4tvj9ugd", "bm25_score": 218.6923828125}, {"text": "PURPOSE: Covid-19 is a pandemic of unprecedented proportion, whose understanding and management is still under way. In the emergency setting new or available therapies to contrast the spread of COVID-19 are urgently needed. Elderly males, especially those affected by previous diseases or with comorbidities, are more prone to develop interstitial pneumonia that can deteriorate evolving to ARDS (acute respiratory distress syndrome) that require hospitalization in Intensive Care Units (ICUs). Even children and young patients are not spared by SARS-CoV 2 infection, yet they seem to develop a milder form of disease. In this setting the immunomodulatory role of Vitamin D, should be further investigated. Methods: We reviewed the literature about the immunomodulatory role of Vitamin D collecting data from the databases Medline and Embase. RESULTS: Vitamin D proved to interact both with the innate immune system, by activating Toll-like receptors (TLRs) or increasing the levels of cathelicidins and β-defensins, and adaptive immune system, by reducing immunoglobulin secretion by plasma cells and pro-inflammatory cytokines production, thus modulating T cells function. Promising results have been extensively described as regards the supplementation of vitamin D in respiratory tract infections, autoimmune diseases and even pulmonary fibrosis. CONCLUSIONS: In this review, we suggest that vitamin D supplementation might play a role in the prevention and/or treatment to SARS-CoV-2 infection disease, by modulating the immune response to the virus both in the adult and pediatric population.", "title": "Possible role of vitamin D in Covid-19 infection in pediatric population", "pid": "rvwxysvc", "bm25_score": 218.67999267578125}, {"text": "", "title": "Vitamin D and SARS-CoV-2 virus/COVID-19 disease", "pid": "j2wjid4y", "bm25_score": 218.66729736328125}, {"text": "", "title": "Vitamin d and covid-19: A note of caution", "pid": "hj9zco81", "bm25_score": 218.6585235595703}, {"text": "The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D3 for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40-60 ng/mL (100-150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D3 doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.", "title": "Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths", "pid": "9vsi8hfx", "bm25_score": 218.6584930419922}, {"text": "Background Recent research has indicated that vitamin D may have immune supporting properties through modulation of both the adaptive and innate immune system through cytokines and regulation of cell signalling pathways. We hypothesize that vitamin D status may influence the severity of responses to Covid-19 and that the prevalence of vitamin D deficiency in Europe will be closely aligned to Covid-19 mortality. Methods We conducted a literature search on PubMed (no language restriction) of vitamin D status (for older adults) in countries/areas of Europe affected by Covid-19 infection. Countries were selected by severity of infection (high and low) and were limited to national surveys or where not available, to geographic areas within the country affected by infection. Covid-19 infection and mortality data was gathered from the World Health Organisation. Results Counter-intuitively, lower latitude and typically 'sunny' countries such as Spain and Italy (particularly Northern Italy), had low mean concentrations of 25(OH)D and high rates of vitamin D deficiency. These countries have also been experiencing the highest infection and death rates in Europe. The northern latitude countries (Norway, Finland, Sweden) which receive less UVB sunlight than Southern Europe, actually had much higher mean 25(OH)D concentrations, low levels of deficiency and for Norway and Finland, lower infection and death rates. The correlation between 25(OH)D concentration and mortality rate reached conventional significance (P=0.046) by Spearman's Rank Correlation. Conclusions Optimising vitamin D status to recommendations by national and international public health agencies will certainly have benefits for bone health and potential benefits for Covid-19. There is a strong plausible biological hypothesis and evolving epidemiological data supporting a role for vitamin D in Covid-19.", "title": "Vitamin D and Inflammation: Potential Implications for Severity of Covid-19.", "pid": "jvyr7pq4", "bm25_score": 218.6541290283203}, {"text": "Vitamin D deficiency and insufficiency (VDD) are widely recognized as risk factors for respiratory tract infections. Vitamin D influences expression of many genes with well-established relevance to airway infections and relevant to immune system function. Recently, VDD has been shown to be a risk factor for acquisition and severity of COVID-19. Thus, treating VDD presents a safe and inexpensive opportunity for modulating the severity of the disease. VDD is common in those over 60 years of age, many with co-morbid conditions and in people with skin pigmentation sufficient to reduce synthesis of vitamin D. Exposure to fine particulate air pollution is also associated with worse outcomes from COVID19. Vitamin D stimulates transcription of cathelicidin which is cleaved to generate LL37. LL37 is an innate antimicrobial with demonstrated activity against a wide range of microbes including envelope viruses. LL37 also modulates cytokine signaling at the site of infections. Fine particles in air pollution can interfere with LL37 destruction of viruses and may reduce effective immune signaling modulation by LL37. While vitamin D influences transcription of many immune related genes, the weakened antimicrobial response of those with VDD against SARS-CoV-2 may be in part due to reduced LL37. Conclusion: Vitamin D plays an important role reducing the impact of viral lung disease processes. VDD is an acknowledged public health threat that warrants population-wide action to reduce COVID-19 morbidity and mortality. While vitamin D influences transcription of many immune related genes, the weakened antimicrobial response of those with VDD against SARS-CoV-2 may be in part due to reduced LL37. Action is needed to address COVID-19 associated risks of air pollution from industry, transportation, domestic sources and from primary and second hand tobacco smoke.", "title": "Vitamin D Deficiency and Air Pollution Exacerbate COVID-19 Through Suppression of Antiviral Peptide LL37", "pid": "wr9hkvd3", "bm25_score": 218.6202392578125}, {"text": "There is an ongoing debate on the use of vitamin D supplementation in reducing the risk of influenza and COVID-19 infections and deaths. A recently published article highlights a relationship between vitamin D supplementation and reduced risk of COVID-19 and influenza. This comment aims to discuss the evidence on the use of Vitamin D in people who are at risk of developing COVID-19, focusing on safety issues of the Vitamin D supplementation.", "title": "Vitamin D Supplementation in Influenza and COVID-19 Infections Comment on: “Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths” Nutrients 2020, 12(4), 988", "pid": "svc2xeh1", "bm25_score": 218.59521484375}, {"text": "We thank Dr [...].", "title": "Reply: “Vitamin D Supplementation in Influenza and COVID-19 Infections. Comment on: Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths Nutrients 2020, 12(4), 988”", "pid": "6ny0t9g0", "bm25_score": 218.5576171875}, {"text": "", "title": "Letter: Covid-19, and vitamin D", "pid": "780skv92", "bm25_score": 218.55245971679688}, {"text": "", "title": "Letter: does vitamin D have a potential role against COVID-19?", "pid": "at0tm7tp", "bm25_score": 218.53353881835938}, {"text": "Given the succession of communications in scientific and popular circuits, tending to take for granted a role for vitamin D in the control of the coronavirus pandemic, the authors conducted an analysis of the literature currently available in order to recognize what is supported by opinions personal and what evidence of effectiveness. At the end of the bibliographic survey there is the current absence of evidence of efficacy in favor of vitamin D in the treatment of coronavirus infection in its various expressions. The diffusion of personal opinions as if they were evidence can be a disturbing factor for adequate assistance and for correct research.", "title": "[Vitamin D and coronavirus: a new field of use?]", "pid": "34f1ie66", "bm25_score": 218.5313720703125}, {"text": "We thank Dr [...].", "title": "Reply: \"Vitamin D Supplementation in Influenza and COVID-19 Infections. Comment on: Evidence That Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths Nutrients 2020, 12(4), 988\"", "pid": "z3el2v61", "bm25_score": 218.5068359375}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19), with a clinical outcome ranging from mild to severe, including death. To date, it is unclear why some patients develop severe symptoms. Many authors have suggested the involvement of vitamin D in reducing the risk of infections; thus, we retrospectively investigated the 25-hydroxyvitamin D (25(OH)D) concentrations in plasma obtained from a cohort of patients from Switzerland. In this cohort, significantly lower 25(OH)D levels (p = 0.004) were found in PCR-positive for SARS-CoV-2 (median value 11.1 ng/mL) patients compared with negative patients (24.6 ng/mL); this was also confirmed by stratifying patients according to age >70 years. On the basis of this preliminary observation, vitamin D supplementation might be a useful measure to reduce the risk of infection. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations and to confirm our preliminary observation.", "title": "25-Hydroxyvitamin D Concentrations Are Lower in Patients with Positive PCR for SARS-CoV-2", "pid": "xsaj0fzu", "bm25_score": 218.48370361328125}, {"text": "There is an ongoing debate on the use of vitamin D supplementation in reducing the risk of influenza and COVID-19 infections and deaths. A recently published article highlights a relationship between vitamin D supplementation and reduced risk of COVID-19 and influenza. This comment aims to discuss the evidence on the use of Vitamin D in people who are at risk of developing COVID-19, focusing on safety issues of the Vitamin D supplementation.", "title": "Vitamin D Supplementation in Influenza and COVID-19 Infections Comment on: \"Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths\" Nutrients 2020, 12(4), 988", "pid": "pt1i1au3", "bm25_score": 218.4735870361328}, {"text": "The world is in the grip of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing the risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increasing concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced the risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D (25(OH)D) concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome; and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce the risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D(3) for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/mL (100–150 nmol/L). For treatment of people who become infected with COVID-19, higher vitamin D(3) doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.", "title": "Evidence that Vitamin D Supplementation Could Reduce Risk of Influenza and COVID-19 Infections and Deaths", "pid": "iqe6sdq2", "bm25_score": 218.47239685058594}, {"text": "", "title": "Covid-19: Public health agencies review whether vitamin D supplements could reduce risk.", "pid": "c393bp1g", "bm25_score": 218.45877075195312}, {"text": "The authors have withdrawn this manuscript because they have noticed idiosyncrasies in the reporting of 25(OH)D data across different countries. Therefore, the authors do not wish this work to be cited until after this issue is addressed. If you have any questions, please contact the corresponding author.", "title": "The Role of Vitamin D in Suppressing Cytokine Storm in COVID-19 Patients and Associated Mortality", "pid": "dc8z4jzo", "bm25_score": 218.458251953125}, {"text": "", "title": "Vitamin-D and COVID-19: do deficient risk a poorer outcome?", "pid": "qbr4wfrj", "bm25_score": 218.45083618164062}, {"text": "", "title": "Vitamin D supplementation in the COVID-19 pandemic", "pid": "3b2e8x8z", "bm25_score": 218.42095947265625}, {"text": "", "title": "Optimisation of Vitamin D Status for Enhanced Immuno-protection Against Covid-19.", "pid": "9mh3ix4m", "bm25_score": 218.38404846191406}, {"text": "", "title": "Letter: does vitamin D have a potential role against COVID‐19?", "pid": "lcqn2fk1", "bm25_score": 218.3642578125}, {"text": "Background: Following emerge of a novel coronavirus from Wuhan, China, in December 2019, it has affected the whole world and after months of efforts by the medical communities, there is still no specific approach for prevention and treatment against the Coronavirus Disease 2019 (COVID-19). Evidence recommends that vitamin D might be an important supportive agent for the immune system, mainly in cytokine response regulation against COVID-19. Hence, we carried out a rapid systematic review and meta-analysis along with an ecological investigation in order to maximize the use of everything that exists about the role of vitamin D in the COVID-19. Methods: A systematic search was performed in PubMed, Scopus, Embase, Cochrane Library, Web of Science and Google Scholar (intitle) as well as preprint database of medRxiv, bioRxiv, Research Square, preprints.org, search engine of ScienceDirect and a rapid search through famous journals up to May 26, 2020. Studies focused on the role of vitamin D in confirmed COVID-19 patients were entered into the systematic review. Along with our main aim, to find the second objective: correlation of global vitamin D status and COVID-19 recovery and mortality we carried out a literature search in PubMed database to identify the national or regional studies reported the vitamin D status globally. CMA v. 2.2.064 and SPSS v.16 were used for data analysis. Results: Out of nine studies entered into our systematic review, six studies containing 3,822 participants entered into the meta-analysis. The meta-analysis indicated that 46.5% of COVID-19 patients were suffering from vitamin D deficiency (95% CI, 28.2%-65.8%) and in 43.3% of patients, levels of vitamin D were insufficient (95% CI, 27.4%-60.8%). In regard to our ecological investigation on 51 countries including 408,748 participants, analyses indicated no correlation between vitamin D levels and recovery rate (r= 0.041) as well as mortality rate (r=-0.073) globally. However, given latitude, a small reverse correlation between mortality rate and vitamin D status was observed throughout the globe (r= -0.177). In Asia, a medium direct correlation was observed for recovery rate (r= 0.317) and a significant reveres correlation for mortality rate (r= -0.700) with vitamin D status in such patients. In Europe, there were no correlations for both recovery (r= 0.040) and mortality rate (r= -0.035). In Middle East, the recovery rate (r= 0.267) and mortality rate (r= -0.217) showed a medium correlation. In North and Sought America, surprisingly, both recovery and mortality rate demonstrated a direct correlation respectively (r= 1.000, r=0.500). In Oceania, unexpectedly, recovery (r= -1.000) and mortality (r= -1.000) rates were in considerable reverse correlation with vitamin D levels. Conclusion: In this systematic review and meta-analysis with an ecological approach, we found a high percentage of COVID-19 patients who suffer from vitamin D deficiency or insufficiency. Much more important, our ecological investigation resulted in substantial direct and reverse correlations between recovery and mortality rates of COVID-19 patients with vitamin D status in different countries. Considering latitudes, a small reverse correlation between vitamin D status and mortality rate was found globally. It seems that populations with lower levels of vitamin D might be more susceptible to the novel coronavirus infection. Nevertheless, due to multiple limitations, if this study does not allow to quantify a value of the Vitamin D with full confidence, it allows at least to know what the Vitamin D might be and that it would be prudent to invest in this direction through comprehensive large randomized clinical trials.", "title": "The Role of Vitamin D in The Age of COVID-19: A Systematic Review and Meta-Analysis Along with an Ecological Approach", "pid": "8hvve871", "bm25_score": 218.35586547851562}, {"text": "", "title": "Phototherapy and vitamin D: the importance in COVID-19 era.", "pid": "8twhzb8c", "bm25_score": 218.32681274414062}, {"text": "", "title": "Synergistic effect of Vitamin D and Remdesivir can fight COVID-19.", "pid": "ke5hxd8o", "bm25_score": 218.28961181640625}, {"text": "", "title": "Reply to Jakovac: About COVID-19 and vitamin D", "pid": "znl466c4", "bm25_score": 218.28793334960938}, {"text": "", "title": "Phototherapy and vitamin D: the importance in COVID-19 era", "pid": "b88d5igl", "bm25_score": 218.284912109375}, {"text": "Vitamin D is produced in the skin under the influence of UVB-light from the sun or obtained via the diet by eating fatty fish, enriched dairy products or supplements. Vitamin D is known to support a healthy bone and severe deficiency may lead to osteomalacia or the rickets, which still occur in poor areas of the world. In addition, vitamin D support key functions in many organs, including the brain, muscle and the immune systems (Holick, 2007). In fact, the vitamin D receptor (VDR) is expressed in most cell types and may activate somewhere between 200-500 genes, many related to the immune system.", "title": "The link between Vitamin D and Covid-19: distinguishing facts from fiction.", "pid": "n2ku9n0d", "bm25_score": 218.26766967773438}, {"text": "Importance: Vitamin D treatment has been found to decrease incidence of viral respiratory tract infection, especially in vitamin D deficiency. It is unknown whether COVID-19 incidence is associated with vitamin D deficiency and treatment. Objective: To examine whether vitamin D deficiency and treatment are associated with testing positive for COVID-19. Design: Retrospective cohort study Setting: University of Chicago Medicine Participants: Patients tested for COVID-19 from 3/3/2020-4/10/2020. Vitamin D deficiency was defined by the most recent 25-hydroxycholecalciferol <20ng/ml or 1,25-dihydroxycholecalciferol <18pg/ml within 1 year before COVID-19 testing. Treatment was defined by the most recent vitamin D type and dose, and treatment changes between the time of the most recent vitamin D level and time of COVID-19 testing. Vitamin D deficiency and treatment changes were combined to categorize vitamin D status at the time of COVID-19 testing as likely deficient(last-level-deficient/treatment-not-increased), likely sufficient(last-level-not-deficient/treatment-not-decreased), or uncertain deficiency(last-level-deficient/treatment-increased or last-level-not-deficient/treatment-decreased). Main Outcomes and Measures: The main outcome was testing positive for COVID-19. Multivariable analysis tested whether the most recent vitamin D level and treatment changes after that level were associated with testing positive for COVID-19 controlling for demographic and comorbidity indicators. Bivariate analyses of associations of treatment with vitamin D deficiency and COVID-19 were performed. Results: Among 4,314 patients tested for COVID-19, 499 had a vitamin D level in the year before testing. Vitamin D status at the time of COVID-19 testing was categorized as likely deficient for 127(25%) patients, likely sufficient for 291(58%) patients, and uncertain for 81(16%) patients. In multivariate analysis, testing positive for COVID-19 was associated with increasing age(RR(age<50)=1.05,p<0.021;RR(age[≥]50)=1.02,p<0.064)), non-white race(RR=2.54,p<0.01) and being likely vitamin D deficient (deficient/treatment-not-increased:RR=1.77,p<0.02) as compared to likely vitamin D sufficient(not-deficient/treatment-not-decreased), with predicted COVID-19 rates in the vitamin D deficient group of 21.6%(95%CI[14.0%-29.2%] ) versus 12.2%(95%CI[8.9%-15.4%]) in the vitamin D sufficient group. Vitamin D deficiency declined with increasing vitamin D dose, especially of vitamin D3. Vitamin D dose was not significantly associated with testing positive for COVID-19. Conclusions and Relevance: Vitamin D deficiency that is not sufficiently treated is associated with COVID-19 risk. Testing and treatment for vitamin D deficiency to address COVID-19 warrant aggressive pursuit and study.", "title": "Association of Vitamin D Deficiency and Treatment with COVID-19 Incidence", "pid": "4v71xohx", "bm25_score": 218.2432861328125}, {"text": "", "title": "Optimisation of Vitamin D Status for Enhanced Immuno-protection Against Covid-19", "pid": "kif5wp1r", "bm25_score": 218.2355499267578}, {"text": "While we are still learning more about COVID-19, caused by the novel SARS-CoV-2 virus, finding alternative and already available methods to reduce the risk and severity of the disease is paramount. One such option is vitamin D, in the form of vitamin D(3) (cholecalciferol) supplementation, due to its potential antiviral properties. It has become apparent that older individuals have a greater risk of developing severe COVID-19, and compared to younger adults, the elderly have lower levels of vitamin D due to a variety of biological and behavioral factors. Older adults are also more likely to be diagnosed with Parkinson’s disease (PD), with advanced age being the single greatest risk factor. In addition to its immune-system-modulating effects, it has been suggested that vitamin D supplementation plays a role in slowing PD progression and improving PD-related quality of life. We completed a review of the literature to determine the relationship between vitamin D, PD, and COVID-19. We concluded that the daily supplementation of 2000–5000 IU/day of vitamin D(3) in older adults with PD has the potential to slow the progression of PD while also potentially offering additional protection against COVID-19.", "title": "Potential Role of Vitamin D in the Elderly to Resist COVID-19 and to Slow Progression of Parkinson’s Disease", "pid": "wfz010d5", "bm25_score": 218.21383666992188}, {"text": "", "title": "Covid-19: Public health agencies review whether vitamin D supplements could reduce risk", "pid": "1c1etyto", "bm25_score": 218.162841796875}, {"text": "", "title": "Does vitamin D status impact mortality from SARS-CoV-2 infection?", "pid": "9itdow8a", "bm25_score": 218.15647888183594}, {"text": "Early reports indicate an association between the severity of the COVID-19 infection and the widespread 25-hydroxy vitamin D deficiency known to exist in populations around the world. Vitamin D deficiency is extremely common among African American (AA) communities, where the COVID-19 infection rate is three-fold higher, and the mortality rate nearly six-fold higher, compared with rates in predominantly white communities. COVID-19 infection primarily affects the lungs and airways. Previous reports have linked 25-hydroxy vitamin D deficiency with subclinical interstitial lung disease. AA are at risk for lower cellular glutathione (GSH) levels, and GSH deficiency epigenetically impairs VD biosynthesis pathway genes. Compared with vitamin D alone, co-supplementation of vitamin D and L-cysteine (a GSH precursor) showed a better efficacy in improving levels of GSH and VD-regulatory genes at the cellular/tissue level, increasing 25(OH) vitamin D levels, and reducing inflammation biomarkers in the blood in mice studies. We propose that randomized clinical trials are needed to examine the potential of co-supplementation with anti-inflammatory antioxidants, vitamin D and L-cysteine in correcting the 25(OH)VD deficiency and preventing the 'cytokine storm,' one of the most severe consequences of infection with COVID-19, thereby preventing the adverse clinical effects of COVID-19 infection in the vulnerable AA population.", "title": "Can Vitamin D and L-Cysteine Co-Supplementation Reduce 25(OH)-Vitamin D Deficiency and the Mortality Associated with COVID-19 in African Americans?", "pid": "q0tu1pja", "bm25_score": 218.15530395507812}, {"text": "BACKGROUND: SARS-CoV-2 coronavirus infection ranges from asymptomatic through to fatal COVID-19 characterised by a \"cytokine storm\" and lung failure. Vitamin D deficiency has been postulated as a determinant of severity. OBJECTIVES: To review the evidence relevant to vitamin D and COVID-19 METHODS: Narrative review RESULTS: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID-19 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P=0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID-19 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. CONCLUSIONS: Substantial evidence supports a link between vitamin D deficiency and COVID-19 severity but it is all indirect. Community-based placebo-controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID-19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile vitamin D supplementation should be strongly advised for people likely to be deficient.", "title": "Perspective: Vitamin D deficiency and COVID-19 severity - plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2, and thrombosis (R1)", "pid": "8fu7w0be", "bm25_score": 218.0847625732422}, {"text": "", "title": "Hypovitaminosis D and COVID-19: Matter of Concern in India?", "pid": "loiv8z0r", "bm25_score": 218.08250427246094}, {"text": "BACKGROUND AND AIMS: Data show that vitamin D deficiency may play a role in patients with diabetes mellitus and COVID-19 infection. In this article, we review evidence of vitamin D deficiency and COVID-19 infection in context of diabetes mellitus. METHODS: A literature search was carried out by using the key term ‘COVID 19’ combined with ‘Diabetes’, ‘Vitamin D’, ‘Extra skeletal effects’, ‘immunity’, ‘infection’, ‘India’ from Pub Med (National Library of Medicine, Bethesda, MD and Google Scholar from December 2019 to May 2020. A manual search of the references was also carried out. RESULTS: Vitamin D deficiency has been linked to increased morbidity and mortality in COVID -19 infections but convincing data on diabetic subgroup of patients in particular is still awaited. CONCLUSION: Robust studies are required to ascertain if Vitamin D supplementation could be beneficial in patients with diabetes and COVID-19.", "title": "Vitamin D deficiency in patients with diabetes and COVID- 19 infection", "pid": "ktzx5lz6", "bm25_score": 218.0664825439453}, {"text": "BACKGROUND AND AIMS: Data show that vitamin D deficiency may play a role in patients with diabetes mellitus and COVID-19 infection. In this article, we review evidence of vitamin D deficiency and COVID-19 infection in context of diabetes mellitus. METHODS: A literature search was carried out by using the key term 'COVID 19' combined with 'Diabetes', 'Vitamin D', 'Extra skeletal effects', 'immunity', 'infection', 'India' from Pub Med (National Library of Medicine, Bethesda, MD and Google Scholar from December 2019 to May 2020. A manual search of the references was also carried out. RESULTS: Vitamin D deficiency has been linked to increased morbidity and mortality in COVID -19 infections but convincing data on diabetic subgroup of patients in particular is still awaited. CONCLUSION: Robust studies are required to ascertain if Vitamin D supplementation could be beneficial in patients with diabetes and COVID-19.", "title": "Vitamin D deficiency in patients with diabetes and COVID- 19 infection", "pid": "99zkwrso", "bm25_score": 218.0569610595703}, {"text": "Vitamin D is produced in the skin under the influence of UVB-light from the sun or obtained via the diet by eating fatty fish, enriched dairy products or supplements. Vitamin D is known to support a healthy bone and severe deficiency may lead to osteomalacia or the rickets, which still occur in poor areas of the world. In addition, vitamin D support key functions in many organs, including the brain, muscle and the immune systems (Holick, 2007). In fact, the vitamin D receptor (VDR) is expressed in most cell types and may activate somewhere between 200-500 genes, many related to the immune system.", "title": "The link between Vitamin D and Covid-19: distinguishing facts from fiction", "pid": "py0fjygs", "bm25_score": 218.05581665039062}, {"text": "", "title": "Synergistic effect of vitamin D and remdesivir can fight COVID-19", "pid": "b18l7je9", "bm25_score": 218.03106689453125}, {"text": "", "title": "Vitamin D, Covid-19 and Children.", "pid": "gwf79fj6", "bm25_score": 218.0187530517578}, {"text": "BACKGROUND: SARS‐CoV‐2 coronavirus infection ranges from asymptomatic through to fatal COVID‐19 characterised by a “cytokine storm” and lung failure. Vitamin D deficiency has been postulated as a determinant of severity. OBJECTIVES: To review the evidence relevant to vitamin D and COVID‐19 METHODS: Narrative review RESULTS: Regression modelling shows that more northerly countries in the Northern Hemisphere are currently (May 2020) showing relatively high COVID‐19 mortality, with an estimated 4.4% increase in mortality for each 1 degree latitude north of 28 degrees North (P=0.031) after adjustment for age of population. This supports a role for ultraviolet B acting via vitamin D synthesis. Factors associated with worse COVID‐19 prognosis include old age, ethnicity, male sex, obesity, diabetes and hypertension and these also associate with deficiency of vitamin D or its response. Vitamin D deficiency is also linked to severity of childhood respiratory illness. Experimentally, vitamin D increases the ratio of angiotensin converting enzyme 2 (ACE2) to ACE, thus increasing angiotensin II hydrolysis and reducing subsequent inflammatory cytokine response to pathogens and lung injury. CONCLUSIONS: Substantial evidence supports a link between vitamin D deficiency and COVID‐19 severity but it is all indirect. Community‐based placebo‐controlled trials of vitamin D supplementation may be difficult. Further evidence could come from study of COVID‐19 outcomes in large cohorts with information on prescribing data for vitamin D supplementation or assay of serum unbound 25(OH) vitamin D levels. Meanwhile vitamin D supplementation should be strongly advised for people likely to be deficient.", "title": "Perspective: Vitamin D deficiency and COVID‐19 severity – plausibly linked by latitude, ethnicity, impacts on cytokines, ACE2, and thrombosis (R1)", "pid": "mspxtag1", "bm25_score": 218.00509643554688}, {"text": "Background Recent research has indicated that vitamin D may have immune supporting properties through modulation of both the adaptive and innate immune system through cytokines and regulation of cell signalling pathways We hypothesize that vitamin D status may influence the severity of responses to Covid-19 and that the prevalence of vitamin D deficiency in Europe will be closely aligned to Covid-19 mortality Methods We conducted a literature search on PubMed (no language restriction) of vitamin D status (for older adults) in countries/areas of Europe affected by Covid-19 infection Countries were selected by severity of infection (high and low) and were limited to national surveys or where not available, to geographic areas within the country affected by infection Covid-19 infection and mortality data was gathered from the World Health Organisation Results Counter-intuitively, lower latitude and typically ‘sunny’ countries such as Spain and Italy (particularly Northern Italy), had low mean concentrations of 25(OH)D and high rates of vitamin D deficiency These countries have also been experiencing the highest infection and death rates in Europe The northern latitude countries (Norway, Finland, Sweden) which receive less UVB sunlight than Southern Europe, actually had much higher mean 25(OH)D concentrations, low levels of deficiency and for Norway and Finland, lower infection and death rates The correlation between 25(OH)D concentration and mortality rate reached conventional significance (P=0 046) by Spearman's Rank Correlation Conclusions Optimising vitamin D status to recommendations by national and international public health agencies will certainly have benefits for bone health and potential benefits for Covid-19 There is a strong plausible biological hypothesis and evolving epidemiological data supporting a role for vitamin D in Covid-19", "title": "Vitamin D and inflammation: Potential implications for severity of Covid-19", "pid": "lo6u1buy", "bm25_score": 217.9962615966797}, {"text": "COVID-19, the disease caused by SARS-CoV-2 (1), was declared a pandemic by the World Health Organization (WHO) in March 2020 (2). While awaiting a vaccine, several antivirals are being used to manage the disease with limited success (3, 4). To expand this arsenal, we screened 4 compound libraries: a United States Food and Drug Administration (FDA) approved drug library, an angiotensin converting enzyme-2 (ACE2) targeted compound library, a flavonoid compound library as well as a natural product library. Of the 121 compounds identified with activity against SARS-CoV-2, 7 were shortlisted for validation. We show for the first time that the active form of Vitamin D, calcitriol, exhibits significant potent activity against SARS-CoV-2. This finding paves the way for consideration of host-directed therapies for ring prophylaxis of contacts of SARS-CoV-2 patients.", "title": "Calcitriol, the active form of vitamin D, is a promising candidate for COVID-19 prophylaxis", "pid": "sbon3aes", "bm25_score": 217.9900665283203}, {"text": "", "title": "Commentary: Myths and facts on vitamin D amidst the COVID-19 pandemic", "pid": "yfk8e0i4", "bm25_score": 217.98175048828125}, {"text": "We analyse global data for COVID-19 deaths and recoveries and show that outbreak severity displays a striking latitude relationship with a northern hemisphere bias. Transmission rates can be explained by seasonal weather conditions, but this does not account for observed variations in fatality rates. Many factors point to Vitamin D as a candidate explanation but historical controversy surrounding Vitamin D studies and the lack of a coherent framework for causal inference has hampered acceptance of this explanation despite a wealth of evidence in its favour. We analyse global COVID-19 data using Causal Inference, constructing two contrasting directed acyclic graph (DAG) models, one causal and one acausal, and set out clearly multiple predictions made by each model. We show that observed data strongly match predictions made by the causal model but largely contradict those of the acausal model. We explore historic evidence further supporting the causal model. We review biochemical mechanisms that may explain the various ways in which vitamin D acts. We detail the mechanisms by which the SARS-Cov-2 virus causes the disease and known pathways that involve Vitamin D and show how these both protect against viral infection, as well as ameliorating disease symptoms in COVID-19 and other respiratory diseases. We examine the factors that govern confidence in causal inference models and conclude that a high level of confidence in a causal beneficial role for Vitamin D is justified.", "title": "Evidence Supports a Causal Model for Vitamin D in COVID-19 Outcomes", "pid": "rwh56zhg", "bm25_score": 217.97305297851562}, {"text": "", "title": "Myths and Facts on Vitamin D Amidst the COVID-19 Pandemic()", "pid": "usqjkj89", "bm25_score": 217.97067260742188}, {"text": "", "title": "Is Vitamin D One of the Key Elements in COVID-19 Days?", "pid": "re902ol2", "bm25_score": 217.96466064453125}, {"text": "", "title": "Vitamin D and Coronavirus", "pid": "1wfv63mh", "bm25_score": 217.9554443359375}, {"text": "Background: SARS-CoV-2 virus causes a very wide range of COVID-19 disease severity in humans: from completely asymptomatic to fatal, and the reasons behind it are often not understood. There is some data that Vitamin D may have protective effect, so authors decided to analyze European country-wide data to determine if Vitamin D levels are associated with COVID-19 population death rate. Methods: To retrieve the Vitamin D levels data, authors analyzed the Vitamin D European population data compiled by 2019 ECTS Statement on Vitamin D Status published in the European Journal of Endocrinology. For the data set to used for analysis, only recently published data, that included general adult population of both genders ages 40-65 or wider, and must have included the prevalence of Vitamin D deficiency. Results: There were 10 countries data sets that fit the criteria and were analyzed. Severe Vitamin D deficiency was defined as 25(OH)D less than 25 nmol/L (10 ng/dL). Pearson correlation analysis between death rate per million from COVID-19 and prevalence of severe Vitamin D deficiency shows a strong correlation with r = 0.76, p = 0.01, indicating significant correlation. Correlation remained significant, even after adjusting for age structure of the population. Additionally, over time, correlation strengthened, and r coefficient asymptoticaly increased. Conclusions: Authors recommend universal screening for Vitamin D deficiency, and further investigation of Vitamin D supplementation in randomized control studies, which may lead to possible treatment or prevention of COVID-19.", "title": "Strong Correlation Between Prevalence of Severe Vitamin D Deficiency and Population Mortality Rate from COVID-19 in Europe", "pid": "67gsn4sy", "bm25_score": 217.94131469726562}, {"text": "", "title": "Vitamin D deficiency and the COVID-19 pandemic", "pid": "hqyungju", "bm25_score": 217.9193878173828}, {"text": "The study reviews the evidence presented in a recent study linking vitamin D levels and Covid-19 infection and mortality. It was argued that correlation alone may not be useful in establishing a relationship between vitamin D levels and Covid-19 infections and mortality. Appropriate controls need to be included for improved understanding of the relationship. We proposed life expectancy as a potential control. Including this control in a regression model, we find that vitamin D levels are not a statistically significant predictor of Covid-19 infections or mortality. Life expectancy, on the other hand, was found to be statistically significant predictor of infections and mortality at country level.", "title": "Spurious Correlation? A review of the relationship between Vitamin D and Covid-19 infection and mortality", "pid": "hevwcofh", "bm25_score": 217.9176025390625}, {"text": "OBJECTIVES: Vitamin D deficiency (VDD) has been proposed to play a role in Coronavirus Disease 2019 (COVID-19) pathophysiology. We aim to evaluate our implementation of a local protocol for treatment of VDD among patients hospitalized for COVID-19; to assess the prevalence of VDD among COVID-19 inpatients, and examine potential associations with disease severity and fatality. DESIGN AND PARTICIPANTS: We conducted a retrospective interim audit of a local clinical care pathway for 134 inpatients with COVID-19. Prevalence of VDD, compliance with local treatment protocol and relationship of baseline serum 25(OH)D with markers of COVID-19 severity and fatality were analysed. RESULTS: 55.8% of eligible patients received Colecalciferol replacement, albeit not all according to the suggested protocol. Patients admitted to ITU were younger than those managed on medical wards (61.1 years ± 11.8 vs. 76.4 years ± 14.9, respectively, p<0.001), with greater prevalence of hypertension, higher baseline respiratory rate, National Early Warning Score-2 and C-Reactive protein level. While mean serum 25(OH)D levels were comparable (p=0.3), only 19% of ITU patients had 25(OH)D levels greater than 50 nmol/L vs. 39.1% of non-ITU patients (p=0.02). However, there was no association with fatality, potentially due to small sample size and prompt diagnosis and treatment of VDD. CONCLUSIONS: Higher prevalence of VDD was observed in patients requiring ITU admission compared to patients managed on medical wards. Larger prospective studies and/or clinical trials are needed to validate and extend our observations.", "title": "Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID-19 are associated with greater disease severity", "pid": "rtkb45lx", "bm25_score": 217.87686157226562}, {"text": "Vitamin D deficiency, which impedes good immune function, is common during winter and spring in regions of high latitude. There is good evidence that vitamin D deficiency contributes to the seasonal increase of virus infections of the respiratory tract, from the common cold to influenza, and now possibly also COVID-19. This communication explores key factors that make it more likely, particularly in combination, that individuals are vitamin D deficient. These factors include old age, obesity, dark skin tone and common genetic variants that impede vitamin D status. Precision nutrition is an approach that aims to consider known personal risk factors and health circumstances to provide more effective nutrition guidance in health and disease. In regard to avoiding vitamin D deficiency, people with excess body fat, a dark skin tone or older age usually need to use a moderately dosed daily vitamin D supplement, particularly those living in a high-latitude region, getting little ultraviolet B exposure due to air pollution or staying mostly indoors. Carriers of the GC (group-specific component) rs4588 AA genotype also are more likely to become deficient. Very high-dosed supplements with more than 4000 IU vitamin D are rarely needed or justified. A state-by-state Mendelian randomisation analysis of excess COVID-19 mortality of African-Americans in the USA shows a greater disparity in northern states than in southern states. It is conceivable that vitamin D adequacy denies the virus easy footholds and thereby slows spreading of the contagion. This finding should drive home the message that vitamin D supplementation is particularly important for individuals with dark skin tones. Vitamin D deficiency, even for a few months during the winter and spring season, must be rigorously remedied because of its many adverse health impacts that include decreased life expectancy and increased mortality. Slowing the spread of COVID-19 would be an added bonus.", "title": "Avoidance of vitamin D deficiency to slow the COVID-19 pandemic", "pid": "7lb9w9ab", "bm25_score": 217.8526153564453}, {"text": "OBJECTIVES: Vitamin D deficiency (VDD) has been proposed to play a role in Coronavirus Disease 2019 (COVID‐19) pathophysiology. We aim to evaluate our implementation of a local protocol for treatment of VDD among patients hospitalized for COVID‐19; to assess the prevalence of VDD among COVID‐19 inpatients, and examine potential associations with disease severity and fatality. DESIGN AND PARTICIPANTS: We conducted a retrospective interim audit of a local clinical care pathway for 134 inpatients with COVID‐19. Prevalence of VDD, compliance with local treatment protocol and relationship of baseline serum 25(OH)D with markers of COVID‐19 severity and fatality were analysed. RESULTS: 55.8% of eligible patients received Colecalciferol replacement, albeit not all according to the suggested protocol. Patients admitted to ITU were younger than those managed on medical wards (61.1 years ± 11.8 vs. 76.4 years ± 14.9, respectively, p<0.001), with greater prevalence of hypertension, higher baseline respiratory rate, National Early Warning Score‐2 and C‐Reactive protein level. While mean serum 25(OH)D levels were comparable (p=0.3), only 19% of ITU patients had 25(OH)D levels greater than 50 nmol/L vs. 39.1% of non‐ITU patients (p=0.02). However, there was no association with fatality, potentially due to small sample size and prompt diagnosis and treatment of VDD. CONCLUSIONS: Higher prevalence of VDD was observed in patients requiring ITU admission compared to patients managed on medical wards. Larger prospective studies and/or clinical trials are needed to validate and extend our observations.", "title": "Low serum 25‐hydroxyvitamin D (25[OH]D) levels in patients hospitalised with COVID‐19 are associated with greater disease severity", "pid": "tw6f5h2q", "bm25_score": 217.84625244140625}, {"text": "Patients with respiratory diseases such as cystic fibrosis, chronic obstructive pulmonary disease, or asthma often experience an acute worsening of respiratory symptoms, termed exacerbations. Although the course of exacerbations is disease specific, they are mostly triggered by a respiratory infection. Exacerbations often require hospitalization and are an important cause of mortality. Treatments of exacerbations aim to minimize the negative impact and to prevent subsequent events. Despite many existing therapy options, many patients do not benefit from therapy and suffer from recurrent events. Vitamin D deficiency is a worldwide problem and is extremely prevalent in these patients. Vitamin D, known for its calcemic effects, also has immunomodulatory and anti-infectious actions and can therefore be a possible agent to treat or prevent exacerbations. This review will focus on vitamin D as a potential candidate to treat or prevent exacerbations in CF, COPD, and asthma.", "title": "Targeting Vitamin D Deficiency to Limit Exacerbations in Respiratory Diseases: Utopia or Strategy With Potential?", "pid": "edb5546o", "bm25_score": 217.8260498046875}, {"text": "LINKED CONTENT This article is linked to Sands et al papers. To view these articles, visit https://doi.org/10.1111/apt.15555 and https://doi.org/10.1111/apt.15716.", "title": "Letter: Covid‐19, and vitamin D. Authors' reply", "pid": "t8udocx2", "bm25_score": 217.82101440429688}, {"text": "Purpose Vitamin D has been proposed as a potential causal factor in COVID-19 risk. We aimed to establish whether blood 25-hydroxyvitamin D (25(OH)D) concentration was associated with COVID-19 mortality, and inpatient confirmed COVID-19 infection, in UK Biobank participants. Methods UK Biobank recruited 502,624 participants aged 37-73 years between 2006 and 2010. Baseline exposure data, including 25(OH)D concentration, were linked to COVID-19 mortality. Univariable and multivariable Cox proportional hazards regression analyses were performed for the association between 25(OH)D and COVID-19 death, and poisson regression analyses for the association between 25(OH)D and severe COVID-19 infection. Results Complete data were available for 341,484 UK Biobank participants, of which 656 had inpatient confirmed COVID-19 infection and 203 died of COVID-19 infection. Vitamin D was associated with severe COVID-19 infection and mortality univariably (mortality HR=0.99; 95% CI 0.98-0.998; p=0.016), but not after adjustment for confounders (mortality HR=0.998; 95% CI=0.99-1.01; p=0.696). Conclusions Our findings do not support a potential link between vitamin D concentrations and risk of severe COVID-19 infection and mortality. Recommendations for vitamin D supplementation to lessen COVID-19 risks may provide false reassurance.", "title": "Short Communication: Vitamin D and COVID-19 infection and mortality in UK Biobank", "pid": "npk92gra", "bm25_score": 217.805908203125}, {"text": "", "title": "Covid-19, Cocooning and Vitamin D Intake Requirements.", "pid": "78tqcf66", "bm25_score": 217.7981719970703}, {"text": "Importance: Vitamin D deficiency increases the incidence of respiratory virus infections. More than 1 billion people worldwide are vitamin D deficient. If vitamin D deficiency is associated to incidence or severity of SARS-CoV-2 infection, a global call could be made for vitamin D supplementation to mitigate the pandemic. Objective: to determine if lower serum 25-hydroxyvitamin D (25(OH)D) levels are correlated to the risk for COVID-19 and its severity as measured by CT Design: single-center observational study Setting: AZ Delta general hospital Participants: 186 consecutive patients with PCR-confirmed SARS-CoV-2 infection hospitalized for COVID-19 from March 1, 2020 to April 7, 2020 Main outcome and measures: comparative analysis of 25(OH)D levels in patients hospitalized for COVID-19 at various radiological stages and a season/age/sex-matched diseased control population Results: we report on 186 SARS-CoV-2 infected patients requiring hospitalization for severe COVID-19: 109 males (median age 68 years, IQR 53-79 years) and 77 females (median age 71 years, IQR 65-74 years). At admission patients were screened by CT to determine temporal changes of COVID-19 lung disease and classified as stage 1 (ground glass opacities), 2 (crazy paving pattern) and 3 (consolidation). At intake, 25(OH)D levels were measured and compared to a season-matched population of 2717 diseased controls, consisting of 999 males (median age 69 years, IQR 53-81 years) and 1718 females (median age 68 years, IQR 43-83 years). Male and female COVID-19 patients combined showed lower median 25(OH)D than controls (18.6 ng/mL, IQR 12.6-25.3, versus 21.5 ng/mL, IQR 13.9-30.8; P=0.0016) and a higher fraction of vitamin D deficiency (58.6% versus 45.2%, P=0.0005). A strong sexual dimorphism was found: female patients had comparable vitamin D status as control females. Male COVID-19 patients, however, showed markedly higher percentage of vitamin D deficiency than controls (67.0% versus 49.2%, P=0.0006) and this effect was more pronounced with advanced radiological stage ranging from 55.2% in stage 1 to 74% in stage 3. Conclusions and relevance: vitamin D deficiency is a possible risk factor for severe SARS-CoV-2 infection in males. Vitamin D supplementation might be an inexpensive, accessible and safe mitigation for the SARS-CoV-2 pandemic.", "title": "Vitamin D deficiency as risk factor for severe COVID-19: a convergence of two pandemics", "pid": "rpmmadqc", "bm25_score": 217.7838134765625}, {"text": "Given the succession of communications in scientific and popular circuits, tending to take for granted a role for vitamin D in the control of the coronavirus pandemic, the authors conducted an analysis of the literature currently available in order to recognize what is supported by opinions personal and what evidence of effectiveness. At the end of the bibliographic survey there is the current absence of evidence of efficacy in favor of vitamin D in the treatment of coronavirus infection in its various expressions. The diffusion of personal opinions as if they were evidence can be a disturbing factor for adequate assistance and for correct research.", "title": "Viramina D e coronavirus: un nuovo campo di impiego?/ [Vitamin D and coronavirus: a new field of use?]", "pid": "gfyx3nz2", "bm25_score": 217.76976013183594}, {"text": "", "title": "Vitamin D, Covid-19 and Children", "pid": "b4w5k7lh", "bm25_score": 217.76406860351562}, {"text": "LINKED CONTENT This article is linked to Tian et al and Tian and Rong papers. To view these articles, visit https://doi.org/10.1111/apt.15731 and https://doi.org/10.1111/apt.15764.", "title": "Letter: Covid‐19, and vitamin D", "pid": "6vmmm8rp", "bm25_score": 217.7592010498047}, {"text": "There is anecdotal evidence that tocilizumab, an immunosuppressant drug, may be a potential therapeutic option for patients with severe manifestations of coronavirus disease 2019 (COVID-19). Like tocilizumab, Vitamin D appears to modulate the activity of an interleukin (IL-6), which may explain the seasonal variation in prevalence of influenza. While most cases of COVID-19 have, thus far, occurred in the Northern Hemisphere winter, limiting the ability to assess seasonal variation, there remains substantial variation in the severity of this condition that has yet to be explained. A retrospective comparison of Vitamin D levels in previously obtained blood samples between survivors and confirmed fatalities could establish a rationale for implementation of widespread Vitamin D supplementation. This would be far cheaper and simpler than tocilizumab as a therapeutic option to trial.", "title": "Vitamin D: A simpler alternative to tocilizumab for trial in COVID-19?", "pid": "eu7m99a3", "bm25_score": 217.73060607910156}, {"text": "", "title": "Vitamin D Deficiency and ARDS after SARS-CoV-2 Infection.", "pid": "ppm7w9sb", "bm25_score": 217.71041870117188}, {"text": "", "title": "Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)?", "pid": "qzmk1dkg", "bm25_score": 217.68588256835938}, {"text": "", "title": "Vitamin d deficiency and ards after sars-cov-2 infection", "pid": "i4hb58r2", "bm25_score": 217.67706298828125}, {"text": "The current SARS-CoV-2 pandemic has mandated significant isolation measures. Streets in affected countries are mostly empty, and many individuals spend several consecutive days at home to reduce the risk of infection. While determinant for pandemic control, home reclusion may have a significant toll on the health of individuals.", "title": "SARS‐CoV‐2 pandemic and Vitamin D deficiency—A double trouble", "pid": "8n46irf6", "bm25_score": 217.66690063476562}, {"text": "The recent editorial by Rhodes et al considered latitude and mentioned one mechanism that vitamin D is important in regulating and suppressing the inflammatory response of cytokines of respiratory epithelial cells and macrophages to various pathogens, including respiratory viruses and preventing cytokine storm and the subsequent acute respiratory distress syndrome (RDS) (1).", "title": "Letter: low population mortality from COVID‐19 in countries south of latitude 35 degrees North supports vitamin D as a factor determining severity", "pid": "07z1deqg", "bm25_score": 217.6621551513672}, {"text": "", "title": "Association between low vitamin D and COVID-19: don't forget the vitamin D binding protein.", "pid": "ma7cgcvm", "bm25_score": 217.63595581054688}, {"text": "Background: Vitamin D deficiency has been shown to be independently associated with increased risk of viral acute respiratory infection (ARI) in a number of observational studies, and meta-analysis of clinical trials of vitamin D supplementation for prevention of ARI has demonstrated protective effects. Several cellular studies have investigated the effects of vitamin D metabolites on immune responses to respiratory viruses, but syntheses of these reports are lacking. Scope: In this article, we review the literature reporting results of in vitro experiments investigating immunomodulatory actions of vitamin D metabolites in human respiratory epithelial cells infected with respiratory viruses. Key findings: Vitamin D metabolites do not consistently influence replication or clearance of rhinovirus, respiratory syncytial virus (RSV) or influenza A virus in human respiratory epithelial cell culture, although they do modulate expression and secretion of type 1 interferon, chemokines including CXCL8 and CXCL10 and pro-inflammatory cytokines, such as TNF and IL-6. Future research: More studies are needed to clarify the effects of vitamin D metabolites on respiratory virus-induced expression of cell surface markers mediating viral entry and bacterial adhesion to respiratory epithelial cells.", "title": "Modulation of the Immune Response to Respiratory Viruses by Vitamin D", "pid": "tyabf12r", "bm25_score": 217.5693817138672}, {"text": "", "title": "Low serum 25-hydroxyvitamin D (25D) levels in patients hospitalised with COVID-19 are associated with greater disease severity: results of a local audit of practice.", "pid": "pqguvyqt", "bm25_score": 217.50787353515625}, {"text": "", "title": "Association between low vitamin D and COVID-19: don't forget the vitamin D binding protein", "pid": "fxzqdp1o", "bm25_score": 217.4994659423828}, {"text": "The novel coronavirus disease 2019 (COVID-19) is rapidly expanding and causing many deaths all over the world with the World Health Organization (WHO) declaring a pandemic in March 2020. Current therapeutic options are limited and there is no registered and/or definite treatment or vaccine for this disease or the causative infection, severe acute respiratory coronavirus 2 syndrome (SARS-CoV-2). Angiotensin-converting enzyme 2 (ACE2), a part of the renin-angiotensin system (RAS), serves as the major entry point into cells for SARS-CoV-2 which attaches to human ACE2, thereby reducing the expression of ACE2 and causing lung injury and pneumonia. Vitamin D, a fat-soluble-vitamin, is a negative endocrine RAS modulator and inhibits renin expression and generation. It can induce ACE2/Ang-(1-7)/MasR axis activity and inhibits renin and the ACE/Ang II/AT1R axis, thereby increasing expression and concentration of ACE2, MasR and Ang-(1-7) and having a potential protective role against acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Therefore, targeting the unbalanced RAS and ACE2 down-regulation with vitamin D in SARS-CoV-2 infection is a potential therapeutic approach to combat COVID-19 and induced ARDS.", "title": "A brief review of interplay between vitamin D and angiotensin-converting enzyme 2: Implications for a potential treatment for COVID-19", "pid": "vu7lwypg", "bm25_score": 217.49607849121094}, {"text": "A number of clues point to a possible role of vitamin D in fighting COVID-19: a reduction in case growth speed with solar zenith angle, higher fatality rate in black people, lower fatality rate in populations that spend more time outdoors. Yet a direct demonstration that vitamin D deficiency is associated with COVID-19 fatalities has remained elusive. We show here in a comparison of 32 countries that countries with high prevalence of vitamin D deficiency among elderly females show a confirmed case fatality rate twice as high as those with low prevalence. We then show that this effect cannot be explained by differences in life expectancy between countries. A mechanistic role for vitamin D in the severity of COVID-19 is proposed.", "title": "Double COVID-19 Confirmed Case Fatality Rate in Countries with High Elderly Female Vitamin D Deficiency Prevalence", "pid": "jdrhu6l1", "bm25_score": 217.4921112060547}, {"text": "", "title": "Vitamin D deficiency and co-morbidities in COVID-19 patients – A fatal relationship?", "pid": "tloq4oq7", "bm25_score": 217.4875946044922}, {"text": "Aim: To evaluate associations of plasma 25(OH)D status with the likelihood of coronavirus disease (COVID-19) infection and hospitalization. Methods: The study population included the 14,000 members of Leumit Health Services who were tested for COVID-19 infection from February 1st to April 30th, 2020, and who had at least one previous blood test for plasma 25(OH)D level. \"Suboptimal\" or \"low\" plasma 25(OH)D level was defined as plasma 25-hydroxyvitamin D, or 25(OH)D, concentration below 30 ng/mL. Results: Of 7,807 individuals, 782 (10.1%) were COVID-19-positive, and 7,025 (89.9%) COVID-19-negative. The mean plasma vitamin D level was significantly lower among those who tested positive than negative for COVID-19 [19.00 ng/mL (95% confidence interval [CI] 18.41-19.59) vs. 20.55 (95% CI 20.32-20.78)]. Univariate analysis demonstrated an association between low plasma 25(OH)D level and increased likelihood of COVID-19 infection [crude odds ratio (OR) of 1.58 (95% CI 1.24-2.01, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [crude OR of 2.09 (95% CI 1.01-4.30, p<0.05)]. In multivariate analyses that controlled for demographic variables and psychiatric and somatic disorders, the adjusted OR of COVID-19 infection [1.45 (95% CI 1.08-1.95, p<0.001)], and of hospitalization due to the SARS-CoV-2 virus [1.95 (95% CI 0.98-4.845, p=0.061)] were preserved. In the multivariate analyses, age over 50 years, male gender and low-medium socioeconomic status were also positively associated with the risk of COVID-19 infection; age over 50 years was positively associated with the likelihood of hospitalization due to COVID-19.", "title": "Low plasma 25(OH) vitamin D3 level is associated with increased risk of COVID-19 infection: an Israeli population-based study", "pid": "5xhc3h0z", "bm25_score": 217.44137573242188}]}
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METHODS: Crime data representing residential burglary, commercial burglary, theft of vehicle, theft from vehicle, theft, violence, and mischief are analysed at the city level using interrupted time series techniques. RESULTS: While COVID-19 has not had an impact on all crime types, statistically significant change has been identified in a number of cases. Depending on the crime type, the magnitude and direction of the change in frequency varies. It is argued that (mandated) social restrictions, shifted activity patterns and opportunity structures which are responsible for these findings. CONCLUSIONS: We find support for changes in the frequency of particular crime types during the COVID-19 pandemic. This is important for criminal justice and social service practitioners when operating within an extraordinary event.", "title": "Show me a man or a woman alone and I'll show you a saint: Changes in the frequency of criminal incidents during the COVID-19 pandemic", "pid": "ssv1arr1", "bm25_score": 220.70753479003906}, {"text": "In response to the COVID-19 pandemic, state-level governments across the United States issued mandatory stay-at-home orders around the end of March 2020. Though intended to stop the spread of the COVID-19 virus, the lockdowns have had sweeping impacts on life in ways which were not originally planned. This study’s purpose is to investigate the extent to which governmental responses to COVID-19 have impacted crime rates in the U.S. Compared to the pre-pandemic year of 2019, crime – as measured by calls for service to law enforcement – has decreased markedly. However, there are multiple indications that the crime drop is being driven by decreases in minor offenses which are typically committed in peer groups. At the same time, serious crimes which are generally not committed with co-offenders (namely homicide and intimate partner violence) have either remained constant or increased. As such, the crime drop appears to be hiding a very disturbing trend where homicides remain unchanged and intimate partner batteries are increasing. Since many offenders would presumably be committing less serious crimes in a non-pandemic world, we raise attention to the possibility that mandatory lockdown orders may have taken minor offenders and placed them into situations where there is rampant opportunity for intimate partner violence, serious batteries, and homicides. While crime in the U.S. appears to be down overall, this good news should not blind us to a troubling co-occurring reality – a reality that paints a dim picture of unintended consequences to public health and criminal justice finances as a result of COVID-19 lockdowns.", "title": "Has COVID-19 Changed Crime? Crime Rates in the United States during the Pandemic", "pid": "daxggfj5", "bm25_score": 220.48162841796875}, {"text": "Governments have implemented social distancing measures to address the ongoing COVID-19 pandemic. The measures include instructions that individuals maintain social distance when in public, school closures, limitations on gatherings and business operations, and instructions to remain at home. Social distancing may have an impact on the volume and distribution of crime. Crimes such as residential burglary may decrease as a byproduct of increased guardianship over personal space and property. Crimes such as domestic violence may increase because of extended periods of contact between potential offenders and victims. Understanding the impact of social distancing on crime is critical for ensuring the safety of police and government capacity to deal with the evolving crisis. Understanding how social distancing policies impact crime may also provide insights into whether people are complying with public health measures. Examination of the most recently available data from both Los Angeles, CA, and Indianapolis, IN, shows that social distancing has had a statistically significant impact on a few specific crime types. However, the overall effect is notably less than might be expected given the scale of the disruption to social and economic life.", "title": "Impact of social distancing during COVID-19 pandemic on crime in Los Angeles and Indianapolis", "pid": "po2c65nb", "bm25_score": 220.22280883789062}, {"text": "The COVID-19 pandemic has radically altered life, killing hundreds of thousands of people and leading many countries to issue “stay-at-home” orders to contain the virus’s spread. Based on insights from routine activity theory (Cohen & Felson 1979), it is likely that COVID-19 will influence victimization rates as people alter their routines and spend more time at home and less time in public. Yet, the pandemic may affect victimization differently depending on the type of crime as street crimes appear to be decreasing while domestic crimes may be increasing. We consider a third type of crime: cybercrime. Treating the pandemic as a natural experiment, we investigate how the pandemic has affected rates of cybervictimization. We compare pre-pandemic rates of victimization with post-pandemic rates of victimization using datasets designed to track cybercrime. After considering how the pandemic may alter routines and affect cybervictimization, we find that the pandemic has not radically altered cyberroutines nor changed cybervictimization rates. However, a model using routine activity theory to predict cybervictimization offers clear support for the theory’s efficacy both before and after the pandemic. We conclude by considering plausible explanations for our findings.", "title": "Cybercrime in America amid COVID-19: the Initial Results from a Natural Experiment", "pid": "gjdza9bh", "bm25_score": 219.81373596191406}, {"text": "The novel corona virus COVID-19 has become a worldwide public health pandemic that has induced anomic conditions impacting daily routines. COVID-19 response measures specifically alter regular schedules and both restrict and expand opportunities for various types of crime while presenting unprecedented challenges for the criminal justice system. For criminologists and criminal justice scientists, the virus also presents natural experiment conditions allowing for real-world theory tests and observation of the relative effectiveness of practice and policy options under weighty conditions. Toward synthesizing scientific discourse and forthcoming empirical work, we suggest the benefits of a COVID-19 crime and justice research program and offer some anchoring concepts. Contagion, containment measures (social distancing, facemasks, shelter-in-place, economic shutdown, virtual work and schooling, banned group gatherings), and social ordinance compliance (voluntary or enforced) posture a conceptual framework from which to align research on crime, justice, and victimization during the virus. After observing crime trends and justice system challenges, we suggest how the pandemic presents opportunities for review of various criminal justice, especially incarceration, policies. System change is a recurring theme across this special issue of the American Journal of Criminal Justice that features twenty additional contributions from a wide range of authoritative crime and justice scholars. These articles on traditional crime during the virus, virus specific hate crime and domestic violence, and the challenges posed by COVID-19 to law enforcement, the courts, and corrections will hopefully provide initial commentary toward deeper inquiry.", "title": "Crime, Justice & the COVID-19 Pandemic: Toward a National Research Agenda", "pid": "7eksp1sj", "bm25_score": 219.50489807128906}, {"text": "The global spread of 2019-nCoV, a new virus belonging to the coronavirus family, forced national and local governments to apply different sets of measures aimed at containing its outbreak. Los Angeles has been one of the first cities in the United States to declare the state of emergency on March 4th, progressively issuing stronger policies involving--among the others--social distancing, the prohibition of crowded private and public gatherings and closure of leisure premises. These interventions highly disrupt and modify daily activities and habits, urban mobility and micro-level interactions between citizens. One of the many social phenomena that could be influenced by such measures is crime. Exploiting public data on crime in Los Angeles, and relying on routine activity and pattern theories of crime, this work investigates whether and how new coronavirus containment policies have an impact on crime trends in a metropolis using Bayesian structural time-series (BSTS) models. The article specifically focuses on nine urban crime categories, daily monitored from January 1st 2017 to March 28th 2020. The analyses have been updated bi-weekly (up to March 16\\ts{th} and up to March 28\\ts{th} 2020) to dynamically assess the short-term effects of mild and hard interventions to shed light on how crime adapts to such structural modification of the environment. The results show that overall crime in Las Angeles is significantly decreasing, as well as robbery, shoplifting, theft and battery. No significant effect has been found for stolen vehicle, burglary, assault with deadly weapon, intimate partner violence and homicide. In the last section of this article, policy implications are also discussed.", "title": "Exploring the Effect of 2019-nCoV Containment Policies on Crime: The Case of Los Angeles", "pid": "0rdq6g0b", "bm25_score": 219.39390563964844}, {"text": "The COVID-19 pandemic led to substantial changes in the daily activities of millions of Americans, with many businesses and schools closed, public events cancelled and states introducing stay-at-home orders. This article used police-recorded open crime data to understand how the frequency of common types of crime changed in 16 large cities across the United States in the early months of 2020. Seasonal auto-regressive integrated moving average (SARIMA) models of crime in previous years were used to forecast the expected frequency of crime in 2020 in the absence of the pandemic. The forecasts from these models were then compared to the actual frequency of crime during the early months of the pandemic. There were no significant changes in the frequency of serious assaults in public or (contrary to the concerns of policy makers) any change to the frequency of serious assaults in residences. In some cities, there were reductions in residential burglary but little change in non-residential burglary. Thefts of motor vehicles decreased in some cities while there were diverging patterns of thefts from motor vehicles. These results are used to make suggestions for future research into the relationships between the coronavirus pandemic and different crimes.", "title": "Initial evidence on the relationship between the coronavirus pandemic and crime in the United States", "pid": "tkqufxv8", "bm25_score": 219.32127380371094}, {"text": "Governments around the world restricted movement of people, using social distancing and lockdowns, to help stem the global coronavirus (COVID-19) pandemic. We examine crime effects for one UK police force area in comparison to 5-year averages. There is variation in the onset of change by crime type, some declining from the WHO ‘global pandemic’ announcement of 11 March, others later. By 1 week after the 23 March lockdown, all recorded crime had declined 41%, with variation: shoplifting (− 62%), theft (− 52%), domestic abuse (− 45%), theft from vehicle (− 43%), assault (− 36%), burglary dwelling (− 25%) and burglary non-dwelling (− 25%). We use Google Covid-19 Community Mobility Reports to calculate the mobility elasticity of crime for four crime types, finding shoplifting and other theft inelastic but responsive to reduced retail sector mobility (MEC = 0.84, 0.71 respectively), burglary dwelling elastic to increases in residential area mobility (− 1), with assault inelastic but responsive to reduced workplace mobility (0.56). We theorise that crime rate changes were primarily caused by those in mobility, suggesting a mobility theory of crime change in the pandemic. We identify implications for crime theory, policy and future research.", "title": "Crime and coronavirus: social distancing, lockdown, and the mobility elasticity of crime", "pid": "kzpbjvy5", "bm25_score": 219.22796630859375}, {"text": "BACKGROUND The beginning of 2020 has been marked by a historic event of worldwide importance: the Coronavirus pandemic. This emergency has resulted in severe global problems affecting areas such as healthcare and the social and economic fields. What about crime? PURPOSE OF THE WORK The purpose of this work is to reflect about Italy and its crime rate at the time of Coronavirus. METHODS Some crimes will be analysed (the \"conventional\" ones only, ruling out health-related offences) in the light of data resulting from Ministries and Europol reports, as well as from newspapers and news. RESULTS AND CONCLUSIONS The outcome will be explained, and some criminological remarks will be added.", "title": "Crime in Italy at the time of the pandemic.", "pid": "0jv5mnnl", "bm25_score": 218.9305419921875}, {"text": "The COVID-19 pandemic of 2020 has impacted the world in ways not seen in generations. Initial evidence suggests one of the effects is crime rates, which appear to have fallen drastically in many communities around the world. We argue that the principal reason for the change is the government ordered stay-at-home orders, which impacted the routine activities of entire populations. Because these orders impacted countries, states, and communities at different times and in different ways, a naturally occurring, quasi-randomized control experiment has unfolded, allowing the testing of criminological theories as never before. Using new and traditional data sources made available as a result of the pandemic criminologists are equipped to study crime in society as never before. We encourage researchers to study specific types of crime, in a temporal fashion (following the stay-at-home orders), and placed-based. The results will reveal not only why, where, when, and to what extent crime changed, but also how to influence future crime reduction.", "title": "Crime Rates in a Pandemic: the Largest Criminological Experiment in History", "pid": "lcmkribq", "bm25_score": 218.74493408203125}, {"text": "This paper uses the public health framework to address the apparent impact of the coronavirus on the victimization experiences with a specific focus given to those over the age of 50. The bulk of attention is given to fraud victimization, with consideration also given to parent abuse, partner violence, and patient abuse. A review of data from the Federal Trade Commission shows that reports of most types of fraud grew significantly in the first three months of 2020 in comparison to the same time period in 2019. Differences between fraud experiences based on age are considered. Older persons lost much more to fraud than younger persons, and far more in 2020 than 2019. In addition, they reported being targeted more often for certain types of cybercrime (i.e., tech support scams). While devastating to everyone, it is concluded that the coronavirus will potentially have a more significant impact on the financial health of older persons than younger persons. It is concluded that minimizing the consequences of all forms of crimes targeting older adults will be best achieved by using a public health approach.", "title": "Criminals Work from Home during Pandemics Too: a Public Health Approach to Respond to Fraud and Crimes against those 50 and above", "pid": "rx7dlpid", "bm25_score": 218.7144317626953}, {"text": "This paper examines the impact of Covid-19 on community-based violence interventions, especially hospital-based violence interventions and street outreach organizations. Guided by our work in Rochester, New York, we explore how the emergence of covid-19, and the subsequent social restrictions, have hampered the ability of community-based organizations to respond to violence. We also examine ways that community-based organizations can adapt to the challenges associated with Covid-19 and continue providing services to the community.", "title": "The Impact of Covid-19 on Community-Based Violence Interventions", "pid": "urlsn7vv", "bm25_score": 218.63442993164062}, {"text": "The novel coronavirus pandemic (hereafter COVID-19) is likely to have unprecedented impacts on the incidence and impacts of crime and violence globally. This includes impacts to the risk, consequences, and decision-making of women experiencing violence by an intimate partner (hereafter IPV). Most importantly, the COVID-19 pandemic, and its impact on the risk of IPV is likely to differentially impact vulnerable populations, including minority women and those with long histories of victimization and mental health issues. This review paper explores the potential short- and long-term implications of COVID-19 on the risk of IPV, highlighting some of the most recent preliminary data. The economic impact of the COVID-19 pandemic, record levels of male unemployment, added stressors in the home, including the care and home schooling of children, and the social distancing measures required by the epidemiological response, may serve to undermine the decades of progress made in keeping women and children safe at home. Victim police reporting, help-seeking decisions, and social service utilization during the pandemic are likely to be impacted by stay-at-home orders and social distancing requirements. The paper concludes with a discussion of the implications for providing safety planning and self-care for victims and their children.", "title": "When Stay-at-Home Orders Leave Victims Unsafe at Home: Exploring the Risk and Consequences of Intimate Partner Violence during the COVID-19 Pandemic", "pid": "ekajojon", "bm25_score": 218.37486267089844}, {"text": "Domestic violence is a global public health problem. It takes many different forms and leads to significant physical and psychological consequences for the victim and the whole family. Situations that may prompt episodes of violence in the family include stress, emotional disappointment, economic factors, bad and cramped housing, and alcohol or drug abuse. How does the government's forced home isolation to contain Covid-19 infections impact on this type of abuse? Numerous articles have reported a decrease in reports of domestic violence since quarantine began but how reliable is these data? Is it a potential wake-up call for public institutions? We discuss the risks associated with quarantine measures during the pandemic and suggest the measures to prevent and improve the reporting of abuse cases.", "title": "The impact of the Covid-19 pandemic on domestic violence: The dark side of home isolation during quarantine.", "pid": "miem1poh", "bm25_score": 218.3173370361328}, {"text": "Abstract Though necessary to slow the spread of the novel Coronavirus (Covid-19), actions such as social-distancing, sheltering in-place, restricted travel, and closures of key community foundations are likely to dramatically increase the risk for family violence around the globe. In fact many countries are already indicating a dramatic increase in reported cases of domestic violence. While no clear precedent for the current crisis exists in academic literature, exploring the impact of natural disasters on family violence reports may provide important insight for family violence victim-serving professionals. Improving collaborations between human welfare and animal welfare agencies, expanding community partnerships, and informing the public of the great importance of reporting any concerns of abuse are all critical at this time.", "title": "An increasing risk of family violence during the Covid-19 pandemic: Strengthening community collaborations to save lives", "pid": "v9fdn4uu", "bm25_score": 218.23458862304688}, {"text": "Domestic violence is a global public health problem. It takes many different forms and leads to significant physical and psychological consequences for the victim and the whole family. Situations that may prompt episodes of violence in the family include stress, emotional disappointment, economic factors, bad and cramped housing, and alcohol or drug abuse. How does the government's forced home isolation to contain Covid-19 infections impact on this type of abuse? Numerous articles have reported a decrease in reports of domestic violence since quarantine began but how reliable is these data? Is it a potential wake-up call for public institutions? We discuss the risks associated with quarantine measures during the pandemic and suggest the measures to prevent and improve the reporting of abuse cases.", "title": "The impact of the Covid-19 pandemic on domestic violence: The dark side of home isolation during quarantine", "pid": "onxosato", "bm25_score": 218.20999145507812}, {"text": "", "title": "Domestic violence in the COVID-19 pandemic: a forensic psychiatric perspective.", "pid": "j0w0yzbj", "bm25_score": 218.1534881591797}, {"text": "", "title": "Domestic violence in the COVID-19 pandemic: a forensic psychiatric perspective", "pid": "2oskze33", "bm25_score": 217.90023803710938}, {"text": "The pandemic of COVID-19 has resulted in quarantines imposed all around the world; these and other restrictions could produce an increase in domestic violence.", "title": "Coronavirus and Quarantine: Catalysts of Domestic Violence.", "pid": "427mkwsj", "bm25_score": 217.83038330078125}, {"text": "", "title": "The pandemic paradox: The consequences of COVID-19 on domestic violence", "pid": "rosqr2a5", "bm25_score": 217.77989196777344}, {"text": "The spread of the coronavirus has led to containment policies in many places, with concomitant shifts in routine activities. Major declines in crime have been reported as a result. However, those declines depend on crime type and may differ by parts of a city and land uses. This paper examines burglary in Detroit, Michigan during the month of March, 2020, a period of considerable change in routine activities. We examine 879 block groups, separating those dominated by residential land use from those with more mixed land use. We divide the month into three periods: pre-containment, transition period, and post-containment. Burglaries increase in block groups with mixed land use, but not blocks dominated by residential land use. The impact of containment policies on burglary clarifies after taking land use into account.", "title": "Routine activity effects of the Covid-19 pandemic on burglary in Detroit, March, 2020", "pid": "g2mjj7my", "bm25_score": 217.6436767578125}, {"text": "COVID-19 (the new strain of coronavirus) has been declared a global pandemic. Measures announced over recent weeks to tackle it have seen people's day-to-day life drastically altered. These changes are essential to beat coronavirus and protect health systems (UK Home Office 2020). However, there are unintended, negative consequences. As the virus continues to spread across the world, it brings with it multiple new stresses, including physical and psychological health risks, isolation and loneliness, the closure of many schools and businesses, economic vulnerability and job losses. Through all of that, children (and their mothers) are particularly vulnerable (End Violence against Children, 2020) to the risk of domestic violence. Domestic violence refers to a range of violations that happen within a domestic space. It is a broad term that encompasses intimate partner violence (IPV), a form of abuse that is perpetrated by a current or ex-partner.", "title": "The pandemic paradox: The consequences of COVID‐19 on domestic violence", "pid": "1uwdekl3", "bm25_score": 217.57342529296875}, {"text": "The pandemic of COVID-19 has resulted in quarantines imposed all around the world; these and other restrictions could produce an increase in domestic violence.", "title": "Coronavirus and Quarantine: Catalysts of Domestic Violence", "pid": "luef3iok", "bm25_score": 217.56582641601562}, {"text": "The novel coronavirus (SARS-CoV-2) and the associated disease it causes, COVID-19, have caused unprecedented social disruption. Due to sweeping stay-at-home orders across the United States and internationally, many victims and survivors of domestic violence (DV), now forced to be isolated with their abusers, run the risk of new or escalating violence. Numerous advocates, organizations, and service centers anticipated this: Upticks in domestic violence were reported in many regions soon after stay-at-home directives were announced. In this commentary, we delineate some of the recent events leading up to the reported spike in DV; review literature on previously documented disaster-related DV surges; and discuss some of the unique challenges, dilemmas, and risks victims and survivors face during this pandemic. We conclude with recommendations to allocate resources to DV front-liners and utilize existing DV guidelines for disaster preparedness, response, and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Home is not always a haven: The domestic violence crisis amid the COVID-19 pandemic.", "pid": "54mxjzfc", "bm25_score": 217.5272216796875}, {"text": "While the novel coronavirus (COVID-19) has broad health implications across the globe, being overlooked in response and policy debates is the impact on women’s reproductive rights and violence risk. This is especially salient for minoritized women. In this commentary, we describe the potential negative impact of mandates such as shelter-in-place for domestic violence victims, and how public reproductive health policy is being shaped to disadvantage women, especially minoritized women. We argue that now is the time for violence prevention leaders to advocate for bold action. This includes prioritizing the needs of women (especially minoritized women) in medical, social and legal settings using innovative intervention and service engagement (e.g., e-filing for protection orders, virtual advocacy services), urging policy makers to pass legislation to support women, and shining an accountability spotlight on leadership.", "title": "Novel Coronavirus (COVID-19): Violence, Reproductive Rights and Related Health Risks for Women, Opportunities for Practice Innovation", "pid": "nc74h4tp", "bm25_score": 217.48538208007812}, {"text": "Family violence refers to threatening or other violent behaviour within families that may be physical, sexual, psychological, or economic, and can include child abuse and intimate partner violence (Peterman et al. 2020, van Gelder et al. 2020). Family violence during pandemics is associated with a range of factors including economic stress, disaster-related instability, increased exposure to exploitative relationships, and reduced options for support (Peterman et al. 2020). Due to the social isolation measures implemented across the globe to help reduce the spread of COVID-19, people living in volatile situations of family violence are restricted to their homes. Social isolation exacerbates personal and collective vulnerabilities while limiting accessible and familiar support options (van Gelder et al. 2020). In many countries, including Australia, we have already seen an increase in demand for domestic violence services and reports of increased risk for children not attending schools (Duncan, 2020); a pattern similar to previous episodes of social isolation associated with epidemics and pandemics (Boddy, Young & O'Leary 2020).", "title": "Family violence and COVID‐19: Increased vulnerability and reduced options for support", "pid": "4jjuwc9r", "bm25_score": 217.4740447998047}, {"text": "An early examination of the impact of COVID-19 on juvenile delinquency and juvenile justice in America, this review provides initial scholarship to rapidly evolving areas of research. Our appraisals of these topics are made after nearly 2 months of national COVID-19 mitigation measures, like social distancing and limited “non-essential” movement outside the home but also as states are gradually lifting stricter directives and reopening economic sectors. We consider the impact of these pandemic-related changes on twenty-first century youths, their behaviors, and their separate justice system. To forecast the immediate future, we draw from decades of research on juvenile delinquency and the justice system, as well as from reported patterns of reactions and responses to an unprecedented and ongoing situation. As post-pandemic studies on juvenile delinquency and juvenile justice proliferate, we urge careful consideration as to how they might influence societal and the system responses to youths’ delinquency. Additional practical implications are discussed.", "title": "It’s F**ing Chaos: COVID-19’s Impact on Juvenile Delinquency and Juvenile Justice", "pid": "judp4703", "bm25_score": 217.42620849609375}, {"text": "The novel coronavirus (SARS-CoV-2) and the associated disease it causes, COVID-19, have caused unprecedented social disruption. Due to sweeping stay-at-home orders across the United States and internationally, many victims and survivors of domestic violence (DV), now forced to be isolated with their abusers, run the risk of new or escalating violence. Numerous advocates, organizations, and service centers anticipated this: Upticks in domestic violence were reported in many regions soon after stay-at-home directives were announced. In this commentary, we delineate some of the recent events leading up to the reported spike in DV; review literature on previously documented disaster-related DV surges; and discuss some of the unique challenges, dilemmas, and risks victims and survivors face during this pandemic. We conclude with recommendations to allocate resources to DV front-liners and utilize existing DV guidelines for disaster preparedness, response, and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Home is not always a haven: The domestic violence crisis amid the COVID-19 pandemic", "pid": "ypzpui37", "bm25_score": 217.38746643066406}, {"text": "A heightened risk of domestic violence has been associated with infection-reducing measures undertaken by governments during the COVID-19 pandemic. Psychiatric services can play a key role in addressing this issue by (a) addressing certain risk factors for perpetration of domestic violence through, for example, assertive identification and management of substance misuse; (b) providing support, advocacy and treatment services for victims of domestic violence; and (c) multi-agency working to strengthen medical and social responses to domestic violence. At a time like this, it is important that multi-disciplinary mental health services are strengthened, rather than depleted, in order to address the pressing issues at hand.", "title": "Domestic violence against women and the COVID-19 pandemic: What is the role of psychiatry?", "pid": "slfyv0cu", "bm25_score": 217.34719848632812}, {"text": "This essay aimed to discuss the implications of social isolation due to the COVID-19 pandemic for the intensive use of the internet among children and adolescents and its possible consequences for the practice of self-inflicted violence. We briefly discussed the anxiogenic potential and the reproduction of a \"global fear\" that are consolidated with the massive and unmediated exposure of the content consumed, which can increase the vulnerabilities to stress and suicidal ideas. We centered our debate on \"recreational\" practices, called \"challenges\" with self-harm power, carried out by teenagers on the YouTube website. This practice has been shown to increase with the social isolation measures. Our reflection on these risks builds on the theoretical perspective of digital sociability, and its implications for the internet-mediated interactions of adolescents.", "title": "The intensive use of the internet by children and adolescents in the context of COVID-19 and the risks for self-inflicted violence.", "pid": "me58dqhi", "bm25_score": 217.32489013671875}, {"text": "The COVID-19 pandemic was a remarkable unprecedented event which altered the lives of billions of citizens globally resulting in what became commonly referred to as the new-normal in terms of societal norms and the way we live and work. Aside from the extraordinary impact on society and business as a whole, the pandemic generated a set of unique cyber-crime related circumstances which also affected society and business. The increased anxiety caused by the pandemic heightened the likelihood of cyber-attacks succeeding corresponding with an increase in the number and range of cyber-attacks. This paper analyses the COVID-19 pandemic from a cyber-crime perspective and highlights the range of cyber-attacks experienced globally during the pandemic. Cyber-attacks are analysed and considered within the context of key global events to reveal the modus-operandi of cyber-attack campaigns. The analysis shows how following what appeared to be large gaps between the initial outbreak of the pandemic in China and the first COVID-19 related cyber-attack, attacks steadily became much more prevalent to the point that on some days, 3 or 4 unique cyber-attacks were being reported. The analysis proceeds to utilise the UK as a case study to demonstrate how cyber-criminals leveraged key events and governmental announcements to carefully craft and design cyber-crime campaigns.", "title": "Cyber Security in the Age of COVID-19: A Timeline and Analysis of Cyber-Crime and Cyber-Attacks during the Pandemic", "pid": "j0qperwz", "bm25_score": 217.12965393066406}, {"text": "", "title": "Trauma Does not Quarantine: Violence During the COVID-19 Pandemic", "pid": "uan6rlvo", "bm25_score": 217.10787963867188}, {"text": "Intimate Partner Violence (IPV) is a global pandemic and many have been victims of it long before Covid-19. International organizations have documented an increase in IPV reports during the current pandemic, raising awareness of the potential causes for such an increase. Reflecting on risk factors associated with IPV, and the underlying need of the perpetrators to exert control over the victims, it becomes increasingly important to understand how the current policies of social distancing, self-isolation, and lockdown can precipitate episodes of IPV. Furthermore, access to specialized services and health care can be compromised, and health care professionals face new challenges and demands imposed by the pandemic while managing IPV cases. This article begins by examining the main risk factors more commonly associated with IPV in the literature. It proceeds by reflecting on how these risk factors may be exacerbated during the Covid-19 pandemic, which can explain the increased number of reports. Finally, it emphasizes the new challenges faced by health care professionals, while assisting IPV victims during the pandemic and provides possible recommendations on actions to implement during and beyond the Covid-19 pandemic to prevent such cases.", "title": "The impact of the Covid-19 pandemic in the precipitation of intimate partner violence", "pid": "0einpgeu", "bm25_score": 217.00167846679688}, {"text": "While a virus is hardly \"choosy\" in finding a host, the consequences of government responses to a pandemic, such as to Covid-19, have deep implications for those already-marginalised, such as women and girls. In the absence of a systematic database examining the details of the impact, this comment synthesises existing opinions, reviews and the limited available data to show how, not only the outbreak, but particularly our response to it, are increasing the incidence of domestic violence (DV) across the globe, including in India. Despite tackling a much higher Covid caseload and mortality rate than India has, countries such as France and Spain have prioritised responding to DV in their respective societies, working out contingent mitigation mechanisms. Admittedly, low resource settings (LRS) such as India, have a bevy of additional infrastructure and budgetary challenges; but would that imply we do not respond to DV? This comment argues that in reality we have two public health emergencies to confront, the Covid-19 and domestic violence. It builds on the author's observations in the course of working on DV in an LRS context in India, and concludes with a set of recommendations on better responding to DV during Covid/lockdown times. Keywords Domestic violence, gender-based violence, Covid-19, lockdown, pandemic, low resource settings.", "title": "Twin public health emergencies: Covid-19 and domestic violence.", "pid": "1h5a4bit", "bm25_score": 216.94174194335938}, {"text": "In times of disaster, domestic violence rates tend to increase. This is a concern in the context of COVID-19, which is a more prolonged crisis than most of those studied.", "title": "Domestic violence and COVID-19: Our hidden epidemic.", "pid": "vgti6b71", "bm25_score": 216.924072265625}, {"text": "Abstract Background Intimate partner violence (IPV) is defined as physical or sexual violence, emotional abuse and stalking. It is typically experienced by women but can also be experienced by men. During quarantine due to the COVID-19, home risks to become a very dangerous place for victims of domestic violence. Method Very recent studies focusing on abusive situations during COVID emergence were identified in PubMed/Medline, Scopus, Embase. Results During the COVID-19 outbreak people have encountered an invisible and dark enemy and an experience of impotence. Due to the feelings of frustration and agitation, aggression arises with possible transgenerational transmission of trauma and violence. Conclusions Especially during quarantine and COVID emergence around the world there is a need of programs aimed to prevent acts of domestic violence and to achieve accurate assessment of multiple domains of abuse (psychological, physical, sexual) provided by trained multidisciplinary staffs (including psychiatrists, psychologists, social and legal services).", "title": "DANGER IN DANGER: INTERPERSONAL VIOLENCE DURING COVID-19 QUARANTINE", "pid": "ksa48c30", "bm25_score": 216.8870849609375}, {"text": "Can the presence of green space in urban environments reduce the frequency of violent crime? To ascertain the evidence on this topic, we conducted an in-depth literature review using the PRISMA checklist. The search parameters included US articles written in English and published since 2000. More than 30,000 potential paper titles were identified and ultimately, 45 papers were selected for inclusion. Green spaces typically comprised tree cover, parks and ground cover. Criminal behaviors typically included murder, assault, and theft. The majority of the research reviewed involved quantitative methods (e.g., comparison of green space area to crime data). We extracted multiple mechanisms from the literature that may account for the impact of green space on crime including social interaction and recreation, community perception, biophilic stress reduction, climate modulation, and spaces expressing territorial definition. Recommendations are made for future research, such as meta-analysis of existing data and the development of grounded theory through qualitative data-gathering methods. By providing evidence that access to nature has a mitigating impact on violence in urban settings, city governments and communities are empowered to support these interventions.", "title": "The Impact of Green Space on Violent Crime in Urban Environments: An Evidence Synthesis.", "pid": "8ywevius", "bm25_score": 216.849853515625}, {"text": "BACKGROUND: Intimate partner violence (IPV) is defined as physical or sexual violence, emotional abuse and stalking. It is typically experienced by women but can also be experienced by men. During quarantine due to the COVID-19, home risks to become a very dangerous place for victims of domestic violence. METHOD: Very recent studies focusing on abusive situations during COVID emergence were identified in PubMed/Medline, Scopus, Embase. RESULTS: During the COVID-19 outbreak people have encountered an invisible and dark enemy and an experience of impotence. Due to the feelings of frustration and agitation, aggression arises with possible transgenerational transmission of trauma and violence. CONCLUSIONS: Especially during quarantine and COVID emergence around the world there is a need of programs aimed to prevent acts of domestic violence and to achieve accurate assessment of multiple domains of abuse (psychological, physical, sexual) provided by trained multidisciplinary staffs (including psychiatrists, psychologists, social and legal services).", "title": "Danger in danger: Interpersonal violence during COVID-19 quarantine", "pid": "ayip4r22", "bm25_score": 216.83663940429688}, {"text": "OBJECTIVE: The COVID-19 pandemic affected today more than 3,000,000 worldwide, and more than half of humanity has been placed in quarantine. The scientific community and the political authorities fear an epidemic of suicide secondary to this crisis. The aim of this review is to analyze the impact of the COVID-19 pandemic on the dimensions of the suicidal process and its interaction with the various risk factors. We also propose innovative strategies to manage suicidal behavior in the context of pandemic. METHODS: We carried out a narrative review of international publications dealing with major pandemics (COVID-19, SARS) and their influence on suicidal vulnerability. RESULTS: Many factors are likely to increase the emergence of suicidal ideation and suicide attempts during this crisis. Social distancing and quarantine could increase the feeling of disconnection and the perception of social pain in vulnerable individuals. Some populations at high suicidal risk could be further impacted by the current pandemic: the elderly, medical staff and individuals exposed to economic insecurity. Several innovative tools adapted to the constraints of social distancing and quarantine may prevent suicide risk: e-health, VigilanS, buddhist-derived practices and art engagement. CONCLUSIONS: This unprecedented crisis may interact with certain dimensions of the suicidal process. However, it is time to innovate. Several suicide prevention tools all have their place in new modes of care and should be tested on a large scale.", "title": "Épidémie de COVID-19 et prise en charge des conduites suicidaires : challenge et perspectives./ [Suicidal behavior in light of COVID-19 outbreak: Clinical challenges and treatment perspectives]", "pid": "2bfqbs19", "bm25_score": 216.76812744140625}, {"text": "While a virus is hardly \"choosy\" in finding a host, the consequences of government responses to a pandemic, such as to Covid-19, have deep implications for those already-marginalised, such as women and girls. In the absence of a systematic database examining the details of the impact, this comment synthesises existing opinions, reviews and the limited available data to show how, not only the outbreak, but particularly our response to it, are increasing the incidence of domestic violence (DV) across the globe, including in India. Despite tackling a much higher Covid caseload and mortality rate than India has, countries such as France and Spain have prioritised responding to DV in their respective societies, working out contingent mitigation mechanisms. Admittedly, low resource settings (LRS) such as India, have a bevy of additional infrastructure and budgetary challenges; but would that imply we do not respond to DV? This comment argues that in reality we have two public health emergencies to confront, the Covid-19 and domestic violence. It builds on the author's observations in the course of working on DV in an LRS context in India, and concludes with a set of recommendations on better responding to DV during Covid/lockdown times. Keywords Domestic violence, gender-based violence, Covid-19, lockdown, pandemic, low resource settings.", "title": "Twin public health emergencies: Covid-19 and domestic violence", "pid": "clt4l6wz", "bm25_score": 216.69802856445312}, {"text": "Purpose: This study explored the COVID-19 pandemic's impacts on domestic violence (DV) with the following research questions: 1) Did DV occurring during the pandemic differ on certain variables from cases occurring on a typical day the previous year? 2) Did DV occurring after the implementation of shelter-in-place orders differ (on these same variables) from cases occurring prior to shelter-in-place orders? Methods: Two logistic regression models were developed to predict DV case differences before and during the pandemic. DV reports (N=4618) were collected from the Chicago Police Department. Cases from March 2019 and March 2020 were analyzed based on multiple variables. One model was set to predict case differences since the pandemic began, and another model was set to predict case differences during the shelter-in-place period later that month. Results: Both models were significant with multiple significant predictors. During the pandemic period, cases with arrests were 3% less likely to have occurred, and cases at residential locations were 22% more likely to have occurred. During the shelter-in-place period, cases at residential locations were 64% more likely to have occurred, and cases with child victims were 67% less likely to have occurred. Conclusions: This study offers a rapid analysis of DV case differences since the pandemic and shelter-in-place began. Additional variables and data sources could improve model explanatory power. Research, policy, and practice in this area must pivot to focus on protecting children whose access to mandated reporters has decreased and moving victims out of dangerous living situations into safe spaces.", "title": "When \"Shelter-in-Place\" Isn't Shelter That's Safe: A Rapid Analysis of Domestic Violence Case Differences During the COVID-19 Pandemic and Stay-at-Home Orders", "pid": "c3xcmkuc", "bm25_score": 216.6947784423828}, {"text": "", "title": "Gun violence during COVID-19 pandemic: Paradoxical trends in New York City, Chicago, Los Angeles and Baltimore", "pid": "57k6dw89", "bm25_score": 216.6709747314453}, {"text": "In March-April, 2020, we communicated with a cohort of criminal justice-involved (CJI) women to see how they were navigating COVID-19, chronic illness, homelessness, and shelter-in-place orders in Oakland, Birmingham, and Kansas City. We report on conversations with N = 35 women (out of the cohort of 474 women) and our own observations from ongoing criminal justice involvement studies. Women reported barriers to protecting themselves given widespread unstable housing and complex health needs, though many tried to follow COVID-19 prevention recommendations. Women expressed dissatisfaction with the suspension of research activities, as the pandemic contributed to a heightened need for study incentives, such as cash, emotional support, and other resources. COVID-19 is illuminating disparities between those who can follow recommended actions to prevent infection and those who lack resources to do so. Concerted efforts are required to reduce inequities that put the 1.3 million U.S. women under criminal justice supervision at risk for infection and mortality.", "title": "Criminal Justice-Involved Women Navigate COVID-19: Notes From the Field.", "pid": "xeqcfqp9", "bm25_score": 216.66510009765625}, {"text": "In March-April, 2020, we communicated with a cohort of criminal justice-involved (CJI) women to see how they were navigating COVID-19, chronic illness, homelessness, and shelter-in-place orders in Oakland, Birmingham, and Kansas City. We report on conversations with N = 35 women (out of the cohort of 474 women) and our own observations from ongoing criminal justice involvement studies. Women reported barriers to protecting themselves given widespread unstable housing and complex health needs, though many tried to follow COVID-19 prevention recommendations. Women expressed dissatisfaction with the suspension of research activities, as the pandemic contributed to a heightened need for study incentives, such as cash, emotional support, and other resources. COVID-19 is illuminating disparities between those who can follow recommended actions to prevent infection and those who lack resources to do so. Concerted efforts are required to reduce inequities that put the 1.3 million U.S. women under criminal justice supervision at risk for infection and mortality.", "title": "Criminal Justice-Involved Women Navigate COVID-19: Notes From the Field", "pid": "svyy9hym", "bm25_score": 216.64779663085938}, {"text": "One of the biggest challenges facing modern policing in recent years has been the lack of police legitimacy. The tipping point of this phenomenon is often attributed to the Rodney King incident in Los Angeles in 1991, where Los Angeles Police Department (LAPD) officers were videoed assaulting a lone black male. They were arrested and charged but eventually all were acquitted, thereby etching deep distrust between communities and police. Now the Rodney King example is an extreme and criminal act by police but it was the beginning of communities and media focusing on what the police were doing and how they were doing it. This lack of legitimacy coupled with what is referred to as the militarization of policing have lasting consequences and impacts on police–community relations and how interactions between police and community shape society today. In the wake of pandemic policing due to COVID-19, there are tales of two eventualities for police legitimacy that will be explored in this article: (1) The police response to the pandemic results in further militarization and draws deeper divides between police and communities or (2) the police response is compassionate and build on procedurally just operations resulting in the rebuilding of police legitimacy post-pandemic.", "title": "The Potential Impacts of Pandemic Policing on Police Legitimacy: Planning Past the COVID-19 Crisis", "pid": "jxxcvbna", "bm25_score": 216.64646911621094}, {"text": "Crises, emergencies and times of unrest have been linked to increased interpersonal violence, including violence against women. Following the declaration of alarm status and quarantine, different measures have been implemented to mitigate the possible effect of gender violence (Contingency Plan against Gender-Based Violence in Coronavirus Crisis or Royal Decree Law on Emergency Measures). This document reviews the measures adopted so far by the government of Spain, the autonomous governments and the initiatives formulated in different countries. In the absence of concrete economic measures to date, and the scenario of economic uncertainty, we conclude that it is not possible to prevent gender-based violence in a comprehensive way, without considering the increase in unemployment, temporary and instability employment, economic dependency or the overload of household chores and reproductive tasks, among other elements that facilitate it.", "title": "Medidas de contención de la violencia de género durante la pandemia de COVID-19./ [Measures to contain gender-based violence during the COVID-19 pandemic]", "pid": "lrypyg58", "bm25_score": 216.63478088378906}, {"text": "", "title": "Violence against women, children, and adolescents during the COVID-19 pandemic: overview, contributing factors, and mitigating measures.", "pid": "r9lw01x1", "bm25_score": 216.6244659423828}, {"text": "Introduction: Although lockdown measures to stop COVID-19 have direct effects on disease transmission, their impact on violent and accidental deaths remains unknown. Our study aims to assess the early impact of COVID-19 lockdown on violent and accidental deaths in Peru. Methods: Based on data from the Peruvian National Death Information System, an interrupted time series analysis was performed to assess the immediate impact and change in the trend of COVID-19 lockdown on external causes of death including homicide, suicide, and traffic accidents. The analysis was stratified by sex and the time unit was every 15 days. Results: All forms of deaths examined presented a sudden drop after the lockdown. The biggest drop was in deaths related to traffic accidents, with a reduction of 12.66 deaths per million men per month (95% CI: -15.56, -9.76) and 3.64 deaths per million women per month (95% CI:-5.25, -2.03). Homicide and suicide presented similar level drop in women, while the homicide reduction was twice the size of the suicide reduction in men. The slope in suicide in men during the lock-down period increased by 3.62 deaths per million men per year (95% CI:0.06, 7.18). No other change in slope was detected. Conclusions: Violent and accidental deaths presented a sudden drop after the lockdown was implemented and an increase in suicide in men was observed. Falls in mobility have a natural impact on traffic accidents, however, the patterns for suicide and homicide are less intuitive and reveal important characteristics of these events, although we expect all of these changes to be transient.", "title": "Impact of COVID-19 Lockdown Policy on Homicide, Suicide, and Motor Vehicle Deaths in Peru", "pid": "chmmxehj", "bm25_score": 216.619873046875}, {"text": "In times of disaster, domestic violence rates tend to increase. This is a concern in the context of COVID-19, which is a more prolonged crisis than most of those studied.", "title": "Domestic violence and COVID-19: Our hidden epidemic", "pid": "ygh0atqq", "bm25_score": 216.59725952148438}, {"text": "The hidden and often unspoken impact of the 2019 novel coronavirus (COVID-19) has been the prevalence of intimate partner violence (IPV). This commentary addresses this issue and highlights a study undertaken to address this public health issue by generating empirical research on the relationship between COVID-19 and IPV. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "The hidden disaster of COVID-19: Intimate partner violence.", "pid": "meey1l87", "bm25_score": 216.57373046875}, {"text": "The Covid-19 pandemic is currently a major worldwide public health problem. Contagion within prisons and in other custodial settings will need to be addressed promptly, but the management of preventive measures will be difficult due to overcrowding and inmates and officers' close physical contact. There may also be less access to care than in community settings. Accordingly, prisons are particularly vulnerable to outbreaks of infection, and in addition to the likely greater risks of contagion attention must be paid to the psychological problems that the pandemic can have on the prison population. Riots and episodes of violence have already taken place in various prisons. With the inevitable restrictions on social contact and family meetings, prisoners who already are at increased risk of mental illness and suicide are more susceptible to adverse psychological repercussions. From a forensic point of view, therefore, we stress the need for the development of a strong support network by mental health workers for the prison population.", "title": "Covid-19 emergency in prison: Current management and forensic perspectives.", "pid": "ymzigce5", "bm25_score": 216.5547332763672}, {"text": "", "title": "Increased Risk for Family Violence During the COVID-19 Pandemic.", "pid": "xn795tcm", "bm25_score": 216.52688598632812}, {"text": "Some violence related to CoViD-19 counteracting measures occurred in some Italian prison last month. Epidemic CoViD-19 reflects the higher risk of infections among inmates and personnel, due to closed proximity, prison overcrowding and structural conditions of Italian prisons. In the world, the higher risk infections among prisoners has been investigated in many studies, showing that, compared with the general public, people in prisons have a higher prevalence of infection such as HIV, hepatitis C virus (HCV) and tuberculosis. This is recognized as a major issue for the health of people in prisons, as well as the general population, because the majority of people who have been incarcerated will subsequently return to their communities. In Italy there are no enough available data to know the sanitary impact of such epidemic, so that preventive measures are extremely urgent.", "title": "Un altro effetto di CoViD-19: accendere le luci sulla situazione carceraria italiana./ [Another effect of CoViD-19: turning on the lights on the Italian prison situation.]", "pid": "q7km1toq", "bm25_score": 216.52584838867188}, {"text": "Importance: Anecdotal evidence such as increased calls to domestic violence (DV) hotlines across the globe suggest that there may be an increase of IPV prevalence in association with the COVID-19 outbreak; however, no study has investigated this phenomenon empirically. Objective: To evaluate the association between COVID-19 related conditions and recent use or experience of IPV (since the pandemic outbreak in the U.S). Design, Setting, and Participants: This cross-sectional study analyzed data collected online from a sample of noninstitutionalized adults (age 18+) in the U.S. (N=2,045). More than half of the sample self-identified as being in an intimate relationship at the time of the study. Main Outcomes and Measures: A four-item tool was used to assess IPV perpetration and victimization since the outbreak of COVID-19. The rapid tool inquired about two forms of IPV, psychological and physical. Participants self-reported demographic data and recent health histories, including COVID-19 tests results, related symptoms and degree of personal social distancing. We hypothesized that COVID-19 related factors would increase risks of IPV. Results: In this study, self-reported COVID-19 impacted respondents had an increased risk of IPV victimization and perpetration. Among those who reported having symptoms consistent with coronavirus, but were denied access to testing, psychological IPV victimization was 3 times greater than those who did not (Exp[B] =3.15, [1.19, 2.29] p <.05). For participants who reported testing positive to COVID-19, the odds of using psychological IPV (Exp[B] =3.24, [1.18, 8.89] p <.05) and physical IPV (Exp[B]=3.02, [1.12, 8.17] p <.05) against an intimate partner increased by more than 3 times. Conclusions and Relevance: Patient education and community outreach/health care system initiatives focused on IPV risk behaviors may help reduce the potential development of IPV. Continued surveillance is imperative to improve health and well-being along with effective intervention development and implementation.", "title": "Intimate Partner Violence Victimization and Perpetration among U.S. Adults during COVID-19: A Brief Report", "pid": "jzjhhn23", "bm25_score": 216.50152587890625}, {"text": "The hidden and often unspoken impact of the 2019 novel coronavirus (COVID-19) has been the prevalence of intimate partner violence (IPV). This commentary addresses this issue and highlights a study undertaken to address this public health issue by generating empirical research on the relationship between COVID-19 and IPV. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "The hidden disaster of COVID-19: Intimate partner violence", "pid": "35izipky", "bm25_score": 216.4672088623047}, {"text": "COVID-19 has emerged as a global health threat. The catastrophic reaction to a pandemic in spite of knowing the deadly outcomes, has been referred to as the 'social absurdity’. Such reaction creates a negativistic outlook with regard to the infection, thus contributing to chaos and preventing containment. In this article, the current pandemic of COVID-19 is revisited through the lens of Camus' ‘La Peste, 1947’. The philosophical roots of social ‘absurdity’ during a pandemic are critically discussed in the context of death anxiety. Subsequently, ways of reshaping it are highlighted, borrowing from the theories of existentialism and positive psychology.", "title": "Revisiting ‘The Plague’ by Camus: Shaping the ‘Social Absurdity’ of the COVID-19 Pandemic", "pid": "gdefrz2p", "bm25_score": 216.4425048828125}, {"text": "The Covid-19 pandemic is currently a major worldwide public health problem. Contagion within prisons and in other custodial settings will need to be addressed promptly, but the management of preventive measures will be difficult due to overcrowding and inmates and officers' close physical contact. There may also be less access to care than in community settings. Accordingly, prisons are particularly vulnerable to outbreaks of infection, and in addition to the likely greater risks of contagion attention must be paid to the psychological problems that the pandemic can have on the prison population. Riots and episodes of violence have already taken place in various prisons. With the inevitable restrictions on social contact and family meetings, prisoners who already are at increased risk of mental illness and suicide are more susceptible to adverse psychological repercussions. From a forensic point of view, therefore, we stress the need for the development of a strong support network by mental health workers for the prison population.", "title": "Covid-19 emergency in prison: Current management and forensic perspectives", "pid": "nvmp6cql", "bm25_score": 216.42300415039062}, {"text": "The phenomenon of suicide is a much studied but still little-known issue. In this particular period of health emergency, quarantine and mandatory restrictions could play a role in the genesis of fatal events or suicide attempts not only in people at risk. However, this issue has not yet been adequately addressed in the literature. The influence of the global pandemic could change the way suicide cases are analyzed; in the future, it is necessary to reconsider and analyze the various risk groups by population but above all to evaluate new methods of intervention for avoiding the increase in fatal events related to the current emergency whose duration is still unknown. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "The role of the COVID-19 pandemic as a risk factor for suicide: What is its impact on the public mental health state today?", "pid": "nmtudk18", "bm25_score": 216.36990356445312}, {"text": "", "title": "COVID-19 Exposes Need for Progressive Criminal Justice Reform", "pid": "zwtqc774", "bm25_score": 216.34719848632812}, {"text": "In this essay, we review how the COVID-19 (coronavirus) pandemic that began in the United States in early 2020 has elevated the risks of Asian Americans to hate crimes and Asian American businesses to vandalism. During the COVID-19 pandemic, the incidents of negative bias and microaggressions against Asian Americans have also increased. COVID-19 is directly linked to China, not just in terms of the origins of the disease, but also in the coverage of it. Because Asian Americans have historically been viewed as perpetually foreign no matter how long they have lived in the United States, we posit that it has been relatively easy for people to treat Chinese or Asian Americans as the physical embodiment of foreignness and disease. We examine the historical antecedents that link Asian Americans to infectious diseases. Finally, we contemplate the possibility that these experiences will lead to a reinvigoration of a panethnic Asian American identity and social movement.", "title": "The Anxiety of Being Asian American: Hate Crimes and Negative Biases During the COVID-19 Pandemic", "pid": "uiezqa4p", "bm25_score": 216.34518432617188}, {"text": "OBJECTIVE: This study explored a multiple mediation model in Wuhan's college students. Positive thinking and resilience were identified as mediators between 2019 novel coronavirus (2019-nCoV) victimization experiences and mental health. METHOD: The sample included 384 from 4 universities in Wuhan, China. Four structured instruments were applied to the college students, including scale of the 2019-nCoV coronavirus victimization experience, scale of the positive thinking, scale of the resilience, and scale of the mental health. The responses were scored using a 5-point Likert scale. Structural equation models were used to construct measurement and structural models. RESULTS: The findings confirmed that the 2019-nCoV victimization experience was a negative predictor of mental health; positive thinking and resilience were strong mediators between 2019-nCoV victimization experience and mental health. CONCLUSIONS: The results indicated that a complete model was significant because positive thinking compensated for resilience. Notably, these 2 strong mediators will vastly resist the negative influences of 2019-nCoV victimization experience on mental health in Wuhan's college students until the end of the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "The effect of the 2019 novel coronavirus pandemic on college students in Wuhan", "pid": "izkd802l", "bm25_score": 216.34426879882812}, {"text": "The COVID-19 pandemic has dramatically changed the lives of people around the globe since it appeared in Wuhan, China, at the beginning of December 2019. The burden of disease and its death toll have had an unprecedented impact on the healthcare, economic, and financial systems of low-, middle-, and high-income countries [1–3]. Peoples’ lives have been disrupted and negatively impacted by COVID-19-related suffering and lockdowns at community and household level.", "title": "Social stigma in the time of Coronavirus", "pid": "bhmt5l8y", "bm25_score": 216.28704833984375}, {"text": "Importance. Firearm violence is a significant public health and safety problem in the United States. A surge in firearm purchases following the onset of the coronavirus pandemic may increase rates of firearm violence. Objective. To estimate the association between changes in firearm purchasing and interpersonal firearm violence during the coronavirus pandemic. Design. Cross-sectional time series study. We estimate the difference between observed rates of firearm purchases and those predicted by seasonal autoregressive integrated moving average models. Using negative binomial models, we then estimate the association between excess firearm purchases and rates of interpersonal firearm violence within states, controlling for confounders. Setting. The 48 contiguous states and the District of Columbia. Hawaii and Alaska are excluded due to missing or incomplete data. Exposure. The difference between observed and expected rates of firearm purchases in March through May 2020, approximated by National Instant Criminal Background Check System records. Main Outcome and Measure. Fatal and nonfatal injuries from interpersonal firearm violence, recorded in the Gun Violence Archive. Results. We estimate that there were 2.1 million excess firearm purchases from March through May 2020--a 64.3% increase over expected volume, and an increase of 644.4 excess purchases per 100,000 population. We estimate a relative rate of death and injury from firearm violence of 1.015 (95% Confidence Interval (CI): 1.005 to 1.025) for every 100 excess purchases per 100,000, in models that incorporate variation in purchasing across states and control for effects of the pandemic common to all states. This reflects an increase of 776 fatal and nonfatal injuries (95% CI: 216 to 1,335) over the number expected had no increase in purchasing occurred. Conclusions and Relevance. We find a significant increase in firearm violence in the United States associated with the coronavirus pandemic-related surge in firearm purchasing. Our findings are consistent with existing research. Firearm violence prevention strategies may be particularly important during the pandemic.", "title": "Firearm Purchasing and Firearm Violence in the First Months of the Coronavirus Pandemic in the United States", "pid": "bmqt33yw", "bm25_score": 216.2832794189453}, {"text": "", "title": "Increased Risk for Family Violence During the COVID-19 Pandemic", "pid": "k6j789p9", "bm25_score": 216.273193359375}, {"text": "The recent severity and frequency of cybercrime has been dominated by a single theme–the COVID-19 pandemic. This research develops a multi-level influence model to explore how cybercriminals are exploiting the COVID-19 pandemic by assessing situational factors, identifying victims, impersonating trusted sources, selecting attack methods, and employing social engineering techniques. The model extends upon prior work on influence techniques and emotional appeals that cybercriminals employ, by bringing into sharper focus the role of situational factors in COVID-19 related cybercrime attacks. Content and thematic analysis was conducted on 185 distinct COVID-19 cybercrime scam incident documents, including text, images, and photos, provided by a global online fraud and cybersecurity company tracking COVID-19 related cybercrime. The analysis reveals interesting patterns about the sheer breadth and diversity of COVID-19 related cybercrime and how these crimes are continually evolving in response to changing situational factors. It is hoped that these insights and recommendations for end-users and organisations can contribute to a safer digital world as we cope with many other pressing challenges during the COVID-19 pandemic.", "title": "A multi-level influence model of COVID-19 themed cybercrime", "pid": "3nk9kvdy", "bm25_score": 216.2439727783203}, {"text": "During pandemics, like COVID-19, law enforcement agencies are responsible for working with government and public health officials to contain spread, serve the local community, and maintain public order. Given the person-to-person spread of COVID-19 through respiratory droplets, law enforcement officers are also at a heightened risk of exposure due to their close contact with members of the public. To protect officers, the Centers for Disease Control and Prevention (CDC) and other agencies have made numerous recommendations for law enforcement agencies to protect officers and the public. Departments around the country have responded to the pandemic in various ways, such as reassigning personnel to high-traffic areas, suspending training, roll calls, and community outreach initiatives, only issuing citations for low-level crimes, implementing safety precautions for officers, and limiting access to department facilities. The COVID-19 pandemic also has exposed some key obstacles for law enforcement, related to communication, resource management, the enforcement of public health restrictions, and changes to crime and service patterns. Based on these early/initial responses and obstacles during the COVID-19 outbreak, the current paper highlights directions for future responses to pandemics to ensure the safety and security of police officers and the communities they serve.", "title": "The Immediate Impact of COVID-19 on Law Enforcement in the United States", "pid": "mvof320m", "bm25_score": 216.22056579589844}, {"text": "In March 2020, two cases of attempted murder were opened against people who had tested positive for COVID-19 and had not remained in quarantine. Criminal law has previously been used to criminalise intentional transmission of HIV in both South Africa (SA) and other countries. However, it has been found that criminalisation laws undermine public health and measures to control outbreaks by stigmatising those infected and deterring testing. This article explores whether SA's existing HIV criminalisation laws can be applied to the transmission of SARS-CoV-2, and the potential effect such measures could have on efforts to control the COVID-19 epidemic.", "title": "Criminalisation of transmission of SARS-CoV-2: A potential challenge to controlling the outbreak in South Africa", "pid": "v94bcou8", "bm25_score": 216.21109008789062}, {"text": "Household isolation measures to reduce coronavirus transmission during the COVID-19 pandemic have resulted in increased risk of domestic violence and abuse (DVA). DVA physical injury most frequently involves the face. Dentists, dental care professionals, oral surgeons and oral and maxillofacial surgeons all have a critical part to play in identifying patients experiencing DVA, who present with dental and facial injury, and in making referrals to specialist agencies. This paper describes how to ask questions about DVA sensitively and how to make an appropriate referral. Early intervention and referral to a DVA advocate can prevent an abusive situation becoming worse with more intense violence. It can save lives.", "title": "COVID-19, domestic violence and abuse, and urgent dental and oral and maxillofacial surgery care", "pid": "cf26y8t6", "bm25_score": 216.14584350585938}, {"text": "", "title": "Supporting adolescents and young adults exposed to or experiencing violence during the COVID-19 pandemic", "pid": "063yv6mm", "bm25_score": 216.131103515625}, {"text": "", "title": "Supporting Adolescents and Young Adults Exposed to or Experiencing Violence During the COVID-19 Pandemic", "pid": "wggg89wr", "bm25_score": 216.131103515625}, {"text": "Abstract COVID-19 has wreaked havoc on the lives of persons around the world and social scientists are just beginning to understand its consequences on human behavior. One policy that public health officials put in place to help stop the spread of the virus were stay-at-home/shelter-in-place lockdown-style orders. While designed to protect people from the coronavirus, one potential and unintended consequence of such orders could be an increase in domestic violence – including abuse of partners, elders or children. Stay-at-home orders result in perpetrators and victims being confined in close quarters for long periods of time. In this study, we use data from Dallas, Texas to examine the extent to which a local order was associated with an increase in domestic violence. Our results provide some evidence for a short-term spike in the 2 weeks after the lockdown was instituted but a decrease thereafter. We note that it is difficult to determine just how much the lockdown was the cause of this increase as the domestic violence trend was increasing prior to the order.", "title": "Staying Home, Staying Safe? A Short-Term Analysis of COVID-19 on Dallas Domestic Violence", "pid": "7o6ij2qj", "bm25_score": 216.11306762695312}, {"text": "The COVID-19 pandemic exposes underlying inequalities in our socio-economic and health systems, such as gender-based violence (GBV). In emergencies, particularly ones that involve quarantine, GBV often increases. Policymakers must utilize community expertise, technology and existing global guidelines to disrupt these trends in the early stages of the COVID-19 epidemic. Gender norms and roles relegating women to the realm of care work puts them on the frontlines in an epidemic, while often excluding them from developing the response. It is critical to value women's roles in society and include their voices in the decision-making process to avoid unintended consequences and ensure a comprehensive response that caters to the needs of the most vulnerable groups.", "title": "Lessons Never Learned: Crisis and gender-based violence", "pid": "qaa2e83a", "bm25_score": 216.10577392578125}, {"text": "This manuscript highlights the risk that shelter-in-place instructions during COVID-19 places on victims of domestic violence and serves as a call-to-action to address this crisis. In the midst of the COVID-19 pandemic, \"stay at home\" has become the mantra of governments and public health organizations alike. But for victims of domestic violence, home is often not a place of safety. Staying at home not only places survivors of domestic violence at risk for further violence, but also isolates them from networks of support. Containment policies may lead to higher rates of domestic violence, substance abuse, anxiety, major depression, suicide, and other manifestations of unmet mental health needs. Job losses and financial insecurity may tip at-risk relationships into violence.", "title": "Domestic violence amid COVID-19.", "pid": "er50rvxw", "bm25_score": 216.10537719726562}, {"text": "Since the declaration of COVID-19 restrictions and lockdowns, countries across the world have seen an increase in reports of interpersonal violence. During these trying times, digital mental health resources tailored to interpersonal violence are needed. Through the use of online platforms such as websites, mobile applications, and social media, survivors and perpetrators alike can access tools that help them manage stressors induced by the coronavirus as well as practice emotional regulation techniques and communication strategies at home. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Coronavirus and interpersonal violence: A need for digital mental health resources.", "pid": "0xc276mq", "bm25_score": 216.0841522216797}, {"text": "OBJECTIVE This study explored a multiple mediation model in Wuhan's college students. Positive thinking and resilience were identified as mediators between 2019 novel coronavirus (2019-nCoV) victimization experiences and mental health. METHOD The sample included 384 from 4 universities in Wuhan, China. Four structured instruments were applied to the college students, including scale of the 2019-nCoV coronavirus victimization experience, scale of the positive thinking, scale of the resilience, and scale of the mental health. The responses were scored using a 5-point Likert scale. Structural equation models were used to construct measurement and structural models. RESULTS The findings confirmed that the 2019-nCoV victimization experience was a negative predictor of mental health; positive thinking and resilience were strong mediators between 2019-nCoV victimization experience and mental health. CONCLUSIONS The results indicated that a complete model was significant because positive thinking compensated for resilience. Notably, these 2 strong mediators will vastly resist the negative influences of 2019-nCoV victimization experience on mental health in Wuhan's college students until the end of the pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "The effect of the 2019 novel coronavirus pandemic on college students in Wuhan.", "pid": "pp58yv3l", "bm25_score": 216.07009887695312}, {"text": "Pandemics leave significant marks on the memories of societies with their permanent impacts. Going beyond a cause of disease or death, they can have consequences in many aspects, psychological, social and economic ones being in the first place. The Covid-19 outbreak, which first emerged in China and has spread to the whole world as of the first months of 2020, has the potential to constitute a breaking the course of history, as well. Turkey is located on the transit point between Asia and Europe with its geographical position, and thus, received its share from the outbreak of Covid-19, which spreads through social contact. The first official case was recorded on 11 March 2020, and then the virus spread rapidly. This study aims to assess the attitude of the public towards Covid-19 at times when the impact of the disease reached maximum. To this end, data were collected from 1586 people with different socio-demographic features through Covid-19 Pandemic Community Scale. The impact of the pandemic on the society was measured in three dimensions as Sensitivity to Pandemic, Protection against Pandemic and Social Trust. The research results showed that the people had high levels of sensitivity to the pandemic, exerted the maximum effort for protection and social trust was above the average although it fell behind the other dimensions. As a consequence, it can be concluded that Covid-19 has had a significant impact on the Turkish people.", "title": "The effect of COVID-19 pandemic on the Turkish society", "pid": "98dztptq", "bm25_score": 216.05953979492188}, {"text": "The emergence of COVID-19 presents unprecedented challenges in keeping individuals experiencing intimate partner violence (IPV) safe in the United States and abroad. This commentary explores how COVID-19 may be increasing risk for IPV and what strategies may be used presently, and in the future, to mitigate IPV risk during crises. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Staying safe during COVID-19: How a pandemic can escalate risk for intimate partner violence and what can be done to provide individuals with resources and support", "pid": "vpptmanx", "bm25_score": 216.02914428710938}, {"text": "Multiple lines of evidence indicate that the COVID-19 pandemic has profound psychological and social effects. The psychological sequelae of the pandemic will probably persist for months and years to come. Studies indicate that the COVID-19 pandemic is associated with distress, anxiety, fear of contagion, depression, and insomnia in the general population and among health care professionals. Social isolation, anxiety, fear of contagion, uncertainty, chronic stress, and economic difficulties may lead to the development or exacerbation of depressive, anxiety, substance use, and other psychiatric disorders in vulnerable populations including individuals with pre-existing psychiatric disorders and people who reside in high COVID-19 prevalence areas. Stress-related psychiatric conditions including mood and substance use disorders are associated with suicidal behavior. COVID-19 survivors may also be at elevated suicide risk. The COVID-19 crisis may increase suicide rates during and after the pandemic. Mental health consequences of the COVID-19 crisis including suicidal behavior are likely to be present for a long time and peak later than the actual pandemic. To reduce suicides during the COVID-19 crisis it is imperative to decrease stress, anxiety, fears and loneliness in the general population. There should be traditional and social media campaigns to promote mental health and reduce distress. Active outreach is necessary, especially for people with a history of psychiatric disorders, COVID-19 survivors, and older adults. Research studies are needed of how mental health consequences can be mitigated during and after the COVID-19 pandemic.", "title": "The impact of the COVID-19 pandemic on suicide rates", "pid": "y9vx7coj", "bm25_score": 216.02142333984375}, {"text": "Since the declaration of COVID-19 restrictions and lockdowns, countries across the world have seen an increase in reports of interpersonal violence. During these trying times, digital mental health resources tailored to interpersonal violence are needed. Through the use of online platforms such as websites, mobile applications, and social media, survivors and perpetrators alike can access tools that help them manage stressors induced by the coronavirus as well as practice emotional regulation techniques and communication strategies at home. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Coronavirus and interpersonal violence: A need for digital mental health resources", "pid": "p6uroywe", "bm25_score": 216.02003479003906}, {"text": "This paper aims at providing the summary of the Global Data Science Project (GDSC) for COVID-19. as on May 31 2020. COVID-19 has largely impacted on our societies through both direct and indirect effects transmitted by the policy measures to counter the spread of viruses. We quantitatively analysed the multifaceted impacts of the COVID-19 pandemic on our societies including people's mobility, health, and social behaviour changes. People's mobility has changed significantly due to the implementation of travel restriction and quarantine measurements. Indeed, the physical distance has widened at international (cross-border), national and regional level. At international level, due to the travel restrictions, the number of international flights has plunged overall at around 88 percent during March. In particular, the number of flights connecting Europe dropped drastically in mid of March after the United States announced travel restrictions to Europe and the EU and participating countries agreed to close borders, at 84 percent decline compared to March 10th. Similarly, we examined the impacts of quarantine measures in the major city: Tokyo (Japan), New York City (the United States), and Barcelona (Spain). Within all three cities, we found the significant decline in traffic volume. We also identified the increased concern for mental health through the analysis of posts on social networking services such as Twitter and Instagram. Notably, in the beginning of April 2020, the number of post with #depression on Instagram doubled, which might reflect the rise in mental health awareness among Instagram users. Besides, we identified the changes in a wide range of people's social behaviors, as well as economic impacts through the analysis of Instagram data and primary survey data.", "title": "Global Data Science Project for COVID-19 Summary Report", "pid": "ltbvpv8b", "bm25_score": 216.01416015625}, {"text": "The emergence of COVID-19 presents unprecedented challenges in keeping individuals experiencing intimate partner violence (IPV) safe in the United States and abroad. This commentary explores how COVID-19 may be increasing risk for IPV and what strategies may be used presently, and in the future, to mitigate IPV risk during crises. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Staying safe during COVID-19: How a pandemic can escalate risk for intimate partner violence and what can be done to provide individuals with resources and support.", "pid": "zbv1ilyx", "bm25_score": 216.01138305664062}, {"text": "The purpose of this article is to provide a brief report on how the Indonesian population has experienced the COVID-19 pandemic in the first 2 months since the establishment of COVID-19 Rapid Response Task Force on March 13. The discussion will focus on the psychological trauma that the population has experienced due to the lack of preparedness, the poorly equipped health care system, and lockdown policies in dealing with the spread of the coronavirus. Four different types of psychological trauma were increasingly observed, based on digital communication with people affected and reports from the news and social media. These 4 types of psychological trauma were social withdrawal, hysteria, individual violence, and collective violence. On the basis of the described psychological consequences of the pandemic, it can be assumed that both the individual and collective reactions must be considered to reduce harm of the coronavirus pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "COVID-19: Threat and fear in Indonesia.", "pid": "bw80dxu7", "bm25_score": 216.0112762451172}, {"text": "The COVID-19 pandemic has amplified decades of vulnerabilities, disparities, and injustices within the U.S. correctional system. The spread of the coronavirus poses a particularly serious threat to those that comprise the system, including personnel, attorneys, prisoners, their families and extends into the communities in which facilities are located. These correctional facilities and communities were especially underprepared for the sudden onset of a highly contagious virus, which has resulted in an exceedingly high number of infections among those who work and are held in the facilities. Rampant overcrowding in the U.S. correctional system, an aging population, and a population exhibiting high rates of underlying health conditions are highly likely to exacerbate the spread of this highly contagious virus. This potentially dire set of interrelated circumstances necessitates rapid decarceration measures that effectively balance public safety and public health. Unfortunately, there has been unclear guidance as well as changing and even contradictory information coming from the federal government concerning rapid measures to mitigate the spread of infection to justice system personnel and federal prisoners. In this paper we summarize the federal response and how it has impacted those responsible for implementation. Furthermore, we discuss how systemic deleterious conditions of the U.S. correctional system serve as both accelerants to as well as effects of the pandemic. We end highlighting critical issues relating to early release due to COVID-19 that will necessitate future research.", "title": "How COVID-19’s Disruption of the U.S. Correctional System Provides an Opportunity for Decarceration", "pid": "5i0zxhs1", "bm25_score": 216.00970458984375}, {"text": "The importance of bringing an end to all forms of violence against women and girls has been fully recognized as central to the achievement of the Sustainable Development Goals (SDG), with particular emphasis on SDG 5 on gender equality and women's empowerment.[1] However, the extent of violence against women and girls across the world is alarming. One in three women around the world have experienced physical and/or sexual violence by an intimate partner or sexual violence by any perpetrator in their lifetime.", "title": "Violence against women in Italy during the COVID-19 pandemic", "pid": "yklvopjo", "bm25_score": 216.00721740722656}, {"text": "We examine crime patterns in Santa Monica, California before and after passage of Proposition 47, a 2014 initiative that reclassified some non-violent felonies to misdemeanors. We also study how the 2016 opening of four new light rail stations, and how more community-based policing starting in late 2018, impacted crime. A series of statistical analyses are performed on reclassified (larceny, fraud, possession of narcotics, forgery, receiving/possessing stolen property) and non-reclassified crimes by probing publicly available databases from 2006 to 2019. We compare data before and after passage of Proposition 47, city-wide and within eight neighborhoods. Similar analyses are conducted within a 450 meter radius of the new transit stations. Reports of monthly reclassified crimes increased city-wide by approximately 15% after enactment of Proposition 47, with a significant drop observed in late 2018. Downtown exhibited the largest overall surge. The reported incidence of larceny intensified throughout the city. Two new train stations, including Downtown, reported significant crime increases in their vicinity after service began. While the number of reported reclassified crimes increased after passage of Proposition 47, those not affected by the new law decreased or stayed constant, suggesting that Proposition 47 strongly impacted crime in Santa Monica. Reported crimes decreased in late 2018 concurrent with the adoption of new policing measures that enhanced outreach and patrolling. These findings may be relevant to law enforcement and policy-makers. Follow-up studies needed to confirm long-term trends may be affected by the COVID-19 pandemic that drastically changed societal conditions.", "title": "Impacts of California Proposition 47 on Crime in Santa Monica, CA", "pid": "gd0v5vfg", "bm25_score": 216.00363159179688}, {"text": "The importance of bringing an end to all forms of violence against women and girls has been fully recognized as central to the achievement of the Sustainable Development Goals (SDG), with particular emphasis on SDG 5 on gender equality and women's empowerment.[1] However, the extent of violence against women and girls across the world is alarming. One in three women around the world have experienced physical and/or sexual violence by an intimate partner or sexual violence by any perpetrator in their lifetime.", "title": "Violence against women in Italy during the COVID-19 pandemic.", "pid": "4xq4otsd", "bm25_score": 215.98475646972656}, {"text": "The purpose of this article is to provide a brief report on how the Indonesian population has experienced the COVID-19 pandemic in the first 2 months since the establishment of COVID-19 Rapid Response Task Force on March 13. The discussion will focus on the psychological trauma that the population has experienced due to the lack of preparedness, the poorly equipped health care system, and lockdown policies in dealing with the spread of the coronavirus. Four different types of psychological trauma were increasingly observed, based on digital communication with people affected and reports from the news and social media. These 4 types of psychological trauma were social withdrawal, hysteria, individual violence, and collective violence. On the basis of the described psychological consequences of the pandemic, it can be assumed that both the individual and collective reactions must be considered to reduce harm of the coronavirus pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "COVID-19: Threat and fear in Indonesia", "pid": "824miiwu", "bm25_score": 215.95425415039062}, {"text": "", "title": "Alarming trends in US domestic violence during the COVID-19 pandemic", "pid": "mcyvnxji", "bm25_score": 215.93943786621094}, {"text": "Modeling conducted by the Centers for Disease Control and Prevention calculates that as many as 160 to 214 million people in the United States could become infected by the 2019 novel coronavirus (SARS-CoV-2, which causes the disease COVID-19) and that as many as 200 000 to 1.7 million may die from COVID-19.1 Prisons and jails are amplifiers of infectious diseases because of overcrowding and unsanitary living conditions and will most certainly contribute to these estimates. COVID-19 outbreaks have already been identified in New York City and Cook County, Illinois, jails, with infection rates at the Rikers Island jail complex far exceeding community rates. In response, correctional systems are implementing changes to mitigate the spread of COVID-19, including reducing jail and prison admissions and releasing people from facilities. In tandem, jails and prisons must also initiate facility-level policies to help stop the spread of COVID-19. (Am J Public Health. Published online ahead of print April 29, 2020: e1-e2. doi:10.2105/AJPH.2020.305707).", "title": "COVID-19 Exposes Need for Progressive Criminal Justice Reform.", "pid": "ykq2uhe3", "bm25_score": 215.92291259765625}, {"text": "The infection of the novel coronavirus that originated from Wuhan, China in December 2019 converted rapidly into a pandemic by March 11, 2020. Whereas the infection mortality rate is not completely understood, it seems to be significantly beyond that of other recent pandemics (e.g., H1N1 pandemic). This paper discusses moral injury in the context of disaster and epidemic and how easily the moral psychology of individuals and society can be shaken. Moral injury is a multiscientific concept involving psychology, culture, and religion. Amid the outbreak of the novel coronavirus pneumonia, immoral behaviors and events such as violence, injury, and illness have also caused different degrees of impact on the moral standards of individuals, confusing moral cognition, destroying moral emotion, and weakening moral toughness, resulting in varying degrees of moral injury. If there is no national health, there will be no positive society for all. Based on this, the public needs to pay close attention to the moral health of the whole people and effectively avoid the occurrence of moral injury. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Analysis of the causes of moral injury in the outbreak of 2019-nCoV.", "pid": "2hq2seh5", "bm25_score": 215.92098999023438}, {"text": "Abstract The coronavirus disease (COVID-19) pandemic has created an unprecedented public health emergency Extraordinary measures have been implemented to reduce the spread of the virus, including mass quarantines and social distancing However, these preventive measures come at a price Economic stress, social isolation, decreased access to community activities, etc , is the new reality for a large part of the global community, and may have detrimental effects on mental health", "title": "COVID-19-related self-harm and suicidality among individuals with mental disorders", "pid": "itefsyv4", "bm25_score": 215.91278076171875}, {"text": "The high numbers of COVID-19 infections and deaths, economic difficulties, uncertainty about the future, as well as the approaches needed to contain the spread of the virus are all playing critical roles in the short and long-term social and psychological impact of the COVID-19 pandemic. Inequities based on race and socioeconomic status influence the rates of infection and deaths and steps that are needed to achieve recovery. This commentary focuses on similarities and differences after other disasters and efforts being initiated to provide support and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Psychological and social impact of COVID-19.", "pid": "hdy4h13e", "bm25_score": 215.90911865234375}, {"text": "The COVID-19 pandemic created social upheaval and altered norms for all members of society, but its effects on first responders have been particularly profound. Law enforcement officers have been expected to coordinate local shutdowns, encourage social distancing, and enforce stay-at-home mandates all while completing the responsibilities for which they are already understaffed and underfunded. The impact of the COVID-19 pandemic on officer stress, mental health, resiliency, and misconduct is explored drawing insight from reactions to the HIV epidemic over two decades earlier and the terrorist attacks of September 11, 2001. COVID-19 policing is hypothesized to serve as a significant stressor for officers and compound the general and organizational stress associated with the occupation. Avenues for providing officer support are discussed and recommendations for research into the phenomenon presented.", "title": "Police Stress, Mental Health, and Resiliency during the COVID-19 Pandemic", "pid": "e44nuhh9", "bm25_score": 215.89059448242188}, {"text": "", "title": "Violence against women in the covid-19 pandemic: we need upstream approaches to break the intergenerational cycle.", "pid": "scflj8jc", "bm25_score": 215.87322998046875}, {"text": "The high numbers of COVID-19 infections and deaths, economic difficulties, uncertainty about the future, as well as the approaches needed to contain the spread of the virus are all playing critical roles in the short and long-term social and psychological impact of the COVID-19 pandemic. Inequities based on race and socioeconomic status influence the rates of infection and deaths and steps that are needed to achieve recovery. This commentary focuses on similarities and differences after other disasters and efforts being initiated to provide support and recovery. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Psychological and social impact of COVID-19", "pid": "nj2dllu3", "bm25_score": 215.86114501953125}, {"text": "History shows that pandemics rarely impact on the population equally - the 14th century Black Death plague reduced the global population by a third, with the greatest number of deaths occurring among the poor.1 Fast forward six centuries, and the same pandemic inequities are prevailing due to COVID-19; with Smith and Judd articulating that \"while COVID-19 has the potential to impact everyone in society, these impacts will be felt differentially… the most vulnerable will be hardest hit\"2 in their recent Health Promotion Journal of Australia editorial.", "title": "People experiencing homelessness urgently need to be recognised as a high risk group for COVID-19.", "pid": "qz4qsm32", "bm25_score": 215.85365295410156}, {"text": "", "title": "COVID-19 Policies can Perpetuate Violence Against Transgender Communities: Insights from Peru", "pid": "il8j9jsw", "bm25_score": 215.83155822753906}, {"text": "The infection of the novel coronavirus that originated from Wuhan, China in December 2019 converted rapidly into a pandemic by March 11, 2020. Whereas the infection mortality rate is not completely understood, it seems to be significantly beyond that of other recent pandemics (e.g., H1N1 pandemic). This paper discusses moral injury in the context of disaster and epidemic and how easily the moral psychology of individuals and society can be shaken. Moral injury is a multiscientific concept involving psychology, culture, and religion. Amid the outbreak of the novel coronavirus pneumonia, immoral behaviors and events such as violence, injury, and illness have also caused different degrees of impact on the moral standards of individuals, confusing moral cognition, destroying moral emotion, and weakening moral toughness, resulting in varying degrees of moral injury. If there is no national health, there will be no positive society for all. Based on this, the public needs to pay close attention to the moral health of the whole people and effectively avoid the occurrence of moral injury. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Analysis of the causes of moral injury in the outbreak of 2019-nCoV", "pid": "i9jx8qwq", "bm25_score": 215.818115234375}, {"text": "", "title": "Violence against women during covid-19 pandemic restrictions", "pid": "fh1rg0kc", "bm25_score": 215.80979919433594}, {"text": "", "title": "Violence against women in the covid-19 pandemic: we need upstream approaches to break the intergenerational cycle", "pid": "6k956e5h", "bm25_score": 215.8040313720703}]}
{"idx": 43, "qid": "44", "q_text": "How much impact do masks have on preventing the spread of the COVID-19?", "qrels": {"019lj813": 2, "047asp3a": 0, "056hmnru": 2, "05vx82oo": 0, "05w4l6ta": 0, "06o7pa3d": 0, "0999t5x0": 0, "09e8bwee": 0, "0a371595": 0, "i5i8hb80": 2, "0durj95f": 2, "0emibwp3": 1, "0en2sl3q": 1, "0eyp98j2": 0, "0gbbht2x": 0, "0hki5u13": 2, "0javg3m8": 2, "vygsubve": 2, "0l78gpg3": 2, "0lndg8s2": 2, "0lxzrk8l": 1, "0mn4jua2": 0, "0n5n7p4b": 0, "0nv7yqn0": 0, "0ppscgin": 0, "0r0zdpds": 1, "0rq0wdpq": 0, "0undodih": 0, "0v51a4f9": 2, "0xymzkzn": 0, "0y049q14": 1, "0yolq3ub": 0, "0z3vfou2": 2, "0zjdgqv3": 2, "ycw846fe": 0, "10p3mth2": 0, "120uu4dh": 0, "124czudi": 0, "kz2z0mbp": 0, "147yc66p": 0, "14x4uqq7": 2, "1558088w": 2, "17tucoy7": 0, "18crkfzj": 2, "19vj647z": 0, "1aqf98e0": 2, "1atoairy": 0, "1c3fpazy": 2, "istfvvd0": 0, "imv1ygf6": 2, "1fdmmdll": 0, "1j3ou5yv": 2, "1jpf9kc4": 2, "1kpw4ru0": 0, "1lugzjbv": 1, "1mbztn72": 1, "1mwf49bw": 1, "1nliar3p": 1, 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Masks are thought to have two modes of effect: they prevent infection with COVID-19 in wearers; and prevent transmission by individuals with subclinical infection. We used a simple next-generation matrix approach to estimate the conditions under which masks would reduce the reproduction number of COVID-19 under a threshold of 1. Our model takes into account the possibility of assortative mixing, where mask users interact preferentially with other mask users. We make 3 key observations: 1. Masks, even with suboptimal efficacy in both prevention of acquisition and transmission of infection, could substantially decrease the reproduction number for COVID-19 if widely used. 2. Widespread masking may be sufficient to suppress epidemics where R has been brought close to 1 via other measures (e.g., distancing). 3. “Assortment” within populations (the tendency for interactions between masked individuals to be more likely than interactions between masked and unmasked individuals) would rapidly erode the impact of masks. As such, mask uptake needs to be fairly universal to have an effect. This simple model suggests that widespread uptake of masking could be determinative in suppressing COVID-19 epidemics in regions with R(t) at or near 1.", "title": "Brief research report: Bidirectional impact of imperfect mask use on reproduction number of COVID-19: A next generation matrix approach()", "pid": "dt2pew66", "bm25_score": 219.39764404296875}, {"text": "Background: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. Results: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials, case-control studies and retrospective studies. Conclusions: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "title": "Efficacy of face mask in preventing respiratory virus transmission: a systematic review and meta-analysis", "pid": "ropgq7tr", "bm25_score": 218.91683959960938}, {"text": "BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24-0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11-0.37) and 47% (OR = 0.53, 95% CI = 0.36-0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "title": "Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis", "pid": "b4znk2wr", "bm25_score": 218.88613891601562}, {"text": "BACKGROUND: Conflicting recommendations exist related to whether masks have a protective effect on the spread of respiratory viruses. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement was consulted to report this systematic review. Relevant articles were retrieved from PubMed, Web of Science, ScienceDirect, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI), VIP (Chinese) database. RESULTS: A total of 21 studies met our inclusion criteria. Meta-analyses suggest that mask use provided a significant protective effect (OR = 0.35 and 95% CI = 0.24–0.51). Use of masks by healthcare workers (HCWs) and non-healthcare workers (Non-HCWs) can reduce the risk of respiratory virus infection by 80% (OR = 0.20, 95% CI = 0.11–0.37) and 47% (OR = 0.53, 95% CI = 0.36–0.79). The protective effect of wearing masks in Asia (OR = 0.31) appeared to be higher than that of Western countries (OR = 0.45). Masks had a protective effect against influenza viruses (OR = 0.55), SARS (OR = 0.26), and SARS-CoV-2 (OR = 0.04). In the subgroups based on different study designs, protective effects of wearing mask were significant in cluster randomized trials and observational studies. CONCLUSIONS: This study adds additional evidence of the enhanced protective value of masks, we stress that the use masks serve as an adjunctive method regarding the COVID-19 outbreak.", "title": "Efficacy of face mask in preventing respiratory virus transmission: A systematic review and meta-analysis", "pid": "x9sfgtim", "bm25_score": 218.76158142089844}, {"text": "The effect of masking the general population on a COVID-19 epidemic is estimated by computer simulation using two separate state-of-the-art web-based softwares, one of them calibrated for the SARS-CoV-2 virus. The questions addressed are these: 1. Can mask use by the general population limit the spread of SARS-CoV-2 in a country? 2. What types of masks exist, and how elaborate must a mask be to be effective against COVID-19? 3. Does the mask have to be applied early in an epidemic? 4. A brief general discussion of masks and some possible future research questions regarding masks and SARS-CoV-2. Results are as follows: (1) The results indicate that any type of mask, even simple home-made ones, may be effective. Masks use seems to have an effect in lowering new patients even the protective effect of each mask (here dubbed\"one-mask protection\") is low. Strict adherence to mask use does not appear to be critical. However, increasing the one-mask protection to>50% was found to be advantageous. Masks seemed able to reduce overflow of capacity, e.g. of intensive care. As the default parameters of the software included another intervention, it seems possible to combine mask and other interventions. (2) Masks do seem to reduce the number of new cases even if introduced at a late stage in an epidemic. However, early implementation helps reduce the cumulative and total number of cases. (3) The simulations suggest that it might be possible to eliminate a COVID-19 outbreak by widespread mask use during a limited period. The results from these simulations are encouraging, but do not necessarily represent the real-life situation, so it is suggested that clinical trials of masks are now carried out while continuously monitoring effects and side-effects.", "title": "Masking the general population might attenuate COVID-19 outbreaks", "pid": "ugkxxaeb", "bm25_score": 218.51925659179688}, {"text": "We use the synthetic control method to analyze the effect of face masks on the spread of Covid-19 in Germany. Our identification approach exploits regional variation in the point in time when face masks became compulsory. Depending on the region we analyse, we find that face masks reduced the cumulative number of registered Covid-19 cases between 2.3% and 13% over a period of 10 days after they became compulsory. Assessing the credibility of the various estimates, we conclude that face masks reduce the daily growth rate of reported infections by around 40%.", "title": "Face Masks Considerably Reduce Covid-19 Cases in Germany", "pid": "yx9oa2ra", "bm25_score": 218.4957275390625}, {"text": "Background The pandemic of COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2), has become a serious worldwide public health emergency. This systematic review aims to summarize the available evidence regarding the role of face mask in community settings in slowing the spread of respiratory viruses such as SARS- CoV-2. Methods The preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines were used for this review. A literature search using PUBMED, Google Scholar, and Cochrane database were performed using Medical subject heading (MeSH) words from the year 2000-2020. The articles focused on the use of masks and N95 respirators in healthcare workers were excluded. Results A total of 305 records were identified, out of which 14 articles were included in the review based upon quality and eligibility criteria. All the articles mentioned about the role of face masks in preventing the spread of respiratory viruses like influenza, SARS, and SARS-CoV-2, in the community or experimental setting. Studies also suggested that early initiation of face mask usage was more effective. Masks were also reported to be more effective in viruses that transmit easily from asymptomatic individuals, as is now known in SARS-CoV-2. Conclusion Theoretical, experimental, and clinical evidence suggested that usage of face masks in a general population offered significant benefit in preventing the spread of respiratory viruses especially in the pandemic situation, but its utility is limited by inconsistent adherence to mask usage.", "title": "The use of facemasks by the general population to prevent transmission of Covid 19 infection: A systematic review.", "pid": "f7rcijh4", "bm25_score": 218.4252471923828}, {"text": "Zhang et al. (2020) reported that mandating face coverings in public is necessary to decrease the rate of new COVID-19 infections. We present a counterexample that disproves this finding. We agree with Zhang et al. that masks can be an important element in reducing virus transmission and that widespread use may be essential for returning to full activity. However, their analysis neglects the potential importance of physical distancing for limiting COVID-19 transmission by misattributing its effect to mask requirements. A full suite of epidemiological tools is necessary in these challenging times.", "title": "Reply to Zhang et al.: Slowing the rate of spread of COVID-19", "pid": "8t8psk46", "bm25_score": 218.37521362304688}, {"text": "COVID-19, caused by SARS-CoV2 is a rapidly spreading global pandemic. Although precise transmission routes and dynamics are unknown, SARS-CoV2 is thought primarily to spread via contagious respiratory droplets. Unlike with SARS-CoV, maximal viral shedding occurs in the early phase of illness, and this is supported by models that suggest 40-80% of transmission events occur from pre- and asymptomatic individuals. One widely-discussed strategy to limit transmission of SARS-CoV2, particularly from presymptomatic individuals, has been population-level wearing of masks. Modelling for pandemic influenza suggests some benefit in reducing total numbers infected with even 50% mask-use. COVID-19 has a higher hospitalization and mortality rate than influenza, and the impacts on these parameters, and critically, at what point in the pandemic trajectory mask-use might exert maximal benefit are completely unknown. We derived a simplified SIR model to investigate the effects of near-universal mask-use on COVID-19 assuming 8 or 16% mask efficacy. We decided to model, in particular, the impact of masks on numbers of critically-ill patients and cumulative mortality, since these are parameters that are likely to have the most severe consequences in the COVID-19 pandemic. Whereas mask use had a relatively minor benefit on critical-care and mortality rates when transmissibility (Reff) was high, the reduction on deaths was dramatic as the effective R approached 1, as might be expected after aggressive social-distancing measures such as wide-spread lockdowns. One major concern with COVID-19 is its potential to overwhelm healthcare infrastructures, even in resource-rich settings, with one third of hospitalized patients requiring critical-care. We incorporated this into our model, increasing death rates for when critical-care resources have been exhausted. Our simple model shows that modest efficacy of masks could avert substantial mortality in this scenario. Importantly, the effects on mortality became hyper-sensitive to mask-wearing as the effective R approaches 1, i.e. near the tipping point of when the infection trajectory is expected to revert to exponential growth, as would be expected after effective lockdown. Our model suggests that mask-wearing might exert maximal benefit as nations plan their post-lockdown strategies and suggests that mask-wearing should be included in further more sophisticated models of the current pandemic.", "title": "Impact of population mask wearing on Covid-19 post lockdown", "pid": "uc37poce", "bm25_score": 218.3275146484375}, {"text": "The mandatory face mask wearing was implemented in the Czech Republic and Slovakia shortly after the COVID-19 outbreak in Central Europe. So far, the number of COVID-19-associated deaths per 100,000 individuals is far lower in these countries as compared with other neighbouring or close countries. The use of face masks in public may not protect the general public from contracting the virus, however, presumptively decreases the viral load and contributes to a favourable clinical outcome in COVID-19 disease. A certain time is required for antigen-specific T cells and B cells to fully develop. Obligatory face mask wearing in public favours the virus transmission through oral mucosa and/or conjunctival epithelium, which enables the adaptive immune responses to evolve. In the case of inhalation of high loads of SARS-CoV-2, the time for the development of fully protective adaptive immune responses seems to be insufficient. Then, a less specific and more damaging innate immune response prevails.", "title": "Can wearing face masks in public affect transmission route and viral load in COVID-19?", "pid": "p93u753c", "bm25_score": 218.2865447998047}, {"text": "Abstract Background Face mask usage by the healthy population in the community to reduce risk of transmission of respiratory viruses remains controversial. We assessed the effect of community-wide mask usage to control coronavirus disease 2019 (COVID-19) in Hong Kong Special Administrative Region (HKSAR). Methods Patients presenting with respiratory symptoms at outpatient clinics or hospital wards were screened for COVID-19 per protocol. Epidemiological analysis was performed for confirmed cases, especially persons acquiring COVID-19 during mask-off and mask-on settings. The incidence of COVID-19 per-million-population in HKSAR with community-wide masking was compared to that of non-mask-wearing countries which are comparable with HKSAR in terms of population density, healthcare system, BCG vaccination and social distancing measures but not community-wide masking. Compliance of face mask usage in the HKSAR community was monitored. Findings Within first 100 days (31 December 2019 to 8 April 2020), 961 COVID-19 patients were diagnosed in HKSAR. The COVID-19 incidence in HKSAR (129.0 per-million-population) was significantly lower (p<0.001) than that of Spain (2983.2), Italy (2250.8), Germany (1241.5), France (1151.6), U.S. (1102.8), U.K. (831.5), Singapore (259.8), and South Korea (200.5). The compliance of face mask usage by HKSAR general public was 96.6% (range: 95.7% to 97.2%). We observed 11 COVID-19 clusters in recreational ‘mask-off’ settings compared to only 3 in workplace ‘mask-on’ settings (p = 0.036 by Chi square test of goodness-of-fit). Conclusion Community-wide mask wearing may contribute to the control of COVID-19 by reducing virus shedding in saliva and respiratory droplets from individuals with subclinical or mild COVID-19.", "title": "The role of community-wide wearing of face mask for control of coronavirus disease 2019 (COVID-19) epidemic due to SARS-CoV-2", "pid": "9mn6trtn", "bm25_score": 218.14466857910156}, {"text": "Background The reasons for the large differences between countries in the sizes of their SARS CoV2 epidemics is unknown. Individual level studies have found that the use of face masks was protective for the acquisition and transmission of a range of respiratory viruses including SARS CoV1. We hypothesized that population level usage of face masks may be negatively associated SARS CoV2 spread. Methods At a country level, linear regression was used to assess the association between COVID19 diagnoses per inhabitant and the national promotion of face masks in public (coded as a binary variable), controlling for the age of the COVID19 epidemic and testing intensity. Results Eight of the 49 countries with available data advocated wearing face masks in public: China, Czechia, Hong Kong, Japan, Singapore, South Korea, Thailand and Malaysia. In multivariate analysis face mask use was negatively associated with number of COVID19 cases/inhabitant (coef. -326, 95% CI -601- -51, P=0.021). Testing intensity was positively associated with COVID-19 cases (coef. 0.07, 95% CI 0.05-0.08, P<0.001). Conclusion Whilst these results are susceptible to residual confounding, they do provide ecological level support to the individual level studies that found face mask usage to reduce the transmission and acquisition of respiratory viral infections.", "title": "Widespread use of face masks in public may slow the spread of SARS CoV-2: an ecological study", "pid": "5wsj003j", "bm25_score": 218.13841247558594}, {"text": "Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. We develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. Model simulations, using data relevant to COVID-19 dynamics in the US states of New York and Washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths. Moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. Notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. Hypothetical mask adoption scenarios, for Washington and New York state, suggest that immediate near universal (80%) adoption of moderately (50%) effective masks could prevent on the order of 17--45% of projected deaths over two months in New York, while decreasing the peak daily death rate by 34--58%, absent other changes in epidemic dynamics. Even very weak masks (20% effective) can still be useful if the underlying transmission rate is relatively low or decreasing: In Washington, where baseline transmission is much less intense, 80% adoption of such masks could reduce mortality by 24--65% (and peak deaths 15--69%), compared to 2--9% mortality reduction in New York (peak death reduction 9--18%). Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high.", "title": "To mask or not to mask: Modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic", "pid": "28utunid", "bm25_score": 218.1370086669922}, {"text": "", "title": "Are face masks useful for limiting the spread of COVID-19?", "pid": "a6gaoeie", "bm25_score": 218.1266632080078}, {"text": "BACKGROUND: Face mask usage by the healthy population in the community to reduce risk of transmission of respiratory viruses remains controversial. We assessed the effect of community-wide mask usage to control coronavirus disease 2019 (COVID-19) in Hong Kong Special Administrative Region (HKSAR). METHODS: Patients presenting with respiratory symptoms at outpatient clinics or hospital wards were screened for COVID-19 per protocol. Epidemiological analysis was performed for confirmed cases, especially persons acquiring COVID-19 during mask-off and mask-on settings. The incidence of COVID-19 per million population in HKSAR with community-wide masking was compared to that of non-mask-wearing countries which are comparable with HKSAR in terms of population density, healthcare system, BCG vaccination and social distancing measures but not community-wide masking. Compliance of face mask usage in the HKSAR community was monitored. FINDINGS: Within first 100 days (31 December 2019 to 8 April 2020), 961 COVID-19 patients were diagnosed in HKSAR. The COVID-19 incidence in HKSAR (129.0 per million population) was significantly lower (p<0.001) than that of Spain (2983.2), Italy (2250.8), Germany (1241.5), France (1151.6), U.S. (1102.8), U.K. (831.5), Singapore (259.8), and South Korea (200.5). The compliance of face mask usage by HKSAR general public was 96.6% (range: 95.7% to 97.2%). We observed 11 COVID-19 clusters in recreational 'mask-off' settings compared to only 3 in workplace 'mask-on' settings (p = 0.036 by Chi square test of goodness-of-fit). CONCLUSION: Community-wide mask wearing may contribute to the control of COVID-19 by reducing the amount of emission of infected saliva and respiratory droplets from individuals with subclinical or mild COVID-19.", "title": "The role of community-wide wearing of face mask for control of coronavirus disease 2019 (COVID-19) epidemic due to SARS-CoV-2", "pid": "wiel6zen", "bm25_score": 218.11883544921875}, {"text": "State policies mandating public or community use of face masks or covers in mitigating novel coronavirus disease (COVID-19) spread are hotly contested. This study provides evidence from a natural experiment on effects of state government mandates in the US for face mask use in public issued by 15 states plus DC between April 8 and May 15. The research design is an event study examining changes in the daily county-level COVID-19 growth rates between March 31, 2020 and May 22, 2020. Mandating face mask use in public is associated with a decline in the daily COVID-19 growth rate by 0.9, 1.1, 1.4, 1.7, and 2.0 percentage-points in 1-5, 6-10, 11-15, 16-20, and 21+ days after signing, respectively. Estimates suggest as many as 230,000-450,000 COVID-19 cases possibly averted By May 22, 2020 by these mandates. The findings suggest that requiring face mask use in public might help in mitigating COVID-19 spread. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "title": "Community Use Of Face Masks And COVID-19: Evidence From A Natural Experiment Of State Mandates In The US.", "pid": "9b6cepf4", "bm25_score": 218.1090087890625}, {"text": "In the context of Coronavirus Disease (2019) (COVID-19) cases globally, there is a lack of consensus across cultures on whether wearing face masks is an effective physical intervention against disease transmission. This study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context. To achieve this goal, government should establish a risk adjusted strategy of mask use to scientifically publicize the use of masks, guarantee sufficient supply of masks, and cooperate for reducing health resources inequities.", "title": "Mask use during COVID-19: A risk adjusted strategy", "pid": "6tod4abn", "bm25_score": 218.0952606201172}, {"text": "In the context of Coronavirus Disease (2019) (COVID-19) cases globally, there is a lack of consensus across cultures on whether wearing face masks is an effective physical intervention against disease transmission. This study 1) illustrates transmission routes of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); 2) addresses controversies surrounding the mask from perspectives of attitude, effectiveness, and necessity of wearing the mask with evidence that the use of mask would effectively interrupt the transmission of infectious diseases in both hospital settings and community settings; and 3) provides suggestion that the public should wear the mask during COVID-19 pandemic according to local context. To achieve this goal, government should establish a risk adjusted strategy of mask use to scientifically publicize the use of masks, guarantee sufficient supply of masks, and cooperate for reducing health resources inequities.", "title": "Mask use during COVID-19: A risk adjusted strategy()", "pid": "iaiosjlu", "bm25_score": 218.04222106933594}, {"text": "State policies mandating public or community use of face masks or covers in mitigating novel coronavirus disease (COVID-19) spread are hotly contested. This study provides evidence from a natural experiment on effects of state government mandates in the US for face mask use in public issued by 15 states plus DC between April 8 and May 15. The research design is an event study examining changes in the daily county-level COVID-19 growth rates between March 31, 2020 and May 22, 2020. Mandating face mask use in public is associated with a decline in the daily COVID-19 growth rate by 0.9, 1.1, 1.4, 1.7, and 2.0 percentage-points in 1-5, 6-10, 11-15, 16-20, and 21+ days after signing, respectively. Estimates suggest as many as 230,000-450,000 COVID-19 cases possibly averted By May 22, 2020 by these mandates. The findings suggest that requiring face mask use in public might help in mitigating COVID-19 spread. [Editor's Note: This Fast Track Ahead Of Print article is the accepted version of the peer-reviewed manuscript. The final edited version will appear in an upcoming issue of Health Affairs.].", "title": "Community Use Of Face Masks And COVID-19: Evidence From A Natural Experiment Of State Mandates In The US", "pid": "h2ahzau7", "bm25_score": 218.03411865234375}, {"text": "The coronavirus disease 2019 (COVID-19) [2019-nCoV; severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] was first detected in Wuhan, China at the end of 2019. In current status, spread of CO-VID-19 in person-to-person could be caused mainly by respiratory droplets, which leads to the spread of the influenza virus in both community and clinicians. Thus, in order to reduce the risk of that, the urgent management strategies against COVID-19 are to block transmission, isolation, protection, and using drug or vaccine updated on an ongoing basis. unfortunately, no drugs or vaccines still has yet been allowed to treat patients with COVID-19, so the rapid detection of effective intercessions against COVID-19 is seemed a major challenge on the all world. Herein, this article attempts summarizing to introduce the characterization of COVID-19, the influence of droplets travel in person-to-person transmission and the effect of wearing masks in the infection prevention of influenza virus, as well as understanding its advantage and role in the coronavirus infection prevention.", "title": "Coronavirus infection prevention by wearing masks", "pid": "q0ey3wib", "bm25_score": 217.97869873046875}, {"text": "As the COVID-19 pandemic progressed across the world, governments, international agencies, policymakers, and public health officials began recommending widespread use of nonmedical cloth masks to reduce the transmission of SARS-CoV-2. The authors of this article suggest that there is convincing evidence to support this recommendation.", "title": "Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach", "pid": "8je46886", "bm25_score": 217.96023559570312}, {"text": "Evidence that face masks provide effective protection against respiratory infections in the community is scarce. However, face masks are widely used by health workers as part of droplet precautions when caring for patients with respiratory infections. It would therefore be reasonable to suggest that consistent widespread use of face masks in the community could prevent further spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2). In this study we examine public face mask wearing in Uganda where a proportion wears masks to protect against acquiring, and the other to prevent from transmitting SARS-CoV-2. The objective of this study was to determine what percentage of the population would have to wear face masks to reduce susceptibility to and infectivity of COVID-19 in Uganda, keeping the basic reproduction number below unity and/or flattening the curve. We used an SEIAQRD model for the analysis. Results show that implementation of facemasks has a relatively large impact on the size of the coronavirus epidemic in Uganda. We find that the critical mask adherence is 5 per 100 when 80% wear face masks. A cost-effective analysis shows that utilizing funds to provide 1 public mask to the population has a per capita compounded cost of USD 1.34. If provision of face masks is done simultaneously with supportive care, the per capita compounded cost is USD 1.965, while for the case of only treatment and no provision of face masks costs each Ugandan USD 4.0579. We conclude that since it is hard to achieve a 100% adherence to face masks, government might consider provision of face masks in conjunction with provision of care.", "title": "Estimating the Effect and Cost-Effectiveness of Facemasks in Reducing the Spread of the Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) in Uganda", "pid": "zwyueevh", "bm25_score": 217.9222412109375}, {"text": "The medical community agrees that breathborne infectious materials can be spread with exhaled aerosols and that asymptomatic people, i.e., those showing no symptoms, could be unknowingly infectious. With the current worldwide pandemic of the respiratory coronavirus disease 2019 (COVID-19), various health bodies and governments are recommending that the population wear some form of mask or improvised facial covers while out in public in an effort to reduce the spread of disease . The general concept is that more accessible masks or mask-like materials (scarves, bandanas, etc.) could serve to reduce the amount of infectious aerosol from infected people, and reduce the viral load in the environment. This editorial addresses the underlying scientific rationale that such inexpensive or improvised could indeed serve to reduce the emissions of infectious aerosol by the mechanism of surface adhesion and particle kinetics in addition to the filtration effect.", "title": "The scientific rationale for the use of simple masks or improvised facial coverings to trap exhaled aerosols and possibly reduce the breathborne spread of COVID-19", "pid": "m17j5u0y", "bm25_score": 217.8872833251953}, {"text": "ABSTRACT Background The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally. Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public. Methods A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms. Results A total of 19 randomised controlled trials were included in this study – 8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be more effective than hand hygiene alone, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently. Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts. Conclusion The study suggests that community mask use by well people could be beneficial, particularly for COVID-19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift. This may prevent health worker infections and deaths from COVID-19, as aerosolisation in the hospital setting has been documented.", "title": "A RAPID SYSTEMATIC REVIEW OF THE EFFICACY OF FACE MASKS AND RESPIRATORS AGAINST CORONAVIRUSES AND OTHER RESPIRATORY TRANSMISSIBLE VIRUSES FOR THE COMMUNITY, HEALTHCARE WORKERS AND SICK PATIENTS", "pid": "h7ftu3ax", "bm25_score": 217.86839294433594}, {"text": "BACKGROUND: The pandemic of COVID-19 is growing, and a shortage of masks and respirators has been reported globally. Policies of health organizations for healthcare workers are inconsistent, with a change in policy in the US for universal face mask use. The aim of this study was to review the evidence around the efficacy of masks and respirators for healthcare workers, sick patients and the general public. METHODS: A systematic review of randomized controlled clinical trials on use of respiratory protection by healthcare workers, sick patients and community members was conducted. Articles were searched on Medline and Embase using key search terms. RESULTS: A total of 19 randomised controlled trials were included in this study - 8 in community settings, 6 in healthcare settings and 5 as source control. Most of these randomised controlled trials used different interventions and outcome measures. In the community, masks appeared to be effective with and without hand hygiene, and both together are more protective. Randomised controlled trials in health care workers showed that respirators, if worn continually during a shift, were effective but not if worn intermittently. Medical masks were not effective, and cloth masks even less effective. When used by sick patients randomised controlled trials suggested protection of well contacts. CONCLUSION: The study suggests that community mask use by well people could be beneficial, particularly for COVID-19, where transmission may be pre-symptomatic. The studies of masks as source control also suggest a benefit, and may be important during the COVID-19 pandemic in universal community face mask use as well as in health care settings. Trials in healthcare workers support the use of respirators continuously during a shift. This may prevent health worker infections and deaths from COVID-19, as aerosolisation in the hospital setting has been documented.", "title": "A rapid systematic review of the efficacy of face masks and respirators against coronaviruses and other respiratory transmissible viruses for the community, healthcare workers and sick patients", "pid": "in16u4pm", "bm25_score": 217.851318359375}, {"text": "Background There is paucity of evidence on the effectiveness of facemask use in COVID-19 in community settings. Objectives We aimed to estimate the effectiveness of facemask use alone or along with hand hygiene in community settings in reducing the transmission of viral respiratory illness. Methods We searched PubMed and Embase for randomized controlled trials on facemask use in community settings to prevent viral respiratory illnesses published up to April 25, 2020. Two independent reviewers were involved in synthesis of data. Data extraction and risk-of-bias assessment were done in a standard format from the selected studies. Outcome data for clinically diagnosed or self-reported influenza-like illness (ILI) was recorded from individual studies. Pooled effect size was estimated by random-effects model for \"facemask only versus control\" and \"facemask plus hand hygiene versus control.\" Results Of the 465 studies from PubMed and 437 studies from Embase identified from our search, 9 studies were included in qualitative synthesis and 8 studies in quantitative synthesis. Risk of bias was assessed as low (n = 4), medium (n = 3), or high (n = 1) risk. Interventions included using a triple-layered mask alone or in combination with hand hygiene. Publication bias was not significant. There was no significant reduction in ILI either with facemask alone (n = 5, pooled effect size: -0.17; 95% confidence interval [CI]: -0.43-0.10; P = 0.23; I2 = 10.9%) or facemask with handwash (n = 6, pooled effect size: (n=6, pooled effect size: -0.09; 95% CI: -0.58 to 0.40; P = 0.71, I2 = 69.4%). Conclusion : Existing data pooled from randomized controlled trials do not reveal a reduction in occurrence of ILI with the use of facemask alone in community settings.", "title": "Facemasks for prevention of viral respiratory infections in community settings: A systematic review and meta-analysis.", "pid": "9ncpsg7g", "bm25_score": 217.83709716796875}, {"text": "Background: There is paucity of evidence on the effectiveness of facemask use in COVID-19 in community settings. Objectives: We aimed to estimate the effectiveness of facemask use alone or along with hand hygiene in community settings in reducing the transmission of viral respiratory illness. Methods: We searched PubMed and Embase for randomized controlled trials on facemask use in community settings to prevent viral respiratory illnesses published up to April 25, 2020. Two independent reviewers were involved in synthesis of data. Data extraction and risk-of-bias assessment were done in a standard format from the selected studies. Outcome data for clinically diagnosed or self-reported influenza-like illness (ILI) was recorded from individual studies. Pooled effect size was estimated by random-effects model for \"facemask only versus control\" and \"facemask plus hand hygiene versus control.\" Results: Of the 465 studies from PubMed and 437 studies from Embase identified from our search, 9 studies were included in qualitative synthesis and 8 studies in quantitative synthesis. Risk of bias was assessed as low (n = 4), medium (n = 3), or high (n = 1) risk. Interventions included using a triple-layered mask alone or in combination with hand hygiene. Publication bias was not significant. There was no significant reduction in ILI either with facemask alone (n = 5, pooled effect size: -0.17; 95% confidence interval [CI]: -0.43-0.10; P = 0.23; I2 = 10.9%) or facemask with handwash (n = 6, pooled effect size: (n=6, pooled effect size: -0.09; 95% CI: -0.58 to 0.40; P = 0.71, I2 = 69.4%). Conclusion: : Existing data pooled from randomized controlled trials do not reveal a reduction in occurrence of ILI with the use of facemask alone in community settings.", "title": "Facemasks for prevention of viral respiratory infections in community settings: A systematic review and meta-analysis", "pid": "l77gla9f", "bm25_score": 217.80642700195312}, {"text": "Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), is now overwhelming spreading in the world. As of April 11, 2020, totally 1.61 million COVID‐19 patients were confirmed in more than 200 countries and regions with 99690 deaths. This article is protected by copyright. All rights reserved.", "title": "Possibly critical role of wearing masks in general population in controlling COVID‐19", "pid": "deg5hqtl", "bm25_score": 217.80401611328125}, {"text": "Evidence from the 2003 SARS epidemic and 2009 H1N1 pandemic shows that face masks can be an effective non-pharmaceutical intervention in minimizing the spread of airborne viruses. Recent studies have shown that using face masks is correlated to an individual’s age and gender, where females and older adults are more likely to wear a mask than males or youths. There are only a few studies quantifying the impact of using face masks to slow the spread of an epidemic at the population level, and even fewer studies that model their impact in a population where the use of face masks depends upon the age and gender of the population. We use a state-of-the-art agent-based simulation to model the use of face masks and quantify their impact on three levels of an influenza epidemic and compare different mitigation scenarios. These scenarios involve changing the demographics of mask usage, the adoption of mask usage in relation to a perceived threat level, and the combination of masks with other non-pharmaceutical interventions such as hand washing and social distancing. Our results shows that face masks alone have limited impact on the spread of influenza. However, when face masks are combined with other interventions such as hand sanitizer, they can be more effective. We also observe that monitoring social internet systems can be a useful technique to measure compliance. We conclude that educating the public on the effectiveness of masks to increase compliance can reduce morbidity and mortality.", "title": "Understanding the Impact of Face Mask Usage Through Epidemic Simulation of Large Social Networks", "pid": "14x4uqq7", "bm25_score": 217.78880310058594}, {"text": "A novel Coronavirus pandemic emerged in December of 2019, causing devastating public health impact across the world. In the absence of a safe and effective vaccine or antiviral, strategies for mitigating the burden of the pandemic are focused on non-pharmaceutical interventions, such as social-distancing, contact-tracing, quarantine, isolation and the use of face-masks in public. We develop a new mathematical model for assessing the population-level impact of these mitigation strategies. Simulations of the model, using data relevant to COVID-19 transmission in New York state and the entire US, show that the pandemic will peak in mid and late April, respectively. The worst-case scenario projections for cumulative mortality (based on the baseline levels of anti-COVID non-pharmaceutical interventions considered in the study) in New York State and the entire US decrease dramatically by 80% and 64%, respectively, if the strict social-distancing measures implemented are maintained until the end of May or June, 2020. This study shows that early termination of strict social-distancing could trigger a devastating second wave with burden similar to that projected before the onset of strict social-distance. The use of efficacious face-masks (efficacy greater than 70%) could lead to the elimination of the pandemic if at least 70% of the residents of New York state use such masks consistently (nationwide, a compliance of at least 80% will be required using such masks). The use of low efficacy masks, such as cloth masks (of efficacy less than 30%), could also lead to significant reduction of COVID-19 burden (albeit, they are not able to lead to elimination). Combining low efficacy masks with improved levels of other anti-COVID-19 intervention measures can lead to elimination of the pandemic. The mask coverage needed to eliminate COVID-19 decreases if mask-use is combined with strict social-distancing.", "title": "Mathematical assessment of the impact of non-pharmaceutical interventions on curtailing the 2019 novel Coronavirus", "pid": "6gsg0u53", "bm25_score": 217.7620391845703}, {"text": "The use of face masks in public settings has been widely recommended by public health officials during the current COVID-19 pandemic. The masks help mitigate the risk of cross-infection via respiratory droplets; however, there are no specific guidelines on mask materials and designs that are most effective in minimizing droplet dispersal. While there have been prior studies on the performance of medical-grade masks, there are insufficient data on cloth-based coverings, which are being used by a vast majority of the general public. We use qualitative visualizations of emulated coughs and sneezes to examine how material- and design-choices impact the extent to which droplet-laden respiratory jets are blocked. Loosely folded face masks and bandana-style coverings provide minimal stopping-capability for the smallest aerosolized respiratory droplets. Well-fitted homemade masks with multiple layers of quilting fabric, and off-the-shelf cone style masks, proved to be the most effective in reducing droplet dispersal. These masks were able to curtail the speed and range of the respiratory jets significantly, albeit with some leakage through the mask material and from small gaps along the edges. Importantly, uncovered emulated coughs were able to travel notably farther than the currently recommended 6-ft distancing guideline. We outline the procedure for setting up simple visualization experiments using easily available materials, which may help healthcare professionals, medical researchers, and manufacturers in assessing the effectiveness of face masks and other personal protective equipment qualitatively.", "title": "Visualizing the effectiveness of face masks in obstructing respiratory jets", "pid": "ohkki0ke", "bm25_score": 217.76065063476562}, {"text": "The current pandemic of COVID-19 has lead to conflicting opinions on whether wearing facemasks outside of health care facilities protects against the infection. To better understand the value of wearing facemasks we undertook a rapid systematic review of existing scientific evidence about development of respiratory illness, linked to use of facemasks in community settings. METHODS: We included all study designs. There were 31 eligible studies (including 12 RCTs). Narrative synthesis and random-effects meta-analysis of attack rates for primary and secondary prevention in 28 studies were performed. Results were reported by design, setting and type of face barrier in primary prevention, and by who wore the facemask (index patient or well contacts) in secondary prevention trials. The preferred outcome was influenza-like illness (ILI) but similar outcomes were pooled with ILI when ILI was unavailable. GRADE quality assessment was based on RCTs with support from observational studies. RESULTS: Where specific information was available, most studies reported about use of medical grade (surgical paper masks). In 3 RCTs, wearing a facemask may very slightly reduce the odds of developing ILI/respiratory symptoms, by around 6% (OR 0.94, 95% CI 0.75 to 1.19, I2 29%, low certainty evidence). Greater effectiveness was suggested by observational studies. When both house-mates and an infected household member wore facemasks the odds of further household members becoming ill may be modestly reduced by around 19% (OR 0.81, 95%CI 0.48 to 1.37, I 2 45%, 5 RCTs, low certainty evidence). The protective effect was very small if only the well person(OR 0.93, 95% CI 0.68 to 1.28, I2 11%, 2 RCTs, low uncertainty evidence) or the infected person wore the facemask (very low certainty evidence). DISCUSSION: Based on the RCTs we would conclude that wearing facemasks can be very slightly protective against primary infection from casual community contact, and modestly protective against household infections when both infected and uninfected members wear facemasks. However, the RCTs often suffered from poor compliance and controls using facemasks. Across observational studies the evidence in favour of wearing facemasks was stronger. We expect RCTs to under-estimate the protective effect and observational studies to exaggerate it. The evidence is not sufficiently strong to support widespread use of facemasks as a protective measure against COVID-19. However, there is enough evidence to support the use of facemasks for short periods of time by particularly vulnerable individuals when in transient higher risk situations. Further high quality trials are needed to assess when wearing a facemask in the community is most likely to be protective.", "title": "Facemasks and similar barriers to prevent respiratory illness such as COVID-19: A rapid systematic review", "pid": "844229sb", "bm25_score": 217.74447631835938}, {"text": "Re-examination of the large dataset collected and meta-analysed by Dr Chu and his colleagues contradicts their conclusions about the effects of separation distance on infection risk. Their conclusion was based on misunderstandings of the datasets. Each of these estimated risk relative to that incurred when touching infected individuals. Allowing for this suggests that the main advantage of social distancing, a perhaps 78% (95% CI 24, 92) reduction in risk of infection, occurs at distances below 1m. The data imply an 11% chance of further distances reducing the risk, with any effects likely to be small. However the limitations of the dataset do limit the strength of these conclusions.", "title": "Even one metre seems generous. A reanalysis of data in: Chu et al. (2020) Physical distancing, face masks, and eye protection to prevent person-to-person transmission of SARS-CoV-2 and COVID-19.", "pid": "ws8licyf", "bm25_score": 217.74185180664062}, {"text": "Cloth masks are a simple, economic and sustainable alternative to surgical mask as a means of source control of SARS-CoV-2 for general community.", "title": "Universal use of face masks for success against COVID-19: evidence and implications for prevention policies", "pid": "z86g8dzs", "bm25_score": 217.70687866210938}, {"text": "The emergence of coronavirus disease 19 pandemic and novel research on the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised controversies over the use of face masks to prevent community transmission. Specific regulations need to be fulfilled to use a face mask as part of the personal protective equipment and high quality of evidence supporting its use to prevent respiratory viral infections, including SARS-CoV-2, is lacking. However, its widespread use is becoming a standard practice in some countries and discrepancies between health authorities on their policy have led to controversy. The aim of this review is to provide an outlook on recent research in this matter and areas of opportunity.", "title": "UNIVERSAL MASKING DURING COVID-19 PANDEMIC - CURRENT EVIDENCE AND CONTROVERSIES.", "pid": "cvulb9t6", "bm25_score": 217.69854736328125}, {"text": "BACKGROUND: Respiratory protective devices are critical in protecting against infection in healthcare workers at high risk of novel 2019 coronavirus disease (COVID-19); however, recommendations are conflicting and epidemiological data on their relative effectiveness against COVID-19 are limited. PURPOSE: To compare medical masks to N95 respirators in preventing laboratory-confirmed viral infection and respiratory illness including coronavirus specifically in healthcare workers. DATA SOURCES: MEDLINE, Embase, and CENTRAL from January 1, 2014, to March 9, 2020. Update of published search conducted from January 1, 1990, to December 9, 2014. STUDY SELECTION: Randomized controlled trials (RCTs) comparing the protective effect of medical masks to N95 respirators in healthcare workers. DATA EXTRACTION: Reviewer pair independently screened, extracted data, and assessed risk of bias and the certainty of the evidence. DATA SYNTHESIS: Four RCTs were meta-analyzed adjusting for clustering. Compared with N95 respirators; the use of medical masks did not increase laboratory-confirmed viral (including coronaviruses) respiratory infection (OR 1.06; 95% CI 0.90-1.25; I2 = 0%; low certainty in the evidence) or clinical respiratory illness (OR 1.49; 95% CI: 0.98-2.28; I2 = 78%; very low certainty in the evidence). Only one trial evaluated coronaviruses separately and found no difference between the two groups (P = .49). LIMITATIONS: Indirectness and imprecision of available evidence. CONCLUSIONS: Low certainty evidence suggests that medical masks and N95 respirators offer similar protection against viral respiratory infection including coronavirus in healthcare workers during non-aerosol-generating care. Preservation of N95 respirators for high-risk, aerosol-generating procedures in this pandemic should be considered when in short supply.", "title": "Medical masks vs N95 respirators for preventing COVID-19 in healthcare workers: A systematic review and meta-analysis of randomized trials", "pid": "8khrecrf", "bm25_score": 217.68113708496094}, {"text": "Background . Widespread use of masks in the general population is being used in many countries for Covid-19 . There has been reluctance on the part of the WHO and some governments to recommend this . Methodology . A basic model has been constructed to show the relative risk of aerosol from normal breathing in various situations together with the benefit from use of masks which is multiplicative . Results . Social distancing at 2 metres is validated but in confined areas is time limited and the use of masks in the absence of extremely good ventilation is important. Where social distancing is not possible at all times or an infectious person is in a confined area for a prolonged period there is a higher risk of infection requiring protection . Conclusions . The use of masks should be factored into models and used at an early stage as widespread use of more efficient masks could have a large impact on control and spread of infection . Public health planning requires stockpiling masks and encouraging everyone to have suitable masks in their household when supplies are normalised . The use of a cloth mask will be better than no protection at all .", "title": "A simple model to show the relative risk of viral aerosol infection and the benefit of wearing masks in different settings with implications for Covid-19 .", "pid": "sqr11fpv", "bm25_score": 217.67369079589844}, {"text": "The emergence of coronavirus disease 19 pandemic and novel research on the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has raised controversies over the use of face masks to prevent community transmission. Specific regulations need to be fulfilled to use a face mask as part of the personal protective equipment and high quality of evidence supporting its use to prevent respiratory viral infections, including SARS-CoV-2, is lacking. However, its widespread use is becoming a standard practice in some countries and discrepancies between health authorities on their policy have led to controversy. The aim of this review is to provide an outlook on recent research in this matter and areas of opportunity.", "title": "Universal Masking during Covid-19 Pandemic - Current Evidence and Controversies", "pid": "fdkqs3rg", "bm25_score": 217.6548309326172}, {"text": "BACKGROUND: Recommendations on masks for preventing coronavirus disease 2019 (COVID-19) vary. PURPOSE: To examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks. DATA SOURCES: Multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server (2003 through 14 April 2020; surveillance through 2 June 2020), and reference lists. STUDY SELECTION: Randomized trials of masks and risk for respiratory virus infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and observational studies of mask use and coronavirus infection risk were included. New evidence will be incorporated by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; a second reviewer provided verification. DATA SYNTHESIS: 39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies. In high- or moderate-risk health care settings, observational studies found that risk for infection with SARS-CoV-1 and Middle East respiratory syndrome coronavirus probably decreased with mask use versus nonuse and possibly decreased with N95 versus surgical mask use. Randomized trials in community settings found possibly no difference between N95 versus surgical masks and probably no difference between surgical versus no mask in risk for influenza or influenza-like illness, but compliance was low. In health care settings, N95 and surgical masks were probably associated with similar risks for influenza-like illness and laboratory-confirmed viral infection; clinical respiratory illness had inconsistency. Bothersome symptoms were common. LIMITATIONS: There were few SARS-CoV-2 studies, observational studies have methodological limitations, and the review was done by using streamlined methods. CONCLUSION: Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.", "title": "Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings: A Living Rapid Review", "pid": "kshjqsdj", "bm25_score": 217.58648681640625}, {"text": "BACKGROUND: Recommendations on masks for preventing coronavirus disease 2019 (COVID-19) vary. PURPOSE: To examine the effectiveness of N95, surgical, and cloth masks in community and health care settings for preventing respiratory virus infections, and effects of reuse or extended use of N95 masks. DATA SOURCES: Multiple electronic databases, including the World Health Organization COVID-19 database and medRxiv preprint server (2003 through 14 April 2020; surveillance through 2 June 2020), and reference lists. STUDY SELECTION: Randomized trials of masks and risk for respiratory virus infection, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and observational studies of mask use and coronavirus infection risk were included. New evidence will be incorporated by using living review methods. DATA EXTRACTION: One reviewer abstracted data and assessed methodological limitations; a second reviewer provided verification. DATA SYNTHESIS: 39 studies (18 randomized controlled trials and 21 observational studies; 33 867 participants) were included. No study evaluated reuse or extended use of N95 masks. Evidence on SARS-CoV-2 was limited to 2 observational studies with serious limitations. Community mask use was possibly associated with decreased risk for SARS-CoV-1 infection in observational studies. In high- or moderate-risk health care settings, observational studies found that risk for infection with SARS-CoV-1 and Middle East respiratory syndrome coronavirus probably decreased with mask use versus nonuse and possibly decreased with N95 versus surgical mask use. Randomized trials in community settings found possibly no difference between N95 versus surgical masks and probably no difference between surgical versus no mask in risk for influenza or influenza-like illness, but compliance was low. In health care settings, N95 and surgical masks were probably associated with similar risks for influenza-like illness and laboratory-confirmed viral infection; clinical respiratory illness had inconsistency. Bothersome symptoms were common. LIMITATIONS: There were few SARS-CoV-2 studies, observational studies have methodological limitations, and the review was done by using streamlined methods. CONCLUSION: Evidence on mask effectiveness for respiratory infection prevention is stronger in health care than community settings. N95 respirators might reduce SARS-CoV-1 risk versus surgical masks in health care settings, but applicability to SARS-CoV-2 is uncertain. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality. Update Alerts: The authors have specified in the Methods section the interval and stop date for updates to this Living Review. As Annals receives updates, they will appear in the Comments section of the article on Annals.org. Reader inquiries about updates that are not available at approximately the specified intervals should be submitted as Comments to the article.", "title": "Masks for Prevention of Respiratory Virus Infections, Including SARS-CoV-2, in Health Care and Community Settings: A Living Rapid Review", "pid": "j0lpy07l", "bm25_score": 217.58648681640625}, {"text": "", "title": "Cloth Masks May Prevent Transmission of COVID-19: An Evidence-Based, Risk-Based Approach", "pid": "84asc8do", "bm25_score": 217.5778045654297}, {"text": "Face mask use by the general public for limiting the spread of the COVID-19 pandemic is controversial, though increasingly recommended, and the potential of this intervention is not well understood. We develop a compartmental model for assessing the community-wide impact of mask use by the general, asymptomatic public, a portion of which may be asymptomatically infectious. Model simulations, using data relevant to COVID-19 dynamics in the US states of New York and Washington, suggest that broad adoption of even relatively ineffective face masks may meaningfully reduce community transmission of COVID-19 and decrease peak hospitalizations and deaths. Moreover, mask use decreases the effective transmission rate in nearly linear proportion to the product of mask effectiveness (as a fraction of potentially infectious contacts blocked) and coverage rate (as a fraction of the general population), while the impact on epidemiologic outcomes (death, hospitalizations) is highly nonlinear, indicating masks could synergize with other non-pharmaceutical measures. Notably, masks are found to be useful with respect to both preventing illness in healthy persons and preventing asymptomatic transmission. Hypothetical mask adoption scenarios, for Washington and New York state, suggest that immediate near universal (80%) adoption of moderately (50%) effective masks could prevent on the order of 17–45% of projected deaths over two months in New York, while decreasing the peak daily death rate by 34–58%, absent other changes in epidemic dynamics. Even very weak masks (20% effective) can still be useful if the underlying transmission rate is relatively low or decreasing: In Washington, where baseline transmission is much less intense, 80% adoption of such masks could reduce mortality by 24–65% (and peak deaths 15–69%), compared to 2–9% mortality reduction in New York (peak death reduction 9–18%). Our results suggest use of face masks by the general public is potentially of high value in curtailing community transmission and the burden of the pandemic. The community-wide benefits are likely to be greatest when face masks are used in conjunction with other non-pharmaceutical practices (such as social-distancing), and when adoption is nearly universal (nation-wide) and compliance is high.", "title": "To mask or not to mask: Modeling the potential for face mask use by the general public to curtail the COVID-19 pandemic", "pid": "qi1henyy", "bm25_score": 217.55731201171875}, {"text": "Considerable debates about the general community use of face masks for protection against COVID-19 stemmed out from differing views taken by health authorities. Misconceptions and stigmatization towards the use of face masks may hinder the containment of the COVID-19 pandemic. We address this previous debate by analyzing the advice on the community use of masks across different credible health authorities: countries that promoted the use of masks acknowledged that masks are effective, but also explained the importance of their proper use along with other hygiene measures. In contrast, authorities that recommended against the community use of masks mainly cited shortage of supplies, the argument that the public do not have the adequate skills to wear them, or that wearing masks might reduce compliance with other important behaviors. We suggest promoting effective behavioral changes in personal protective measures by teaching microbiological knowledge instead of just listing out the \"dos-and-don'ts\".", "title": "Importance of face masks for COVID-19 - a call for effective public education", "pid": "wee1133a", "bm25_score": 217.53128051757812}, {"text": "Considerable debates about the general community use of face masks for protection against COVID-19 stemmed out from differing views taken by health authorities. Misconceptions and stigmatization towards the use of face masks may hinder the containment of the COVID-19 pandemic. We address this previous debate by analyzing the advice on the community use of masks across different credible health authorities: countries that promoted the use of masks acknowledged that masks are effective, but also explained the importance of their proper use along with other hygiene measures. In contrast, authorities that recommended against the community use of masks mainly cited shortage of supplies, the argument that the public do not have the adequate skills to wear them, or that wearing masks might reduce compliance with other important behaviors. We suggest promoting effective behavioral changes in personal protective measures by teaching microbiological knowledge instead of just listing out the “dos-and-don’ts”.", "title": "Importance of face masks for COVID-19 – a call for effective public education", "pid": "p2ufydgs", "bm25_score": 217.52833557128906}, {"text": "We present two models for the COVID-19 pandemic predicting the impact of universal face mask wearing upon the spread of the SARS-CoV-2 virus--one employing a stochastic dynamic network based compartmental SEIR (susceptible-exposed-infectious-recovered) approach, and the other employing individual ABM (agent-based modelling) Monte Carlo simulation--indicating (1) significant impact under (near) universal masking when at least 80% of a population is wearing masks, versus minimal impact when only 50% or less of the population is wearing masks, and (2) significant impact when universal masking is adopted early, by Day 50 of a regional outbreak, versus minimal impact when universal masking is adopted late. These effects hold even at the lower filtering rates of homemade masks. To validate these theoretical models, we compare their predictions against a new empirical data set we have collected that includes whether regions have universal masking cultures or policies, their daily case growth rates, and their percentage reduction from peak daily case growth rates. Results show a near perfect correlation between early universal masking and successful suppression of daily case growth rates and/or reduction from peak daily case growth rates, as predicted by our theoretical simulations. Our theoretical and empirical results argue for urgent implementation of universal masking. As governments plan how to exit societal lockdowns, it is emerging as a key NPI; a\"mouth-and-nose lockdown\"is far more sustainable than a\"full body lockdown\", on economic, social, and mental health axes. An interactive visualization of the ABM simulation is at http://dek.ai/masks4all. We recommend immediate mask wearing recommendations, official guidelines for correct use, and awareness campaigns to shift masking mindsets away from pure self-protection, towards aspirational goals of responsibly protecting one's community.", "title": "Universal Masking is Urgent in the COVID-19 Pandemic: SEIR and Agent Based Models, Empirical Validation, Policy Recommendations", "pid": "m5udub60", "bm25_score": 217.5122833251953}, {"text": "Abstract OBJECTIVE: To examine the effectiveness of eye protection, face masks, or person distancing on interrupting or reducing the spread of respiratory viruses. DESIGN: Update of a Cochrane review that included a meta-analysis of observational studies during the SARS outbreak of 2003. DATA SOURCES: Eligible trials from the previous review; search of Cochrane Central Register of Controlled Trials, PubMed, Embase and CINAHL from October 2010 up to 1 April 2020; and forward and backward citation analysis. DATA SELECTION: Randomised and cluster-randomised trials of people of any age, testing the use of eye protection, face masks, or person distancing against standard practice, or a similar physical barrier. Outcomes included any acute respiratory illness and its related consequences. DATA EXTRACTION AND ANALYSIS: Six authors independently assessed risk of bias using the Cochrane tool and extracted data. We used a generalised inverse variance method for pooling using a random-effects model and reported results with risk ratios and 95% Confidence Intervals (CI). RESULTS: We included 15 randomised trials investigating the effect of masks (14 trials) in healthcare workers and the general population and of quarantine (1 trial). We found no trials testing eye protection. Compared to no masks there was no reduction of influenza-like illness (ILI) cases (Risk Ratio 0.93, 95%CI 0.83 to 1.05) or influenza (Risk Ratio 0.84, 95%CI 0.61-1.17) for masks in the general population, nor in healthcare workers (Risk Ratio 0.37, 95%CI 0.05 to 2.50). There was no difference between surgical masks and N95 respirators: for ILI (Risk Ratio 0.83, 95%CI 0.63 to 1.08), for influenza (Risk Ratio 1.02, 95%CI 0.73 to 1.43). Harms were poorly reported and limited to discomfort with lower compliance. The only trial testing quarantining workers with household ILI contacts found a reduction in ILI cases, but increased risk of quarantined workers contracting influenza. All trials were conducted during seasonal ILI activity. CONCLUSIONS: Most included trials had poor design, reporting and sparse events. There was insufficient evidence to provide a recommendation on the use of facial barriers without other measures. We found insufficient evidence for a difference between surgical masks and N95 respirators and limited evidence to support effectiveness of quarantine. Based on observational evidence from the previous SARS epidemic included in the previous version of our Cochrane review we recommend the use of masks combined with other measures.", "title": "Physical interventions to interrupt or reduce the spread of respiratory viruses. Part 1 - Face masks, eye protection and person distancing: systematic review and meta-analysis", "pid": "1vcc1khg", "bm25_score": 217.50820922851562}, {"text": "As cases of coronavirus disease 2019 (COVID-19) ballooned last month, people in Europe and North America scrambled to get their hands on surgical masks to protect themselves Health officials jumped in to discourage them, worried about the limited supply of masks for health care personnel “Seriously people-STOP BUYING MASKS!” began a 29 February tweet from U S Surgeon General Jerome Adams The World Health Organization and U S Centers for Disease Control and Prevention (CDC) have both said that only people with COVID-19 symptoms and those caring for them should wear masks But some health experts, including the director of the Chinese Center for Disease Control and Prevention, think that’s a mistake Health authorities in parts of Asia have encouraged all citizens to wear masks in public to prevent the spread of the virus, regardless of whether they have symptoms And the Czech Republic took the uncommon step last week of making nose and mouth coverings mandatory in public spaces, prompting a grassroots drive to hand make masks", "title": "Would everyone wearing face masks help us slow the pandemic?", "pid": "ydazitgp", "bm25_score": 217.48025512695312}, {"text": "The ongoing novel coronavirus disease (COVID-19) pandemic has rapidly spread in early 2020, causing tens of thousands of deaths, over a million cases and widespread socioeconomic disruption. With no vaccine available and numerous national healthcare systems reaching or exceeding capacity, interventions to limit transmission are urgently needed. While there is broad agreement that travel restrictions and closure of non-essential businesses and schools are beneficial in limiting local and regional spread, recommendations around the use of face masks for the general population are less consistent internationally. In this study, we examined the role of face masks in mitigating the spread of COVID-19 in the general population, using epidemic models to estimate the total reduction of infections and deaths under various scenarios. In particular, we examined the optimal deployment of face masks when resources are limited, and explored a range of supply and demand dynamics. We found that face masks, even with a limited protective effect, can reduce infections and deaths, and can delay the peak time of the epidemic. We consistently found that a random distribution of masks in the population was a suboptimal strategy when resources were limited. Prioritizing coverage among the elderly was more beneficial, while allocating a proportion of available resources for diagnosed infected cases provided further mitigation under a range of scenarios. In summary, face mask use, particularly for a pathogen with relatively common asymptomatic carriage, can effectively provide some mitigation of transmission, while balancing provision between vulnerable healthy persons and symptomatic persons can optimize mitigation efforts when resources are limited.", "title": "Face mask use in the general population and optimal resource allocation during the COVID-19 pandemic", "pid": "qdamvwxl", "bm25_score": 217.46337890625}, {"text": "The main form of COVID-19 transmission is via oral-respiratory droplet contamination (droplet; very small drop of liquid) produced when individuals talk, sneeze or cough. In hospitals, health-care workers wear facemasks as a minimum medical droplet precaution to protect themselves. Due to the shortage of masks during the pandemic, priority is given to hospitals for their distribution. As a result, the availability/use of medical masks is discouraged for the public. However, given that asymptomatic individuals, not wearing masks within the public, can be highly contagious for COVID-19, prevention of environmental droplet contamination (EnDC) from coughing/sneezing/speech is fundamental to reducing transmission. As an immediate solution to promote public droplet safety, we assessed household textiles to quantify their potential as effective environmental droplet barriers (EDBs). The synchronized implementation of a universal community droplet reduction solution is discussed as a model against COVID-19. Using a bacterial-suspension spray simulation model of droplet ejection (mimicking a sneeze), we quantified the extent by which widely available clothing fabrics reduce the dispersion of droplets onto surfaces within 1.8m, the minimum distance recommended for COVID-19 social distancing. All textiles reduced the number of droplets reaching surfaces, restricting their dispersion to <30cm, when used as single layers. When used as double-layers, textiles were as effective as medical mask/surgical-cloth materials, reducing droplet dispersion to <10cm, and the area of circumferential contamination to ~0.3%. The synchronized implementation of EDBs as a community droplet reduction solution (i.e., face covers/scarfs/masks & surface covers) could reduce EnDC and the risk of transmitting or acquiring infectious respiratory pathogens, including COVID-19.", "title": "Textile Masks and Surface Covers - A 'Universal Droplet Reduction Model' Against Respiratory Pandemics", "pid": "t697xw4y", "bm25_score": 217.45828247070312}, {"text": "Ma's research shows N95 masks, medical masks, even homemade masks could block at least 90% of the virus in aerosols(1). This study puts the debate on whether the public wear masks back on the table. Recently Science interviewed Dr. Gao, director‐general of Chinese Center for Disease Control and Prevention (CDC). This article is protected by copyright. All rights reserved.", "title": "Mask is the possible key for self‐isolation in COVID‐19 pandemic", "pid": "p5hljkkm", "bm25_score": 217.4492950439453}, {"text": "INTRODUCTION: Transmission of COVID-19 within families and close contacts accounts for the majority of epidemic growth. Community mask wearing, hand washing and social distancing are thought to be effective but there is little evidence to inform or support community members on COVID-19 risk reduction within families. METHODS: A retrospective cohort study of 335 people in 124 families and with at least one laboratory confirmed COVID-19 case was conducted from 28 February to 27 March 2020, in Beijing, China. The outcome of interest was secondary transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the family. Characteristics and practices of primary cases, of well family contacts and household hygiene practices were analysed as predictors of secondary transmission. RESULTS: The secondary attack rate in families was 23.0% (77/335). Face mask use by the primary case and family contacts before the primary case developed symptoms was 79% effective in reducing transmission (OR=0.21, 95% CI 0.06 to 0.79). Daily use of chlorine or ethanol based disinfectant in households was 77% effective (OR=0.23, 95% CI 0.07 to 0.84). Wearing a mask after illness onset of the primary case was not significantly protective. The risk of household transmission was 18 times higher with frequent daily close contact with the primary case (OR=18.26, 95% CI 3.93 to 84.79), and four times higher if the primary case had diarrhoea (OR=4.10, 95% CI 1.08 to 15.60). Household crowding was not significant. CONCLUSION: The study confirms the highest risk of transmission prior to symptom onset, and provides the first evidence of the effectiveness of mask use, disinfection and social distancing in preventing COVID-19. We also found evidence of faecal transmission. This can inform guidelines for community prevention in settings of intense COVID-19 epidemics.", "title": "Reduction of secondary transmission of SARS-CoV-2 in households by face mask use, disinfection and social distancing: a cohort study in Beijing, China", "pid": "nr0fu2qb", "bm25_score": 217.43081665039062}, {"text": "Recently, COVID-19 has attracted a lot of attention of researchers from different fields. Wearing masks is a frequently adopted precautionary measure. In this paper, we investigate the effect of behavior of wearing masks on epidemic dynamics in the context of COVID-19. At each time, every susceptible individual chooses whether to wear a mask or not in the next time step, which depends on an evaluation of the potential costs and perceived risk of infection. When the cost of infection is high, the majority of the population choose to wear masks, where global awareness plays a significant role. However, if the mask source is limited, global awareness may give rise to a negative result. In this case, more mask source should be allocated to the individuals with high risk of infection.", "title": "The effect of behavior of wearing masks on epidemic dynamics", "pid": "2iokkog5", "bm25_score": 217.41600036621094}, {"text": "The SARS-CoV-2 virus is primarily transmitted through virus-laden fluid particles ejected from the mouth of infected people. In some countries, the public has been asked to use face covers to mitigate the risk of virus transmission - yet, their outward effectiveness is not ascertained. We used a Background Oriented Schlieren technique to investigate the air flow ejected by a person while quietly and heavily breathing, while coughing, and with different face covers. We found that all face covers without an outlet valve reduce the front flow through jet by more than 90 per cent. For the FFP1 and FFP2 masks without exhalation valve, the front throughflow does not extend beyond one half and one quarter of a metre, respectively. Surgical and hand-made masks, and face shields, generate several leakage jets, including intense backward and downwards jets that may present major hazards. We also simulated an aerosol generating procedure (extubation) and we showed that this is a major hazard for clinicians. These results can aid policy makers to make informed decisions and PPE developers to improve their product effectiveness by design.", "title": "Face Coverings, Aerosol Dispersion and Mitigation of Virus Transmission Risk", "pid": "r1zsbq1w", "bm25_score": 217.3616180419922}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic is causing a huge toll on individuals, families, communities and societies across the world. Currently, whether wearing facemasks in public should be a measure to prevent transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) remains contraversial.1 This is largely because there have been no randomized controlled trials (RCTs) for coronavirus to directly support this. However, lessons may be taken from published RCTs examining influenza-like illness (ILI).2,3 Recent studies suggested that SARS-CoV-2 shares similar transmission route with influenza virus,4 and the incidence of community transmission of SARS-CoV-2 in individuals with ILI is high.5 Therefore, we undertook this meta-analysis of RCTs examining the efficacy of wearing facemasks to prevent ILI in community settings, irrespective of confirmatory testing for the causative virus. We undertook a systematic literature search for RCTs related to facemasks and ILI between 1966 and April 2020 using PUBMED, EMBASE, and Cochrane library. RCTs undertaken in community (not hospital) settings comparing wearing and not wearing facemasks for ILI were included. Incidence of ILI (e.g., fever, cough, headache, sore throat, aches or pains in muscles or joints) was estimated per group. Relative risk (RR) and 95% confidence interval (CI) were calculated. We screened 899 related abstracts and eventually included 8 RCTs (Figure S1). Basic characteristics and quality of included RCTs are listed in Supplement. Participants wearing facemasks had a significantly lower risk of developing ILI than those not wearing facemasks (pooled RR=0.81, 95% CI: 0.70-0.95) and there was no heterogeneity (Figure 1). The decreased risk of ILI was more pronounced if everyone wore facemask irrespective of whether they were infected or not (RR=0.77, 95% CI: 0.65-0.91), compared to those wearing facemasks when infected (RR=0.95, 95% CI: 0.58-1.56) or uninfected (RR=1.26, 95% CI: 0.69-2.31). This study shows that wearing facemasks, irrespective of infection status, is effective in preventing ILI spread in the community. This situation mirrors what is happening now in public settings where we do not know who has been infected and who has not. Although there are no RCTs of facemasks for SARS-CoV-2, as with other simple measures such as social distancing and handwashing, these data support the recommendation to wear facemasks in public to further reduce transmission of SARS-CoV-2 and flatten the curve of this pandemic, especially when social distancing is impractical, such as shopping, or travelling with public transport for work that cannot be done from home.", "title": "Facemasks prevent influenza-like illness: implications for COVID-19", "pid": "py38vnwc", "bm25_score": 217.35302734375}, {"text": "The surge of patients in the pandemic of COVID-19 caused by the novel coronavirus SARS-CoV-2 may overwhelm the medical systems of many countries. Mask-wearing and handwashing can slow the spread of the virus, but currently, masks are in shortage in many countries, and timely handwashing is often impossible. In this study, the efficacy of three types of masks and instant hand wiping was evaluated using the avian influenza virus to mock the coronavirus. Virus quantification was performed using real-time reverse transcription-polymerase chain reaction. Previous studies on mask-wearing were reviewed. The results showed that instant hand wiping using a wet towel soaked in water containing 1.00% soap powder, 0.05% active chlorine, or 0.25% active chlorine from sodium hypochlorite removed 98.36%, 96.62%, and 99.98% of the virus from hands, respectively. N95 masks, medical masks, and homemade masks made of four-layer kitchen paper and one-layer cloth could block 99.98%, 97.14%, and 95.15% of the virus in aerosols. Medical mask-wearing which was supported by many studies was opposed by other studies possibly due to erroneous judgment. With these data, we propose the approach of mask-wearing plus instant hand hygiene (MIH) to slow the exponential spread of the virus. This MIH approach has been supported by the experiences of seven countries in fighting against COVID-19. Collectively, a simple approach to slow the exponential spread of SARS-CoV-2 was proposed with the support of experiments, literature review, and control experiences.", "title": "Potential utilities of mask-wearing and instant hand hygiene for fighting SARS-CoV-2", "pid": "v0trjjni", "bm25_score": 217.31057739257812}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can be transmitted via respiratory secretions. Since there are currently no specific therapeutics or vaccines available against the SARS-CoV-2, the commen nonpharmaceutical interventions (NPIs) are still the main measures to curb the COVID-19 epidemic. Face mask wearing is one important measure to suppress the pandemic. In order to know how efficient is face mask wearing in reducing the pandemic even with low efficiency non-professional face masks, we exploit physical abstraction to model the non-professional face masks made from cotton woven fabrics and characterize them by a parameter virus penetration rate (VPR){gamma}. Monte Carlo simulations exhibit that the effective reproduction number R of COVID-19 or similar pandemics can be approximately reduced by factor {gamma}4 with respect to the basic reproduction number R0,if the face masks with 70% <{gamma}< 90% are universally applied for the entire network. Furthermore, thought experiments and practical exploitation examples in country-level and city-level are enumerated and discussed to support our discovery in this study and indicate that the outbreak of a COVID-19 like pandemic can be even suppressed by the low efficiency non-professional face masks.", "title": "How Efficient Can Non-Professional MasksSuppress COVID-19 Pandemic?", "pid": "1yf1ae1d", "bm25_score": 217.30282592773438}, {"text": "Respiratory infections may spread through droplets, airborne particles, and aerosols from infected individuals through coughing, sneezing, and speaking. In the case of Coronavirus Disease 2019 (COVID-19), droplet spread can occur from symptomatic as well as pre-symptomatic and asymptomatic persons. The U.S. Centers for Disease Control and Prevention (CDC) has therefore recently recommended home-made cloth face coverings for use by the general public in areas of significant community-based transmission. Because medical masks and N95 respirators are in short supply, these are to be reserved for healthcare workers. There is, however, little information on the effectiveness of home-made face coverings in reducing droplet dissemination. Here, we ascertained the performance of ten different fabrics, ranging from cotton to silk, in blocking high velocity droplets, using a 3-layered commercial medical mask as a benchmark material. We also assessed their breathability and ability to soak water. We reason that the materials should be as breathable as possible, without compromising blocking efficiency, to reduce air flow through the sides of the mask since such flow would defeat the purpose of the mask. We found that most home fabrics substantially block droplets, even as a single layer. With two layers, blocking performance can reach that of surgical mask without significantly compromising breathability. Furthermore, we observed that home fabrics are hydrophilic to varying degrees, and hence soak water. In contrast, medical masks are hydrophobic, and tend to repel water. Incoming droplets are thus soaked and 'held back' by home fabrics, which might offer an as of yet untapped and understudied advantage of home-made cloth masks. Overall, our study suggests that most double-layered cloth face coverings may help reduce droplet transmission of respiratory infections.", "title": "Performance of fabrics for home-made masks against spread of respiratory infection through droplets: a quantitative mechanistic study", "pid": "o71haprj", "bm25_score": 217.302001953125}, {"text": "BACKGROUND: Respiratory protective devices are critical in protecting against infection in healthcare workers at high risk of novel 2019 coronavirus disease (COVID‐19); however, recommendations are conflicting and epidemiological data on their relative effectiveness against COVID‐19 are limited. PURPOSE: To compare medical masks to N95 respirators in preventing laboratory‐confirmed viral infection and respiratory illness including coronavirus specifically in healthcare workers. DATA SOURCES: MEDLINE, Embase, and CENTRAL from January 1, 2014, to March 9, 2020. Update of published search conducted from January 1, 1990, to December 9, 2014. STUDY SELECTION: Randomized controlled trials (RCTs) comparing the protective effect of medical masks to N95 respirators in healthcare workers. DATA EXTRACTION: Reviewer pair independently screened, extracted data, and assessed risk of bias and the certainty of the evidence. DATA SYNTHESIS: Four RCTs were meta‐analyzed adjusting for clustering. Compared with N95 respirators; the use of medical masks did not increase laboratory‐confirmed viral (including coronaviruses) respiratory infection (OR 1.06; 95% CI 0.90‐1.25; I (2) = 0%; low certainty in the evidence) or clinical respiratory illness (OR 1.49; 95% CI: 0.98‐2.28; I (2) = 78%; very low certainty in the evidence). Only one trial evaluated coronaviruses separately and found no difference between the two groups (P = .49). LIMITATIONS: Indirectness and imprecision of available evidence. CONCLUSIONS: Low certainty evidence suggests that medical masks and N95 respirators offer similar protection against viral respiratory infection including coronavirus in healthcare workers during non–aerosol‐generating care. Preservation of N95 respirators for high‐risk, aerosol‐generating procedures in this pandemic should be considered when in short supply.", "title": "Medical masks vs N95 respirators for preventing COVID‐19 in healthcare workers: A systematic review and meta‐analysis of randomized trials", "pid": "1aqf98e0", "bm25_score": 217.29116821289062}, {"text": "This paper evaluates the dynamic impact of various policies, such as school, business, and restaurant closures, adopted by the US states on the growth rates of confirmed Covid-19 cases and social distancing behavior measured by Google Mobility Reports, where we take into consideration of people's voluntarily behavioral response to new information of transmission risks. Using the US state-level data, our analysis finds that both policies and information on transmission risks are important determinants of people's social distancing behavior, and shows that a change in policies explains a large fraction of observed changes in social distancing behavior. Our counterfactual experiments indicate that removing all policies on April 1st of 2020 would have lead to 30 to 200 times more additional cases by late May. Removing only the non-essential businesses closures (while maintaining restrictions on movie theaters and restaurants) would have increased the weekly growth rate of cases between -0.02 and 0.06 and would have lead to -10% to 40% more cases by late May. Finally, nationally mandating face masks for employees on April 1st would have reduced the case growth rate by 0.1-0.25. This leads to 30% to 57% fewer reported cases by late May, which translates into, roughly, 30-57 thousand saved lives.", "title": "Causal Impact of Masks, Policies, Behavior on Early Covid-19 Pandemic in the U.S.", "pid": "2fokjcjr", "bm25_score": 217.28700256347656}, {"text": "Introduction Many countries including Pakistan are currently using face masks in their pandemic control plans. Being highly prevalent, the correct use of these masks is particularly important, as an incorrect use and disposal may actually increase the rate of transmission. The purpose of this study was to investigate the knowledge, attitude, and practices of healthcare workers (HCWs) in wearing a surgical face mask to limit the spread of the new coronavirus disease 2019 (COVID-19). Materials and Methods This survey was conducted by interviewing HCWs using a questionnaire consisting of the basic demographic characteristics, and the knowledge, attitude, and practices regarding the use of surgical face mask to limit the new COVID-19 exposure. Each correct answer was scored 1 and each incorrect answer scored 0. The total number of questions was 16, and the final score was calculated and then labeled according to the percentage (out of 16) of correct responses as good (>80%), moderate (60-80%), and poor (<60%). Results A total of 392 participants with a mean age of 42.37 ± 13.34 years (341 males and 51 females) were included in the study. The overall final results were good in 138 (35.2%), moderate in 178 (45.4%), and poor in 76 (19.3%). Around 43.6% of participants knew about the correct method of wearing the masks, 68.9% knew that there are three layers, 53% stated that the middle layer act as a filter media barrier, and 75.5% knew the recommended maximum duration of wearing it. The majority (88.2%) of participants knew that a cloth face mask is not much effective, around 79.8% knew that used face mask cannot be re-used, and 44.8% knew about the yellow-coded bag for disposal. Conclusions Knowledge, attitude, and practice of HCWs regarding the use of face masks were found to be inadequate. Studied HCWs had a positive attitude but moderate-to-poor level of knowledge and practice regarding the use of face mask. HCWs and general public awareness campaigns regarding the proper use of face mask by utilizing all social media available resources would be helpful during this pandemic.", "title": "Knowledge, Attitude, and Practices of Healthcare Workers Regarding the Use of Face Mask to Limit the Spread of the New Coronavirus Disease (COVID-19)", "pid": "0javg3m8", "bm25_score": 217.28341674804688}, {"text": "The use of face masks for the general public has been suggested in literature as a means to decrease virus transmission during the global COVID-19 pandemic. However, literature findings indicate that most mask designs do not provide reliable protection. This paper investigates the hypothesis that the impaired protection is mainly due to imperfect fitting of the masks, so that airflow, which contains virus-transporting droplets, can leak through gaps into or out of the mask. The fluid dynamics of face masks are investigated via analytical and numerical computations. The results demonstrate that the flow can be satisfactorily predicted by simplified analytical 1D-flow models, by efficient 2D-flow simulations and by 3D-flow simulations. The present results show that already gap heights larger than 0.1mm can result in the mask not fulfilling FFP2 or FFP3 standards, and for gap heights of ca. 1mm most of the airflow and droplets may pass through the gap. The implications of these findings are discussed and improvements to existing mask designs are suggested.", "title": "Analytical and numerical investigation of the airflow in face masks used for protection against COVID-19 virus -- implications for mask design and usage", "pid": "hiierdmt", "bm25_score": 217.27923583984375}, {"text": "", "title": "Possibly critical role of wearing masks in general population in controlling COVID-19", "pid": "appqx6sc", "bm25_score": 217.2776336669922}, {"text": "Cloth masks have been used in healthcare and community settings to protect the wearer from respiratory infections. The use of cloth masks during the coronavirus disease (COVID-19) pandemic is under debate. The filtration effectiveness of cloth masks is generally lower than that of medical masks and respirators; however, cloth masks may provide some protection if well designed and used correctly. Multilayer cloth masks, designed to fit around the face and made of water-resistant fabric with a high number of threads and finer weave, may provide reasonable protection. Until a cloth mask design is proven to be equally effective as a medical or N95 mask, wearing cloth masks should not be mandated for healthcare workers. In community settings, however, cloth masks may be used to prevent community spread of infections by sick or asymptomatically infected persons, and the public should be educated about their correct use.", "title": "Effectiveness of Cloth Masks for Protection Against Severe Acute Respiratory Syndrome Coronavirus 2", "pid": "tcijnphu", "bm25_score": 217.26629638671875}, {"text": "Masks play a role in the protection of health-care workers (HCWs) from acquiring respiratory infections, including coronavirus disease 2019 (COVID-19) in health-care settings. This observational study was conducted among 382 HCWs in a tertiary care setting over a period of 1 month. Descriptive analysis was done to assess the rational and recommended use of masks/respirators during COVID-19 pandemic using a structured observation checklist as a survey tool. A total of 374 HCWs were included, 64.9% of whom were using face masks rationally as mentioned per risk area categorization with a predominance of triple-layered mask during all 4 weeks. Overall, 64.1% used masks correctly. Clear guidelines and strategies can help to increase the compliance of HCWs with rational use of face masks.", "title": "Rational use of face mask in a tertiary care hospital setting during COVID-19 pandemic: An observational study.", "pid": "t2e4bxsu", "bm25_score": 217.26307678222656}, {"text": "Face masks have become an emblem of the public response to COVID-19, with many governments mandating their use in public spaces. The logic is that face masks are low cost and might help prevent some transmission. However, from the start, the assumption that face masks are \"low cost\" was questioned. Early on, there were warnings of the opportunity cost of public use of medical masks given shortages of personal protective equipment for healthcare providers. This led to recommendations for cloth masks and other face coverings, with little evidence of their ability to prevent transmission. However, there may also be a high cost to these recommendations if people rely on face masks in place of other more effective ways to break transmission, such as staying home. We use SafeGraph smart device location data to show that the representative American in states that have face mask mandates spent 20-30 minutes less time at home, and increase visits to a number of commercial locations, following the mandate. Since the reproductive rate of SAR-COV2, the pathogen that causes COVID-19 is hovering right around one, such substitution behavior could be the difference between controlling the epidemic and a resurgence of cases.", "title": "Do Face Masks Create a False Sense of Security? A COVID-19 Dilemma", "pid": "1c3fpazy", "bm25_score": 217.2592010498047}, {"text": "On June 11, 2009, the World Health Organization declared the outbreak of novel influenza A (H1N1) a pandemic. With limited supplies of antivirals and vaccines, countries and individuals are looking at other ways to reduce the spread of pandemic (H1N1) 2009, particularly options that are cost effective and relatively easy to implement. Recent experiences with the 2003 SARS and 2009 H1N1 epidemics have shown that people are willing to wear facemasks to protect themselves against infection; however, little research has been done to quantify the impact of using facemasks in reducing the spread of disease. We construct and analyze a mathematical model for a population in which some people wear facemasks during the pandemic and quantify impact of these masks on the spread of influenza. To estimate the parameter values used for the effectiveness of facemasks, we used available data from studies on N95 respirators and surgical facemasks. The results show that if N95 respirators are only 20% effective in reducing susceptibility and infectivity, only 10% of the population would have to wear them to reduce the number of influenza A (H1N1) cases by 20%. We can conclude from our model that, if worn properly, facemasks are an effective intervention strategy in reducing the spread of pandemic (H1N1) 2009.", "title": "Mathematical Modeling of the Effectiveness of Facemasks in Reducing the Spread of Novel Influenza A (H1N1)", "pid": "36bfeoqv", "bm25_score": 217.23582458496094}, {"text": "Masks play a role in the protection of health-care workers (HCWs) from acquiring respiratory infections, including coronavirus disease 2019 (COVID-19) in health-care settings. This observational study was conducted among 382 HCWs in a tertiary care setting over a period of 1 month. Descriptive analysis was done to assess the rational and recommended use of masks/respirators during COVID-19 pandemic using a structured observation checklist as a survey tool. A total of 374 HCWs were included, 64.9% of whom were using face masks rationally as mentioned per risk area categorization with a predominance of triple-layered mask during all 4 weeks. Overall, 64.1% used masks correctly. Clear guidelines and strategies can help to increase the compliance of HCWs with rational use of face masks.", "title": "Rational use of face mask in a tertiary care hospital setting during COVID-19 pandemic: An observational study", "pid": "57zwd3y6", "bm25_score": 217.22801208496094}, {"text": "Cloth masks have been used in healthcare and community settings to protect the wearer from respiratory infections. The use of cloth masks during the coronavirus disease (COVID-19) pandemic is under debate. The filtration effectiveness of cloth masks is generally lower than that of medical masks and respirators; however, cloth masks may provide some protection if well designed and used correctly. Multilayer cloth masks, designed to fit around the face and made of water-resistant fabric with a high number of threads and finer weave, may provide reasonable protection. Until a cloth mask design is proven to be equally effective as a medical or N95 mask, wearing cloth masks should not be mandated for healthcare workers. In community settings, however, cloth masks may be used to prevent community spread of infections by sick or asymptomatically infected persons, and the public should be educated about their correct use.", "title": "Effectiveness of Cloth Masks for Protection Against Severe Acute Respiratory Syndrome Coronavirus 2.", "pid": "xtraspw2", "bm25_score": 217.22113037109375}, {"text": "", "title": "Impact of Population Mask Wearing on Covid-19 Post Lockdown", "pid": "yzt14a4g", "bm25_score": 217.187255859375}, {"text": "", "title": "Universal use of face masks for success against COVID-19: evidence and implications for prevention policies", "pid": "t3gr6bc8", "bm25_score": 217.17544555664062}, {"text": "Objective: To determine the effectiveness of non-medical grade washable masks or face coverings in controlling airborne dispersion from exhalation (both droplet and aerosol), and to aid in establishing public health strategies on the wearing of masks to reduce COVID-19 transmission. Design: This comparative effectiveness study using an exhalation simulator to conduct 94 experiment runs with combinations of 8 different fabrics, 5 mask designs, and airflows for both talking and coughing. Setting: Non-airtight fume hood and multiple laser scattering particle sensors. Participants: No human participants. Exposure: 10% NaCl nebulized solution delivered by an exhalation simulator through various masks and fabrics with exhalation airflows representative of \"coughing\" and \"talking or singing.\" Main Outcomes and Measures: The primary outcome was reduction in aerosol dispersion velocity, quantity of particles, and change in dispersion direction. Measurements used in this study included peak expiratory flow (PEF), aerosol velocity, concentration area under curve (AUC), and two novel metrics of expiratory flow dispersion factor (EDF) and filtration efficiency indicator (FEI). Results: Three-way multivariate analysis of variance establishes that factors of fabric, mask design, and exhalation breath level have a statistically significant effect on changing direction, reducing velocity or concentration (Fabric: P = < .001, Wilks' {Lambda} = .000; Mask design: P = < .001, Wilks' {Lambda} = .000; Breath level: P = < .001, Wilks' {Lambda} = .004). There were also statistically significant interaction effects between combinations of all primary factors. Conclusions and Relevance: The application of facial coverings or masks can significantly reduce the airborne dispersion of aerosolized particles from exhalation. The results show that wearing of non-medical grade washable masks or face coverings can help increase the effectiveness of non-pharmaceutical interventions (NPI) especially where infectious contaminants may exist in shared air spaces. However, the effectiveness varies greatly between the specific fabrics and mask designs used.", "title": "Quantifying Respiratory Airborne Particle Dispersion Control Through Improvised Reusable Masks", "pid": "nt378esz", "bm25_score": 217.1719207763672}, {"text": "BACKGROUND: Concerns have been raised by healthcare organisations in New Zealand that routine mask use by healthcare workers (HCW) may increase the risk of transmission of SARS-CoV-2 through increased face touching. Routine mask use by frontline HCW was not recommended when seeing 'low risk' patients. The aim of this review was to determine the carriage of respiratory viruses on facemasks used by HCW. METHODS: A systematic review was conducted with structured searches of medical and allied health databases. Two authors independently screened articles for inclusion, with substantial agreement (k=0.66, 95%CI 0.54 to 0.79). Studies that at least one author recommended for full text review were reviewed in full for inclusion. Two authors independently extracted data from included studies including the setting, method of analysis and results. There was exact agreement on the proportion of virus detected on masks. RESULTS: 1233 titles were retrieved, 47 underwent full text review and five studies reported in four articles were included. The studies were limited by small numbers and failure to test all eligible masks in some studies. The proportion in each study ranged from 0 (95% CI 0-10) to 25% (95%CI 8-54). No study reported clinical respiratory illness as a result of virus on the masks. CONCLUSIONS: Although limited, current evidence suggests that viral carriage on the outer surface of surgical masks worn by HCW treating patients with clinical respiratory illness is low and there was not strong evidence to support the assumption that mask use may increase the risk of viral transmission. This article is protected by copyright. All rights reserved.", "title": "What proportion of healthcare worker masks carry virus? A systematic review", "pid": "s8bwq0d5", "bm25_score": 217.1671905517578}, {"text": "With cases of COVID-19 growing rapidly in the US and evidence mounting that the virus responsible, SARS-CoV-2, can be spread by infected people before they develop symptoms, the US Centers for Disease Control and Prevention recommended April 3 that people wear cloth face coverings in public places This guidance is a shift from the center’s previous position that healthy people needed to wear masks only when caring for a sick person The recommendation also follows recent calls by experts on social media and other platforms for the general public to don nonmedical, cloth masks to help reduce the transmission of the novel coronavirus “Members of the general public should wear non-medical fabric face masks when going out in public in one additional societal effort to slow the spread of the virus down,” Tom Inglesby, director of the Johns Hopkins Center for Health Security, tweeted March 29 These experts hope the View: PDF ;Full Text HTML", "title": "How effective can homemade face masks be?", "pid": "zfea3qg7", "bm25_score": 217.1578369140625}, {"text": "Protecting Health Care Workers (HCWs) during routine care of suspected or confirmed COVID-19 patients is of paramount importance to halt the SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) pandemic. The WHO, ECDC and CDC have issued conflicting guidelines on the use of respiratory filters (N95) by HCWs. We searched PubMed, Embase and The Cochrane Library from the inception to March 21, 2020 to identify randomized controlled trials (RCTs) comparing N95 respirators versus surgical masks for prevention of COVID-19 or any other respiratory infection among HCWs. The grading of recommendations, assessment, development, and evaluation (GRADE) was used to evaluate the quality of evidence. Four RCTs involving 8736 HCWs were included. We did not find any trial specifically on prevention of COVID-19. However, wearing N95 respirators can prevent 73 more (95% CI 46-91) clinical respiratory infections per 1000 HCWs compared to surgical masks (2 RCTs; 2594 patients; low quality of evidence). A protective effect of N95 respirators in laboratory-confirmed bacterial colonization (RR = 0.41; 95%CI 0.28-0.61) was also found. A trend in favour of N95 respirators was observed in preventing laboratory-confirmed respiratory viral infections, laboratory-confirmed respiratory infection, and influenza like illness. We found no direct high quality evidence on whether N95 respirators are better than surgical masks for HCWs protection from SARS-CoV-2. However, low quality evidence suggests that N95 respirators protect HCWs from clinical respiratory infections. This finding should be contemplated to decide the best strategy to support the resilience of healthcare systems facing the potentially catastrophic SARS-CoV-2 pandemic.", "title": "The need of health policy perspective to protect Healthcare Workers during COVID-19 pandemic. A GRADE rapid review on the N95 respirators effectiveness", "pid": "334hmwmj", "bm25_score": 217.1378631591797}, {"text": "OBJECTIVES: Pandemic COVID-19 has become a seriously public health priority worldwide. Comprehensive strategies including travel restrictions and mask-wearing have been implemented to mitigate the virus circulation. However, detail information on community transmission is unavailable yet. METHODS: From January 23 to March 1, 2020, 127 patients (median age: 46 years; range: 11-80) with 71 male and 56 female, were confirmed to be infected with the SARS-CoV-2 in Taizhou, Zhejiang, China. Epidemiological trajectory and clinical features of these COVID-19 cases were retrospectively retrieved from electronic medical records and valid individual questionnaire. RESULTS: The disease onset was between January 9 to February 14, 2020. Among them, 64 patients are local residents, and 63 patients were back home from Wuhan from January 10 to 24, 2020 before travel restriction. 197 local residents had definite close-contact with 41 pre-symptomatic patients back from Wuhan. 123 and 74 of them contact with mask-wearing or with no mask-wearing pre-symptomatic patients back from Wuhan, respectively. Data showed that incidence of COVID-19 was significantly higher for local residents close-contact with no mask-wearing Wuhan returned pre-symptomatic patients (19.0% vs. 8.1%, p < 0.001). Among 57 close-contact individuals, 21 sequential local COVID-19 patients originated from a pre-symptomatic Wuhan returned couple, indicated dense gathering in congested spaces is a high risk for SARS-CoV-2 transmission. CONCLUSIONS: Our findings provided valuable details of pre-symptomatic patient mask-wearing and restriction of mass gathering in congested spaces particularly, are important interventions to mitigate the SARS-CoV-2 transmission.", "title": "Mask wearing in pre-symptomatic patients prevents SARS-CoV-2 transmission: An epidemiological analysis", "pid": "hxzas6gf", "bm25_score": 217.1199951171875}, {"text": "The present COVID-19 pandemic, caused by the airborne SARS-CoV-2 virus, has highlighted the vital importance of appropriate personal protective equipment for all exposed health care workers The single most important part of this armor is the N-95 mask With the awareness that the virus is spread by both droplets and through the aerosolized route, the N-95 provides protection that a surgical mask cannot match This timely review looks at the special advantages that an N-95 offers over a surgical mask with specific reference to the COVID-19 epidemic It also emphasizes the crucial importance of ensuring quality masks with a proper fit Finally, with acute scarcities of N-95 masks being reported from hospitals globally, it reviews recent literature which attempts to prolong the life of these masks with extended use, reuse and decontamination of used masks", "title": "The N-95 mask: invaluable ally in the battle against the COVID-19 pandemic", "pid": "i1w2snyy", "bm25_score": 217.11569213867188}, {"text": "Face masks have traditionally been used in general infection control, but their efficacy at the population level in preventing transmission of influenza viruses has not been studied in detail. Data from published clinical studies indicate that the infectivity of influenza A virus is probably very high, so that transmission of infection may involve low doses of virus. At low doses, the relation between dose and the probability of infection is approximately linear, so that the reduction in infection risk is proportional to the reduction in exposure due to particle retention of the mask. A population transmission model was set up to explore the impact of population‐wide mask use, allowing estimation of the effects of mask efficacy and coverage (fraction of the population wearing masks) on the basic reproduction number and the infection attack rate. We conclude that population‐wide use of face masks could make an important contribution in delaying an influenza pandemic. Mask use also reduces the reproduction number, possibly even to levels sufficient for containing an influenza outbreak.", "title": "The Effect of Mask Use on the Spread of Influenza During a Pandemic", "pid": "mfb2or98", "bm25_score": 217.1089324951172}, {"text": "", "title": "The scientific rationale for the use of simple masks or improvised facial coverings to trap exhaled aerosols and possibly reduce the breathborne spread of COVID-19", "pid": "jg1cz1fa", "bm25_score": 217.10122680664062}, {"text": "During the COVID-19 pandemic, the scientific community developed predictive models to evaluate potential governmental interventions. However, the analysis of the effects these interventions had is less advanced. Here, we propose a data-driven framework to assess these effects retrospectively. We use a regularized regression to find a parsimonious model that fits the data with the least changes in the Rt parameter. Then, we postulate each jump in Rt as the effect of an intervention. Following the do-operator prescriptions, we simulate the counterfactual case by forcing Rt to stay at the pre-jump value. We then attribute a value to the intervention from the difference between true evolution and simulated counterfactual. We show that the recommendation to use facemasks for all activities would reduce the number of cases by 170000 (95% CI 160000 to 180000) in Connecticut, Massachusetts, and New York State. The framework presented here might be used in any case where cause and effects are sparse in time.", "title": "Masks and COVID-19: a causal framework for imputing value to public-health interventions", "pid": "qgp7ksq8", "bm25_score": 217.0947723388672}, {"text": "Abstract In the United States, there is currently an exponential growth for the COVID-19 cases. The US president’s coronavirus guidelines for Americans “30 Days to Slow The Spread” are necessary. To effectively curb the rapid spread of SARS-CoV-2, two more control measures masks and thermometers are strongly suggested to be included in the Guidelines.", "title": "Masks and thermometers: Paramount measures to stop the rapid spread of SARS-CoV-2 in the United States", "pid": "r66eulqj", "bm25_score": 217.06884765625}, {"text": "Background: Several studies among various population groups have been conducted to investigate the level of knowledge, attitudes, perceptions, and risk reduction practices (KAP) related to COVID-19. A comprehensive review on this topic is important to highlight the areas for improvement and interventions to prevent COVID-19. Thus, the purpose of this study was to summarize the level of KAP about COVID-19 via a systematic review Methods: A systematic literature search was performed using a combination of selected keywords in four scientific databases to identify relevant literature published from January 1 to May 31, 2020. Nineteen articles were included in the systematic review, and sixteen studies in the meta-analysis. The data was analyzed using a random-effects model due to the heterogeneity between the studies. Results: Lack of COVID-19-related knowledge, positive perceptions, and preventive practices was detected and seems widespread. In particular, 56.6% (95%CI: 45.9-67%) of the health care workers (HCWs) and medical students had poor knowledge about COVID-19 and only 46% (95%CI: 15-77) of the total study sample had positive perceptions towards COVID-19. Besides, 81.7% of the sample prioritized practicing hand hygiene to prevent COVID-19, but wearing a face mask to prevent COVID-19 transmission was suboptimal (73.4%). Finally, less than a tenth (8%) of the subjects had good knowledge about COVID-19 symptoms (79%) and its transmission (82%) and reported that they avoided crowded places to prevent getting COVID-19 (89%). Conclusion: Evidence-based practices on risk communication and raising awareness should be planned by local governments in collaboration with healthcare organizations. Specifically, educational initiatives for HCWs to prioritize wearing a face mask and practicing hand hygiene should be considered a priority.", "title": "Knowledge, Attitude, Perceptions and Practice towards COVID-19: A systematic review and Meta-analysis", "pid": "l593auaj", "bm25_score": 217.06153869628906}, {"text": "Controversy exists around the appropriate types of masks and the situations in which they should be used in community and health care settings for the prevention of SARS-CoV-2 infection. In this article, the American College of Physicians (ACP) provides recommendations based on the best available evidence through 14 April 2020 on the effectiveness of N95 respirators, surgical masks, and cloth masks in reducing transmission of infection. The ACP plans periodic updates of these recommendations on the basis of ongoing surveillance of the literature for 1 year from the initial search date.", "title": "Use of N95, Surgical, and Cloth Masks to Prevent COVID-19 in Health Care and Community Settings: Living Practice Points From the American College of Physicians (Version 1)", "pid": "f4sd7vbi", "bm25_score": 217.0584716796875}, {"text": "OBJECTIVES: Pandemic COVID-19 has become a seriously public health priority worldwide. Comprehensive strategies including travel restrictions and mask-wearing have been implemented to mitigate the virus circulation. However, detail information on community transmission is unavailable yet. METHODS: From January 23 to March 1, 2020, 127 patients (median age: 46 years; range: 11–80) with 71 male and 56 female, were confirmed to be infected with the SARS-CoV-2 in Taizhou, Zhejiang, China. Epidemiological trajectory and clinical features of these COVID-19 cases were retrospectively retrieved from electronic medical records and valid individual questionnaire. RESULTS: The disease onset was between January 9 to February 14, 2020. Among them, 64 patients are local residents, and 63 patients were back home from Wuhan from January 10 to 24, 2020 before travel restriction. 197 local residents had definite close-contact with 41 pre-symptomatic patients back from Wuhan. 123 and 74 of them contact with mask-wearing or with no mask-wearing pre-symptomatic patients back from Wuhan, respectively. Data showed that incidence of COVID-19 was significantly higher for local residents close-contact with no mask-wearing Wuhan returned pre-symptomatic patients (19.0% vs. 8.1%, p < 0.001). Among 57 close-contact individuals, 21 sequential local COVID-19 patients originated from a pre-symptomatic Wuhan returned couple, indicated dense gathering in congested spaces is a high risk for SARS-CoV-2 transmission. CONCLUSIONS: Our findings provided valuable details of pre-symptomatic patient mask-wearing and restriction of mass gathering in congested spaces particularly, are important interventions to mitigate the SARS-CoV-2 transmission.", "title": "Mask wearing in pre-symptomatic patients prevents SARS-CoV-2 transmission: An epidemiological analysis", "pid": "u69gequt", "bm25_score": 217.05624389648438}, {"text": "Protecting Health Care Workers (HCWs) during routine care of suspected or confirmed COVID-19 patients is of paramount importance to halt the SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) pandemic. The WHO, ECDC and CDC have issued conflicting guidelines on the use of respiratory filters (N95) by HCWs. We searched PubMed, Embase and The Cochrane Library from the inception to March 21, 2020 to identify randomized controlled trials (RCTs) comparing N95 respirators versus surgical masks for prevention of COVID-19 or any other respiratory infection among HCWs. The grading of recommendations, assessment, development, and evaluation (GRADE) was used to evaluate the quality of evidence. Four RCTs involving 8736 HCWs were included. We did not find any trial specifically on prevention of COVID-19. However, wearing N95 respirators can prevent 73 more (95% CI 46–91) clinical respiratory infections per 1000 HCWs compared to surgical masks (2 RCTs; 2594 patients; low quality of evidence). A protective effect of N95 respirators in laboratory-confirmed bacterial colonization (RR = 0.41; 95%CI 0.28–0.61) was also found. A trend in favour of N95 respirators was observed in preventing laboratory-confirmed respiratory viral infections, laboratory-confirmed respiratory infection, and influenza like illness. We found no direct high quality evidence on whether N95 respirators are better than surgical masks for HCWs protection from SARS-CoV-2. However, low quality evidence suggests that N95 respirators protect HCWs from clinical respiratory infections. This finding should be contemplated to decide the best strategy to support the resilience of healthcare systems facing the potentially catastrophic SARS-CoV-2 pandemic.", "title": "The need of health policy perspective to protect Healthcare Workers during COVID-19 pandemic. A GRADE rapid review on the N95 respirators effectiveness", "pid": "no8bgglk", "bm25_score": 217.05218505859375}, {"text": "Masks are widely discussed during the course of the ongoing COVID-19 pandemic Most hospitals have implemented universal masking for their healthcare workers, and the Center for Disease Control currently advises even the general public to wear cloth masks when outdoors The pertinent need for masks arises from plausible dissemination of the SARS-CoV-2 through close contacts, as well as the possibility of virus transmission from asymptomatic, pre-symptomatic, and mildly symptomatic individuals Given current global shortages in personal protective equipment, the efficacy of various types of masks: N95 respirators, surgical masks, and cloth masks are researched To accommodate limited supplies, techniques for extended use, reuse, and sterilization of masks are strategized However, masks alone may not greatly slow down the COVID-19 pandemic unless they are coupled with adequate social distancing, diligent hand hygiene, and other proven preventive measures", "title": "Comprehensive review of mask utility and challenges during the COVID-19 pandemic", "pid": "7qj00qi9", "bm25_score": 217.04383850097656}, {"text": "COVID-19 is characterized by an infectious presymptomatic period,when newly infected individuals can unwittingly infect others We are interested in what benefits facemasks could offer as a nonpharmaceutical intervention, especially in the settings where high-technology interventions, such as contact tracing using mobile apps or rapid case detection via molecular tests, are not sustainable Here, we report the results of two mathematical models and show that facemask use by the public could make a major contribution to reducing the impact of the COVID-19 pandemic Our intention is to provide a simple modelling framework to examine the dynamics of COVID-19 epidemics when facemasks are worn by the public, with or without imposed 'lock-down' periods Our results are illustrated for a number of plausible values for parameter ranges describing epidemiological processes and mechanistic properties of facemasks, in the absence of current measurements for these values We show that, when facemasks are used by the public all the time (not just from when symptoms first appear), the effective reproduction number, Re, can be decreased below 1, leading to the mitigation of epidemic spread Under certain conditions, when lock-down periods are implemented in combination with 100% facemask use, there is vastly less disease spread, secondary and tertiary waves are flattened and the epidemic is brought under control The effect occurs even when it is assumed that facemasks are only 50% effective at capturing exhaled virus inoculum with an equal or lower efficiency on inhalation Facemask use by the public has been suggested to be ineffective because wearers may touch their facesmore often, thus increasing the probability of contracting COVID-19 For completeness, our models show that facemask adoption provides population-level benefits, even in circumstances where wearers are placed at increased risk At the time of writing, facemask use by the public has not been recommended in many countries, but a recommendation for wearing face-coverings has just been announced for Scotland Even if facemask use began after the start of the first lock-down period, our results show that benefits could still accrue by reducing the risk of the occurrence of further COVID-19 waves We examine the effects of different rates of facemask adoption without lock-down periods and show that, even at lower levels of adoption, benefits accrue to the facemask wearers These analyses may explain why some countries, where adoption of facemask use by the public is around 100%, have experienced significantly lower rates of COVID-19 spread and associated deaths We conclude that facemask use by the public, when used in combination with physical distancing or periods of lock-down, may provide an acceptable way of managing the COVID- 19 pandemic and re-opening economic activity These results are relevant to the developed as well as the developing world, where large numbers of people are resource poor, but fabrication of home-made, effective facemasks is possible A key message from our analyses to aid the widespread adoption of facemasks would be: 'my mask protects you, your mask protects me' [ABSTRACT FROM AUTHOR] Copyright of Proceedings of the Royal Society A: Mathematical, Physical & Engineering Sciences is the property of Royal Society and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use This abstract may be abridged No warranty is given about the accuracy of the copy Users should refer to the original published version of the material for the full abstract (Copyright applies to all Abstracts )", "title": "A modelling framework to assess the likely effectiveness of facemasks in combination with 'lock-down' in managing the COVID-19 pandemic", "pid": "30pl5tx3", "bm25_score": 217.0350799560547}, {"text": "Background Protecting Health Care Workers (HCWs) during routine care of suspected or confirmed COVID-19 patients is of paramount importance to halt the SARS-CoV-2 (Severe Acute Respiratory Syndrome-Coronavirus-2) pandemic. The WHO, ECDC and CDC have issued conflicting guidelines on the use of respiratory filters (N95) by HCWs. Methods We searched PubMed, Embase and The Cochrane Library from the inception to March 21, 2020 to identify randomized controlled trials (RCTs) comparing N95 respirators versus surgical masks for prevention of COVID-19 or any other respiratory infection among HCWs. The grading of recommendations, assessment, development, and evaluation (GRADE) was used to evaluate the quality of evidence. Findings Four RCTs involving 8736 HCWs were included. We did not find any trial specifically on prevention of COVID-19. However, wearing N95 respirators can prevent 73 more (95% CI 46-91) clinical respiratory infections per 1000 HCWs compared to surgical masks (2 RCTs; 2594 patients; low quality of evidence). A protective effect of N95 respirators in laboratory-confirmed bacterial colonization (RR= 0.41; 95%CI 0.28-0.61) was also found. A trend in favour of N95 respirators was observed in preventing laboratory-confirmed respiratory viral infections, laboratory-confirmed respiratory infection, and influenza like illness. Interpretation We found no direct high quality evidence on whether N95 respirators are better than surgical masks for HCWs protection from SARS-CoV-2. However, low quality evidence suggests that N95 respirators protect HCWs from clinical respiratory infections. This finding should be contemplated to decide the best strategy to support the resilience of healthcare systems facing the potentially catastrophic SARS-CoV-2 pandemic.", "title": "The need of health policy perspective to protect Healthcare Workers during COVID-19 pandemic. A GRADE rapid review on the N95 respirators effectiveness.", "pid": "1q8tqeg7", "bm25_score": 217.00657653808594}, {"text": "", "title": "Wearing face masks regardless of symptoms is crucial for preventing the spread of COVID-19 in hospitals", "pid": "st7c4v9v", "bm25_score": 217.0029296875}, {"text": "Various mitigation measures have been implemented to fight the coronavirus disease 2019 (COVID-19) pandemic, including widely adopted social distancing and mandated face covering. However, assessing the effectiveness of those intervention practices hinges on the understanding of virus transmission, which remains uncertain. Here we show that airborne transmission is highly virulent and represents the dominant route to spread the disease. By analyzing the trend and mitigation measures in Wuhan, China, Italy, and New York City, from January 23 to May 9, 2020, we illustrate that the impacts of mitigation measures are discernable from the trends of the pandemic. Our analysis reveals that the difference with and without mandated face covering represents the determinant in shaping the pandemic trends in the three epicenters. This protective measure alone significantly reduced the number of infections, that is, by over 78,000 in Italy from April 6 to May 9 and over 66,000 in New York City from April 17 to May 9. Other mitigation measures, such as social distancing implemented in the United States, are insufficient by themselves in protecting the public. We conclude that wearing of face masks in public corresponds to the most effective means to prevent interhuman transmission, and this inexpensive practice, in conjunction with simultaneous social distancing, quarantine, and contact tracing, represents the most likely fighting opportunity to stop the COVID-19 pandemic. Our work also highlights the fact that sound science is essential in decision-making for the current and future public health pandemics.", "title": "Identifying airborne transmission as the dominant route for the spread of COVID-19", "pid": "9ye2okm5", "bm25_score": 217.0018768310547}, {"text": "Italy was the first Western country to be seriously affected by COVID-19, and the first to implement drastic measures, which have successfully curtailed the epidemic. To understand which contain measures effected disease dynamics, we estimate change points in COVID-19 dynamics by fitting a compartmental model to official Italian data. Our results indicate that lockdowns managed to cause the epidemic to peak in late March 2020. Surprisingly, we found a change point during the decay from the peak, which does not correspond to obvious drastic legal interventions, but may be explained by widespread promotion and mandatory use of face masks. We confirm these interpretations at regional levels, and find that the gradual reopening of society since early May has caused no change in disease dynamics. We speculate that widespread use of face masks and other protective means has contributed substantially to keeping the number of new Italian COVID-19 cases under control in spite of society turning towards a new normality.", "title": "Data-driven estimation of change points reveal correlation between face mask use and accelerated curtailing of the COVID-19 epidemic in Italy", "pid": "papz6uoa", "bm25_score": 216.99868774414062}, {"text": "In December 2019, transmission of the novel coronavirus (SARS-CoV-2) that causes coronavirus disease 2019(COVID-19) occurred in Wuhan, China1 .And later the virus began to be transmitted from person to person2 .Face masks are a type of personal protective equipment used to prevent the spread of respiratory infections，it may be effective at helping prevent transmission of respiratory viruses and bacteria3 .Here, we share a case of face masks are be used to prevent the transmission of COVID-19 infection.", "title": "COVID‐19: Face masks and human‐to‐human transmission", "pid": "wni08lks", "bm25_score": 216.95559692382812}, {"text": "The COVID-19 pandemic presents a severe and acute public health emergency around the world. The event of the pandemic has seen an upsurge in the general public wearing of disposable surgical masks (DSM) and other types of face masks. The World Health Organisation of mask wearing has been widely debated in the press a(WHO) have changed their advice, to now recommend the routine wearing of fabric masks by the general public as a means of preventing the spread of COVID-19 (WHO 2020a).", "title": "'Masking the evidence': perspectives of the COVID-19 pandemic", "pid": "sjenehbl", "bm25_score": 216.95547485351562}, {"text": "In the human population, social contacts are a key for transmission of bacteria and viruses. The use of face masks seems to be critical to prevent the transmission of SARS-CoV-2 for the period, in which therapeutic interventions are lacking. In this review, we describe the history of masks from the middle age to modern times.", "title": "The history and value of face masks", "pid": "jyju71r1", "bm25_score": 216.9501953125}, {"text": "The current COVID-19 pandemic has spurred concern about what interventions may be effective at reducing transmission. The city and county of San Francisco imposed a shelter-in-place order in March 2020, followed by use of a contact tracing program and a policy requiring use of cloth face masks. We used statistical estimation and simulation to estimate the effectiveness of these interventions in San Francisco. We estimated that self-isolation and other practices beginning at the time of San Francisco’s shelter-in-place order reduced the effective reproduction number of COVID-19 by 35.4% (95% CI, −20.1%–81.4%). We estimated the effect of contact tracing on the effective reproduction number to be a reduction of approximately 44% times the fraction of cases that are detected, which may be modest if the detection rate is low. We estimated the impact of cloth mask adoption on reproduction number to be approximately 8.6%, and note that the benefit of mask adoption may be substantially greater for essential workers and other vulnerable populations, residents return to circulating outside the home more often. We estimated the effect of those interventions on incidence by simulating counterfactual scenarios in which contact tracing was not adopted, cloth masks were not adopted, and neither contact tracing nor cloth masks was adopted, and found increases in case counts that were modest, but relatively larger than the effects on reproduction numbers. These estimates and model results suggest that testing coverage and timing of testing and contact tracing may be important, and that modest effects on reproduction numbers can nonetheless cause substantial effects on case counts over time.", "title": "Estimation of effects of contact tracing and mask adoption on COVID-19 transmission in San Francisco: a modeling study", "pid": "7hdx4ik4", "bm25_score": 216.94105529785156}, {"text": "On December 31, 2019, the World Health Organization (WHO) reported a cluster of cases of pneumonia of unknown cause detected in Wuhan City, Hubei Province, China. As of February 29, 2020, the National Health Commission of China has reported 79,389 confirmed cases of SARS-CoV-2 infection in 34 provinces. The masks can be used to block respiratory transmission from human to human, and are an effective way to control influenza. It is, therefore, necessary to wear a mask when respiratory infectious diseases are prevalent. China has a population of 1.4 billion. Assuming that two-thirds of the people in China must wear a mask every day, the daily demand for masks will reach 900 million. The Chinese government has taken many measures to solve these problems. Additionally, more measures should be taken to properly dispose of mask garbage. Although the outbreak originated in China, person-to-person transmission of SARS-CoV-2 has been confirmed, which means that it can be spread to anywhere in the world if prevention measures fail. The issues regarding face mask shortages and garbage in China, therefore, deserve worldwide attention.", "title": "Mask crisis during the COVID-19 outbreak.", "pid": "61qrwza2", "bm25_score": 216.93153381347656}, {"text": "In the United States, there is currently an exponential growth for the COVID-19 cases. The US president's coronavirus guidelines for Americans \"30 Days to Slow The Spread\" are necessary. To effectively curb the rapid spread of SARS-CoV-2, two more control measures masks and thermometers are strongly suggested to be included in the Guidelines.", "title": "Masks and thermometers: Paramount measures to stop the rapid spread of SARS-CoV-2 in the United States", "pid": "nyoscm1m", "bm25_score": 216.92062377929688}, {"text": "This systematic review and meta-analysis quantified the protective effect of facemasks and respirators against respiratory infections among healthcare workers. Relevant articles were retrieved from Pubmed, EMBASE, and Web of Science. Meta-analyses were conducted to calculate pooled estimates. Meta-analysis of randomized controlled trials (RCTs) indicated a protective effect of masks and respirators against clinical respiratory illness (CRI) (risk ratio [RR] = 0.59; 95% confidence interval [CI]:0.46–0.77) and influenza-like illness (ILI) (RR = 0.34; 95% CI:0.14–0.82). Compared to masks, N95 respirators conferred superior protection against CRI (RR = 0.47; 95% CI: 0.36–0.62) and laboratory-confirmed bacterial (RR = 0.46; 95% CI: 0.34–0.62), but not viral infections or ILI. Meta-analysis of observational studies provided evidence of a protective effect of masks (OR = 0.13; 95% CI: 0.03–0.62) and respirators (OR = 0.12; 95% CI: 0.06–0.26) against severe acute respiratory syndrome (SARS). This systematic review and meta-analysis supports the use of respiratory protection. However, the existing evidence is sparse and findings are inconsistent within and across studies. Multicentre RCTs with standardized protocols conducted outside epidemic periods would help to clarify the circumstances under which the use of masks or respirators is most warranted.", "title": "Effectiveness of Masks and Respirators Against Respiratory Infections in Healthcare Workers: A Systematic Review and Meta-Analysis", "pid": "gin90aef", "bm25_score": 216.88253784179688}, {"text": "On December 31, 2019, the World Health Organization (WHO) reported a cluster of cases of pneumonia of unknown cause detected in Wuhan City, Hubei Province, China. As of February 29, 2020, the National Health Commission of China has reported 79,389 confirmed cases of SARS-CoV-2 infection in 34 provinces. The masks can be used to block respiratory transmission from human to human, and are an effective way to control influenza. It is, therefore, necessary to wear a mask when respiratory infectious diseases are prevalent. China has a population of 1.4 billion. Assuming that two-thirds of the people in China must wear a mask every day, the daily demand for masks will reach 900 million. The Chinese government has taken many measures to solve these problems. Additionally, more measures should be taken to properly dispose of mask garbage. Although the outbreak originated in China, person-to-person transmission of SARS-CoV-2 has been confirmed, which means that it can be spread to anywhere in the world if prevention measures fail. The issues regarding face mask shortages and garbage in China, therefore, deserve worldwide attention.", "title": "Mask crisis during the COVID-19 outbreak", "pid": "r95u121j", "bm25_score": 216.8701171875}, {"text": "", "title": "Wearing masks and the fight against the novel coronavirus (COVID-19)", "pid": "s65ffpf1", "bm25_score": 216.85897827148438}, {"text": "", "title": "Face masks - a sustainable measure to mitigate COVID-19.", "pid": "n18gp3wj", "bm25_score": 216.83535766601562}]}
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This commentary serves to tie existing literature on mental health and COVID-19 to the clinical experiences of a psychologist working in the Canadian hospital sector. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "A population mental health perspective on the impact of COVID-19.", "pid": "4q1j6g44", "bm25_score": 219.55813598632812}, {"text": "With the advent of the COVID-19 pandemic we have witnessed the greatest global challenge in a generation. The full extent of the mental health impact is, as yet, unknown, but is anticipated to be severe and enduring. In this Special Issue dedicated to mental health and the COVID-19 pandemic, we aim to lay the foundation for an improved understanding of how COVID-19 is affecting mental health services both in Ireland and globally. This Special Issue highlights how the mental health effects of COVID-19 stretch to almost every element of society. The issue includes perspectives from several countries across multiple disciplines and healthcare settings. The drive for rapid innovation and service development is clearly evident throughout, and provides hope that by working collaboratively we can positively impact population mental health in the months and years ahead.", "title": "Mental Health and the COVID19 Pandemic.", "pid": "hze88sr4", "bm25_score": 219.53439331054688}, {"text": "The Coronavirus disease 2019 (COVID-19) pandemic emerged in Wuhan, China and has spread all over the world and has caused huge threats to health and lives. It has affected different frontiers of lives and induced many psychiatric individual and collective problems such as panic, anxiety, depression, post-traumatic stress disorders, suspiciousness, infodemia, cacophony, xenophobia, racisms, etc. The COVID-19 outbreak has induced public and global mental health crisis as well as a huge psycho-social experiment. Psychiatry and other mental health sciences can play very useful role in supporting the well-being of COVID-19 patients and their families, healthcare personnel and the society. For successful fighting with present and future pandemics we have to learn more about psychiatric and psychological aspects of COVID-19 from the perspectives of public and global mental health.", "title": "COVID-19 Pandemia and Public and Global Mental Health from the Perspective of Global Health Securit.", "pid": "1vehveqk", "bm25_score": 219.44122314453125}, {"text": "The global pandemic of coronavirus disease 2019 (COVID-19) has resulted in massive societal, economic, and environmental impacts that have both short- and long-term mental health influences. This commentary serves to tie existing literature on mental health and COVID-19 to the clinical experiences of a psychologist working in the Canadian hospital sector. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "A population mental health perspective on the impact of COVID-19", "pid": "6ngsyo8o", "bm25_score": 219.4196319580078}, {"text": "With the advent of the COVID-19 pandemic we have witnessed the greatest global challenge in a generation. The full extent of the mental health impact is, as yet, unknown, but is anticipated to be severe and enduring. In this Special Issue dedicated to mental health and the COVID-19 pandemic, we aim to lay the foundation for an improved understanding of how COVID-19 is affecting mental health services both in Ireland and globally. This Special Issue highlights how the mental health effects of COVID-19 stretch to almost every element of society. The issue includes perspectives from several countries across multiple disciplines and healthcare settings. The drive for rapid innovation and service development is clearly evident throughout, and provides hope that by working collaboratively we can positively impact population mental health in the months and years ahead.", "title": "Mental Health and the COVID19 Pandemic", "pid": "wbwd7m5w", "bm25_score": 219.4107666015625}, {"text": "The Coronavirus disease 2019 (COVID-19) pandemic emerged in Wuhan, China and has spread all over the world and has caused huge threats to health and lives. It has affected different frontiers of lives and induced many psychiatric individual and collective problems such as panic, anxiety, depression, post-traumatic stress disorders, suspiciousness, infodemia, cacophony, xenophobia, racisms, etc. The COVID-19 outbreak has induced public and global mental health crisis as well as a huge psycho-social experiment. Psychiatry and other mental health sciences can play very useful role in supporting the well-being of COVID-19 patients and their families, healthcare personnel and the society. For successful fighting with present and future pandemics we have to learn more about psychiatric and psychological aspects of COVID-19 from the perspectives of public and global mental health.", "title": "COVID-19 Pandemia and Public and Global Mental Health from the Perspective of Global Health Securit", "pid": "u81fflce", "bm25_score": 219.37789916992188}, {"text": "As a result of the emergence of coronavirus disease 2019 (COVID-19) outbreak caused by acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Chinese city of Wuhan, a situation of socio-economic crisis and profound psychological distress rapidly occurred worldwide. Various psychological problems and important consequences in terms of mental health including stress, anxiety, depression, frustration, uncertainty during COVID-19 outbreak emerged progressively. This work aimed to comprehensively review the current literature about the impact of COVID-19 infection on the mental health in the general population. The psychological impact of quarantine related to COVID-19 infection has been additionally documented together with the most relevant psychological reactions in the general population related to COVID-19 outbreak. The role of risk and protective factors against the potential to develop psychiatric disorders in vulnerable individuals has been addressed as well. The main implications of the present findings have been discussed.", "title": "The psychological impact of COVID-19 on the mental health in the general population", "pid": "5uhen4qe", "bm25_score": 219.14181518554688}, {"text": "", "title": "[The Impact of the COVID-19 Pandemic on Mental Health].", "pid": "1m5juaqg", "bm25_score": 219.09808349609375}, {"text": "", "title": "The COVID‐19 pandemic and mental health impacts", "pid": "26yvryhw", "bm25_score": 219.0453643798828}, {"text": "As a result of the emergence of coronavirus disease 2019 (COVID-19) outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the Chinese city of Wuhan, a situation of socio-economic crisis and profound psychological distress rapidly occurred worldwide. Various psychological problems and important consequences in terms of mental health including stress, anxiety, depression, frustration, uncertainty during COVID-19 outbreak emerged progressively. This work aimed to comprehensively review the current literature about the impact of COVID-19 infection on the mental health in the general population. The psychological impact of quarantine related to COVID-19 infection has been additionally documented together with the most relevant psychological reactions in the general population related to COVID-19 outbreak. The role of risk and protective factors against the potential to develop psychiatric disorders in vulnerable individuals has been addressed as well. The main implications of the present findings have been discussed.", "title": "The psychological impact of COVID-19 on the mental health in the general population", "pid": "by4js46v", "bm25_score": 219.0265350341797}, {"text": "The outbreak of the Novel Coronavirus (COVID-19) in December 2019 has progressed to the status of a global pandemic, with countries across the seven continents adversely affected and the number of human cases exceeding two million. With no available vaccine, the treatment is primarily symptomatic for those affected and preventative for those at risk. Most countries have taken action to curtail the spread of COVID-19 through measures such as lockdowns, social distancing and voluntary self-isolation. Whilst necessary, such measures and the disease itself, may have an adverse impact on mental health. In view of research from previous pandemic crises, it is known that such situations are likely to increase stress levels and have negative psychiatric effects. The impact is likely to be felt by the general public, sufferers of COVID-19, their families and friends, persons with pre-existing mental health conditions and healthcare workers.", "title": "Impact of the COVID-19 Pandemic on Adult Mental Health", "pid": "880lwnde", "bm25_score": 218.96588134765625}, {"text": "Similarities exist between our past experience of viral diseases and COVID-19 concerning the mental health issues of sufferers of an epidemic, frontline health workers and the social and psychological impact on society. There is significant evidence that a novel illness such as COVID-19 can cause widespread fear, panic, anxiety and xenophobia. Dr Chakraborty explores the latest literature and what it means for mental health.", "title": "The COVID-19 pandemic and its impact on mental health", "pid": "xqmw84dz", "bm25_score": 218.85256958007812}, {"text": "The coronavirus disease 2019 (CoViD-19) caused by the novel Coronavirus strain SARS-CoV-2 is currently a pandemic. On January 30, 2020, the World Health Organization declared that the CoViD-19 outbreak is a public health emergency of international concern. The virus has already had a direct impact on the physical health of million people, and besides, it is supposed to pose a mental health threat of great magnitude globally. This review aims at synthesizing mounting evidence concerning the immediate psychological responses during the initial stage of the CoViD-19 pandemic among the general population, the health-care workers, and clinical populations. Experts point out the need to pay specific attention to other groups at risk of further distress that may need tailored interventions. Providing psychological first aid is an essential care component for populations that have been victims of emergencies and disasters, before, during and after the event. With the aim of dealing better with the urgent psychological problems of people involved in the CoViD-19 pandemic, a new psychological crisis intervention model is needed. Given the recommendation to minimize face-to-face interaction, online mental health services have been widely adopted in China and are urged in other countries.", "title": "Mental health outcomes of the CoViD-19 pandemic.", "pid": "zlg51bpt", "bm25_score": 218.84857177734375}, {"text": "Deep emotional traumas in societies overwhelmed by large-scale human disasters, like, global pandemic diseases, natural disasters, man-made tragedies, war conflicts, social crises, etc., can cause massive stress-related disorders. Motivated by the ongoing global coronavirus pandemic, the article provides an overview of scientific evidence regarding adverse impact of diverse human disasters on mental health in afflicted groups and societies. Following this broader context, psychosocial impact of COVID-19 as a specific global human disaster is presented, with an emphasis on disturbing mental health aspects of the ongoing pandemic. Limited resources of mental health services in a number of countries around the world are illustrated, which will be further stretched by the forthcoming increase in demand for mental health services due to the global COVID-19 pandemic. Mental health challenges are particularly important for the Republic of Croatia in the current situation, due to disturbing stress of the 2020 Zagreb earthquake and the high pre-pandemic prevalence of chronic Homeland-War-related posttraumatic stress disorders. Comprehensive approach based on digital psychiatry is proposed to address the lack of access to psychiatric services, which includes artificial intelligence, telepsychiatry and an array of new technologies, like internet-based computer-aided mental health tools and services. These tools and means should be utilized as an important part of the whole package of measures to mitigate negative mental health effects of the global coronavirus pandemic. Our scientific and engineering experiences in the design and development of digital tools and means in mitigation of stress-related disorders and assessment of stress resilience are presented. Croatian initiative on enhancement of interdisciplinary research of psychiatrists, psychologists and computer scientists on the national and EU level is important in addressing pressing mental health concerns related to the ongoing pandemic and similar human disasters.", "title": "Impact of Human Disasters and COVID-19 Pandemic on Mental Health: Potential of Digital Psychiatry", "pid": "2wam1qls", "bm25_score": 218.83160400390625}, {"text": "The coronavirus disease 2019 (CoViD-19) caused by the novel Coronavirus strain SARS-CoV-2 is currently a pandemic. On January 30, 2020, the World Health Organization declared that the CoViD-19 outbreak is a public health emergency of international concern. The virus has already had a direct impact on the physical health of million people, and besides, it is supposed to pose a mental health threat of great magnitude globally. This review aims at synthesizing mounting evidence concerning the immediate psychological responses during the initial stage of the CoViD-19 pandemic among the general population, the health-care workers, and clinical populations. Experts point out the need to pay specific attention to other groups at risk of further distress that may need tailored interventions. Providing psychological first aid is an essential care component for populations that have been victims of emergencies and disasters, before, during and after the event. With the aim of dealing better with the urgent psychological problems of people involved in the CoViD-19 pandemic, a new psychological crisis intervention model is needed. Given the recommendation to minimize face-to-face interaction, online mental health services have been widely adopted in China and are urged in other countries.", "title": "Mental health outcomes of the CoViD-19 pandemic", "pid": "f7qh7lvo", "bm25_score": 218.82595825195312}, {"text": "Deep emotional traumas in societies overwhelmed by large-scale human disasters, like, global pandemic diseases, natural disasters, man-made tragedies, war conflicts, social crises, etc., can cause massive stress-related disorders. Motivated by the ongoing global coronavirus pandemic, the article provides an overview of scientific evidence regarding adverse impact of diverse human disasters on mental health in afflicted groups and societies. Following this broader context, psychosocial impact of COVID-19 as a specific global human disaster is presented, with an emphasis on disturbing mental health aspects of the ongoing pandemic. Limited resources of mental health services in a number of countries around the world are illustrated, which will be further stretched by the forthcoming increase in demand for mental health services due to the global COVID-19 pandemic. Mental health challenges are particularly important for the Republic of Croatia in the current situation, due to disturbing stress of the 2020 Zagreb earthquake and the high pre-pandemic prevalence of chronic Homeland-War-related posttraumatic stress disorders. Comprehensive approach based on digital psychiatry is proposed to address the lack of access to psychiatric services, which includes artificial intelligence, telepsychiatry and an array of new technologies, like internet-based computer-aided mental health tools and services. These tools and means should be utilized as an important part of the whole package of measures to mitigate negative mental health effects of the global coronavirus pandemic. Our scientific and engineering experiences in the design and development of digital tools and means in mitigation of stress-related disorders and assessment of stress resilience are presented. Croatian initiative on enhancement of interdisciplinary research of psychiatrists, psychologists and computer scientists on the national and EU level is important in addressing pressing mental health concerns related to the ongoing pandemic and similar human disasters.", "title": "Impact of Human Disasters and COVID-19 Pandemic on Mental Health: Potential of Digital Psychiatry.", "pid": "qkjyv0d2", "bm25_score": 218.81686401367188}, {"text": "BACKGROUND The current outbreak of COVID-19 coronavirus infection among humans in Wuhan (China) and its spreading around the globe is heavily impacting on the global health and mental health. Despite all resources employed to counteract the spreading of the virus, additional global strategies are needed to handle the related mental health issues. METHODS Published articles concerning mental health related to the COVID-19 outbreak and other previous global infections have been considered and reviewed. COMMENTS This outbreak is leading to additional health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger and fear globally. Collective concerns influence daily behaviors, economy, prevention strategies and decision-making from policy makers, health organizations and medical centers, which can weaken strategies of COVID-19 control and lead to more morbidity and mental health needs at global level.", "title": "The outbreak of COVID-19 coronavirus and its impact on global mental health.", "pid": "own7llhw", "bm25_score": 218.81243896484375}, {"text": "The 2019 novel coronavirus (COVID-19) has gained global attention after it originated from China at the end of 2019, and later turned into pandemic as it affected about 118,000 in 114 countries by March 11, 2020. By March 13, 2020, it was declared a national emergency in the United States as the number of COVID-19 cases, and the death toll rose exponentially. To contain the spread of the disease, the world scientist community came together. However, the unpreparedness of the nations, even with the advanced medical sciences and resources, has failed to address the mental health aspect amongst the public, as all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of COVID-19 pneumonia. Our efforts in this review are to evaluate and study similar outbreaks from the past to understand its adverse impact on mental health, implement adequate steps to tackle and provide a background to physicians and healthcare workers at the time of such outbreaks to apply psychological first aid.", "title": "Focus on Mental Health During the Coronavirus (COVID-19) Pandemic: Applying Learnings from the Past Outbreaks", "pid": "feqwdynl", "bm25_score": 218.78927612304688}, {"text": "BACKGROUND: The current outbreak of COVID-19 coronavirus infection among humans in Wuhan (China) and its spreading around the globe is heavily impacting on the global health and mental health. Despite all resources employed to counteract the spreading of the virus, additional global strategies are needed to handle the related mental health issues. METHODS: Published articles concerning mental health related to the COVID-19 outbreak and other previous global infections have been considered and reviewed. COMMENTS: This outbreak is leading to additional health problems such as stress, anxiety, depressive symptoms, insomnia, denial, anger and fear globally. Collective concerns influence daily behaviors, economy, prevention strategies and decision-making from policy makers, health organizations and medical centers, which can weaken strategies of COVID-19 control and lead to more morbidity and mental health needs at global level.", "title": "The outbreak of COVID-19 coronavirus and its impact on global mental health", "pid": "jh82mj62", "bm25_score": 218.7765350341797}, {"text": "", "title": "Mental Health and the Covid-19 Pandemic.", "pid": "to8cqodw", "bm25_score": 218.7141571044922}, {"text": "Mental disorders (MD) are commonly comorbid with cardiovascular, metabolic, and some infectious diseases. Since the current SARS-CoV-2 epidemic is affecting the most multimorbid individuals, we might expect that the epidemic will be particularly problematic for people with MD. Understanding the burden of an outbreak on mental health is fundamental to effective action towards containing the spread of the disease, as psychopathology might reduce endurance during the lockdown. This can potentially reduce adhesion to ongoing treatment resulting in avoidable recurrence of a disorder. Additionally, there is the stress caused by the eminent risk of infection or economic uncertainty, especially in low-middle income settings. This is an overview on the expected influence of the COVID-19 on mental health from a research group that has not long ago been involved in the Zika epidemic. It aims to discuss the effects of the pandemic on a Low and Middle-Income country (LMIC), Brazil.", "title": "Impact of COVID-19 on mental health in a Low and Middle-Income Country.", "pid": "oaf3zj2z", "bm25_score": 218.70863342285156}, {"text": "Throughout the world, the public is being informed about the physical effects of SARS-CoV-2 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID-19 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID-19 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID-19 outbreak on the mental health of people.", "title": "The coronavirus (COVID-19) pandemic's impact on mental health", "pid": "5cmcri6u", "bm25_score": 218.63714599609375}, {"text": "This study anonymously screened 13,332 individuals worldwide for psychological symptoms related to Corona virus disease 2019 (COVID-19) pandemic from March 29th to April 14th, 2020. A total of n=12,817 responses were considered valid with responses from 12 featured countries and five WHO regions. Female gender, pre-existing psychiatric condition, and prior exposure to trauma were identified as notable riskfactors, whereas optimism, ability to share concerns with family and friends like usual,positive prediction about COVID-19, and daily exercise predicted fewer psychologicalsymptoms. These results could aid in dynamic optimization of mental health services during and following the COVID-19 pandemic.", "title": "Mental Health Impact of COVID-19: A global study of risk and resilience factors", "pid": "3qgknhmv", "bm25_score": 218.61041259765625}, {"text": "", "title": "Mental Health and the Covid-19 Pandemic", "pid": "68pl1t5i", "bm25_score": 218.5871124267578}, {"text": "The COVID-19 pandemic is a major health crisis affecting several nations, with over 720,000 cases and 33,000 confirmed deaths reported to date. Such widespread outbreaks are associated with adverse mental health consequences. Keeping this in mind, existing literature on the COVID-19 outbreak pertinent to mental health was retrieved via a literature search of the PubMed database. Published articles were classified according to their overall themes and summarized. Preliminary evidence suggests that symptoms of anxiety and depression (16-28%) and self-reported stress (8%) are common psychological reactions to the COVID-19 pandemic, and may be associated with disturbed sleep. A number of individual and structural variables moderate this risk. In planning services for such populations, both the needs of the concerned people and the necessary preventive guidelines must be taken into account. The available literature has emerged from only a few of the affected countries, and may not reflect the experience of persons living in other parts of the world. In conclusion, subsyndromal mental health problems are a common response to the COVID-19 pandemic. There is a need for more representative research from other affected countries, particularly in vulnerable populations.", "title": "COVID-19 and mental health: A review of the existing literature", "pid": "6gtgohci", "bm25_score": 218.57142639160156}, {"text": "Abstract The COVID-19 pandemic is a major health crisis affecting several nations, with over 720,000 cases and 33,000 confirmed deaths reported to date. Such widespread outbreaks are associated with adverse mental health consequences. Keeping this in mind, existing literature on the COVID-19 outbreak pertinent to mental health was retrieved via a literature search of the PubMed database. Published articles were classified according to their overall themes and summarized. Preliminary evidence suggests that symptoms of anxiety and depression (16–28%) and self-reported stress (8%) are common psychological reactions to the COVID-19 pandemic, and may be associated with disturbed sleep. A number of individual and structural variables moderate this risk. In planning services for such populations, both the needs of the concerned people and the necessary preventive guidelines must be taken into account. The available literature has emerged from only a few of the affected countries, and may not reflect the experience of persons living in other parts of the world. In conclusion, subsyndromal mental health problems are a common response to the COVID-19 pandemic. There is a need for more representative research from other affected countries, particularly in vulnerable populations.", "title": "COVID-19 and mental health: A review of the existing literature", "pid": "o72unm3q", "bm25_score": 218.55035400390625}, {"text": "", "title": "Mental health in the COVID-19 pandemic", "pid": "8vdcjeeq", "bm25_score": 218.54989624023438}, {"text": "", "title": "Mental health in the Covid-19 pandemic", "pid": "tpkuc9u5", "bm25_score": 218.54989624023438}, {"text": "INTRODUCTION: Healthcare professionals (HPs) have been confronted by unprecedented traumatic experiences during the COVID-19 pandemic, especially in countries that had not experienced similar epidemic outbreaks in recent years. AIM: To analyze the impact of the COVID-19 pandemic on the mental health of HPs. METHOD: We comprehensively reviewed the studies published in MEDLINE (PubMed), Web of Science and Google Scholar between December 2019 and May 2020. RESULTS: Most studies report a high prevalence of anxiety and depressive symptoms among HPs that can be associated with: a) COVID-19 exposure; b) epidemiological issues; c) material resources; d) human resources; and e) personal factors. The role of certain variables, before, during and after the pandemic, remains unexplored. Longitudinal studies will help elucidate which factors are associated with a higher risk of developing long-lasting negative effects. Qualitative studies may contribute to understanding the influence of individual and social narratives in HPs' distress. CONCLUSION: A deeper analysis on the individual, institutional, political and socio-cultural factors, meanings and values influencing HPs distress and resilience during the COVID-19 pandemic is needed.", "title": "The impact of the COVID-19 pandemic on the mental health of healthcare professionals", "pid": "t9t2qlw4", "bm25_score": 218.5403289794922}, {"text": "The novel SARS-CoV-2 coronavirus pandemic has emerged as a truly formidable threat to humankind’s existence. In the wake of the massively volatile global situation created by COVID-19, it is vital to recognize that the trauma it causes can affect people in different ways, at the individual and collective levels, resulting in mental health challenges for many. Although mental health problems account for about one-third of the world’s disability among adults, these issues tend to be under-addressed and overlooked in society and are closely associated with deadly disease outbreaks. In large scale outbreaks, the mental health problems experienced are not limited to infected persons but also extend to involve frontline health workers and community members alike. While it is crucial to limit the spread of infections during an outbreak, previous experience suggests that mental and behavioural health interventions should be fully included in public health response strategies.", "title": "Mental health and psychosocial well-being during the COVID-19 pandemic: the invisible elephant in the room", "pid": "ypgor52g", "bm25_score": 218.52162170410156}, {"text": "Mental disorders (MD) are commonly comorbid with cardiovascular, metabolic, and some infectious diseases. Since the current SARS-CoV-2 epidemic is affecting the most multimorbid individuals, we might expect that the epidemic will be particularly problematic for people with MD. Understanding the burden of an outbreak on mental health is fundamental to effective action towards containing the spread of the disease, as psychopathology might reduce endurance during the lockdown. This can potentially reduce adhesion to ongoing treatment resulting in avoidable recurrence of a disorder. Additionally, there is the stress caused by the eminent risk of infection or economic uncertainty, especially in low-middle income settings. This is an overview on the expected influence of the COVID-19 on mental health from a research group that has not long ago been involved in the Zika epidemic. It aims to discuss the effects of the pandemic on a Low and Middle-Income country (LMIC), Brazil.", "title": "Impact of COVID-19 on mental health in a Low and Middle-Income Country", "pid": "6wioennp", "bm25_score": 218.50332641601562}, {"text": "INTRODUCTION: Healthcare professionals (HPs) have been confronted by unprecedented traumatic experiences during the novel coronavirus disease (COVID-19) pandemic, especially in countries that had not experienced similar epidemic outbreaks in recent years. AIM: To analyze the impact of the COVID-19 pandemic on the mental health of HPs. METHOD: We comprehensively reviewed the studies published in MEDLINE (PubMed), Web of Science and Google Scholar between December 2019 and May 2020. RESULTS: Most studies report a high prevalence of anxiety and depressive symptoms among HPs that can be associated with: (i) COVID-19 exposure; (ii) epidemiological issues; (iii) material resources; (iv) human resources; and (v) personal factors. The role of certain variables, before, during and after the pandemic, remains unexplored. Longitudinal studies will help elucidate which factors are associated with a higher risk of developing long-lasting negative effects. Qualitative studies may contribute to understanding the influence of individual and social narratives in HPs’ distress. CONCLUSION: A deeper analysis on the individual, institutional, political and socio-cultural factors, meanings and values influencing HPs distress and resilience during the COVID-19 pandemic is needed.", "title": "The impact of the COVID-19 pandemic on the mental health of healthcare professionals", "pid": "5mq7h8ng", "bm25_score": 218.49542236328125}, {"text": "The 2019 novel coronavirus disease emerged in China in late 2019–early 2020 and spread rapidly. China has been implementing emergency psychological crisis interventions to reduce the negative psychosocial impact on public mental health, but challenges exist. Public mental health interventions should be formally integrated into public health preparedness and emergency response plans.", "title": "Public Mental Health Crisis during COVID-19 Pandemic, China", "pid": "302hphhx", "bm25_score": 218.449951171875}, {"text": "The 2019 novel coronavirus disease emerged in China in late 2019-early 2020 and spread rapidly. China has been implementing emergency psychological crisis interventions to reduce the negative psychosocial impact on public mental health, but challenges exist. Public mental health interventions should be formally integrated into public health preparedness and emergency response plans.", "title": "Public Mental Health Crisis during COVID-19 Pandemic, China", "pid": "k8gavf50", "bm25_score": 218.41708374023438}, {"text": "", "title": "The Mental Health Impact of the COVID-19 Pandemic Across Different Cohorts", "pid": "o4zoxrod", "bm25_score": 218.41220092773438}, {"text": "Similar to other nations in the world, Vietnam has swiftly implemented measures to contain the spread of COVID-19, and these have been transforming many aspects of society. The country is showing resilience to fear, stress, and anxiety related to the COVID-19 pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Impacts of the COVID-19 pandemic upon mental health: Perspectives from Vietnam.", "pid": "95i5jd73", "bm25_score": 218.4036407470703}, {"text": "", "title": "Mental health during the coronavirus disease 2019 (Covid-19) pandemic: more is still to be done", "pid": "9sc000kv", "bm25_score": 218.3668212890625}, {"text": "Throughout the world, the public is being informed about the physical effects of SARS‐CoV‐2 infection and steps to take to prevent exposure to the coronavirus and manage symptoms of COVID‐19 if they appear. However, the effects of this pandemic on one's mental health have not been studied at length and are still not known. As all efforts are focused on understanding the epidemiology, clinical features, transmission patterns, and management of the COVID‐19 outbreak, there has been very little concern expressed over the effects on one's mental health and on strategies to prevent stigmatization. People's behavior may greatly affect the pandemic's dynamic by altering the severity, transmission, disease flow, and repercussions. The present situation requires raising awareness in public, which can be helpful to deal with this calamity. This perspective article provides a detailed overview of the effects of the COVID‐19 outbreak on the mental health of people.", "title": "The coronavirus (COVID‐19) pandemic's impact on mental health", "pid": "0n5n7p4b", "bm25_score": 218.34893798828125}, {"text": "", "title": "COVID 19 and its mental health consequences.", "pid": "tfy7jtg6", "bm25_score": 218.31124877929688}, {"text": "", "title": "The consequences of the COVID-19 pandemic on mental health and implications for clinical practice", "pid": "9801cp3x", "bm25_score": 218.28976440429688}, {"text": "", "title": "Impact of social distancing on mental health during the COVID-19 pandemic: An urgent discussion.", "pid": "u0cr5ic0", "bm25_score": 218.28880310058594}, {"text": "", "title": "The next pandemic: COVID-19 mental health pandemic.", "pid": "9n575m2c", "bm25_score": 218.28262329101562}, {"text": "", "title": "The next pandemic: COVID-19 mental health pandemic", "pid": "m709y2os", "bm25_score": 218.2591094970703}, {"text": "COVID-19 along with the mitigation strategies being used to address the virus pose significant threats to our individual and collective mental health. As the crisis evolves and persists, it will be increasingly important for the research community to conduct investigations that address the mental health consequences of COVID-19. The causes of mental health effects in the context of COVID-19 are multifactorial and likely include biological, behavioral, and environmental determinants. We argue that the COVID-19 crisis significantly threatens our basic human need for human connection, which might serve as a crucial environmental factor that could underlie the overall insult to our mental health. Furthermore, \"brain styles,\" which we have previously conceptualized as \"biotypes\" that are informed by a neural taxonomy, might interact with the universal threat to our need for human connection to explain the mental health consequences of COVID-19 from a precision psychiatry perspective. The goal of this commentary is to inspire research on the mental health consequences of COVID-19 from an individualized, brain-based perspective that honors the profound threat that the virus poses to our basic human motivations.", "title": "The Impact of Covid-19 on Mental Health: the Interactive Roles of Brain Biotypes and Human Connection", "pid": "zwevcojh", "bm25_score": 218.22998046875}, {"text": "", "title": "Reflections about the impact of the SARS-COV-2/COVID-19 pandemic on mental health", "pid": "44zwfz09", "bm25_score": 218.22122192382812}, {"text": "Similar to other nations in the world, Vietnam has swiftly implemented measures to contain the spread of COVID-19, and these have been transforming many aspects of society. The country is showing resilience to fear, stress, and anxiety related to the COVID-19 pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Impacts of the COVID-19 pandemic upon mental health: Perspectives from Vietnam", "pid": "3bisbqlo", "bm25_score": 218.2194061279297}, {"text": "Coronovirus disease 2019 (COVID-19) first broke out in Wuhan, Hubei Province, China in 2019, and now it spreads in more than 100 countries around the world. On January 30th, the World Health Organization (WHO) declared COVID-19 a public health emergency (PHEIC) of international concern. It was classified as a pandemic by (WHO) of the World Health Organization on March 11, 2020. With the increase in the number of cases reported by various countries every day, the COVID-19 pandemic has attracted more and more attention around the world. At the same time, this public health emergency has caused a variety of psychological problems, such as panic disorder, anxiety and depression. In addition, the Wuhan Mental Health Center's analysis of 2144 calls from the psychological hotline from February 4 to February 20, 2020 showed that general public accounted for 70%, medical workers accounted for 2.2%, patients with mental disorders accounted for 19.5%, and other personnel accounted for 8.3% (https://mp.weixin.qq.com/s/kmff1vnaLsT2d9xQkK5pwg). Therefore, while controlling the pandemic, the government should also pay attention to the mental health of the general public, medical workers and patients with mental disorders. Community mental health service system, online mental health service, telemedicine and other measures for patients with mental disorders may play a vital role during the pandemic.", "title": "Psychological influence of Coronovirus disease 2019 (COVID-19) pandemic on the general public, medical workers and patients with mental disorders and its countermeasures", "pid": "k1dkbg32", "bm25_score": 218.21470642089844}, {"text": "Abstract COVID-19 along with the mitigation strategies being used to address the virus pose significant threats to our individual and collective mental health. As the crisis evolves and persists, it will be increasingly important for the research community to conduct investigations that address the mental health consequences of COVID-19. The causes of mental health effects in the context of COVID-19 are multifactorial and likely include biological, behavioral, and environmental determinants. We argue that the COVID-19 crisis significantly threatens our basic human need for human connection, which might serve as a crucial environmental factor that could underlie the overall insult to our mental health. Furthermore, “brain styles,” which we have previously conceptualized as “biotypes” that are informed by a neural taxonomy, might interact with the universal threat to our need for human connection to explain the mental health consequences of COVID-19 from a precision psychiatry perspective. The goal of this commentary is to inspire research on the mental health consequences of COVID-19 from an individualized, brain-based perspective that honors the profound threat that the virus poses to our basic human motivations.", "title": "THE IMPACT OF COVID-19 ON MENTAL HEALTH: THE INTERACTIVE ROLES OF BRAIN BIOTYPES AND HUMAN CONNECTION", "pid": "yqasahn3", "bm25_score": 218.17404174804688}, {"text": "", "title": "Impact of social distancing on mental health during the COVID-19 pandemic: An urgent discussion", "pid": "u2id5egd", "bm25_score": 218.16844177246094}, {"text": "In times of crisis, people have historically had to band together to overcome. What happens when they cannot? This article examines the reality of people forced to isolate from one another during one of the most turbulent events of their lives: the COVID-19 pandemic. Connecting the dots of topics including fear, social stigmas, global public response and previous disease outbreaks, this article discusses the negative mental health effects that individuals and communities will likely suffer as the result of social distancing, isolation and physical infection.", "title": "COVID-19: the perfect vector for a mental health epidemic", "pid": "bnswhhpu", "bm25_score": 218.1571044921875}, {"text": "", "title": "Letter To The Editor - The Covid-19 Pandemic And Mental Health As Issues Considered Within The Context Of Adjustment Disorder And Psychosocial Interventions.", "pid": "cin3i3wj", "bm25_score": 218.14352416992188}, {"text": "The COVID-19 pandemic has had a devastating impact on health, economies, and other societal pillars. The Maltese archipelago has also been affected by this viral threat. Due to Malta's characteristics as one of the smallest islands in Europe, the picture, which shall be portrayed in this article, may have some unique features, especially in terms of mental health and societal well-being. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "COVID-19 in Malta: The mental health impact.", "pid": "gnkupwdv", "bm25_score": 218.10552978515625}, {"text": "With the spread of coronavirus disease 2019 (COVID-19), strict isolation strategies to limit virus transmission have been applied worldwide. The lockdown has affected and challenged different medical areas. Doctors, nurses, dentists, and other health care workers are concerned about contagion, not only for themselves, but also for their families and colleagues. Furthermore, the oral mucosa has been accepted as a high-risk route of transmission for COVID-19. In many countries, dentists have been forced to stop working during quarantine until further notification. Isolation and its financial impact have produced physical and psychological pressure, depression, social anxiety, and other mental health concerns. This article aims to provide a comprehensive review of the consequences of past epidemics on mental health and to assess possible aspects that might be associated with mental implications in dentists during the COVID-19 pandemic. Finally, some concrete actions to avoid subsequent potential consequences are recommended.", "title": "The Mental Health Consequences of Coronavirus Disease 2019 Pandemic in Dentistry", "pid": "mitvv9rp", "bm25_score": 218.08506774902344}, {"text": "Background: The 2020 Coronavirus pandemic is a major international public health challenge. Governments have taken public health protection measures to reduce the spread of the virus through non-pharmalogical measures. The impact of the pandemic and the public health response on individual and population mental health is unknown. Methods: We used Google Trends data (1 Jan 2020 - 30 Mar 2020) to investigate the impact of the pandemic and government measures to curb it on people’s concerns, as indexed by changes in search frequency for topics indicating mental distress, social and economic stressors and mental health treatment-seeking. We explored the changes of key topics in Google trends in Italy, Spain, USA, UK, and Worldwide in relation to sentinel events during the pandemic. Results: Globally there appears to be significant concerns over the financial and work-related consequences of the pandemic, with some evidence that levels of fear are rising. Conversely relative searching for topics related to depression and suicide fell after the pandemic was announced, with some evidence that searches for the latter have risen recently. Concerns over education and access to medication appear to be particular social stressors. Whilst searches for face-to-face treatments have declined, those for self-care have risen. Conclusions: Monitoring Google trends shows promise as a means of tracking changing public concerns. In weeks to come it may enable policy makers to assess the impact of their interventions including those aiming to limit negative consequences, such as government funded financial safety nets.", "title": "Mapping population mental health concerns related to COVID-19 and the consequences of physical distancing: a Google trends analysis", "pid": "9659rpgy", "bm25_score": 218.08468627929688}, {"text": "The USA is in the midst of the COVID-19 pandemic. We assess the impact of COVID-19 on psychiatric symptoms in healthcare workers, those with psychiatric comorbidities, and the general population. We highlight the challenges ahead and discuss the increased relevance of telepsychiatry. We analyzed all available literature available as of March 25, 2020, on PubMed, Ovid Medline, and PsychInfo. We utilized the MeSH term “covid AND (psychiatry OR mental health)” and included all articles. Duplicates were removed resulting in 32 articles, of which 19 are cited. Four additional references are included to examine suicide data. During the review process, an additional 7 articles were identified which are also included. Frontline healthcare workers are currently experiencing increased psychiatric symptoms and this is more severe in females and nurses. Non-frontline healthcare workers, as well as the general population, are experiencing vicarious traumatization. People with psychiatric comorbidities, and the general population, face increased psychiatric symptom burden. Migrant workers, the elderly, children, and the homeless may be disproportionately impacted. Suicide rates may be impacted. The COVID-19 pandemic has resulted in a severe disruption to the delivery of mental healthcare. Psychiatric facilities are facing unprecedented disruptions in care provision as they struggle to manage an infected population with comorbid psychiatric symptoms. Telepsychiatry is a flawed but reasonable solution to increase the availability of mental healthcare during COVID-19.", "title": "Current and Future Challenges in the Delivery of Mental Healthcare during COVID-19", "pid": "y2vgo55k", "bm25_score": 218.08396911621094}, {"text": "BACKGROUND: The coronavirus disease (COVID-19) pandemic has produced substantial health challenges from the perspective of both its direct health complications and the disruption to delivery of standard care for individuals with a range of acute and chronic health issues. In parallel, the widespread application of social isolation initiatives in most countries raises the potential for significant mental health consequences and psychosocial impacts. This has major implications for cardiovascular health care professionals and the management of their patients. CHALLENGES: The COVID-19 pandemic and associated physical isolation practices are likely to result in a range of mental health and psychosocial challenges. In addition to an increasing incidence of anxiety, depression, suicidal ideation and post-traumatic stress, the pandemic may also witness an increase in substance abuse, domestic violence and relationship discord. The consequences of these complications will be further magnified, when considering their potential effect on cardiovascular disease and its management. PURPOSE: This commentary aims to summarise some of the potential mental health and psychosocial challenges that may arise in the setting of the COVID-19 pandemic.", "title": "Mental Health and Psychosocial Challenges in the COVID-19 Pandemic: Food for Thought for Cardiovascular Health Care Professionals", "pid": "d7vo3l8e", "bm25_score": 218.07460021972656}, {"text": "The novel coronavirus (COVID-19) pandemic has created an unprecedented global health challenge. There is risk that the outbreak will create a \"second pandemic\" of mental health crises in health systems and communities. Thus, a comprehensive public health response to the pandemic must include (a) attention to the psychological aspects of hospitalization for patients, families, and staff affected by COVID-19; (b) planning for emergency and acute psychiatric patient care if hospitals become overwhelmed with COVID-19 patients; and (c) innovations for providing mental health care in communities while social distancing is required and health system resources are strained. Nurses and nurse leaders must anticipate these mental health challenges, assist with preparedness in health systems and communities, and advocate for a coordinated response to promote mental wellness and resilience.", "title": "A Second Pandemic: Mental Health Spillover From the Novel Coronavirus (COVID-19).", "pid": "5e8q6ybz", "bm25_score": 218.07301330566406}, {"text": "In this commentary, I argue that the mental health impact of COVID-19 will show substantial variation across individuals, contexts, and time. Further, one key contributor to this variation will be the proximal and long-term impact of COVID-19 on the social environment. In addition to the mental health costs of the pandemic, it is likely that a subset of people will experience improved social and mental health functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Heterogeneous mental health consequences of COVID-19: Costs and benefits.", "pid": "u02vjcjs", "bm25_score": 218.0570831298828}, {"text": "Background The coronavirus disease (COVID-19) pandemic has produced substantial health challenges from the perspective of both its direct health complications and the disruption to delivery of standard care for individuals with a range of acute and chronic health issues. In parallel, the widespread application of social isolation initiatives in most countries raises the potential for significant mental health consequences and psychosocial impacts. This has major implications for cardiovascular health care professionals and the management of their patients. Challenges The COVID-19 pandemic and associated physical isolation practices are likely to result in a range of mental health and psychosocial challenges. In addition to an increasing incidence of anxiety, depression, suicidal ideation and post-traumatic stress, the pandemic may also witness an increase in substance abuse, domestic violence and relationship discord. The consequences of these complications will be further magnified, when considering their potential effect on cardiovascular disease and its management. Purpose This statement aims to summarise some of the potential mental health and psychosocial challenges that may arise in the setting of the COVID-19 pandemic.", "title": "Mental Health and Psychosocial Challenges in the COVID-19 Pandemic: Food for Thought for Cardiovascular Health Care Professionals", "pid": "pf1f9fhc", "bm25_score": 218.05332946777344}, {"text": "The current health crisis scenario has exposed the negative impact on mental health. This commentary highlights the main challenges and barriers that the Deaf community faces in access to health care resources and psychological support during the COVID-19 pandemic. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Deafness and mental health: Clinical challenges during the COVID-19 pandemic.", "pid": "4e9kn96f", "bm25_score": 218.05140686035156}, {"text": "Youth Mental Health is a rapidly developing field with a focus on prevention, early identification, treatment innovation and service development. In this perspective piece, we discuss the effects of COVID-19 on young people's mental health. The psychosocial effects of COVID-19 disproportionately affect young people. Both immediate and longer-term factors through which young people are affected include social isolation, changes to the delivery of therapeutic services and almost complete loss of all structured occupations (school, work and training) within this population group. Longer-term mechanisms include the effects of the predicted recession on young people's mental health. Opportunities within this crisis exist for service providers to scale up telehealth and digital services that may benefit service provision for young people's mental health in the future.", "title": "Youth Mental Health in the time of COVID-19.", "pid": "fa9g65kw", "bm25_score": 218.04595947265625}, {"text": "The novel coronavirus (SARS-CoV-2) that emerged in late 2019 in Wuhan, China, commonly presents as a severe acute respiratory disease referred to as coronavirus disease-2019 (COVID-19). The rapid spread of the disease created challenges for healthcare systems and forced healthcare workers to grapple with clinical and nonclinical stressors, including shortages of personal protective equipment, mortality and morbidity associated with COVID-19, fear of bringing the virus home to family members, and the reality of losing colleagues to the disease. Evidence from previous outbreaks, along with early evidence from the COVID-19 pandemic, suggests that these events have significant short- and long-term effects on the mental health of healthcare workers. All healthcare stakeholders should create short- and long-term plans to support the mental health of workers during and after the COVID-19 pandemic.", "title": "The effect of the COVID-19 pandemic on healthcare workers' mental health.", "pid": "436hvwtr", "bm25_score": 218.0347900390625}, {"text": "In light of the unprecedented public health crisis of the COVID-19 pandemic, it is highly important to acknowledge the psychological impact of this mounting threat on healthcare professionals. Previous experience from smaller scale epidemics and emerging literature around COVID-19 show that the unparalleled amount of stress that healthcare workers are dealing with, is associated with increased psychological morbidities. We have depicted the psychological burden that the COVID-19 pandemic has posed on healthcare professionals in Greece and have reviewed the literature around the effect of previous epidemics on frontline healthcare staff. Moreover, we discuss potential triggers and the need for measures to minimise the psychological pressure on those at the frontline against this biothreat.", "title": "COVID-19 pandemic and its impact on mental health of healthcare professionals", "pid": "nr9ymy84", "bm25_score": 218.03369140625}, {"text": "The response to the global COVID-19 pandemic has important ramifications for mental health systems and the patients they serve. This article describes significant changes in mental health policy prompted by the COVID-19 crisis across five major areas: legislation, regulation, financing, accountability, and workforce development. Special considerations for mental health policy are discussed, including social determinants of health, innovative technologies, and research and evaluation. These extraordinary advances provide an unprecedented opportunity to evaluate the effects of mental health policies that may be adopted in the post-COVID-19 era in the United States.", "title": "Mental Health Policy in the Era of COVID-19.", "pid": "zg8l6std", "bm25_score": 218.03237915039062}, {"text": "The novel coronavirus (COVID-19) pandemic has created an unprecedented global health challenge. There is risk that the outbreak will create a \"second pandemic\" of mental health crises in health systems and communities. Thus, a comprehensive public health response to the pandemic must include (a) attention to the psychological aspects of hospitalization for patients, families, and staff affected by COVID-19; (b) planning for emergency and acute psychiatric patient care if hospitals become overwhelmed with COVID-19 patients; and (c) innovations for providing mental health care in communities while social distancing is required and health system resources are strained. Nurses and nurse leaders must anticipate these mental health challenges, assist with preparedness in health systems and communities, and advocate for a coordinated response to promote mental wellness and resilience.", "title": "A Second Pandemic: Mental Health Spillover From the Novel Coronavirus (COVID-19)", "pid": "4rngmow8", "bm25_score": 218.02476501464844}, {"text": "OBJECTIVE This study examines the impact of the COVID-19 pandemic and the lock-down on patients with mental illness. METHODS Patients in inpatient or outpatient psychiatric treatment received a questionnaire, examining psychological distress and psychiatric care during the COVID-19 pandemic. RESULTS More than half of the patients indicated that the state of emergency had a negative impact on their mental illness. Severely ill patients were more affected. CONCLUSION Patients with mental illness are a particularly vulnerable group in the current crisis. Psychiatric and psychotherapeutic care needs to be adapted accordingly; the specific burden and distress needs to be examined actively in patients from all diagnostic groups.", "title": "[COVID-19 Concerns and Worries in Patients with Mental Illness].", "pid": "96wi5b3a", "bm25_score": 218.02328491210938}, {"text": "The COVID-19 pandemic with its subsequent mental health consequences has challenged the word view of most people. A genome typically of 26,000-32,000 bases long RNA has shut down the wheel of man made progress. The social isolation after the lock-down has not only led to economic difficulties but also adverse psychological reactions. The most common reaction is stress, anxiety and depression when faced with life-threatening circumstances. People have to deal with the imminent issue of death which is anxiety provoking in itself. This calls for dealing with the immediate mental health consequences with the aide of technological advancements as discussed in this write-up. A new inter-personal ethics need to emerge which is scientifically correct and in-line with age old values.", "title": "Mental health in the aftermath of COVID-19: A new normal.", "pid": "argwu7p2", "bm25_score": 218.0010223388672}, {"text": "The increase in organisms transference and infectious pandemics across the globe have been accelerated by an increase in travel, international exchange and global changes in earth's climate. COVID-19, a virus caused by the novel coronavirus that was initially identified on December 2019, in Wuhan city of China is currently affecting 146 territories, states and countries raising distress, panic and increasing anxiety in individuals exposed to the (actual or supposed) peril of the virus across the globe. Fundamentally, these concerns ascend with all infections, including those of flu and other agents, and the same worldwide safeguards are compulsory and suggested for protection and the prevention of further diffusion. However, media has underlined COVID-19 as rather an exclusive threat, which has added to panic and stress in masses which can lead to several mental health issues like anxiety, obsessive compulsive disorder and post-traumatic stress disorder which should be contained immediately in its initial phases.", "title": "COVID-19 Pandemic and Impending Global Mental Health Implications.", "pid": "gq96t5vy", "bm25_score": 217.97244262695312}, {"text": "", "title": "COVID 19 and its mental health consequences", "pid": "7jn40hi7", "bm25_score": 217.96600341796875}, {"text": "The novel coronavirus (SARS-CoV-2) that emerged in late 2019 in Wuhan, China, commonly presents as a severe acute respiratory disease referred to as coronavirus disease-2019 (COVID-19). The rapid spread of the disease created challenges for healthcare systems and forced healthcare workers to grapple with clinical and nonclinical stressors, including shortages of personal protective equipment, mortality and morbidity associated with COVID-19, fear of bringing the virus home to family members, and the reality of losing colleagues to the disease. Evidence from previous outbreaks, along with early evidence from the COVID-19 pandemic, suggests that these events have significant short- and long-term effects on the mental health of healthcare workers. All healthcare stakeholders should create short- and long-term plans to support the mental health of workers during and after the COVID-19 pandemic.", "title": "The effect of the COVID-19 pandemic on healthcare workers' mental health", "pid": "wn6h1fha", "bm25_score": 217.9596405029297}, {"text": "The current Covid-19 pandemic is not just a medical and social tragedy, but within the threat of the outbreak looms the potential for a significant and persistent negative mental health impact, based on previous experience with other pandemics such as SARS in 2003 and the earlier H1N1 outbreak of 1918. This piece will highlight the links between depression and viral illnesses and explore important overlaps with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, potentially implicating inflammatory mechanisms in those exposed to a range of viral agents. While containment of psychological distress currently focuses on social anxiety and quarantine measures, a second wave of psychological morbidity due to viral illness may be imminent.", "title": "Fallout from the Covid-19 pandemic - should we prepare for a tsunami of post viral depression?", "pid": "drrrstgr", "bm25_score": 217.9585418701172}, {"text": "", "title": "Covid-19 and the pandemic of fear: reflections on mental health", "pid": "z7v4xf9e", "bm25_score": 217.95013427734375}, {"text": "The COVID-19 pandemic has had a devastating impact on health, economies, and other societal pillars. The Maltese archipelago has also been affected by this viral threat. Due to Malta's characteristics as one of the smallest islands in Europe, the picture, which shall be portrayed in this article, may have some unique features, especially in terms of mental health and societal well-being. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "COVID-19 in Malta: The mental health impact", "pid": "2crp8fnq", "bm25_score": 217.947509765625}, {"text": "Youth Mental Health is a rapidly developing field with a focus on prevention, early identification, treatment innovation and service development. In this perspective piece, we discuss the effects of COVID-19 on young people's mental health. The psychosocial effects of COVID-19 disproportionately affect young people. Both immediate and longer-term factors through which young people are affected include social isolation, changes to the delivery of therapeutic services and almost complete loss of all structured occupations (school, work and training) within this population group. Longer-term mechanisms include the effects of the predicted recession on young people's mental health. Opportunities within this crisis exist for service providers to scale up telehealth and digital services that may benefit service provision for young people's mental health in the future.", "title": "Youth Mental Health in the time of COVID-19", "pid": "burw3quf", "bm25_score": 217.9438018798828}, {"text": "", "title": "Impact of COVID-19 pandemic on pre-existing mental health problems", "pid": "43rpqe53", "bm25_score": 217.92674255371094}, {"text": "The COVID-19 pandemic with its subsequent mental health consequences has challenged the word view of most people. A genome typically of 26,000-32,000 bases long RNA has shut down the wheel of man made progress. The social isolation after the lock-down has not only led to economic difficulties but also adverse psychological reactions. The most common reaction is stress, anxiety and depression when faced with life-threatening circumstances. People have to deal with the imminent issue of death which is anxiety provoking in itself. This calls for dealing with the immediate mental health consequences with the aide of technological advancements as discussed in this write-up. A new inter-personal ethics need to emerge which is scientifically correct and in-line with age old values.", "title": "Mental health in the aftermath of COVID-19: A new normal", "pid": "75rztshj", "bm25_score": 217.9124755859375}, {"text": "The COVID-19 pandemic has placed front-line health care professionals—who were already at higher risk for negative effects of chronic stress before the pandemic—at even greater risk for depression and anxiety. This article reminds us of the importance of mutual support and caring for our own mental health, including seeking help from our mental health colleagues when needed.", "title": "Mental Health Treatment for Front-Line Clinicians During and After the Coronavirus Disease 2019 (COVID-19) Pandemic: A Plea to the Medical Community", "pid": "vzmlkk79", "bm25_score": 217.90640258789062}, {"text": "South Africa’s national lockdown introduced serious threats to public mental health in a society where one in three individuals develop a psychiatric disorder during their life. We aimed to evaluate the mental health impacts of the COVID-19 pandemic using a mixed methods design. This longitudinal study drew from a preexisting sample of 957 adults living in Soweto, a major township near Johannesburg. Psychological assessments were administered across two waves: between August 2019-March 2020 and during the first six weeks of the lockdown (late March-early May 2020). Interviews on COVID-19 experiences were administered in the second wave. Multiple regression models examined relationships between perceived COVID-19 risk and depression. Full data on perceived COVID-19 risk, depression, and covariates were available in 221 adults. 14.5% of adults were at risk for depression. Higher perceived COVID-19 risk predicted greater depressive symptoms (p < 0.001) particularly among adults with histories of childhood trauma, though this effect was marginally significant (p = 0.062). Adults were two times more likely to experience significant depressive symptoms for every one unit increase in perceived COVID-19 risk (p = 0.016; 95% CI [1.14, 3.49]). Qualitative data identified potent experiences of anxiety, financial insecurity, fear of infection, and rumination. Higher perceived risk of COVID-19 infection is associated with greater depressive symptoms among adults with histories of childhood trauma during the first six weeks of quarantine. High rates of severe mental illness and low availability of mental healthcare amidst COVID-19 emphasize the need for immediate and accessible psychological resources in South Africa.", "title": "Evaluating the Mental Health Impacts of the COVID-19 Pandemic in Urban South Africa: Perceived Risk of COVID-19 Infection and Childhood Trauma Predict Adult Depressive Symptoms", "pid": "hug3pz1m", "bm25_score": 217.89857482910156}, {"text": "Abstract The coronavirus disease (COVID-19) pandemic has created an unprecedented public health emergency Extraordinary measures have been implemented to reduce the spread of the virus, including mass quarantines and social distancing However, these preventive measures come at a price Economic stress, social isolation, decreased access to community activities, etc , is the new reality for a large part of the global community, and may have detrimental effects on mental health", "title": "COVID-19-related self-harm and suicidality among individuals with mental disorders", "pid": "itefsyv4", "bm25_score": 217.897705078125}, {"text": "The increase in organisms transference and infectious pandemics across the globe have been accelerated by an increase in travel, international exchange and global changes in earth's climate. COVID-19, a virus caused by the novel coronavirus that was initially identified on December 2019, in Wuhan city of China is currently affecting 146 territories, states and countries raising distress, panic and increasing anxiety in individuals exposed to the (actual or supposed) peril of the virus across the globe. Fundamentally, these concerns ascend with all infections, including those of flu and other agents, and the same worldwide safeguards are compulsory and suggested for protection and the prevention of further diffusion. However, media has underlined COVID-19 as rather an exclusive threat, which has added to panic and stress in masses which can lead to several mental health issues like anxiety, obsessive compulsive disorder and post-traumatic stress disorder which should be contained immediately in its initial phases.", "title": "COVID-19 Pandemic and Impending Global Mental Health Implications", "pid": "2bw8nbyb", "bm25_score": 217.892822265625}, {"text": "BACKGROUND: During the COVID-19 pandemic general medical complications have received the most attention, whereas only few studies address the potential direct effect on mental health of SARS-CoV-2 and the neurotropic potential. Furthermore, the indirect effects of the pandemic on general mental health are of increasing concern, particularly since the SARS-CoV-1 epidemic (2002-2003) was associated with psychiatric complications. METHODS: We systematically searched the database Pubmed including studies measuring psychiatric symptoms or morbidities associated with COVID-19 among infected patients and among none infected groups the latter divided in psychiatric patients, health care workers and non-health care workers. RESULTS: A total of 43 studies were included. Out of these, only two studies evaluated patients with confirmed COVID-19 infection, whereas 41 evaluated the indirect effect of the pandemic (2 on patients with preexisting psychiatric disorders, 20 on medical health care workers, and 19 on the general public). 18 of the studies were case-control studies/compared to norm, while 25 of the studies had no control groups. The two studies investigating COVID-19 patients found a high level of post-traumatic stress symptoms (PTSS) (96.2%) and significantly higher level of depressive symptoms (p = 0.016). Patients with preexisting psychiatric disorders reported worsening of psychiatric symptoms. Studies investigating health care workers found increased depression/depressive symptoms, anxiety, psychological distress and poor sleep quality. Studies of the general public revealed lower psychological well-being and higher scores of anxiety and depression compared to before COVID-19, while no difference when comparing these symptoms in the initial phase of the outbreak to four weeks later. A variety of factors were associated with higher risk of psychiatric symptoms and/or low psychological well-being including female gender, poor-self-related health and relatives with COVID-19. CONCLUSION: Research evaluating the direct neuropsychiatric consequences and the indirect effects on mental health is highly needed to improve treatment, mental health care planning and for preventive measures during potential subsequent pandemics.", "title": "COVID-19 pandemic and mental health consequences: Systematic review of the current evidence", "pid": "0jfwzfge", "bm25_score": 217.88882446289062}, {"text": "BACKGROUND: During the COVID-19 pandemic general medical complications have received the most attention, whereas only few studies address the potential direct effect on mental health of SARS-CoV-2 and the neurotropic potential. Furthermore, the indirect effects of the pandemic on general mental health are of increasing concern, particularly since the SARS-CoV-1 epidemic (2002-2003) was associated with psychiatric complications. METHODS: We systematically searched the database Pubmed including studies measuring psychiatric symptoms or morbidities associated with COVID-19 among infected patients and among none infected groups the latter divided in psychiatric patients, health care workers and non-health care workers. RESULTS: A total of 43 studies were included. Out of these, only two studies evaluated patients with confirmed COVID-19 infection, whereas 41 evaluated the indirect effect of the pandemic (2 on patients with preexisting psychiatric disorders, 20 on medical health care workers, and 19 on the general public). 18 of the studies were case-control studies/compared to norm, while 25 of the studies had no control groups. The two studies investigating COVID-19 patients found a high level of post-traumatic stress symptoms (PTSS) (96.2%) and significantly higher level of depressive symptoms (p=0.016). Patients with preexisting psychiatric disorders reported worsening of psychiatric symptoms. Studies investigating health care workers found increased depression/depressive symptoms, anxiety, psychological distress and poor sleep quality. Studies of the general public revealed lower psychological well-being and higher scores of anxiety and depression compared to before COVID-19, while no difference when comparing these symptoms in the initial phase of the outbreak to four weeks later. A variety of factors were associated with higher risk of psychiatric symptoms and/or low psychological well-being including female gender, poor-self-related health and relatives with COVID-19. CONCLUSION: Research evaluating the direct neuropsychiatric consequences and the indirect effects on mental health is highly needed to improve treatment, mental health care planning and for preventive measures during potential subsequent pandemics.", "title": "COVID-19 pandemic and mental health consequences: systematic review of the current evidence", "pid": "019rcbpg", "bm25_score": 217.88882446289062}, {"text": "The ongoing pandemic of COVID-19 is a global challenge which resulted in significant morbidity and mortality worldwide. It has also adversely affected the economy and social integrity. There is rising concern about the mental health challenges of the general population, COVID-19-infected patients, close contacts, elderly, children and health professionals. This chapter focusses on various mental health challenges during the COVID-19 pandemic.", "title": "Coping with Mental Health Challenges During COVID-19", "pid": "50palac7", "bm25_score": 217.88558959960938}, {"text": "In this commentary, I argue that the mental health impact of COVID-19 will show substantial variation across individuals, contexts, and time. Further, one key contributor to this variation will be the proximal and long-term impact of COVID-19 on the social environment. In addition to the mental health costs of the pandemic, it is likely that a subset of people will experience improved social and mental health functioning. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Heterogeneous mental health consequences of COVID-19: Costs and benefits", "pid": "ingq7m2m", "bm25_score": 217.88485717773438}, {"text": "As of May 20, 2020, the COVID-19 death toll in Japan was 771. The 2020 Tokyo Olympics/Paralympics had to be postponed to 2021 because of the pandemic. Not only the infected patients but also health care workers have been affected from adverse societal dynamics because of COVID-19, such as discrimination and stigmatization. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Mental health impact of the COVID-19 pandemic in Japan", "pid": "6o3u1ak0", "bm25_score": 217.8814697265625}, {"text": "BACKGROUND: A novel form of Coronavirus (2019-nCoV) in Wuhan has created a confused and rapidly evolving situation. In this situational framework, patients and front-line healthcare workers are vulnerable. METHOD: Studies were identified using large-circulation international journals found in two electronic databases: Scopus and Embase. RESULTS: Populations of patients that may require tailored interventions are older adults and international migrant workers. Older adults with psychiatric conditions may be experiencing further distress. The COVID-19 epidemic has underscored potential gaps in mental health services during emergencies. CONCLUSIONS: Most health professionals working in isolation units and hospitals do not receive any training for providing mental health care. Fear seems more certainly a consequence of mass quarantine.", "title": "The emotional impact of Coronavirus 2019-nCoV (new Coronavirus disease)", "pid": "ig0f1zo7", "bm25_score": 217.8790283203125}, {"text": "Background: Previous pandemics have resulted in significant consequences for mental health. Here we report the mental health sequela of the COVID-19 pandemic on the UK population and examine modifiable and non-modifiable explanatory factors associated with mental health outcomes. We focus on the short-term consequences for mental health, as reported during the first four-six weeks of social distancing measures being introduced. Methods: A community cohort study was conducted with adults aged [≥]18 years recruited through a mainstream and social media campaign between 3/4/20-30/4/20. Consenting participants completed an online survey measuring depression, anxiety and stress and explanatory variables hypothesised to be related to these mental health outcomes. Outcomes: N=3097 eligible individuals participated. The cohort was predominantly female (85%); mean age forty-four years; 10% from minority ethnic groups; 50% described themselves as key-workers and 20% identified as having clinical risk factors putting them at increased risk of COVID-19. Mean scores for depression, stress and anxiety significantly exceeded population norms. Analysis of non-modifiable factors indicated that being younger and female were associated with all outcomes, with the final multivariable models accounting for 7-13% of variance. When adding modifiable factors, significant independent effects emerged for positive mood, perceived loneliness and worry about getting COVID-19 for all outcomes, with the final multivariable models accounting for 54-57% of variance. Interpretation: Increased psychological morbidity was evident in this UK cohort, with younger people and women at particular risk. Interventions targeting perceptions of: loneliness, risk of COVID-19, worry about COVID-19, and positive mood may be effective.", "title": "Mental health in the UK during the COVID-19 pandemic: early observations", "pid": "pgrhe3jj", "bm25_score": 217.87448120117188}, {"text": "The pandemic caused by Covid-19 has been an unprecedented social and health emergency worldwide. This is the first study in the scientific literature reporting the psychological impact of the Covid-19 outbreak in a sample of the Spanish population. A cross-sectional study was conducted through an online survey of 3480 people. The presence of depression, anxiety and post-traumatic stress disorder (PTSD) was evaluated with screening tests from 14 March. Sociodemographic and Covid-19-related data was collected. Additionally, spiritual well-being, loneliness, social support, discrimination and sense of belonging were assessed. Descriptive analyses were carried out and linear regression models compiled. The 18.7% of the sample revealed depressive, 21.6% anxiety and 15.8% PTSD symptoms. Being in the older age group, having economic stability and the belief that adequate information had been provided about the pandemic were negatively related to depression, anxiety and PTSD. However, female gender, previous diagnoses of mental health problems or neurological disorders, having symptoms associated with the virus, or those with a close relative infected were associated with greater symptomatology in all three variables. Predictive models revealed that the greatest protector for symptomatology was spiritual well-being, while loneliness was the strongest predictor of depression, anxiety and PTSD. The impact on our mental health caused by the pandemic and the measures adopted during the first weeks to deal with it are evident. In addition, it is possible to identify the need of greater psychological support in general and in certain particularly vulnerable groups.", "title": "Mental health consequences during the initial stage of the 2020 Coronavirus pandemic (COVID-19) in Spain", "pid": "n2pw9uts", "bm25_score": 217.863525390625}, {"text": "The pandemic caused by Covid-19 has been an unprecedented social and health emergency worldwide. This is the first study in the scientific literature reporting the psychological impact of the Covid-19 outbreak in a sample of the Spanish population. A cross-sectional study was conducted through an online survey of 3480 people. The presence of depression, anxiety and post-traumatic stress disorder (PTSD) was evaluated with screening tests from 14 March. Sociodemographic and Covid-19-related data was collected. Additionally, spiritual well-being, loneliness, social support, discrimination and sense of belonging were assessed. Descriptive analyses were carried out and linear regression models compiled. The 18.7% of the sample revealed depressive, 21.6% anxiety and 15.8% PTSD symptoms. Being in the older age group, having economic stability and the belief that adequate information had been provided about the pandemic were negatively related to depression, anxiety and PTSD. However, female gender, previous diagnoses of mental health problems or neurological disorders, having symptoms associated with the virus, or those with a close relative infected were associated with greater symptomatology in all three variables. Predictive models revealed that the greatest protector for symptomatology was spiritual well-being, while loneliness was the strongest predictor of depression, anxiety and PTSD. The impact on our mental health caused by the pandemic and the measures adopted during the first weeks to deal with it are evident. In addition, it is possible to identify the need of greater psychological support in general and in certain particularly vulnerable groups.", "title": "Mental Health Consequences during the Initial Stage of the 2020 Coronavirus Pandemic (COVID-19) in Spain", "pid": "h0ex5siq", "bm25_score": 217.863525390625}, {"text": "", "title": "The COVID-19 pandemic and perinatal mental health.", "pid": "m4euatin", "bm25_score": 217.86253356933594}, {"text": "", "title": "Mental health and the SARS-CoV-2 pandemic", "pid": "lo0mcmx3", "bm25_score": 217.85467529296875}, {"text": "", "title": "The immediate mental health impacts of the COVID-19 pandemic among people with or without quarantine managements", "pid": "r3zk25eq", "bm25_score": 217.8479766845703}, {"text": "The outbreak of novel Coronavirus (COVID-19), later named as a pandemic affecting nearly 210 countries and territories has led to negative emotions of fear and agony in the general population and healthcare staff professionals. The healthcare regulators and the governments have imposed emergencies and lockdowns in their countries which has led to an adverse effect on the mental health of people ultimately leading to a rise in anxiety, depression, and associated mental illness. The fear and uncertainty increased by the COVID-19 crisis are putting extreme pressure on our finite resources. This report aims to synthesis the dilemma of mental illness as a result of pandemic and initiates suggestions to help the general public, healthcare professionals, and workers mitigate the negative emotions to improve the mental wellbeing in this detached period of isolation.", "title": "Fear and agony of the pandemic leading to stress and mental illness: An emerging crisis in the novel coronavirus (COVID-19) outbreak.", "pid": "20bgev65", "bm25_score": 217.84439086914062}, {"text": "Objective: To assess mental health in the US adult population in the Covid-19 pandemic and explore the roles of economic concerns, health worries and social distancing in shaping mental health outcomes. Methods: We analyze online survey data from the \"Understanding America Study\" (UAS) that is representative of the US adult population and covers the period of March 10-31st 2020 (sample size: 6436). Results: About 29% (CI:27.4-.30.4%) of the US adult population reported some depression/anxiety symptoms over the study period, with symptoms deteriorating over the month of March. Worsening mental health was most strongly associated with concerns about the economic consequences of the pandemic, while concerns about the potential impact of the virus on respondents' own health and the practice of social distancing also predicted the presence of depression and anxiety symptoms, albeit less strongly. Conclusions: Our findings point towards a major mental health crisis unfolding simultaneously with the pandemic in the US. They also highlight the importance of economic countermeasures and social policy for mitigating the impact of Covid-19 on adult mental health in the US over and above an effective public health response.", "title": "Predictors of Mental Health during the early Covid-19 Pandemic in the US: role of economic concerns, health worries and social distancing", "pid": "omv50b7j", "bm25_score": 217.83843994140625}, {"text": "The 2019 novel coronavirus (2019-nCoV) pneumonia has been declared a pandemic, citing more than 118,000 cases of the coronavirus illness in more than 110 countries and territories around the world. Public health emergencies have been demonstrated to have an impact on the behavioral health of the affected population as they may experience fear, anxiety, anger and post-traumatic stress disorder as consequences of their experiences. These effects may persist among affected individuals long after the outbreak has been controlled. To date, data on the behavioral distress and psychiatric morbidity of those suspected or diagnosed with the 2019-nCoV and their treating health professionals are lacking. Although the Centers for Disease Control and Prevention (CDC) has outlined some behavioral health guide for affected individuals, how best to respond to psychological challenges during the crisis is not known. There is an urgent need to provide robust and timely psychosocial support in the face of such an outbreak.", "title": "The Unaddressed Behavioral Health Aspect During the Coronavirus Pandemic", "pid": "q13qndic", "bm25_score": 217.8374786376953}, {"text": "", "title": "Covid-19: Mental health consequences of pandemic need urgent research, paper advises.", "pid": "f4ommapt", "bm25_score": 217.83462524414062}, {"text": "The coronavirus pandemic has caused enormous concern among many people. Every morning, we are met with an increasing deluge of dire news about the most recent number of people to contract COVID-19 and to die from it, decreases in the stock market, and countries implementing broad travel restrictions and stay-at-home orders.1,2 The current state of affairs is having a negative effect on the mental well-being of our country's residents. It also highlights the policy gaps in our current system that inhibit the vital conditions for well-being and resiliency.3 Although the primary focus has rightfully been on stopping the spread of COVID-19, we should also quickly prepare to address the mental toll the pandemic is taking on individuals and communities across the country. (Am J Public Health. Published online ahead of print May 21, 2020: e1-e2. doi:10.2105/AJPH.2020.305699).", "title": "COVID-19 Exposes the Cracks in Our Already Fragile Mental Health System.", "pid": "xolflz8g", "bm25_score": 217.83218383789062}, {"text": "• Relapse rates of all pre-existing mental health problems are commonly seen to be increased during COVID 19. • Quarantine is a stressful situation which increases psychiatric morbidity through many different pathways. • Policy changes which can promote tele-psychiatric services will play significant role in during the pandemic.", "title": "Impact of COVID-19 pandemic on pre-existing mental health problems", "pid": "4pwlusqh", "bm25_score": 217.829345703125}, {"text": "OBJECTIVE: As the coronavirus (COVID-19) pandemic sweeps across the world, it is causing widespread concern, fear and stress, all of which are natural and normal reactions to the changing and uncertain situation that everyone finds themselves in. METHODS: In this general review, we examined the literature about the psychological effects of COVID-19 pandemia. In total 65 papers were reviewed using the Medline computer database. Only publications in English were selected. RESULTS: Children are likely to be experiencing worry, anxiety and fear and older people are also those with underlying health conditions, having been identified as more vulnerable to COVID-19, can be extremely frightening and very fear-inducing. China and several other countries took strict isolation measures. Medical staff and affiliated healthcare workers (staff) are under both physical and psychological pressure. CONCLUSION: The COVID-19 pandemic is exceptional. Its effect will likely be imprinted on each individual involved. Extensive stressors will emerge or become worsened. Many medical staff workers will be harmfully psychologically affected.", "title": "Mental Health Effects of COVID-19 Pandemia: A Review of Clinical and Psychological Traits", "pid": "9jl89mry", "bm25_score": 217.82705688476562}]}
{"idx": 45, "qid": "46", "q_text": "what evidence is there for dexamethasone as a treatment for COVID-19?", "qrels": {"0002xs6a": 0, "038lkmye": 1, "uy6wt7od": 0, "07sgpi8l": 0, "07tdrd4w": 2, "0bxt3hr2": 2, "0e9lq1b5": 1, "0eyi1gql": 0, "iybj9o93": 0, "0lk8eujq": 0, "0nwmoua3": 0, "g4xh2b3g": 2, "0spmy8vn": 0, "0u4ar3b5": 0, "0uengr9t": 1, "1n6d1gco": 0, "154amdh9": 0, "kdd9bggz": 0, "1exe5zaj": 0, "1fjb6b8e": 0, "1fm9smfr": 2, "1g2mup0k": 0, "1ijxilpb": 0, "1jpwtd4t": 1, "1kpa6jwe": 0, "r8rd5f2j": 2, "1qvh0kbt": 1, "1rdm355t": 0, "1sqgigqk": 0, "1x2mj0t7": 0, "1ybj2p1n": 0, "1yrhvbch": 0, "23mp5961": 1, "243addff": 2, "24m4rh9w": 0, "2528jrn6": 0, "2697ts31": 1, "2705en59": 1, "27vmjb47": 0, "291kyeo5": 0, "29im4gxw": 0, "2cvpzlu1": 0, "2f6nj4to": 0, "2lovpei3": 0, "2ob62k15": 0, "2s3b82l3": 0, "2sd2x7ux": 0, "2txzi7kb": 0, "dde5gk58": 0, "32ozud9i": 0, "32x48xxy": 0, "369kax2m": 1, "36flecmg": 0, "378cfb23": 0, "37ii08h8": 0, "39msyuxb": 1, "3esrmf0x": 0, "3eub8fs2": 0, "3gjpqyfw": 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associated with diffuse lung damage. Corticosteroids may modulate immune-mediated lung injury and reducing progression to respiratory failure and death. Methods: The Randomised Evaluation of COVID-19 therapy (RECOVERY) trial is a randomized, controlled, open-label, adaptive, platform trial comparing a range of possible treatments with usual care in patients hospitalized with COVID-19. We report the preliminary results for the comparison of dexamethasone 6 mg given once daily for up to ten days vs. usual care alone. The primary outcome was 28-day mortality. Results: 2104 patients randomly allocated to receive dexamethasone were compared with 4321 patients concurrently allocated to usual care. Overall, 454 (21.6%) patients allocated dexamethasone and 1065 (24.6%) patients allocated usual care died within 28 days (age-adjusted rate ratio [RR] 0.83; 95% confidence interval [CI] 0.74 to 0.92; P<0.001). The proportional and absolute mortality rate reductions varied significantly depending on level of respiratory support at randomization (test for trend p<0.001): Dexamethasone reduced deaths by one-third in patients receiving invasive mechanical ventilation (29.0% vs. 40.7%, RR 0.65 [95% CI 0.51 to 0.82]; p<0.001), by one-fifth in patients receiving oxygen without invasive mechanical ventilation (21.5% vs. 25.0%, RR 0.80 [95% CI 0.70 to 0.92]; p=0.002), but did not reduce mortality in patients not receiving respiratory support at randomization (17.0% vs. 13.2%, RR 1.22 [95% CI 0.93 to 1.61]; p=0.14). Conclusions: In patients hospitalized with COVID-19, dexamethasone reduced 28-day mortality among those receiving invasive mechanical ventilation or oxygen at randomization, but not among patients not receiving respiratory support.", "title": "Effect of Dexamethasone in Hospitalized Patients with COVID-19: Preliminary Report", "pid": "ocguwlam", "bm25_score": 218.97364807128906}, {"text": "", "title": "Dexamethasone in the management of covid -19", "pid": "7r7rzq36", "bm25_score": 218.8321075439453}, {"text": "BACKGROUND AND AIMS: Interest in corticosteroid therapy in COVID-19 has been rekindled after the results from Randomized Evaluation of COVid-19 thERapY (RECOVERY) Trial. However, the World health Organization has not recommended corticosteroid in the treatment of COVID-19. We sought to conduct a systematic review on the role of corticosteroid in the management of patients of COVID-19. METHODS: A systematic electronic search of PubMed, Cochrane and MedRxiv database using specific keywords was made up till June 17, 2020. Full text of all the original articles with supplementary appendix that fulfilled the inclusion criteria were retrieved and a detailed analysis of results were represented. RESULTS: Of the 5 studies (4 retrospective studies and 1 quasi-prospective study) conducted for evaluating the role of corticosteroids, 3 studies have shown benefit, while 2 studies shown no benefit and there was a suggestion of significant harm in critical cases in one sub-study. RECOVERY trial is the only randomized controlled trial that has shown a significant reduction of death by 35% in ventilated patients and by 20% amongst patients on supplemental oxygen therapy with the dexamethasone, although no benefit was observed in mild cases. CONCLUSIONS: While the results from retrospective studies are heterogenous and difficult to infer of a definitive protective benefit with corticosteroids, RECOVERY trial found a significantly better outcome with dexamethasone, mostly in severe cases. Nonetheless, more studies are needed to replicate the outcome shown in RECOVERY trial for a substantial conclusion.", "title": "Role of corticosteroid in the management of COVID-19: A systemic review and a Clinician's perspective", "pid": "hswuwtod", "bm25_score": 218.77687072753906}, {"text": "BACKGROUND AND AIMS: Interest in corticosteroid therapy in COVID-19 has been rekindled after the results from Randomized Evaluation of COVid-19 thERapY (RECOVERY) Trial. However, the World health Organization has not recommended corticosteroid in the treatment of COVID-19. We sought to conduct a systematic review on the role of corticosteroid in the management of patients of COVID-19. METHODS: A systematic electronic search of PubMed, Cochrane and MedRxiv database using specific keywords was made up till June 17, 2020. Full text of all the original articles with supplementary appendix that fulfilled the inclusion criteria were retrieved and a detailed analysis of results were represented. RESULTS: Of the 5 studies (4 retrospective studies and 1 quasi-prospective study) conducted for evaluating the role of corticosteroids, 3 studies have shown benefit, while 2 studies shown no benefit and there was a suggestion of significant harm in critical cases in one sub-study. RECOVERY trial is the only randomized controlled trial that has shown a significant reduction of death by 35% in ventilated patients and by 20% amongst patients on supplemental oxygen therapy with the dexamethasone, although no benefit was observed in mild cases. CONCLUSIONS: While the results from retrospective studies are heterogenous and difficult to infer of a definitive protective benefit with corticosteroids, RECOVERY trial found a significantly better outcome with dexamethasone, mostly in severe cases. Nonetheless, more studies are needed to replicate the outcome shown in RECOVERY trial for a substantial conclusion.", "title": "Role of corticosteroid in the management of COVID-19: A systemic review and a Clinician’s perspective", "pid": "zi86r481", "bm25_score": 218.77113342285156}, {"text": "BACKGROUND: In June 2020, a large randomised controlled clinical trial in the UK found that dexamethasone was effective in reducing the number of deaths in patients with severe coronavirus disease 2019 (COVID-19). CASE DESCRIPTION: We describe a patient with rapid worsening of COVID-19 pneumonia and its dramatic improvement under corticosteroids. DISCUSSION: Corticosteroids could be useful in patients with an inflammatory profile, considering that acute respiratory distress syndrome may be the consequence of cytokine storm syndrome. LEARNING POINTS: One of the main pathophysiological hypotheses for severe COVID-19 pneumonia is inappropriate immunological hyperactivation. Corticosteroid therapy may be useful in these patients.", "title": "Rapid Radiological Worsening and Cytokine Storm Syndrome in COVID-19 Pneumonia", "pid": "gc8770l9", "bm25_score": 218.5826873779297}, {"text": "The viral infection by SARS-CoV-2, has revolutionized the life of the majority of human beings, challenging national health systems worldwide, and pushing researchers to rapidly find adequate preventive and treatment strategies. No therapies have been shown effective, with the exception of dexamethasone, a glucocorticoid that was recently proved to be the first life-saving drug in this disease. Remarkably, around 20% of infected people develop a severe form of COVID-19, giving rise to respiratory and multi-organ failures requiring subintensive and intensive care interventions. This phenomenon is due to an excessive immune response that damages pulmonary alveoli, leading to a cytokine and chemokine storm with systemic effects. Indeed glucocorticoids’ role in regulating this immune response is controversial, and they have been used in clinical practice in a variety of countries, even without a previous clear consensus on their evidence-based benefit.", "title": "A critical evaluation of glucocorticoids in the treatment of severe COVID-19", "pid": "m2b836k8", "bm25_score": 218.23336791992188}, {"text": "", "title": "Covid-19: Demand for dexamethasone surges as RECOVERY trial publishes preprint.", "pid": "mtscqxzv", "bm25_score": 218.19715881347656}, {"text": "", "title": "Covid-19: Demand for dexamethasone surges as RECOVERY trial publishes preprint", "pid": "71u261na", "bm25_score": 217.95675659179688}, {"text": "", "title": "Coronavirus breakthrough: dexamethasone is first drug shown to save lives", "pid": "9ygpm1zz", "bm25_score": 217.93714904785156}, {"text": "", "title": "Coronavirus breakthrough: dexamethasone is first drug shown to save lives.", "pid": "3ho8117q", "bm25_score": 217.8909454345703}, {"text": "Recent announcements indicated, without sharing any distinct published set of results, that the corticosteroid dexamethasone may reduce mortality of severe COVID-19 patients only. The recent Coronavirus [severe acute respiratory syndrome (SARS)-CoV-2]-associated multiorgan disease, called COVID-19, has high morbidity and mortality due to autoimmune destruction of the lungs stemming from the release of a storm of pro-inflammatory cytokines. Defense against this Corona virus requires activated T cells and specific antibodies. Instead, cytokines are responsible for the serious sequelae of COVID-19 that damage the lungs. Dexamethasone is a synthetic corticosteroid approved by the FDA 1958 as a broad-spectrum immunosuppressor and it is about 30 times as active and with longer duration of action (2-3 days) than cortisone. Dexamethasone would limit the production of and damaging effect of the cytokines, but will also inhibit the protective function of T cells and block B cells from making antibodies, potentially leading to increased plasma viral load that will persist after a patient survives SARS. Moreover, dexamethasone would block macrophages from clearing secondary, nosocomial, infections. Hence, dexamethasone may be useful for the short-term in severe, intubated, COVID-19 patients, but could be outright dangerous during recovery since the virus will not only persist, but the body will be prevented from generating protective antibodies. Instead, a pulse of intravenous dexamethasone may be followed by administration of nebulized triamcinolone (6 times as active as cortisone) to concentrate in the lungs only. These corticosteroids could be given together with the natural flavonoid luteolin because of its antiviral and anti-inflammatory properties, especially its ability to inhibit mast cells, which are the main source of cytokines in the lungs. At the end, we should remember that \"The good physician treats the disease; the great physician treats the patient who has the disease\" [Sir William Osler's (1849-1919)].", "title": "Dexamethasone for COVID-19? Not so fast.", "pid": "br3ahtf7", "bm25_score": 217.85549926757812}, {"text": "The viral infection by SARS-CoV-2 has irrevocably altered the life of the majority of human beings, challenging national health systems worldwide, and pushing researchers to rapidly find adequate preventive and treatment strategies. No therapies have been shown effective with the exception of dexamethasone, a glucocorticoid that was recently proved to be the first life-saving drug in this disease. Remarkably, around 20 % of infected people develop a severe form of COVID-19, giving rise to respiratory and multi-organ failures requiring subintensive and intensive care interventions. This phenomenon is due to an excessive immune response that damages pulmonary alveoli, leading to a cytokine and chemokine storm with systemic effects. Indeed glucocorticoids' role in regulating this immune response is controversial, and they have been used in clinical practice in a variety of countries, even without a previous clear consensus on their evidence-based benefit.", "title": "A critical evaluation of glucocorticoids in the management of severe COVID-19", "pid": "bhkmax7s", "bm25_score": 217.82315063476562}, {"text": "Recent announcements indicated, without sharing any distinct published set of results, that the corticosteroid dexamethasone may reduce mortality of severe COVID-19 patients only. The recent Coronavirus [severe acute respiratory syndrome (SARS)-CoV-2]-associated multiorgan disease, called COVID-19, has high morbidity and mortality due to autoimmune destruction of the lungs stemming from the release of a storm of pro-inflammatory cytokines. Defense against this Corona virus requires activated T cells and specific antibodies. Instead, cytokines are responsible for the serious sequelae of COVID-19 that damage the lungs. Dexamethasone is a synthetic corticosteroid approved by the FDA 1958 as a broad-spectrum immunosuppressor and it is about 30 times as active and with longer duration of action (2-3 days) than cortisone. Dexamethasone would limit the production of and damaging effect of the cytokines, but will also inhibit the protective function of T cells and block B cells from making antibodies, potentially leading to increased plasma viral load that will persist after a patient survives SARS. Moreover, dexamethasone would block macrophages from clearing secondary, nosocomial, infections. Hence, dexamethasone may be useful for the short-term in severe, intubated, COVID-19 patients, but could be outright dangerous during recovery since the virus will not only persist, but the body will be prevented from generating protective antibodies. Instead, a pulse of intravenous dexamethasone may be followed by administration of nebulized triamcinolone (6 times as active as cortisone) to concentrate in the lungs only. These corticosteroids could be given together with the natural flavonoid luteolin because of its antiviral and anti-inflammatory properties, especially its ability to inhibit mast cells, which are the main source of cytokines in the lungs. At the end, we should remember that \"The good physician treats the disease; the great physician treats the patient who has the disease\" [Sir William Osler's (1849-1919)].", "title": "Dexamethasone for COVID-19? Not so fast", "pid": "6q0y3ewu", "bm25_score": 217.79702758789062}, {"text": "BACKGROUND: Dexamethasone, a synthetic glucocorticoid, has anti-inflammatory and immunosuppressive properties There is a hyperinflammatory response involved in the clinical course of patients with pneumonia due to SARS-CoV-2 To date, there has been no definite therapy for COVID-19 We reviewed the charts of SARS-CoV-2 patients with pneumonia and moderate to severely elevated CRP and worsening hypoxemia who were treated with early, short-term dexamethasone METHODS: We describe a series of 21 patients who tested positive for SARS-CoV-2 and were admitted to The Miriam Hospital in Providence, RI, and were treated with a short course of dexamethasone, either alone or in addition to current investigative therapies RESULTS: CRP levels decreased significantly following the start of dexamethasone from mean initial levels of 129 52 to 40 73 mg/L at time of discharge 71% percent of the patients were discharged home with a mean length of stay of 7 8 days None of the patients had escalation of care, leading to mechanical ventilation Two patients were transferred to inpatient hospice facilities on account of persistent hypoxemia, in line with their documented goals of care CONCLUSIONS: A short course of systemic corticosteroids among inpatients with SARS-CoV-2 with hypoxic respiratory failure was well tolerated, and most patients had improved outcomes This limited case series may not offer concrete evidence towards the benefit of corticosteroids in COVID-19 However, patients' positive response to short-term corticosteroids demonstrates that they may help blunt the severity of inflammation and prevent a severe hyperinflammatory phase, in turn reducing the length of stay, ICU admissions, and healthcare costs", "title": "Short-Term Dexamethasone in Sars-CoV-2 Patients", "pid": "fqh77aaa", "bm25_score": 217.74105834960938}, {"text": "BACKGROUND Dexamethasone, a synthetic glucocorticoid, has anti-inflammatory and immunosuppressive properties. There is a hyperinflammatory response involved in the clinical course of patients with pneumonia due to SARS-CoV-2. To date, there has been no definite therapy for COVID-19. We reviewed the charts of SARS-CoV-2 patients with pneumonia and moderate to severely elevated CRP and worsening hypoxemia who were treated with early, short-term dexamethasone. METHODS We describe a series of 21 patients who tested positive for SARS-CoV-2 and were admitted to The Miriam Hospital in Providence, RI, and were treated with a short course of dexamethasone, either alone or in addition to current investigative therapies. RESULTS CRP levels decreased significantly following the start of dexamethasone from mean initial levels of 129.52 to 40.73 mg/L at time of discharge. 71% percent of the patients were discharged home with a mean length of stay of 7.8 days. None of the patients had escalation of care, leading to mechanical ventilation. Two patients were transferred to inpatient hospice facilities on account of persistent hypoxemia, in line with their documented goals of care. CONCLUSIONS A short course of systemic corticosteroids among inpatients with SARS-CoV-2 with hypoxic respiratory failure was well tolerated, and most patients had improved outcomes. This limited case series may not offer concrete evidence towards the benefit of corticosteroids in COVID-19. However, patients' positive response to short-term corticosteroids demonstrates that they may help blunt the severity of inflammation and prevent a severe hyperinflammatory phase, in turn reducing the length of stay, ICU admissions, and healthcare costs.", "title": "Short-Term Dexamethasone in Sars-CoV-2 Patients.", "pid": "ztd7awzv", "bm25_score": 217.66331481933594}, {"text": "OBJECTIVES: The infection caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) spreads worldwide and is considered a pandemic. The most common manifestation of SARS-CoV2 infection (Coronavirus disease 2019 - COVID-19) is viral pneumonia with varying degrees of respiratory compromise and up to 40% of hospitalized patients might develop Acute Respiratory Distress Syndrome (ARDS). Several clinical trials evaluated the role of corticosteroids in non-COVID-19 ARDS with conflicting results. We designed a trial to evaluate the effectiveness of early intravenous dexamethasone administration on the number of days alive and free of mechanical ventilation within 28 days after randomization in adult patients with moderate or severe ARDS due to confirmed or probable COVID-19. METHODS: This is a pragmatic, prospective, randomized, stratified, multicenter, open-label, controlled trial including 350 patients with early-onset (less than 48h before randomization) moderate or severe ARDS, defined by the Berlin criteria, due to COVID-19. Eligible patients will be randomly allocated to either standard treatment plus dexamethasone (intervention group) or standard treatment without dexamethasone (control group). Patients in the intervention group will receive dexamethasone 20mg IV once daily for 5 days, followed by dexamethasone 10mg IV once daily for additional 5 days or until Intensive Care Unit (ICU) discharge, whichever occurs first. The primary outcome is ventilator-free days within 28 days after randomization, defined as days alive and free from invasive mechanical ventilation. Secondary outcomes are all-cause mortality rates at day 28, evaluation of the clinical status at day 15 assessed with a 6-level ordinal scale, mechanical ventilation duration from randomization to day 28, Sequential Organ Failure Assessment (SOFA) Score evaluation at 48h, 72h and 7 days and ICU-free days within 28. ETHICS AND DISSEMINATION: This trial was approved by the Brazilian National Committee of Ethics in Research (Comissao Nacional de Etica em Pesquisa - CONEP) and National Health Surveillance Agency (ANVISA). An independent data monitoring committee will perform interim analyses and evaluate adverse events throughout the trial. Results will be submitted for publication after enrolment and follow-up are complete.", "title": "COVID-19-associated ARDS treated with DEXamethasone (CoDEX): Study design and rationale for a randomized trial.", "pid": "dgy7qbl5", "bm25_score": 217.5105438232422}, {"text": "The aim was to investigate the effectiveness of glucocorticoid therapy in patients with COVID-19. A systematic search of the literature across nine databases was conducted from inception until 15th March 2020, following the PRISMA guidelines. Patients with a validated diagnosis of COVID-19 and using corticosteroids were included, considering all health outcomes. Four studies with 542 Chinese participants were included. Two studies reported negative findings regarding the use of corticosteroids in patients with COVID-19, i.e., corticosteroids had a detrimental impact on clinical outcomes. One study reported no significant association between the use of corticosteroids and clinical outcomes. However, one study, on 201 participants with different stages of pneumonia due to COVID-19, found that in more severe forms, the administration of methylprednisolone significantly reduced the risk of death by 62%. The literature to date does not fully support the routine use of corticosteroids in COVID-19, but some findings suggest that methylprednisolone could lower mortality rate in more severe forms of the condition.", "title": "Use of Corticosteroids in Coronavirus Disease 2019 Pneumonia: A Systematic Review of the Literature", "pid": "ypeibwje", "bm25_score": 217.3944091796875}, {"text": "Glucocorticoids are widely used in the treatment of different inflammatory diseases. The present study was performed to investigate the effect of dexamethasone (DEX) on acute respiratory distress syndrome (ARDS) induced by the H5N1 viral infection in mice. BALB/c mice, 6-8 weeks old, were divided into three groups with 80 mice in each. The infected group and the DEX-treated infected group were inoculated intranasally with 1 x 10(2) 50% mouse infectious dose of A/Chicken/Hebei/108/2002 (H5N1) viruses, with daily intraperitoneal injections of PBS, or 2.5 mg.kg(-1) DEX at days 3-14 post inoculation, respectively. The control group received noninfectious allantoic fluid and a daily intraperitoneal injection of PBS. In H5N1-infected mice, DEX treatment did not improve the mortality (17 out of 20 versus 16 out of 20 deaths in the DEX-treated infected group versus the infected group), and did not alleviate clinical signs, including weight loss, decreased food intake and inactivity. There was no significant amelioration of the hypoxaemia and ARDS-associated pathological changes in DEX-treated infected mice, as assessed by blood gas analysis and histological score. Furthermore, DEX therapy did not inhibit inflammatory cellular infiltration and cytokine release (interleukin-6 and tumour necrosis factor-alpha) in bronchoalveolar lavage fluid induced by the H5N1 infection. In conclusion, dexamethasone treatment (2.5 mg.kg(-1)) from days 3-14 post inoculation has no beneficial effect on acute respiratory distress syndrome caused by the H5N1 infection in mice.", "title": "Effect of dexamethasone on acute respiratory distress syndrome induced by the H5N1 virus in mice.", "pid": "xrvgpd67", "bm25_score": 217.3835906982422}, {"text": "The SARS-CoV-2 pandemic is continuing relentlessly in many parts of the world and has resulted in the outpouring of literature on various aspects of the infection, including studies and recommendations regarding the optimal treatment of infected patients. Not surprisingly, the use of corticosteroids in the management of such patients has featured prominently in many of these publications. There is considerable debate in the literature as to the likely benefits, as well as the potential detrimental effects of corticosteroid therapy in general viral respiratory infections and, in particular, COVID-19 infections. While the definitive answer may need to await the results of ongoing randomised, controlled trials recent studies suggest that corticosteroid use in COVID-19 cases with hypoxaemia may benefit from low-dose corticosteroid therapy.", "title": "The use of corticosteroids for COVID-19 infection", "pid": "y6fvjsjl", "bm25_score": 217.2142791748047}, {"text": "", "title": "Clinical evidence does not support corticosteroid treatment for 2019-nCoV lung injury", "pid": "wu30vclq", "bm25_score": 217.19993591308594}, {"text": "OBJECTIVES: There is little information about Coronavirus Disease 2019 (COVID-19) management for critically ill patients. Most of these patients develop acute respiratory distress syndrome (ARDS) due to excessive inflammatory response and the ensuing cytokine storm. Anti-inflammatory drugs including corticosteroids can be used to effectively reduce the effect of this cytokine storm and lung damage. However, corticosteroids can have side effects, so simultaneous administration of immunoglobulin (IV-IG) and interferon-beta can help manage treatment using corticosteroids. Therefore, we designed a trial to test our hypothesis that early administration of dexamethasone in combination with IV-IG and interferon-beta can reduce the effect of the cytokine storm in critically ill patients COVID-19. TRIAL DESIGN: A phase two multi-center randomized controlled trial (RCT) with three parallel arms (1:1:1 ratio). PARTICIPANTS: They will be hospitalized patients with severe COVID-19 who have positive RT-PCR test and have blood oxygen saturation levels (SpO2) less than 90% and respiratory rate higher than 24 per minute or have involvement of more than 50% of their lung when viewed using computed tomography (CT)-scan. The age range of patients will be 18-70 years old. EXCLUSION CRITERIA: the need for intubation; allergy, intolerance, or contraindication to any study drug including dexamethasone, IV-IG, and interferon-beta; pregnancy or lactation; known HIV positive or active hepatitis B or C. The study will be conducted in several hospitals of the Golestan province, Iran. INTERVENTION AND COMPARATOR: The study subjects will be randomly allocated to three treatment arms: two experimental groups (two arms: Intervention 1 and Intervention 2) and one Control Group, which will be matched for age and sex using frequency matching method. Each eligible patient in the control arm will receive the standard treatment for COVID-19 based on WHO guidelines and the Ministry of the Health and Medical Education (MOHME) of Iran. Each patient in the Intervention Group 1 will receive the standard treatment for COVID-19 and dexamethasone, at the first 24 hours' time of admission. The intervention begins with the administration of dexamethasone based on the SpO2 levels. If the level of SpO2 does not improve after 24 hours, IV-IG (400 mg/kg once daily for 5 days) and interferon-beta (7 doses every other day) will be prescribed along with dexamethasone administration. In Intervention Group 2, the administration of dexamethasone will be started within the first 24 hours' time of admission and will be continued for 48-72 hours and then the SpO2 level will be checked. Then, if the level of SpO2 has not improved after that time, IV-IG and interferon-beta will be prescribed as the same dosage as Group 1. If the percentages of the SpO2 level are between 85 and 90/ 80 and 85/ 75 and 80/ less than 75, the dosages will be 4 mg every 12 hours/ 4 mg every 8 hours/ 8 mg every 12 hours/ 8 mg every 8 hours, respectively. According to the WHO recommendation, all participants will have the best available supportive care with full monitoring. MAIN OUTCOMES: Primary: An increase in the SpO2 level to reach more than 90% in each case, which will be assessed by the oximeter. Secondary: The duration of hospital stays; intubation status and the percentage of patients who are free of mechanical ventilation; the mortality rates during hospitalization and one month after the admission time. RANDOMISATION: Participants will be allocated into either control or intervention groups with a 1:1:1 allocation ratio using a computer random number generator to generate a table of random numbers for simple randomization. BLINDING (MASKING): The project's principal investigator (PI) is unblinded. However, the PI will not analyse the data and interpret the results. An unblinded researcher (a pharmacist) will cover the drug's bottles with aluminium foil and prepare them interventions and control drugs in a syringe with a code so that patients are blinded. This person will have no patients contact. The staff and nurses, caring for the patients, will be unblinded for each study group due to the nature of this study. The staff that take outcome measurements will be blinded. The laboratory technicians will also be blinded as well as the statistical team. These study statisticians will have access to coded data and will analyse the data labelled as group X, group Y, and group Z. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size will be 105 critically ill COVID-19 patients, who will be allocated randomly to the three trial arms with 35 patients in each group. TRIAL STATUS: Recruitment is ongoing. The study began on April 18 2020 and will be completed June 19 2020. This summary describes protocol version 1; April 2 2020. TRIAL REGISTRATION: https://www.irct.ir/. Identifier: IRCT20120225009124N4 version 1; Registration date: April 2 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The full protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.", "title": "Letter to the editor: efficacy of different methods of combination regimen administrations including dexamethasone, intravenous immunoglobulin, and interferon-beta to treat critically ill COVID-19 patients: a structured summary of a study protocol for a randomized controlled trial", "pid": "mapu4r1z", "bm25_score": 217.18292236328125}, {"text": "OBJECTIVES: There is little information about Coronavirus Disease 2019 (COVID-19) management for critically ill patients. Most of these patients develop acute respiratory distress syndrome (ARDS) due to excessive inflammatory response and the ensuing cytokine storm. Anti-inflammatory drugs including corticosteroids can be used to effectively reduce the effect of this cytokine storm and lung damage. However, corticosteroids can have side effects, so simultaneous administration of immunoglobulin (IV-IG) and interferon-beta can help manage treatment using corticosteroids. Therefore, we designed a trial to test our hypothesis that early administration of dexamethasone in combination with IV-IG and interferon-beta can reduce the effect of the cytokine storm in critically ill patients COVID-19. TRIAL DESIGN: A phase two multi-center randomized controlled trial (RCT) with three parallel arms (1:1:1 ratio). PARTICIPANTS: They will be hospitalized patients with severe COVID-19 who have positive RT-PCR test and have blood oxygen saturation levels (SpO(2)) less than 90% and respiratory rate higher than 24 per minute or have involvement of more than 50% of their lung when viewed using computed tomography (CT)-scan. The age range of patients will be 18-70 years old. Exclusion criteria: the need for intubation; allergy, intolerance, or contraindication to any study drug including dexamethasone, IV-IG, and interferon-beta; pregnancy or lactation; known HIV positive or active hepatitis B or C. The study will be conducted in several hospitals of the Golestan province, Iran. INTERVENTION AND COMPARATOR: The study subjects will be randomly allocated to three treatment arms: two experimental groups (two arms: Intervention 1 and Intervention 2) and one Control Group, which will be matched for age and sex using frequency matching method. Each eligible patient in the control arm will receive the standard treatment for COVID-19 based on WHO guidelines and the Ministry of the Health and Medical Education (MOHME) of Iran. Each patient in the Intervention Group 1 will receive the standard treatment for COVID-19 and dexamethasone, at the first 24 hours’ time of admission. The intervention begins with the administration of dexamethasone based on the SpO(2) levels. If the level of SpO(2) does not improve after 24 hours, IV-IG (400 mg/kg once daily for 5 days) and interferon-beta (7 doses every other day) will be prescribed along with dexamethasone administration. In Intervention Group 2, the administration of dexamethasone will be started within the first 24 hours’ time of admission and will be continued for 48-72 hours and then the SpO(2) level will be checked. Then, if the level of SpO(2) has not improved after that time, IV-IG and interferon-beta will be prescribed as the same dosage as Group 1. If the percentages of the SpO(2) level are between 85 and 90/ 80 and 85/ 75 and 80/ less than 75, the dosages will be 4 mg every 12 hours/ 4 mg every 8 hours/ 8 mg every 12 hours/ 8 mg every 8 hours, respectively. According to the WHO recommendation, all participants will have the best available supportive care with full monitoring. MAIN OUTCOMES: Primary: An increase in the SpO(2) level to reach more than 90% in each case, which will be assessed by the oximeter. Secondary: The duration of hospital stays; intubation status and the percentage of patients who are free of mechanical ventilation; the mortality rates during hospitalization and one month after the admission time. RANDOMISATION: Participants will be allocated into either control or intervention groups with a 1:1:1 allocation ratio using a computer random number generator to generate a table of random numbers for simple randomization. BLINDING (MASKING): The project's principal investigator (PI) is unblinded. However, the PI will not analyse the data and interpret the results. An unblinded researcher (a pharmacist) will cover the drug’s bottles with aluminium foil and prepare them interventions and control drugs in a syringe with a code so that patients are blinded. This person will have no patients contact. The staff and nurses, caring for the patients, will be unblinded for each study group due to the nature of this study. The staff that take outcome measurements will be blinded. The laboratory technicians will also be blinded as well as the statistical team. These study statisticians will have access to coded data and will analyse the data labelled as group X, group Y, and group Z. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The target sample size will be 105 critically ill COVID-19 patients, who will be allocated randomly to the three trial arms with 35 patients in each group. TRIAL STATUS: Recruitment is ongoing. The study began on April 18 2020 and will be completed June 19 2020. This summary describes protocol version 1; April 2 2020. TRIAL REGISTRATION: https://www.irct.ir/. Identifier: IRCT20120225009124N4 version 1; Registration date: April 2 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The full protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines.", "title": "Letter to the editor: efficacy of different methods of combination regimen administrations including dexamethasone, intravenous immunoglobulin, and interferon-beta to treat critically ill COVID-19 patients: a structured summary of a study protocol for a randomized controlled trial", "pid": "t9c26eld", "bm25_score": 217.17935180664062}, {"text": "BACKGROUND: There is no proven specific pharmacological treatment for patients with the acute respiratory distress syndrome (ARDS). The efficacy of corticosteroids in ARDS remains controversial. We aimed to assess the effects of dexamethasone in ARDS, which might change pulmonary and systemic inflammation and result in a decrease in duration of mechanical ventilation and mortality. METHODS: We did a multicentre, randomised controlled trial in a network of 17 intensive care units (ICUs) in teaching hospitals across Spain in patients with established moderate-to-severe ARDS (defined by a ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 mm Hg or less assessed with a positive end-expiratory pressure of 10 cm H2O or more and FiO2 of 0·5 or more at 24 h after ARDS onset). Patients with brain death, terminal-stage disease, or receiving corticosteroids or immunosuppressive drugs were excluded. Eligible patients were randomly assigned based on balanced treatment assignments with a computerised randomisation allocation sequence using blocks of 10 opaque, sealed envelopes to receive immediate treatment with dexamethasone or continued routine intensive care (control group). Patients in the dexamethasone group received an intravenous dose of 20 mg once daily from day 1 to day 5, which was reduced to 10 mg once daily from day 6 to day 10. Patients in both groups were ventilated with lung-protective mechanical ventilation. Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days at 28 days, defined as the number of days alive and free from mechanical ventilation from day of randomisation to day 28. Secondary outcome was all-cause mortality 60 days after randomisation. All analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT01731795. FINDINGS: Between March 28, 2013, and Dec 31, 2018, we enrolled 277 patients and randomly assigned 139 patients to the dexamethasone group and 138 to the control group. The trial was stopped by the data safety monitoring board due to low enrolment rate after enrolling more than 88% (277/314) of the planned sample size. The mean number of ventilator-free days was higher in the dexamethasone group than in the control group (between-group difference 4·8 days [95% CI 2·57 to 7·03]; p<0·0001). At 60 days, 29 (21%) patients in the dexamethasone group and 50 (36%) patients in the control group had died (between-group difference -15·3% [-25·9 to -4·9]; p=0·0047). The proportion of adverse events did not differ significantly between the dexamethasone group and control group. The most common adverse events were hyperglycaemia in the ICU (105 [76%] patients in the dexamethasone group vs 97 [70%] patients in the control group), new infections in the ICU (eg, pneumonia or sepsis; 33 [24%] vs 35 [25%]), and barotrauma (14 [10%] vs 10 [7%]). INTERPRETATION: Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS. FUNDING: Fundación Mutua Madrileña, Instituto de Salud Carlos III, The European Regional Development's Funds, Asociación Científica Pulmón y Ventilación Mecánica.", "title": "Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial", "pid": "3vvsa2wi", "bm25_score": 217.1651153564453}, {"text": "The ongoing pandemic caused by severe acute respiratory syndrome (SARS) coronavirus type 2 (SARS-CoV-2, also known as COVID-19) has caused unprecedented strain on the global healthcare system, causing thousands of deaths worldwide. Patients with underlying conditions such as cancer are at substantial risk of acquiring and dying from this novel coronavirus. Numerous reports have shown that infection with SARS-CoV-2 causes depletion of B- and T-lymphocytes, including CD4 and CD8 T-cells, and is associated with severe illness and death and that patients with higher lymphocyte levels may have better outcomes. Dexamethasone, a widely prescribed antiemetic for acute and delayed nausea and vomiting from a variety of cancer drugs, causes B and T cell depletion, which may augment immunosuppression. Since it seems that lymphocytes are vital in the immune response to novel coronavirus, oncologists should reconsider the routine use of prophylactic dexamethasone in uninfected patients, to avoid inducing lymphopenia, which may increase risk of infection or lead to inferior outcomes if a cancer patient subsequently becomes infected. Since many cancer drugs and malignant diseases inherently cause lymphopenia, further reduction of lymphocytes with dexamethasone should be avoided if possible and if safe and effective alternative antiemetics are available during the COVID-19 crisis.", "title": "Routine antiemetic prophylaxis with dexamethasone during COVID-19: Should oncologists reconsider?", "pid": "pec5ezyy", "bm25_score": 217.1044158935547}, {"text": "Coronavirus disease 2019 (COVID-19) pneumonia, firstly reported in Wuhan, Hubei province, China, has rapidly spread around the world with high mortality rate among critically ill patients. The use of corticosteroids in COVID-19 remains a major controversy. Available evidences are inconclusive. According to WHO guidance, corticosteroids are not recommended to be used unless for another reason. Chinese Thoracic Society (CTS) proposes an expert consensus statement that suggests taking a prudent attitude of corticosteroid usage. In our clinical practice, we do not use corticosteroids routinely; only low-to-moderate doses of corticosteroids were given to several severely ill patients prudently. In this paper, we will present two confirmed severe COVID-19 cases admitted to isolation wards in Optical Valley Campus of Tongji hospital, Tongji Medical College, Huazhong University of Science and Technology. We will discuss questions related to corticosteroids usages.", "title": "Corticosteroid treatment in severe COVID-19 pneumonia: two cases and literature review", "pid": "rml2z32n", "bm25_score": 217.04322814941406}, {"text": "BACKGROUND There is no proven specific pharmacological treatment for patients with the acute respiratory distress syndrome (ARDS). The efficacy of corticosteroids in ARDS remains controversial. We aimed to assess the effects of dexamethasone in ARDS, which might change pulmonary and systemic inflammation and result in a decrease in duration of mechanical ventilation and mortality. METHODS We did a multicentre, randomised controlled trial in a network of 17 intensive care units (ICUs) in teaching hospitals across Spain in patients with established moderate-to-severe ARDS (defined by a ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 mm Hg or less assessed with a positive end-expiratory pressure of 10 cm H2O or more and FiO2 of 0·5 or more at 24 h after ARDS onset). Patients with brain death, terminal-stage disease, or receiving corticosteroids or immunosuppressive drugs were excluded. Eligible patients were randomly assigned based on balanced treatment assignments with a computerised randomisation allocation sequence using blocks of 10 opaque, sealed envelopes to receive immediate treatment with dexamethasone or continued routine intensive care (control group). Patients in the dexamethasone group received an intravenous dose of 20 mg once daily from day 1 to day 5, which was reduced to 10 mg once daily from day 6 to day 10. Patients in both groups were ventilated with lung-protective mechanical ventilation. Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days at 28 days, defined as the number of days alive and free from mechanical ventilation from day of randomisation to day 28. Secondary outcome was all-cause mortality 60 days after randomisation. All analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT01731795. FINDINGS Between March 28, 2013, and Dec 31, 2018, we enrolled 277 patients and randomly assigned 139 patients to the dexamethasone group and 138 to the control group. The trial was stopped by the data safety monitoring board due to low enrolment rate after enrolling more than 88% (277/314) of the planned sample size. The mean number of ventilator-free days was higher in the dexamethasone group than in the control group (between-group difference 4·8 days [95% CI 2·57 to 7·03]; p<0·0001). At 60 days, 29 (21%) patients in the dexamethasone group and 50 (36%) patients in the control group had died (between-group difference -15·3% [-25·9 to -4·9]; p=0·0047). The proportion of adverse events did not differ significantly between the dexamethasone group and control group. The most common adverse events were hyperglycaemia in the ICU (105 [76%] patients in the dexamethasone group vs 97 [70%] patients in the control group), new infections in the ICU (eg, pneumonia or sepsis; 33 [24%] vs 35 [25%]), and barotrauma (14 [10%] vs 10 [7%]). INTERPRETATION Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS. FUNDING Fundación Mutua Madrileña, Instituto de Salud Carlos III, The European Regional Development's Funds, Asociación Científica Pulmón y Ventilación Mecánica.", "title": "Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial.", "pid": "buz3o8x9", "bm25_score": 217.0402374267578}, {"text": "PURPOSE: People with cancer face an elevated risk of infection and severe sequelae from COVID-19. Dexamethasone is commonly used for antiemetic prophylaxis with systemic therapy for cancer. However, dexamethasone is associated with increased risk of viral and respiratory infections, and causes lymphopenia, which is associated with worse outcomes during COVID-19 infections. Our purpose was to minimize dexamethasone exposure during antiemetic prophylaxis for systemic therapy for solid tumors during the COVID-19 pandemic, while maintaining control of nausea and emesis. METHODS: We convened an expert panel to systematically review the literature and formulate consensus recommendations. RESULTS: No studies considered the impact of dexamethasone-based antiemetic regimens on the risk and severity of COVID-19 infection. Expert consensus recommended modifications to the 2019 Cancer Care Ontario Antiemetic Recommendations. CONCLUSION: Clinicians should prescribe the minimally effective dose of dexamethasone for antiemetic prophylaxis. Single-day dexamethasone dosing is recommended over multi-day dosing for regimens with high emetogenic risk excluding high-dose cisplatin, preferably in combination with palonosetron, netupitant, and olanzapine. For regimens with low emetogenic risk, 5-HT(3) antagonists are recommended over dexamethasone.", "title": "Reducing dexamethasone antiemetic prophylaxis during the COVID-19 pandemic: recommendations from Ontario, Canada", "pid": "gd6dd4qm", "bm25_score": 216.96022033691406}, {"text": "PURPOSE: People with cancer face an elevated risk of infection and severe sequelae from COVID-19. Dexamethasone is commonly used for antiemetic prophylaxis with systemic therapy for cancer. However, dexamethasone is associated with increased risk of viral and respiratory infections, and causes lymphopenia, which is associated with worse outcomes during COVID-19 infections. Our purpose was to minimize dexamethasone exposure during antiemetic prophylaxis for systemic therapy for solid tumors during the COVID-19 pandemic, while maintaining control of nausea and emesis. METHODS: We convened an expert panel to systematically review the literature and formulate consensus recommendations. RESULTS: No studies considered the impact of dexamethasone-based antiemetic regimens on the risk and severity of COVID-19 infection. Expert consensus recommended modifications to the 2019 Cancer Care Ontario Antiemetic Recommendations. CONCLUSION: Clinicians should prescribe the minimally effective dose of dexamethasone for antiemetic prophylaxis. Single-day dexamethasone dosing is recommended over multi-day dosing for regimens with high emetogenic risk excluding high-dose cisplatin, preferably in combination with palonosetron, netupitant, and olanzapine. For regimens with low emetogenic risk, 5-HT3 antagonists are recommended over dexamethasone.", "title": "Reducing dexamethasone antiemetic prophylaxis during the COVID-19 pandemic: recommendations from Ontario, Canada", "pid": "b8p4l0yp", "bm25_score": 216.9562225341797}, {"text": "Background. Since December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), responsible for Coronavirus Disease 2019 (COVID-19), is spreading worldwide, causing significant morbidity and mortality. No specific treatment has yet clearly shown to improve the disease's evolution. Validated therapeutic options are urgently needed. Methods. In this retrospective study, we aimed to evaluate determinants of the prognosis of the disease in 70 patients with COVID-19 severe pneumonia (i.e. requiring at least 3 liters of oxygen) hospitalized between 10 March and 9 April, 2020, in the Centre Hospitalier Alpes Leman, France. The main outcome was oro-tracheal intubation and the exposure of interest was corticotherapy. Since this was not a randomized trial, we used propensity score matching to estimate average treatment effect. Results. There was evidence that corticotherapy lowered the risk of intubation with a risk difference of -47.1% (95% confidence interval -71.8% to -22.5%). Conclusion. Corticosteroid, a well-known, easily available, and cheap treatment, could be an important tool in management of severe COVID-19 patients with respiratory failure. Not only could it provide an individual benefit, but also, in the setting of the COVID-19 ongoing pandemic, lower the burden on our vulnerable healthcare systems.", "title": "Beneficial effect of corticosteroids in severe COVID-19 pneumonia: a propensity score matching analysis.", "pid": "39msyuxb", "bm25_score": 216.8941650390625}, {"text": "BACKGROUND: At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. METHODS: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. DISCUSSION: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.", "title": "Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial", "pid": "w5bpoms2", "bm25_score": 216.73814392089844}, {"text": "No specific and effective anti-viral treatment has been approved for COVID-19 so far. Systemic corticosteroid has been sometimes administered to severe infectious diseases combined with the specific treatment. However, as lack of the specific anti-SARS-CoV-2 drug, systemic steroid treatment has not been recommended for COVID-19. We report here three cases of the COVID-19 pneumonia successfully treated with ciclesonide inhalation. Rationale of the treatment is to mitigate the local inflammation with inhaled steroid that stays in the lung and to inhibit proliferation of the virus by antiviral activity. Larger and further studies are warranted to confirm the result of these cases.", "title": "Therapeutic potential of ciclesonide inahalation for COVID-19 pneumonia: Report of three cases", "pid": "3mxfew35", "bm25_score": 216.7296905517578}, {"text": "BACKGROUND: Corticosteroids are commonly used as adjuvant therapy for acute respiratory distress syndrome by many clinicians because of their perceived anti-inflammatory effects. However, for patients with severe viral pneumonia, the corticosteroid treatment is highly controversial. OBJECTIVES: The purpose of this review is to systematically evaluate the effect and potential mechanism of corticosteroid administration in pandemic viral pneumonia. SOURCES: We comprehensively searched all manuscripts on corticosteroid therapy for influenza, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and SARS coronavirus 2 (SARS-CoV-2) viral pneumonia from the PubMed, EMBASE, Web of Science and Cochrane Library databases. CONTENT: We systematically summarized the effects of corticosteroid therapy for pandemic viral pneumonia and the potential mechanism of action for corticosteroids in coronavirus disease 2019 (COVID-19). IMPLICATIONS: Observational studies showed that corticosteroid treatment was associated with increased mortality and nosocomial infections for influenza and delayed virus clearance for SARS-CoV and MERS-CoV. Limited data on corticosteroid therapy for COVID-19 were reported. Corticosteroids were used in about a fifth of patients (670/2995, 22.4%). Although clinical observational studies reported the improvement in symptoms and oxygenation for individuals with severe COVID-19 who received corticosteroid therapy, case fatality rate in the corticosteroid group was significantly higher than that in the non-corticosteroid group (69/443, 15.6% versus 56/1310, 4.3%). Compared individuals with non-severe disease, those with severe disease were more likely to receive corticosteroid therapy (201/382, 52.6% versus 201/1310, 15.3%). Although there is no evidence that corticosteroid therapy reduces mortality in people with COVID-19, some improvements in clinical symptoms and oxygenation were reported in some clinical observational studies. Excessive inflammatory response and lymphopenia might be critical factors associated with severity of and mortality from COVID-19. Sufficiently powered randomized controlled trials with rigorous inclusion/exclusion criteria and standardized dose and duration of corticosteroids are needed to verify the effectiveness and safety of corticosteroid therapy.", "title": "Corticosteroid administration for viral pneumonia: COVID-19 and beyond", "pid": "qwvlwa7q", "bm25_score": 216.66009521484375}, {"text": "", "title": "ACTH 1-24 and other melanocortins for COVID-19 treatment.", "pid": "do82t08l", "bm25_score": 216.64735412597656}, {"text": "Abstract Severe COVID 19 disease is associated with high morbidity and mortality with limited therapeutic options. The role of glucocorticoids in treatment of COVID 19 has been riddled with controversy. The study site has been using glucocorticoids in patients with severe COVID 19 since the first few patients of COVID 19 that were admitted. In the initial cohort of 7 patients with severe COVID disease, use of methylprednisolone in a dose of 30 mg twice daily was associated with rapid improvement in oxygenation and decline in CRP levels. While six patients made a complete clinical recovery, one patient died. There were no secondary infections.", "title": "Initial experience with short-course corticosteroids in a small cohort of adults with severe COVID-19 in a tertiary care hospital in India", "pid": "ma6gmwgl", "bm25_score": 216.60903930664062}, {"text": "BACKGROUND: At the end of 2019, a novel coronavirus outbreak emerged in Wuhan, China, and its causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation. METHODS: The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1–2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks. DISCUSSION: The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019. TRIAL REGISTRATION: ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.", "title": "Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial", "pid": "vyayyk50", "bm25_score": 216.6004180908203}, {"text": "", "title": "[Glucocorticoid for coronavirus disease 2019: a dilemma].", "pid": "s9sp02cz", "bm25_score": 216.59609985351562}, {"text": "", "title": "[Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia].", "pid": "3qx70bsr", "bm25_score": 216.53875732421875}, {"text": "", "title": "[Expert consensus on the use of corticosteroid in patients with 2019-nCoV pneumonia]", "pid": "o1rcm2jx", "bm25_score": 216.49815368652344}, {"text": "Background: Evidence to support the use of steroids in COVID-19 pneumonia is lacking. We aim to determine the impact of steroid use in COVID-19 pneumonia in-hospital mortality.Patients and Methods: We performed a single-center retrospective cohort study in a University hospital in Madrid, Spain, during March 2020. To determine the role of steroids in in-hospital mortality, patients admitted with SARS-CoV-2 pneumonia and treated with steroids were compared to patients not treated with steroids, adjusting by a propensity-score for steroid treatment. Survival times were compared using log-rank test. Different steroid regimens were compared, and adjusted with a second propensity score.Results: During the study period, 463 out of 848 hospitalized patients with COVID19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. Median time to steroid treatment from symptom onset was 10 days (IQR 8-13). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67], HR 0.51 [0.27-0.96], p= 0.044). Steroid treatment reduced mortality by 41.8% relative to no steroid treatment (RRR 0,42 [0.048- 0.65). Initial treatment with 1 mg/kg/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86], OR 0.880 [0.449-1.726], p=0.710).Conclusions: Our results show that survival of patients with SARS-CoV2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. In-hospital mortality was not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.", "title": "IMPACT OF GLUCOCORTICOID TREATMENT IN SARS-COV-2 INFECTION MORTALITY: A RETROSPECTIVE CONTROLLED COHORT STUDY.", "pid": "ory95tz7", "bm25_score": 216.48565673828125}, {"text": "Abstract No specific and effective anti-viral treatment has been approved for COVID-19 so far. Systemic corticosteroid has been sometimes administered to severe infectious diseases combined with the specific treatment. However, as lack of the specific anti-SARS-CoV-2 drug, systemic steroid treatment has not been recommended for COVID-19. We report here three cases of the COVID-19 pneumonia successfully treated with ciclesonide inhalation. Rationale of the treatment is to mitigate the local inflammation with inhaled steroid that stays in the lung and to inhibit proliferation of the virus by antiviral activity. Larger and further studies are warranted to confirm the result of these cases.", "title": "Therapeutic potential of ciclesonide inahalation for COVID-19 pneumonia: Report of three cases", "pid": "uuor5hck", "bm25_score": 216.48263549804688}, {"text": "In December 2019, an outbreak of severe pneumonia was reported in Wuhan, China. Later described as COVID-19 (coronavirus disease 2019), this infection caused by a virus from the Coronaviridae family (SARS-CoV-2) has spread globally. Effective therapies for this new disease are urgently needed. In this short communication, we will evaluate the use of corticosteroids as an adjunctive pharmacological therapy in the management of COVID-19 and describe its pros and cons in light of the latest available evidence.", "title": "Pros and cons of corticosteroid therapy for COVID-19 patients", "pid": "mza0oz89", "bm25_score": 216.4815673828125}, {"text": "BACKGROUND: Corticosteroids are commonly used as adjuvant therapy for acute respiratory distress syndrome (ARDS) by many clinicians due to their perceived anti-inflammatory effects. However, for patients with severe viral pneumonia, the corticosteroid treatment is highly controversial. OBJECTIVES: The purpose of this review is to systematically evaluate the effect and potential mechanism of corticosteroid administration in pandemic viral pneumonia. SOURCES: We comprehensively searched all manuscripts on corticosteroids therapy for influenza, SARS, MERS and SARS-CoV-2 viral pneumonia from the PubMed, EMBASE, Web of Science and Cochrane Library databases. CONTENT: We systematic summarized the effects of corticosteroids therapy for pandemic viral pneumonia and the potential mechanism of corticosteroid worked in COVID-19. IMPLICATIONS: Observational studies showed that corticosteroid treatment was associated with increased mortality and nosocomial infections for influenza and delay virus clearance for SARS-CoV and MERS-CoV. Limited data on corticosteroid therapy for COVID-19 were reported. Corticosteroids were used in about a fifth of patients (670/2995, 22.4%). Although clinical observational studies reported the improvement in symptoms and oxygenation for the severe COVID-19 patients received corticosteroids therapy, case fatality rate in the corticosteroid group was significantly higher than that in the non-corticosteroid group (69/443, 15.6% vs 56/1310, 4.3%). Compared with non-severe patients, severe patients were more likely to receive corticosteroid therapy (201/382, 52.6% vs 201/1310, 15.3%). Although there is no evidence of corticosteroid therapy reduce the mortality of COVID-19 patients, some improvements in clinical symptoms and oxygenation were reported in some clinical observational studies. Excessive inflammatory response and lymphopenia might be critical factors associated with disease severity and mortality of COVID-19. Sufficiently powered randomized controlled trials with rigorous inclusion/exclusion criteria and standardized dose and duration of corticosteroids are needed to verify the effectiveness and safety of corticosteroid therapy.", "title": "Corticosteroid administration for viral pneumonia: COVID-19 and beyond", "pid": "p5cq2is5", "bm25_score": 216.48146057128906}, {"text": "Objective: We aim to determine the impact of steroid use in COVID-19 pneumonia in-hospital mortality. Design: We performed a single-centre retrospective cohort study. Setting: A University hospital in Madrid, Spain, during March 2020. Participants: Patients admitted with SARS-CoV-2 pneumonia. Exposures: Patients treated with steroids were compared to patients not treated with steroids. A propensity-score for steroid treatment was developed. Different steroid regimens were also compared, and adjusted with a second propensity score. Main Outcomes and Measures: To determine the role of steroids in in-hospital mortality, univariable and multivariable analyses were performed, and adjusted including the propensity score as a covariate. Survival times were compared using a log-rank test. Results: During the study period, 463 out of 848 hospitalized patients with COVID19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) consecutive patients were treated with steroids and 67 patients were assigned to the control cohort. Global mortality was 15.1%. Median time to steroid treatment from symptom onset was 10 days (IQR 8 to13). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67], OR 0.51 [0.27 to 0.96], p= 0.044). Steroid treatment reduced mortality by 41.8% relative to no steroid treatment (RRR 0,42 [0.048 to 0.65). Initial treatment with 1 mg/kg/day of methylprednisolone (or equivalent) versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86], OR 0.880 [0.449-1.726], p=0.710). Conclusions: Our results show that survival of patients with SARS-CoV2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. In-hospital mortality was not different between initial regimens of 1 mg/kg/day of methylprednisolone or equivalent and glucocorticoid pulses. These results support the use of glucocorticoids in SARS-CoV2 infection.", "title": "IMPACT OF GLUCOCORTICOID TREATMENT IN SARS-COV-2 INFECTION MORTALITY: A RETROSPECTIVE CONTROLLED COHORT STUDY", "pid": "e28bk3gq", "bm25_score": 216.478271484375}, {"text": "", "title": "[Glucocorticoid for coronavirus disease 2019: a dilemma]", "pid": "cmkx1ybb", "bm25_score": 216.4748992919922}, {"text": "Intensive Care Unit (ICU) admissions and mortality in severe COVID-19 patients are driven by cytokine storms and acute respiratory distress syndrome (ARDS). Interim clinical trial results suggest that the corticosteroid dexamethasone displays superior 28-day survival in severe COVID-19 patients requiring ventilation or oxygen. Among 16 patients with plasma IL-6 measurement post-corticosteroid administration, a higher proportion of patients with an IL-6 value over 10 pg/mL have worse outcomes (i.e. ICU Length of Stay > 15 days or death) when compared to 41 patients treated with non-corticosteroid drugs including antivirals, tocilizumab, azithromycin, and hydroxychloroquine (p-value = 0.0024). Given this unexpected clinical association between post-corticosteroid IL-6 levels and COVID-19 severity, we hypothesized that the Glucocorticoid Receptor (GR or NR3C1) may be coupled to IL-6 expression in specific cell types that govern cytokine release syndrome (CRS). Examining single cell RNA-seq data from bronchoalveolar lavage fluid of severe COVID-19 patients and nearly 2 million human cells from a pan-tissue scan shows that alveolar macrophages, smooth muscle cells, and endothelial cells co-express both NR3C1 and IL-6. The mechanism of Glucocorticoid Receptor (GR) agonists mitigating pulmonary and multi-organ inflammation in some COVID-19 patients with respiratory failure, may be in part due to their successful antagonism of IL-6 production within lung macrophages and vasculature.", "title": "Plasma IL-6 Levels following Corticosteroid Therapy as an Indicator of ICU Length of Stay in Critically ill COVID-19 Patients", "pid": "4ipq7bd4", "bm25_score": 216.45376586914062}, {"text": "Background: Evidence to support the use of steroids in COVID-19 pneumonia is lacking. We aim to determine the impact of steroid use in COVID-19 pneumonia in-hospital mortality.Patients and Methods: We performed a single-center retrospective cohort study in a University hospital in Madrid, Spain, during March 2020. To determine the role of steroids in in-hospital mortality, patients admitted with SARS-CoV-2 pneumonia and treated with steroids were compared to patients not treated with steroids, adjusting by a propensity-score for steroid treatment. Survival times were compared using log-rank test. Different steroid regimens were compared, and adjusted with a second propensity score.Results: During the study period, 463 out of 848 hospitalized patients with COVID19 pneumonia fulfilled inclusion criteria. Among them, 396 (46.7%) patients were treated with steroids and 67 patients were not. Global mortality was 15.1%. Median time to steroid treatment from symptom onset was 10 days (IQR 8-13). In-hospital mortality was lower in patients treated with steroids than in controls (13.9% [55/396] versus 23.9% [16/67], HR 0.51 [0.27-0.96], p= 0.044). Steroid treatment reduced mortality by 41.8% relative to no steroid treatment (RRR 0,42 [0.048- 0.65). Initial treatment with 1 mg/kg/day of methylprednisolone versus steroid pulses was not associated with in-hospital mortality (13.5% [42/310] versus 15.1% [13/86], OR 0.880 [0.449-1.726], p=0.710).Conclusions: Our results show that survival of patients with SARS-CoV2 pneumonia is higher in patients treated with glucocorticoids than in those not treated. In-hospital mortality was not different between initial regimens of 1 mg/kg/day of methylprednisolone and glucocorticoid pulses.", "title": "Impact of Glucocorticoid Treatment in Sars-cov-2 Infection Mortality: a Retrospective Controlled Cohort Study", "pid": "5eflvvht", "bm25_score": 216.4506072998047}, {"text": "Background Coronavirus disease 2019 (COVID-19) is becoming an increasing global health issue which has spread across the globe. We aimed to study the effect of corticosteroids in the treatment of adult inpatients with COVID-19. Methods A retrospective cohort of 115 consecutive adult COVID-19 patients admitted to The Third Peoples Hospital of Hubei Province between Jan 18, 2020, and Feb 28, 2020 was analysed to study the effectiveness of corticosteroid. They were categorized according to whether or not corticosteroid therapy was given, and compared in terms of demographic characteristics, clinical features, laboratory indicators and clinical outcomes. The primary endpoint was defined as either mortality or intensive care unit (ICU) admission. Known adverse prognostic factors were used as covariates in multiple logistic regressions to adjust for their confounding effects on outcomes. Results Among 115 patients, 73 patients (63.5%) received corticosteroid. The levels of age, C-reactive protein, D-dimer and albumin were similar in both groups. The corticosteroid group had more adverse outcomes (32.9% vs. 11.9%) and statistically significant differences were observed (p=0.013). In multivariate analysis, corticosteroid treatment was associated with a 2.155-fold increase in risk of either mortality or ICU admission, although not statistically significant. Conclusion No evidence suggests that adult patients with COVID-19 will benefit from corticosteroids, and they might be more likely to be harmed with such treatment.", "title": "No Clear Benefit to the Use of Corticosteroid as Treatment in Adult Patients with Coronavirus Disease 2019 : A Retrospective Cohort Study", "pid": "7x77e4m5", "bm25_score": 216.41490173339844}, {"text": "Addition of adjuvant corticosteroid therapy to standard antiviral treatment of patients with coronavirus disease (COVID-19) is common in clinical practice. However, evidence is scarce regarding the efficacy of adjuvant corticosteroids in patients who are critically ill. We retrospectively evaluated the effects of adjuvant corticosteroid treatment on the outcome of 244 critically ill patients with COVID-19, using a risk stratification model that adjusts for potential differences between the steroid group (n=151) and the non-steroid group (n=93). We observed that adjuvant corticosteroid therapy was independent from 28-day mortality, either in multivariate logistic regression of the entire cohort after adjustment for major mortality-associated variables (age, SpO2/FiO2, and lymphocyte count) and individual propensity score (adjusted OR: 1.05; 95% CI: -1.92-2.01), or in propensity score-matched (1:1 without replacement) case-control analysis (62 patients in 31 pairs; log-rank test P=0.17). Additionally, subgroup analyses of 147 (60%) patients who had dyspnea and 87 (36%) patients who had ARDS revealed corticosteroid treatment was not associated with clinical outcome (both, P>0.3). However, increased corticosteroids dosage was significantly associated with elevated mortality risk after adjustment for administration duration (P=0.003); every ten-milligram increase in hydrocortisone-equivalent dosage was associated with additional 4% mortality risk (adjusted HR: 1.04, 95% CI: 1.01-1.07). Our findings indicated that limited effect of corticosteroid therapy could pose to overall survival and prudent dose within effective limits may be recommended for critically ill patients under certain circumstances.", "title": "Adjuvant corticosteroid therapy for critically ill patients with COVID-19", "pid": "gi2y4jrn", "bm25_score": 216.38296508789062}, {"text": "", "title": "What can we learn about corticosteroid therapy as a treatment for COVID-19?", "pid": "0bxt3hr2", "bm25_score": 216.36366271972656}, {"text": "", "title": "Rationale for Prolonged Corticosteroid Treatment in the Acute Respiratory Distress Syndrome Caused by Coronavirus Disease 2019", "pid": "nupi7f72", "bm25_score": 216.3519744873047}, {"text": "OBJECTIVES: The aim of this study is to explore the effectiveness and safety of oral corticosteroids (prednisone) in the treatment of early stage SARS-Cov-2 pneumonia in patients who do not yet meet hospital admission criteria. TRIAL DESIGN: Randomized clinical trial, controlled, open, parallel group, to evaluate the effectiveness of steroids in adult patients with confirmed COVID-19, with incipient pulmonary involvement, without hospital admission criteria. Patients will be stratified by the presence or not of radiological data on pneumonia. PARTICIPANTS: We will include patients with early stage SARS-Cov-2 pneumonia who do not meet hospital admission criteria from the reference hospital, the Hospital Universitario de Burgos, in the region of Castilla y León, Spain. Patients will be followed-up by specialist physicians and Primary Health Care professionals. INCLUSION CRITERIA: - Men and women. - Age between 18 and 75 years old. - Diagnosed SARS-CoV-2 infection, by PCR and/or IgM+ antibody test and/or antigen test. - Clinical diagnosis of lung involvement: (respiratory symptoms +/- pathological auscultation +/- O2 desaturation) - Chest X-ray with mild-moderate alterations or normal. - Patients who give their verbal informed consent in front of witnesses, which will be reflected in the patients' medical records. EXCLUSION CRITERIA: - Oxygen desaturation below 93% or P02 < 62. - Moderate-severe dyspnea or significant respiratory or general deterioration that makes admission advisable. - Chest X-ray with multifocal infiltrates. - Insulin-dependent diabetes with poor control or glycaemia in the emergency room test greater than 300 mg/ml (fasting or not). - Other significant comorbidities: Severe renal failure (creatinine clearance < 30 mL/min); cirrhosis or chronic liver disease, poorly controlled hypertension. - Heart rhythm disturbances (including prolonged QT). - Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents); cancer. - Pregnant or breast-feeding women. - Patients under use of glucocorticoids for other diseases. - History of allergy or intolerance to any of the drugs in the study (prednisone, azithromycin or hydroxychloroquine). - Patients who took one or more of the study drugs in the 7 days prior to study inclusion. - Patients taking non-suppressible drugs with risk of QT prolongation or significant interactions. - Patients unwilling or unable to participate until study completion. - Participation in another study. INTERVENTION AND COMPARATOR: Eligible patients will be randomized to receive standard outpatient treatment only (group 1) or standard outpatient treatment plus prednisone (group 2). - Group 1: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days. - Group 2: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days + prednisone 60 mg / 24 h for 3 days, 30 mg / 24 h for 3 days and 15 mg / 24 h for 3 days. MAIN OUTCOMES: If the patient requires ambulatory observation, according to the protocol established in this respect in the Emergency Department, meets all the criteria for inclusion and none for exclusion, data will be taken by the person responsible on the data collection sheet. The main result is admission after 30 days. Secondary outcomes are 30-day ICU admission and hospital stay. The safety variable will be the occurrence of clinical symptoms or delirium related to the steroids. Also, the possible decompensations of diabetes will be measured. All tests will be on an intention-to-treat basis. RANDOMISATION: Treatment will be assigned according to stratified randomization by the presence or absence of radiological data of lung involvement (previously performed by random sequence 1:1 generated with Epidat and kept hidden by opaque, sealed envelopes, which will only be opened after inclusion and basal measurement). BLINDING (MASKING): Participants, caregivers and personnel responsible for outcomes measurement will not be blinded to group assignment, once the patient is included and the basal measurement performed, as per protocol design. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The percentage of patients with incipient lung involvement is unknown, but given that pulmonary involvement already exists it is estimated to be around 20%. We consider that the intervention could reduce this percentage to 5%, so the necessary sample size would be 200 subjects (100 per group), with a power of 80% and an estimated loss percentage of 10%. TRIAL STATUS: The protocol with code TAC-COVID-19, version 2.0 on date: April 16, 2020 is approved by the Spanish Drug Agency (AEMPS) and the local Ethics Committee. The trial is in the recruitment phase. Recruitment began 19 April, 2020 and is anticipated to be complete by April 2021. TRIAL REGISTRATION: The trial was registered under the title \"OUTPATIENT TREATMENT OF EARLY PULMONARY COVID19 WITH CORTICOSTEROIDS AS AN OPPORTUNITY TO MODIFY THE COURSE OF THE DISEASE\" with EudraCT number 2020-001622-64 , registered on 3 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.", "title": "Outpatient treatment of COVID-19 with steroids in the phase of mild pneumonia without the need for admission as an opportunity to modify the course of the disease: A structured summary of a randomised controlled trial", "pid": "bmnmwobu", "bm25_score": 216.34530639648438}, {"text": "Background Glucocorticoids are widely used in the treatment of various pulmonary inflammatory diseases, but they are also often accompanied by significant adverse reactions. Published guidelines point out that low dose and short duration systemic glucocorticoid therapy may be considered for patients with rapidly progressing coronavirus disease 2019 (COVID-19) while the evidence is still limited. Methods We comprehensively searched electronic databases and supplemented the screening by conducting a manual search. We included randomized controlled trials (RCTs) and cohort studies evaluating the effectiveness and safety of glucocorticoids in children and adults with COVID-19, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and conducted meta-analyses of the main indicators that were identified in the studies. Results Our search retrieved 23 studies, including one RCT and 22 cohort studies, with a total of 13,815 patients. In adults with COVID-19, the use of systemic glucocorticoid did not reduce mortality [risk ratio (RR) =2.00, 95% confidence interval (CI): 0.69 to 5.75, I2=90.9%] or the duration of lung inflammation [weighted mean difference (WMD) =-1 days, 95% CI: -2.91 to 0.91], while a significant reduction was found in the duration of fever (WMD =-3.23 days, 95% CI: -3.56 to -2.90). In patients with SARS, glucocorticoids also did not reduce the mortality (RR =1.52, 95% CI: 0.89 to 2.60, I2=84.6%), duration of fever (WMD =0.82 days, 95% CI: -2.88 to 4.52, I2=97.9%) or duration of lung inflammation absorption (WMD =0.95 days, 95% CI: -7.57 to 9.48, I2=94.6%). The use of systemic glucocorticoid therapy prolonged the duration of hospital stay in all patients (COVID-19, SARS and MERS). Conclusions Glucocorticoid therapy was found to reduce the duration of fever, but not mortality, duration of hospitalization or lung inflammation absorption. Long-term use of high-dose glucocorticoids increased the risk of adverse reactions such as coinfections, so routine use of systemic glucocorticoids for patients with COVID-19 cannot be recommend.", "title": "Effectiveness and safety of glucocorticoids to treat COVID-19: a rapid review and meta-analysis.", "pid": "fedbj460", "bm25_score": 216.3419189453125}, {"text": "Given the current SARS-CoV-2 (COVID-19) pandemic, the availability of reliable information for clinicians and patients is paramount. There have been a number of reports stating that non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids may exacerbate symptoms in COVID-19 patients. Therefore, this review aimed to collate information available in published articles to identify any evidence behind these claims with the aim of advising clinicians on how best to treat patients. This review found no published evidence for or against the use of NSAIDs in COVID-19 patients. Meanwhile, there appeared to be some evidence that corticosteroids may be beneficial if utilised in the early acute phase of infection, however, conflicting evidence from the World Health Organisation surrounding corticosteroid use in certain viral infections means this evidence is not conclusive. Given the current availability of literature, caution should be exercised until further evidence emerges surrounding the use of NSAIDs and corticosteroids in COVID-19 patients.", "title": "COVID-19 and treatment with NSAIDs and corticosteroids: should we be limiting their use in the clinical setting?", "pid": "0uengr9t", "bm25_score": 216.3009796142578}, {"text": "", "title": "Contrasting evidence for corticosteroid treatment for coronavirus-induced cytokine storm.", "pid": "j30x8tlz", "bm25_score": 216.2561492919922}, {"text": "", "title": "Caution against corticosteroid-based COVID-19 treatment", "pid": "bxxmetut", "bm25_score": 216.25192260742188}, {"text": "Objective: There are no controlled studies on the role of systemic corticosteroids (CS) in patients with coronavirus disease 2019 (COVID-19). In the absence of high-quality evidence, understandably the recommendations from various organizations are cautious. Several randomized controlled trials are underway but shall take time to conclude. We therefore undertook a meta-analysis to ascertain the role of CS in the management of critically ill patients with COVID-19. Data Sources: Electronic databases, including Pubmed, Cochrane library and Embase, were searched, using the keywords of interest and the PICO search technique, from inception to 12th April 2020. Study Selection: Studies highlighting the use of CS in coronavirus infection with severe acute respiratory syndrome (SARS), Middle East Respiratory Syndrome (MERS) and COVID-19 were selected based on pre-determined inclusion criteria. Data extraction: Data was extracted into an excel sheet and transferred to comprehensive meta-analysis software version 3, Biostat Inc., Englewood, NJ, USA, for analysis. Data synthesis: Five studies with SARS-CoV-2 infection were included in the meta-analysis. The rate ratio (RR) for mortality in patients with SARS-CoV-2 infection was 1.26 (95% CI: 0.96-1.65, I2: 74.46), indicating lack of benefit of CS therapy on mortality in critically ill patients with COVID-19. The RR for mortality on analysis of the three studies that particularly reported on patients with significant pulmonary compromise secondary to SARS-CoV-2 infection was neutral (RR: 0.91, 95% CI: 0.63-1.33, I2: 63.38). Conclusions: The use of CS in critically ill patients with COVID-19 did not improve or worsen mortality. Pending further information from controlled studies, CS can be used in critically ill patients with COVID-19 with critical illness related corticosteroid insufficiency and moderate to severe ARDS without the risk of increased mortality.", "title": "The role of corticosteroids in the management of critically ill patients with coronavirus disease 2019 (COVID-19): A meta-analysis", "pid": "w4ze158q", "bm25_score": 216.24591064453125}, {"text": "OBJECTIVES: The aim of this study is to explore the effectiveness and safety of oral corticosteroids (prednisone) in the treatment of early stage SARS-Cov-2 pneumonia in patients who do not yet meet hospital admission criteria. TRIAL DESIGN: Randomized clinical trial, controlled, open, parallel group, to evaluate the effectiveness of steroids in adult patients with confirmed COVID-19, with incipient pulmonary involvement, without hospital admission criteria. Patients will be stratified by the presence or not of radiological data on pneumonia. PARTICIPANTS: We will include patients with early stage SARS-Cov-2 pneumonia who do not meet hospital admission criteria from the reference hospital, the Hospital Universitario de Burgos, in the region of Castilla y León, Spain. Patients will be followed-up by specialist physicians and Primary Health Care professionals. Inclusion criteria: - Men and women. - Age between 18 and 75 years old. - Diagnosed SARS-CoV-2 infection, by PCR and/or IgM+ antibody test and/or antigen test. - Clinical diagnosis of lung involvement: (respiratory symptoms +/- pathological auscultation +/- O2 desaturation) - Chest X-ray with mild-moderate alterations or normal. - Patients who give their verbal informed consent in front of witnesses, which will be reflected in the patients’ medical records. Exclusion criteria: - Oxygen desaturation below 93% or P0(2) < 62. - Moderate-severe dyspnea or significant respiratory or general deterioration that makes admission advisable. - Chest X-ray with multifocal infiltrates. - Insulin-dependent diabetes with poor control or glycaemia in the emergency room test greater than 300 mg/ml (fasting or not). - Other significant comorbidities: Severe renal failure (creatinine clearance < 30 mL/min); cirrhosis or chronic liver disease, poorly controlled hypertension. - Heart rhythm disturbances (including prolonged QT). - Severe immunosuppression (HIV infection, long-term use of immunosuppressive agents); cancer. - Pregnant or breast-feeding women. - Patients under use of glucocorticoids for other diseases. - History of allergy or intolerance to any of the drugs in the study (prednisone, azithromycin or hydroxychloroquine). - Patients who took one or more of the study drugs in the 7 days prior to study inclusion. - Patients taking non-suppressible drugs with risk of QT prolongation or significant interactions. - Patients unwilling or unable to participate until study completion. - Participation in another study. INTERVENTION AND COMPARATOR: Eligible patients will be randomized to receive standard outpatient treatment only (group 1) or standard outpatient treatment plus prednisone (group 2). - Group 1: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days. - Group 2: paracetamol 1 g/8 h (on demand) + hydroxychloroquine 400 mg/12h the first day, 200 mg/12 h for 4 days + azithromycin 500 mg/24h for 5 days + prednisone 60 mg / 24 h for 3 days, 30 mg / 24 h for 3 days and 15 mg / 24 h for 3 days. MAIN OUTCOMES: If the patient requires ambulatory observation, according to the protocol established in this respect in the Emergency Department, meets all the criteria for inclusion and none for exclusion, data will be taken by the person responsible on the data collection sheet. The main result is admission after 30 days. Secondary outcomes are 30-day ICU admission and hospital stay. The safety variable will be the occurrence of clinical symptoms or delirium related to the steroids. Also, the possible decompensations of diabetes will be measured. All tests will be on an intention-to-treat basis. RANDOMISATION: Treatment will be assigned according to stratified randomization by the presence or absence of radiological data of lung involvement (previously performed by random sequence 1:1 generated with Epidat and kept hidden by opaque, sealed envelopes, which will only be opened after inclusion and basal measurement). BLINDING (MASKING): Participants, caregivers and personnel responsible for outcomes measurement will not be blinded to group assignment, once the patient is included and the basal measurement performed, as per protocol design. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The percentage of patients with incipient lung involvement is unknown, but given that pulmonary involvement already exists it is estimated to be around 20%. We consider that the intervention could reduce this percentage to 5%, so the necessary sample size would be 200 subjects (100 per group), with a power of 80% and an estimated loss percentage of 10%. TRIAL STATUS: The protocol with code TAC-COVID-19, version 2.0 on date: April 16, 2020 is approved by the Spanish Drug Agency (AEMPS) and the local Ethics Committee. The trial is in the recruitment phase. Recruitment began 19 April, 2020 and is anticipated to be complete by April 2021. TRIAL REGISTRATION: The trial was registered under the title “OUTPATIENT TREATMENT OF EARLY PULMONARY COVID19 WITH CORTICOSTEROIDS AS AN OPPORTUNITY TO MODIFY THE COURSE OF THE DISEASE” with EudraCT number 2020-001622-64, registered on 3 April 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.", "title": "Outpatient treatment of COVID-19 with steroids in the phase of mild pneumonia without the need for admission as an opportunity to modify the course of the disease: A structured summary of a randomised controlled trial", "pid": "woyysdvo", "bm25_score": 216.21347045898438}, {"text": "", "title": "Contrasting evidence for corticosteroid treatment for coronavirus-induced cytokine storm", "pid": "xg9nllbn", "bm25_score": 216.21334838867188}, {"text": "Background: Glucocorticoids are widely used in the treatment of various pulmonary inflammatory diseases, but they are also often accompanied by significant adverse reactions. Published guidelines point out that low dose and short duration systemic glucocorticoid therapy may be considered for patients with rapidly progressing COVID-19 while the evidence is still limited. Methods: We comprehensively searched electronic databases and supplemented the screening by conducting a manual search. We included RCTs and cohort studies evaluating the effectiveness and safety of glucocorticoids in children and adults with COVID-19, SARS and MERS, and conducted meta-analyses of the main indicators that were identified in the studies. Results: Our search retrieved 23 studies, including one RCT and 22 cohort studies, with a total of 13,815 patients. In adults with COVID-19, the use of systemic glucocorticoid did not reduce mortality (RR=2.00, 95% CI: 0.69 to 5.75, I 2=90.9%) or the duration of lung inflammation (WMD=-1 days, 95% CI: -2.91 to 0.91), while a significant reduction was found in the duration of fever (WMD=-3.23 days, 95% CI: -3.56 to -2.90). In patients with SARS, glucocorticoids also did not reduce the mortality (RR=1.52, 95% CI: 0.89 to 2.60, I2=84.6%), duration of fever (WMD=0.82 days, 95% CI: -2.88 to 4.52, I2=97.9%) or duration of lung inflammation absorption (WMD=0.95 days, 95% CI: -7.57 to 9.48, I2=94.6%). The use of systemic glucocorticoid therapy prolonged the duration of hospital stay in all patients (COVID-19, SARS and MERS). Conclusions: Glucocorticoid therapy was found to reduce the duration of fever, but not mortality, duration of hospitalization or lung inflammation absorption. Long-term use of high-dose glucocorticoids increased the risk of adverse reactions such as coinfections, so routine use of systemic glucocorticoids for patients with COVID-19 cannot be recommend. Keywords: COVID-19; glucocorticoids; meta-analysis; rapid review", "title": "Effectiveness and Safety of Glucocorticoids to Treat COVID-19: A Rapid Review and Meta-Analysis", "pid": "935r7w01", "bm25_score": 216.2095184326172}, {"text": "BACKGROUND: Anti-inflammatory drugs such as corticosteroids may beneficially modulate the host inflammatory response to CoVID-19 pneumonia. AIMS: To evaluate the impact of addition of corticosteroids to the hospital protocol for treatment of suspected or confirmed CoVID-19 pneumonia on rates of death or intensive care unit (ICU) admission. METHODS: A before-after study was performed to evaluate the effect of addition of corticosteroids to our institution's COVID-19 treatment protocol on hospital mortality. RESULTS: Between March 3(rd) and April 14(th) 2020, 257 patients with CoVID-19 diagnosis were included. As corticosteroids were wide used since 27 March 2020, two periods were considered for the purposes of our study: the before period from March 3(rd) to 20(th) (n= 85) and the “after period” (n=172) from March 26(th) to April 14(th) 2020. The “after” period was associated with a lower risk of death (HR 0.47; 95% CI, 0.23 - 0.97; p=0.04), and a lower risk of intensive care admission or death before ICU admission (HR 0.37 95% CI 0.21 - 0.64; p=0.0005) by multivariate analysis adjusted for age, National Early Warning score and institutionalization status. CONCLUSIONS: In the “after period”, the addition of corticosteroids to our institution's CoVID-19 treatment protocol was associated with a significant reduction in hospital mortality.", "title": "Corticosteroid therapy for patients with CoVID-19 pneumonia: a before-after study", "pid": "vefgi5h6", "bm25_score": 216.1961212158203}, {"text": "Background: Dexamethasone, a synthetic glucocorticoid, has anti-inflammatory and immunosuppressive properties. There is a hyperinflammatory response involved in the clinical course of patients with pneumonia due to SARS-CoV2. To date, there has been no definite therapy for COVID-19. We reviewed the charts of SARS-CoV2 patients with pneumonia and moderate to severely elevated CRP and worsening hypoxemia who were treated with early, short-term dexamethasone. Methods: We describe a series of 21 patients who tested positive for SARS-CoV2 and were admitted to The Miriam Hospital in Providence and were treated with a short course of dexamethasone, either alone or in addition to current investigative therapies. Results: CRP levels decreased significantly following the start of dexamethasone from mean initial levels of 129.52 to 40.73 mg/L at time of discharge. 71% percent of the patients were discharged home with a mean length of stay of 7.8 days. None of the patients had escalation of care, leading to mechanical ventilation. Two patients were transferred to inpatient hospice facilities on account of persistent hypoxemia, in line with their documented goals of care. Conclusions: A short course of systemic corticosteroids among inpatients with SARS-CoV2 with hypoxic respiratory failure was well tolerated, and most patients had improved outcomes. This limited case series may not offer concrete evidence towards the benefit of corticosteroids in COVID-19. However, patients positive response to short-term corticosteroids demonstrates that they may help blunt the severity of inflammation and prevent a severe hyperinflammatory phase, in turn reducing the length of stay, ICU admissions, and healthcare costs.", "title": "Short-Term Corticosteroids in SARS-CoV2 Patients: Hospitalists' Perspective", "pid": "oqgw6ao6", "bm25_score": 216.19158935546875}, {"text": "The use of corticosteroids has been controversial in viral pneumonia. In most cases, application of methylprednisolone in severe and critical viral pneumonia patients can quickly alleviate the symptoms of dyspnea and prevent disease progression. However, some scholars have confirmed that corticosteroids delayed the body's clearance of the virus. In our retrospective non-randomised study, 34 patients under 50 years old and diagnosed with coronavirus disease 2019 (COVID-19) were included, according to given methylprednisolone treatment (n = 18) or not (n = 16), they were separated into 2 groups. By comparing the clinical data we concluded that corticosteroids therapy can effectively release COVID-19 symptoms such as persistent fever and difficult breathing, improve oxygenation and prevent disease progression. However, it can prolong the negative conversion of nucleic acids. This article is protected by copyright. All rights reserved.", "title": "Effects of methylprednisolone use on viral genomic nucleic acid negative conversion and CT imaging lesion absorption in COVID-19 patients under 50 years old", "pid": "xq1lqjua", "bm25_score": 216.1471710205078}, {"text": "BACKGROUND Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. METHODS We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. RESULTS In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. INTERPRETATION Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.", "title": "Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis.", "pid": "ivm2d5rl", "bm25_score": 216.1467742919922}, {"text": "OBJECTIVES: To assess the efficacy of corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19). DESIGN, SETTING: Observational study in the two COVID-19-designated hospitals in Wuhu, Anhui province, China, 24 January - 24 February 2020. PARTICIPANTS: Thirty-one patients infected with the severe acute respiratory coronavirus 2 (SARS-CoV-2) treated at the two designated hospitals. MAIN OUTCOME MEASURES: Virus clearance time, length of hospital stay, and duration of symptoms, by treatment type (including or not including corticosteroid therapy). RESULTS: Eleven of 31 patients with COVID-19 received corticosteroid treatment. Cox proportional hazards regression analysis indicated no association between corticosteroid treatment and virus clearance time (hazard ratio [HR], 1.26; 95% CI, 0.58-2.74), hospital length of stay (HR, 0.77; 95% CI, 0.33-1.78), or duration of symptoms (HR, 0.86; 95% CI, 0.40-1.83). Univariate analysis indicated that virus clearance was slower in two patients with chronic hepatitis B infections (mean difference, 10.6 days; 95% CI, 6.2-15.1 days). CONCLUSIONS: Corticosteroids are widely used when treating patients with COVID-19, but we found no association between therapy and outcomes in patients without acute respiratory distress syndrome. An existing HBV infection may delay SARS-CoV-2 clearance, and this association should be further investigated.", "title": "Corticosteroid treatment of patients with coronavirus disease 2019 (COVID-19)", "pid": "5x1gwcxf", "bm25_score": 216.14666748046875}, {"text": "", "title": "ACTH 1-24 and other melanocortins for COVID-19 treatment", "pid": "ogb0moa3", "bm25_score": 216.14511108398438}, {"text": "", "title": "Blocking mineralocorticoid receptor with spironolactone may have a wide range of therapeutic actions in severe COVID-19 disease", "pid": "l5jtclf6", "bm25_score": 216.11764526367188}, {"text": "Timely and appropriate application of methylprednisolone in severe and critical COVID-19 patients could effectively avoid invasive mechanical ventilation and reduce the mortality.", "title": "Successful use of methylprednisolone for treating severe COVID-19", "pid": "b7snms9w", "bm25_score": 216.11474609375}, {"text": "BACKGROUND: Anti-inflammatory drugs such as corticosteroids may beneficially modulate the host inflammatory response to CoVID-19 pneumonia. AIMS: To evaluate the impact of addition of corticosteroids to the hospital protocol for treatment of suspected or confirmed CoVID-19 pneumonia on rates of death or intensive care unit (ICU) admission. METHODS: A before-after study was performed to evaluate the effect of addition of corticosteroids to our institution's COVID-19 treatment protocol on hospital mortality. RESULTS: Between March 3rd and April 14th 2020, 257 patients with CoVID-19 diagnosis were included. As corticosteroids were wide used since 27 March 2020, two periods were considered for the purposes of our study: the before period from March 3rd to 20th (n= 85) and the \"after period\" (n=172) from March 26th to April 14th 2020. The \"after\" period was associated with a lower risk of death (HR 0.47; 95% CI, 0.23 - 0.97; p=0.04), and a lower risk of intensive care admission or death before ICU admission (HR 0.37 95% CI 0.21 - 0.64; p=0.0005) by multivariate analysis adjusted for age, National Early Warning score and institutionalization status. CONCLUSIONS: In the \"after period\", the addition of corticosteroids to our institution's CoVID-19 treatment protocol was associated with a significant reduction in hospital mortality.", "title": "Corticosteroid therapy for patients with CoVID-19 pneumonia: a before-after study", "pid": "60d5mt42", "bm25_score": 216.1103515625}, {"text": "The COVID‐19 outbreak has disrupted global health care networks and caused thousands of deaths and an international economic downturn. Multiple drugs are being used on patients with COVID‐19 based on theoretical and in vitro therapeutic targets. Several of these therapies have been studied, but many have limited evidence behind their use, and clinical trials to evaluate their efficacy are either ongoing or have not yet begun. This review summarizes the existing evidence for medications currently under investigation for treatment of COVID‐19, including remdesivir, chloroquine/hydroxychlorquine, convalescent plasma, lopinavir/ritonavir, IL‐6 inhibitors, corticosteroids, and angiotensin‐converting enzyme inhibitors.", "title": "COVID‐19: A review of therapeutics under investigation", "pid": "j2u0ny2u", "bm25_score": 216.07693481445312}, {"text": "Background: Systemic corticosteroids are recommended by some treatment guidelines and used in severe and critical COVID-19 patients, though evidence supporting such use is limited. Methods: From December 26, 2019 to March 15, 2020, 1514 severe and 249 critical hospitalized COVID-19 patients were collected from two medical centers in Wuhan, China. We performed multivariable Cox models, Cox model with time-varying exposure and propensity score analysis (both inverse-probability-of-treatment-weighting (IPTW) and propensity score matching (PSM)) to estimate the association of corticosteroid use with the risk of in-hospital mortality among severe and critical cases. Results: Corticosteroids were administered in 531 (35.1%) severe and 159 (63.9%) critical patients. Compared to no corticosteroid use group, systemic corticosteroid use showed no benefit in reducing in-hospital mortality in both severe cases (HR=1.77, 95% CI: 1.08-2.89, p=0.023), and critical cases (HR=2.07, 95% CI: 1.08-3.98, p=0.028). In the time-varying Cox analysis that with time varying exposure, systemic corticosteroid use still showed no benefit in either population (for severe patients, HR=2.83, 95% CI: 1.72-4.64, p< 0.001; for critical patients, HR=3.02, 95% CI: 1.59-5.73, p=0.001). Baseline characteristics were matched after IPTW and PSM analysis. For severe COVID-19 patients at admission, corticosteroid use was not associated with improved outcome in either the IPTW analysis. For critical COVID-19 patients at admission, results were consistent with former analysis that corticosteroid use did not reduce in-hospital mortality. Conclusions: Corticosteroid use showed no benefit in reducing in-hospital mortality for severe or critical cases. The routine use of systemic corticosteroids among severe and critical COVID-19 patients was not recommended.", "title": "Systemic corticosteroids show no benefit in severe and critical COVID-19 patients in Wuhan, China: A retrospective cohort study", "pid": "4yjyqjpe", "bm25_score": 216.07376098632812}, {"text": "", "title": "On the use of corticosteroids for 2019-nCoV pneumonia", "pid": "zyv6lg05", "bm25_score": 216.06158447265625}, {"text": "Background: Severe patients with 2019 novel coronavirus (2019-nCoV) pneumonia progressed rapidly to acute respiratory failure. We aimed to evaluate the definite efficacy and safety of corticosteroid in the treatment of severe COVID-19 pneumonia. Methods: Forty-six hospitalized patients with severe COVID-19 pneumonia hospitalized at Wuhan Union Hospital from January 20 to February 25, 2020, were retrospectively reviewed. The patients were divided into two groups based on whether they received corticosteroid treatment. The clinical symptoms and chest computed tomography(CT) results were compared. Results: A total of 26 patients received intravenous administration of methylprednisolone with a dosage of 1-2mg/kg/d for 5-7 days, while the remaining patients not. There was no significant difference in age, sex, comorbidities, clinical or laboratory parameters between the two groups on admission. The average number of days for body temperature back to the normal range was significantly shorter in patients with administration of methylprednisolone when compared to those without administration of methylprednisolone (2.06 ± 0.28 vs. 5.29 ± 0.70, P=0.010). The patients with administration of methylprednisolone had a faster improvement of SpO2, while patients without administration of methylprednisolone had a significantly longer interval of using supplemental oxygen therapy (8.2days[IQR 7.0-10.3] vs. 13.5days(IQR 10.3-16); P<0.001). In terms of chest CT, the absorption degree of the focus was significantly better in patients with administration of methylprednisolone. Conclusion: Our data indicate that in patients with severe COVID-19 pneumonia, early, low-dose and short-term application of corticosteroid was associated with a faster improvement of clinical symptoms and absorption of lung focus.", "title": "Early, low-dose and short-term application of corticosteroid treatment in patients with severe COVID-19 pneumonia: single-center experience from Wuhan, China", "pid": "23mp5961", "bm25_score": 216.0521240234375}, {"text": "The article provides a review of foreign literature for 2020 on existing methods of drug treatment of coronavirus disease COVID-19. To date, in the treatment of COVID-19 in different countries, a little more than 10 drugs are used. The largest number of studies on the testing of these drugs is carried out by scientists from China, the USA, and European countries. It should be noted that among these drugs there is not a single new drug developed specifically for the treatment of COVID-19, the recommended and used drugs have previously been used to treat, as a rule, diseases of the viral etiology, less often another pathology. These suggestions are often based on analogy, the hypothesis of their supposed effectiveness for COVID-19. It can be assumed that a brake on the development of a drug specific for coronavirus disease is a poor knowledge of the pathogenesis of virus invasion in the body's adhesives and the development of complications. The review provides detailed literature data on drugs such as hydroxychloroquine / chloroquine, lopinavir/natinavir, remdesivir, ACE inhibitors and angiotensin converting enzyme receptor blockers, tissue plasminogen activator, as well as plasma transfusion transfusions.", "title": "[Drug treatment of coronavirus disease COVID-19: evidence exists?]", "pid": "ec5a65l8", "bm25_score": 215.9972686767578}, {"text": "The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has presented many challenges in healthcare, including obstetrics. Therefore, we read with great interest the special editorial published in the AOGS regarding clinical recommendations for the management of coronavirus disease 2019 (COVID-19) in pregnant women.1 As illustrated by the authors, the usefulness and safety of corticosteroids as an adjuvant therapy for COVID-19 pneumonia remains controversial. Corticosteroids may diminish the inflammatory response, a major factor for lung damage and acute respiratory distress syndrome in viral respiratory tract infection. However, previous studies on corticosteroid therapy in severe acute respiratory syndrome coronavirus and Middle East respiratory syndrome coronavirus illustrated delayed viral clearance, with no survival benefit and perhaps even adverse outcomes.2 Some patients with COVID-19 exhibit biphasic disease evolution with a mild presentation followed by a secondary respiratory deterioration due to a cytokine storm, despite decreasing viral load.2 Therefore, timing of corticosteroid therapy might be particularly consequential, with early administration reducing inflammatory response and viral clearance during the initial phase.", "title": "Antenatal corticosteroid therapy and COVID‐19: Pathophysiological considerations", "pid": "kd5h3r28", "bm25_score": 215.9969482421875}, {"text": "Emergency department management of hypoxemia in the setting of COVID-19 is riddled with uncertainty. The lack of high-quality research has translated to an absence of clarity at the bedside. With disease spread outpacing treatment consensus, provider discretion has taken on a heightened role. Here, we report a case of dexmedetomidine use in the setting of worsening hypoxemia, whereby oxygenation improved and intubation was avoided. Well known pharmacologic properties of the drug, namely the lack of respiratory depression and its anti-delirium effects, as well as other possible physiologic effects, suggest potential benefit for patients being managed with a delayed intubation approach. If dexmedetomidine can improve compliance with non-invasive oxygen support (the current recommended first-line therapy) while promoting better oxygenation, it may also decrease the need for mechanical ventilation and thus improve mortality.", "title": "Dexmedetomidine and worsening hypoxemia in the setting of COVID-19: A case report", "pid": "wnxm9t5y", "bm25_score": 215.96441650390625}, {"text": "Coronavirus disease 2019 (COVID-19) is a global health crisis. There is currently a great need for effective and safe therapies directed at the disease, but no drugs are presently registered for use in COVID-19. Several directed therapies have been proposed, and most are still in clinical trials. Currently available published, peer-reviewed results mostly involve small sample sizes with study limitations restricting the interpretation of the findings. Many trials currently published also do not have a control group, limiting the interpretation of the effect of the intervention. Investigational directed therapies as well as investigational supportive therapies against COVID-19 are reviewed here. Chloroquine and hydroxychloroquine show promise as directed therapies, but current trial results are conflicting. Lopinavir/ritonavir also shows potential, but was started late in the disease course in most trials. No randomised controlled evidence is currently available for remdesivir and favipiravir. Corticosteroid use is not recommended for directed therapy against COVID-19, and the role of tocilizumab is currently unclear, based on limited evidence. Early initiation of investigational directed therapies may provide benefit in selected patients. The results from larger randomised controlled trials will clarify the place of these therapies in COVID-19 treatment.", "title": "Current evidence for directed and supportive investigational therapies against COVID-19", "pid": "f33eb1nf", "bm25_score": 215.94937133789062}, {"text": "The use of corticosteroids has been controversial in viral pneumonia. In most cases, application of methylprednisolone in severe and critical viral pneumonia patients can quickly alleviate the symptoms of dyspnea and prevent disease progression. However, some scholars have confirmed that corticosteroids delayed the body's clearance of the virus. In our retrospective non‐randomised study, 34 patients under 50 years old and diagnosed with coronavirus disease 2019 (COVID‐19) were included, according to given methylprednisolone treatment (n = 18) or not (n = 16), they were separated into 2 groups. By comparing the clinical data we concluded that corticosteroids therapy can effectively release COVID‐19 symptoms such as persistent fever and difficult breathing, improve oxygenation and prevent disease progression. However, it can prolong the negative conversion of nucleic acids. This article is protected by copyright. All rights reserved.", "title": "Effects of methylprednisolone use on viral genomic nucleic acid negative conversion and CT imaging lesion absorption in COVID‐19 patients under 50 years old", "pid": "jx1ws18b", "bm25_score": 215.94723510742188}, {"text": "", "title": "Use of glucocorticoids in patients with adrenal insufficiency and COVID-19 infection", "pid": "mvgdi8o6", "bm25_score": 215.94691467285156}, {"text": "BACKGROUND: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses. METHODS: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects. RESULTS: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia. INTERPRETATION: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.", "title": "Efficacy and safety of corticosteroids in COVID-19 based on evidence for COVID-19, other coronavirus infections, influenza, community-acquired pneumonia and acute respiratory distress syndrome: a systematic review and meta-analysis", "pid": "r8rd5f2j", "bm25_score": 215.94651794433594}, {"text": "More than 1,200 active or recruiting clinical trials for novel coronavirus disease 2019 (COVID-19) treatments and vaccines are registered. Many drugs have shown promise for treatment of COVID-19. Nevertheless, up to date, no drugs have been confirmed as a definitive treatment for COVID-19. Trials such as the SOLIDARITY and RECOVERY are ongoing, and first results were announced in favour of therapy with dexamethasone with a significant trend showing greatest benefit among those patients requiring ventilation. The drawbacks of these trials include exposing the patients to drugs with well-documented systemic adverse effects or unknown complications of novel therapies without proof of clinical benefit. We present here the hypothesis that bronchial artery infusion could be an alternative for systemic drug infusion in COVID-19 trials with superadded benefits of high drug concentration and low systemic adverse effects. The concept of this idea has many uncertainties and no current clinical data to support. Perhaps, the technique should be first applied in animal models to determine its safety and calculate the effective dose of the drugs. Guidelines and reviews of pharmacotherapy for COVID-19 should be implemented for this fiction to come true.", "title": "Transcatheter drug delivery through bronchial artery for COVID-19: is it fiction or could it come true?", "pid": "ylcaw0vi", "bm25_score": 215.93353271484375}, {"text": "", "title": "Evidence of Steroids in Patients With Acute Respiratory Distress Syndrome in Coronavirus Disease 2019", "pid": "xc3prue7", "bm25_score": 215.92233276367188}, {"text": "Since the outbreak of COVID-19, chloroquine has been mentioned as a possible treatment. In vitro studies have shown anti-viral activity of chloroquine against SARS-CoV-2. Recently, the Dutch National Institute for Public Health and the Environment published treatment options for antiviral treatment for COVID-19 where chloroquine was suggested as first choice for off-label treatment, beside remdesivir en lopinavir/ritonavir. In this commentary, we provide a background and history of chloroquine, the evidence for antiviral efficacy of chloroquine and the arguments for off-label use of chloroquine in COVID-19.", "title": "[Chloroquine as a possible treatment for COVID-19].", "pid": "mgsvg5gu", "bm25_score": 215.9107666015625}, {"text": "The following systematic review and meta-analysis compile the current data regarding human controlled COVID-19 treatment trials. An electronic search of the literature compiled studies pertaining to human controlled treatment trials with COVID-19. Medications assessed included lopinavir/ritonavir, arbidol, hydroxychloroquine, tocilizumab, favipiravir, heparin, and dexamethasone. Statistical analyses were performed for common viral clearance endpoints whenever possible. Lopinavir/ritonavir showed no significant effect on viral clearance for COVID-19 cases (OR 0.95 [95% CI 0.50–1.83]). Hydroxychloroquine also showed no significant effect on COVID-19 viral clearance rates (OR 2.16 [95% CI 0.80–5.84]). Arbidol showed no 7-day (OR 1.63 [95% CI 0.76–3.50]) or 14-day viral (OR 5.37 [95% CI 0.35–83.30]) clearance difference compared to lopinavir/ritonavir. Review of literature showed no significant clinical improvement with lopinavir/ritonavir, arbidol, hydroxychloroquine, or remdesivir. Tocilizumab showed mixed results regarding survival. Favipiravir showed quicker symptom improvement compared to lopinavir/ritonavir and arbidol. Heparin and dexamethasone showed improvement with severe COVID-19 cases requiring supplemental oxygenation. Current medications do not show significant effect on COVID-19 viral clearance rates. Tocilizumab showed mixed results regarding survival. Favipiravir shows favorable results compared to other tested medications. Heparin and dexamethasone show benefit especially for severe COVID-19 cases.", "title": "Systematic and Statistical Review of Coronavirus Disease 19 Treatment Trials", "pid": "07tdrd4w", "bm25_score": 215.8872833251953}, {"text": "The coronavirus disease 2019 (COVID-19) is an emerging pandemic challenge. Acute respiratory distress syndrome (ARDS) in COVID-19 is characterized by a severe cytokine storm. Patients undergoing glucocorticoid (GC) replacement therapy for adrenal insufficiency (AI) represent a highly vulnerable group that could develop severe complications due to the SARS-CoV-2 infection. In this review, we highlight the strategies to avoid an adrenal crisis in patients with AI and COVID-19. Adrenal crisis is a medical emergency and an important cause of death. Once patients with AI present symptoms of COVID-19, the dose of GC replacement therapy should be immediately doubled. In the presence of any emergency warning signs or inability to administer oral GC doses, we recommend that patients should immediately seek Emergency services to evaluate COVID-19 symptoms and receive 100 mg hydrocortisone by intravenous injection, followed by 50 mg hydrocortisone intravenously every 6 h or 200 mg/day by continuous intravenous infusion.", "title": "Adrenal Insufficiency and Glucocorticoid Use During the COVID-19 Pandemic", "pid": "kpff55on", "bm25_score": 215.86959838867188}, {"text": "BACKGROUND There are no completed randomised trials of the use of corticosteroids in patients with severe influenza infection. Corticosteroid use in influenza is widespread, non-systematic and marked by controversy. A recent meta-analysis of observational studies of adjuvant corticosteroids in influenza found an association with increased mortality but there were important concerns regarding the risks of bias. OBJECTIVES To (1) evaluate whether or not low-dose corticosteroids given as an adjunct to standard treatment is beneficial in patients who are hospitalised with severe pandemic influenza and (2) develop an 'off-the-shelf' clinical trial that is ready to be activated in a future pandemic. DESIGN Multicentre, pragmatic, blinded, randomised placebo-controlled trial. SETTING Thirty to 40 hospitals in the UK. PARTICIPANTS Adults (≥ 16 years) admitted to hospital with an influenza-like illness during a pandemic. INTERVENTION Five-day course of dexamethasone (Dexsol®, Rosemont Pharmaceuticals Ltd) 6 mg daily, started within 24 hours of admission. MAIN OUTCOME MEASURE Admission to Intensive Care Unit, or death, within 30 days of admission to hospital. RESULTS This trial has not yet been activated. It is currently set up with full ethics and regulatory approvals in place, ready for rapid activation at the onset of the next pandemic. Hurdles to setting up a pandemic trial include planning for pandemic-level pressures on UK NHS resources and co-enrolment of patients to multiple pandemic studies, ensuring adequate geographical distribution of participating sites, maintaining long-term low-level engagement with site investigators, addressing future trial-specific training needs of local investigators and resilience planning in trial management. Identified threats to trial delivery include changes to research capabilities or policies during the hibernation phase, lack of staff resources during a pandemic and the influence of media at the time of a pandemic. A mismatch in the approach to informed consent required by current regulations to that preferred by patients and the public was identified. CONCLUSIONS This study demonstrates that advance set-up of a trial to be conducted during a pandemic, with full regulatory approvals in place, is possible. Regular review during the hibernation phase will be required. This study serves as a model for the development of other 'off-the-shelf' trials as part of preparedness planning for public health emergencies. TRIAL REGISTRATION Current Controlled Trials ISRCTN72331452. European Union Drug Regulating Authorities Clinical Trials number: 2013-001051-12. FUNDING This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 19, No. 16. See the NIHR Journals Library website for further project information.", "title": "Blinded randomised controlled trial of low-dose Adjuvant Steroids in Adults admitted to hospital with Pandemic influenza (ASAP): a trial 'in hibernation', ready for rapid activation.", "pid": "dzy34m94", "bm25_score": 215.853759765625}, {"text": "The outbreak of SARS-CoV-2 rapidly spread across China and worldwide. Remdesivir had been proposed as a promising option for treating coronavirus disease 2019 (COVID-19). We provided a rapid review to critically assess the potential anti-coronavirus effect of remdesivir on COVID-19 and other coronaviruses based on the most up-to-date evidence. Even though remdesivir was proposed as a promising option for treating COVID-19 based on laboratory experiments and reports from compassionate use, its safety and effect in humans requires high-quality evidence from well-designed and adequately-powered clinical trials for further clarification.", "title": "Rapid review for the anti-coronavirus effect of remdesivir.", "pid": "4el6qq3n", "bm25_score": 215.85128784179688}, {"text": "The severity of COVID-19 has resulted in a global rush to find the right antiviral treatment to conquer the pandemic and to treat patients. This requires reliable studies to support treatment. In a recently published study by Gautret et al. the authors concluded that hydroxychloroquine monotherapy and hydroxychloroquine in combination with azithromycin reduced viral load. However, this trial has several major methodological issues, including the design, outcome measure and the statistical analyses. In this paper we discuss the background, clinical evidence, pharmacology and methodological issues related to this clinical trial. We understand the rush to release results, however in case conclusions are far reaching the evidence needs to be robust.", "title": "Reply to Gautret et al: hydroxychloroquine sulfate and azithromycin for COVID-19: what is the evidence and what are the risks?", "pid": "wnb4cltt", "bm25_score": 215.8440704345703}, {"text": "The outbreak of severe acute respiratory syndrome‐related coronavirus 2 (SARS‐CoV‐2) started in Wuhan China, has become a global health concern. At present, glucocorticoid therapy is one of the most typically controversial treatments with COVID‐19 patients. Here, we reported an asymptomatic COVID‐19 patient with persistent positive detection of SARS‐CoV‐2 for 3 weeks and proposed that glucocorticoid therapy delays the clearance of SARS‐CoV‐2 RNA. Therefore, more attention must be paid to the COVID‐19 patients receiving glucocorticoid therapy. This article is protected by copyright. All rights reserved.", "title": "Glucocorticoid therapy delays the clearance of SARS‐CoV‐2 RNA in an asymptomatic COVID‐19 patient", "pid": "4j4bdh0q", "bm25_score": 215.84226989746094}, {"text": "", "title": "Corticosteroid use for 2019-nCoV infection: A double-edged sword", "pid": "q4cgt376", "bm25_score": 215.8361053466797}, {"text": "In less than six months, COVID-19 has spread from a marketplace in Wuhan, China to over 150 countries and territories of the world. Therapeutics are desperately needed to reduce the morbidity and mortality of this pandemic disease. It has been reported that hydroxychloroquine (HCQ) is active against SARS-CoV-2 in vitro, and this finding was quickly supported by an open label non-randomized clinical trial that provided the first published clinical evidence HCQ may be a treatment option.", "title": "Hydroxychloroquine for Treatment of SARS‐CoV‐2 Infection? Improving Our Confidence in a Model‐Based Approach to Dose Selection", "pid": "248de4cj", "bm25_score": 215.823486328125}, {"text": "Influenza-related severe pneumonia and acute respiratory distress syndrome (ARDS) are severe threats to human health. The objective of this study was to assess the effects of systematic corticosteroid therapy in patients with pneumonia or ARDS. The PubMed, EMBASE, Web of Science and SCOPUS databases were searched up to July, 2019. Nineteen studies including 6637 individuals were identified, and fifteen studies (6427 patients) were included in the meta-analysis of mortality. Eighteen were observational studies and one was a randomized controlled trial (RCT). The meta-analysis results showed that corticosteroid therapy was associated with significantly higher mortality (OR 1.53, 95% CI [1.16, 2.01]) and incidence of nosocomial infection (OR 3.15, 95% CI [1.54, 6.45]). Subgroup analysis showed that among patients with unadjusted estimates, the odds of mortality were higher in patients receiving corticosteroid treatment (OR 1.98, 95% CI [1.23, 3.17]), however, among patients with adjusted estimates, the result showed no statistically significant difference between corticosteroid group and control group (OR 1.31, 95% CI [0.95, 1.80]). Current data do not support the routine use of corticosteroids in patients with influenza severe pneumonia or ARDS. RCTs are needed to provide more robust evidence.", "title": "Use of corticosteroids in influenza-associated acute respiratory distress syndrome and severe pneumonia: a systemic review and meta-analysis", "pid": "xna32qve", "bm25_score": 215.82261657714844}, {"text": "BACKGROUND AND OBJECTIVE: The effects of corticosteroid treatment on non-severe COVID-19 pneumonia patients are unknown. To determine the impacts of adjuvant corticosteroid administrated to patients with non-severe COVID-19 pneumonia. METHOD: A retrospective cohort study based on propensity score analysis was designed to explore the effects of corticosteroid on several clinical outcomes. RESULTS: 132 patients satisfied the inclusion criteria and 35 pairs were generated according to propensity score matching. Compared to non-corticosteroid group, the CT score on day 7 was significantly higher in corticosteroid group (8.6 (IQR, 2.8-11.5) versus 12.0 (IQR, 5.0-19.3), P = 0.046). In corticosteroid group, more patients progressed to severe cases (11.4% versus 2.9%, P = 0.353), hospital stay (23.5 days (IQR, 19-29 d) versus 20.2 days (IQR, 14-25.3 d), P = 0.079) and duration of viral shedding (20.3 days (IQR, 15.2-24.8 d) versus 19.4 days (IQR, 11.5-28.3 d), P = 0.669) were prolonged, while fever time (9.5 days (IQR, 6.5-12.2 d) versus 10.2 days (IQR, 6.8-14 d), P = 0.28) was shortened, however all these data revealed no statistically significant differences. CONCLUSION: Corticosteroid might have a negative effect on lung injury recovery in non-severe COVID-19 pneumonia patients, however the results of this study must be interpreted with caution because of confounding factors.", "title": "Effects of Corticosteroid Treatment for Non-Severe COVID-19 Pneumonia: A Propensity Score-Based Analysis", "pid": "618tsmvx", "bm25_score": 215.81874084472656}, {"text": "", "title": "COVID-19 infection and glucocorticoids: update from the Italian Society of Endocrinology Expert Opinion on steroid replacement in adrenal insufficiency", "pid": "wfaqzdsa", "bm25_score": 215.7968292236328}, {"text": "", "title": "Covid-19: Low dose steroid cuts death in ventilated patients by one third, trial finds.", "pid": "r2n60nuk", "bm25_score": 215.73983764648438}, {"text": "Objective@#To study the effect of low-to-moderate dose glucocorticoid therapy on viral clearance time in patients with COVID-19.@*Methods@#A total of 72 patients diagnosed with COVID-19 from January 19 to February 17, 2020 at the First Affiliated Hospital, School of Medicine, Zhejiang University were recruited. All patients received oral abidol and/or combined lopinavir/ritonavir, darunavir antiviral, and symptomatic supportive care. Among them, 51 patients received methylprednisolone (0.75-1.50 mg·kg-1·d-1) (glucocorticoid treatment group), and 21 patients who did not use glucocorticoid were the control group. The time of stable virologic conversion insputumand the time of radiologic recovery in lungsince onset were compared between the two groups and among the normal patients.The Kruskal-Wallis test or Fisher exact test was used to compare the difference between groups.@*Results@#The median ages of the glucocorticoid group and the control group were 52 [interquartile range (IQR):45, 62] years and 46 (IQR: 32, 56)years, and the differences were significant (P&lt;0.05). The clinical conditions at hospital admission were different between the two groups (P&lt;0.01). There were 52.0% critical ill patients in the glucocorticoid treatment group, compared to that of 71.4% normal patients in the control group. The median times from the onset tostable virologic conversion to negative in the two groups were 15 (IQR:13,20) days and 14 (IQR:12,20) days (P&gt;0.05), and the difference was no statistically significant. The median times from onset to radiologic recovery were 13 (IQR: 11,15) days and 13 (IQR:12,17) days in the two groups, and there was no difference (P&gt;0.05). In ordinary patients, the median timesfrom the onset tostable virologic conversion insputum were no difference (P&gt;0.05), with 13 (IQR:11,18) days in the glucocorticoid group and 13 (IQR:12,15) days in the control group; The median times from onset to radiologic recovery in lungwere also no difference (P&gt;0.05), with 12 (IQR: 10,15)days in the glucocorticoid group and 13 (IQR: 12,17) days inthe control group.@*Conclusions@#Low-to-moderate glucocorticoid treatment has no effect on the time of virus clearance in patients with different clinical types of COVID-19. The glucocorticoid is not recommended since no effectiveness on accelerating the improvement of radiologic recovery in lung has been observed.", "title": "Retrospective study of low-to-moderate dose glucocorticoids on viral clearance in patients with novel coronavirus pneumonia/ 中华临床感染病杂志", "pid": "4ars6hlm", "bm25_score": 215.73715209960938}, {"text": "BACKGROUND AND OBJECTIVE The effects of corticosteroid treatment on non-severe COVID-19 pneumonia patients are unknown. To determine the impacts of adjuvant corticosteroid administrated to patients with non-severe COVID-19 pneumonia. METHOD A retrospective cohort study based on propensity score analysis was designed to explore the effects of corticosteroid on several clinical outcomes. RESULTS 132 patients satisfied the inclusion criteria and 35 pairs were generated according to propensity score matching. Compared to non-corticosteroid group, the CT score on day 7 was significantly higher in corticosteroid group (8.6 (IQR, 2.8-11.5) versus 12.0 (IQR, 5.0-19.3), P = 0.046). In corticosteroid group, more patients progressed to severe cases (11.4% versus 2.9%, P = 0.353), hospital stay (23.5 days (IQR, 19-29 d) versus 20.2 days (IQR, 14-25.3 d), P = 0.079) and duration of viral shedding (20.3 days (IQR, 15.2-24.8 d) versus 19.4 days (IQR, 11.5-28.3 d), P = 0.669) were prolonged, while fever time (9.5 days (IQR, 6.5-12.2 d) versus 10.2 days (IQR, 6.8-14 d), P = 0.28) was shortened, however all these data revealed no statistically significant differences. CONCLUSION Corticosteroid might have a negative effect on lung injury recovery in non-severe COVID-19 pneumonia patients, however the results of this study must be interpreted with caution because of confounding factors.", "title": "Effects of Corticosteroid Treatment for Non-Severe COVID-19 Pneumonia: A Propensity Score-Based Analysis.", "pid": "h4usqen6", "bm25_score": 215.7241668701172}, {"text": "The COVID-19 pandemic represents the greatest global public health crisis since the pandemic influenza outbreak of 1918. We are facing a new virus, so several antiviral agents previously used to treat other coronavirus infections such as SARS and MERS are being considered as the first potential candidates to treat COVID-19. Thus, several agents have been used by the beginning of the current outbreak in China first and all over the word successively, as reported in several different guidelines and therapeutic recommendations. At the same time, a great number of clinical trials have been launched to investigate the potential efficacy therapies for COVID-19 highlighting the urgent need to get as quickly as possible high-quality evidence. Through PubMed, we explored the relevant articles published on treatment of COVID-19 and on trials ongoing up to April 15, 2020.", "title": "Update on treatment of COVID-19: ongoing studies between promising and disappointing results.", "pid": "nmntjk0i", "bm25_score": 215.71932983398438}, {"text": "Although there are few randomized controlled trials (RCTs) evaluating the efficacy of drugs to treat COVID-19, different molecules have been used empirically and with great interest in those intended to control the excessive inflammatory response produced by SARS-CoV-2. By blocking the IL-6 receptor, tocilizumab has a role in controlling the inflammatory response. Clinical improvement of respiratory parameters and hospital stay have been described in small series in a series of patients without a control group [1]. There are currently numerous ongoing clinical trials aimed to clarifying the role of this molecule in COVID-19. The guidelines for the treatment of SARS-CoV-2 pneumonia from the Spanish Ministry of Health contemplate the use of tocilizumab as a therapeutic tool for those patients with severe respiratory failure or rapid respiratory deterioration with criteria for admission to the intensive care unit (ICU).", "title": "Methylprednisolone added to tocilizumab reduces mortality in SARS-CoV-2 pneumonia: An observational study", "pid": "4zuejb0u", "bm25_score": 215.71034240722656}]}
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underrepresented during the current COVID-19 outbreak. Unlike other respiratory viruses, SARS-CoV-2 rather infects adults who subsequently infect their children. From recent Chinese and Italian data, children commonly present mild to moderate disease, a large proportion of them being asymptomatic. In particular, children present significantly less fever, cough and pneumonia compared to adults. However, more cases of pneumonia were reported from children infected with SARS-CoV-2 compared to those infected with H1N1. No vertical transmission of SARS-CoV-2 has been described so far.", "title": "[Pediatric impact of COVID-19].", "pid": "lyi4pgwy", "bm25_score": 216.57545471191406}, {"text": "Pediatric coronavirus disease-19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis. Mortality in children appears rare. Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission. It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)- Angiotensin converting enzyme 2 (ACE2). Laboratory findings and chest imaging may not be specific in children with COVID-19. Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions. This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment. The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic.", "title": "Coronavirus Disease 2019 (COVID-19) in Children - What We Know So Far and What We Do Not", "pid": "18q23z8l", "bm25_score": 216.50790405273438}, {"text": "Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and declared a worldwide pandemic on March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients and is often milder than that in adults; however, it can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may spread the disease in the community. This review summarizes what is currently known about COVID-19 in children and adolescents.", "title": "Epidemiology and clinical features of coronavirus disease 2019 in children", "pid": "jsyao6qu", "bm25_score": 216.4773406982422}, {"text": "Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) and its related Coronavirus Disease - 19 (COVID-19) has become a health emergency worldwide. The medical community has been concerned since the beginning of the outbreak about the potential impact of COVID-19 in children, especially in those with underlying chronic diseases. Fortunately, COVID-19 has been reported to be less severe in children than in adults. However, epidemiologic and clinical data are scarce. Children show unique features of SARS-CoV-2 involvement that may account for the low rate of infection and death in this age group. The purpose of this review is to summarize the most relevant evidence of COVID-19 in children highlighting similarities and differences with adults.", "title": "Covid-19 in children: A brief overview after three months experience.", "pid": "5gvpjxxp", "bm25_score": 216.42881774902344}, {"text": "Children are less likely to be infected with SARS-CoV-2 than adults and often have a milder course of COVID-19 disease and a lower case fatality rate. Children account for an estimated 1% to 5% of those diagnosed with COVID-19. Even so, preschool-aged children, infants, and children with underlying health conditions may still be at risk for severe disease and complications. Unique aspects of COVID-19 presentation and disease course in children and possible vertical transmission to newborns from COVID-19-positive mothers are discussed.", "title": "Managing COVID-19 disease in pediatric patients", "pid": "4f8v0tou", "bm25_score": 216.4141082763672}, {"text": "Severe Acute Respiratory Syndrome - Coronavirus - 2 (SARS-CoV-2) and its related Coronavirus Disease - 19 (COVID-19) has become a health emergency worldwide. The medical community has been concerned since the beginning of the outbreak about the potential impact of COVID-19 in children, especially in those with underlying chronic diseases. Fortunately, COVID-19 has been reported to be less severe in children than in adults. However, epidemiologic and clinical data are scarce. Children show unique features of SARS-CoV-2 involvement that may account for the low rate of infection and death in this age group. The purpose of this review is to summarize the most relevant evidence of COVID-19 in children highlighting similarities and differences with adults.", "title": "Covid-19 in children: A brief overview after three months experience", "pid": "fuhvsy2j", "bm25_score": 216.41307067871094}, {"text": "Children are less likely to be infected with SARS-CoV-2 than adults and often have a milder course of illness and a lower case fatality rate. Children account for an estimated 1% to 5% of those diagnosed with COVID-19.1 Even so, pre-school-aged children, infants, and children with underlying health conditions may still be at risk for severe disease and complications.2 Unique aspects of COVID-19 presentation and course in children and possible vertical transmission to newborns from COVID-19-positive mothers are discussed.", "title": "Managing COVID-19 Iinfection in pediatric patients.", "pid": "yxatsk8l", "bm25_score": 216.364013671875}, {"text": "Children infected with SARS-CoV-2 are underrepresented during the current COVID-19 outbreak Unlike other respiratory viruses, SARS-CoV-2 rather infects adults who subsequently infect their children From recent Chinese and Italian data, children commonly present mild to moderate disease, a large proportion of them being asymptomatic In particular, children present significantly less fever, cough and pneumonia compared to adults However, more cases of pneumonia were reported from children infected with SARS-CoV-2 compared to those infected with H1N1 No vertical transmission of SARS-CoV-2 has been described so far", "title": "[Pediatric impact of COVID-19]", "pid": "2990fbda", "bm25_score": 216.326416015625}, {"text": "Coronavirus disease-2019 (COVID-19), which started in Wuhan, China, in December 2019 and has been declared a worldwide pandemic in March 11, 2020, is a novel infectious disease that causes respiratory illness and death. Pediatric COVID-19 accounts for a small percentage of patients with outbreaks and is often milder than adults, but can progress to severe disease in some cases. Even neonates can suffer from COVID-19, and children may play a role as a spreader in the community. In this review, we summarize what is known about COVID-19 in children and adolescents until now.", "title": "Epidemiology and Clinical Features of Coronavirus disease 2019 in Children", "pid": "h2cm3cge", "bm25_score": 216.31954956054688}, {"text": "Since the beginning of coronavirus disease 2019 (COVID-19) pandemic outbreak, it has emerged that the clinical course and outcome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is definitely more favourable in children than in adults.1 Few cases of infection in children with cancer are described; also in these patients, except for one reported case,2 the disease was largely asymptomatic.3 Nevertheless, the management of COVID-19 in young patients with comorbidities, particularly cancer, remains a challenge for the clinician; further data are required to optimize the clinical approach to these cases.", "title": "Favourable outcome of coronavirus disease 2019 in a 1‐year‐old girl with acute myeloid leukaemia and severe treatment‐induced immunosuppression", "pid": "4cz2hziz", "bm25_score": 216.25416564941406}, {"text": "The aim of this review was to describe the current knowledge about coronavirus disease 2019 (COVID-19, which is caused by severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) in children, from epidemiological, clinical, and laboratory perspectives, including knowledge on the disease course, treatment, and prognosis. An extensive literature search was performed to identify papers on COVID-19 (SARS-CoV-2 infection) in children, published between January 1, 2020 and April 1, 2020. There were 44 relevant papers on COVID-19 in children. The results showed that COVID-19 occurs in 0.39–12.3% of children. Clinical signs and symptoms are comparable to those in adults, but milder forms and a large percentage of asymptomatic carriers are found among children. Elevated inflammatory markers are associated with complications and linked to various co-infections. Chest computed tomography (CT) scans in children revealed structural changes similar to those found in adults, with consolidations surrounded by halos being somewhat specific for children with COVID-19. The recommended treatment includes providing symptomatic therapy, with no specific drug recommendations for children. The prognosis is much better for children compared to adults. This review highlights that COVID-19 in children is similar to the disease in the adult population, but with particularities regarding clinical manifestations, laboratory test results, chest imaging, and treatment. The prognosis is much better for children compared to adults, but with the progression of the pandemic; the cases in children might change in the future.", "title": "COVID-19 in Children: An Ample Review", "pid": "8du0s33p", "bm25_score": 216.14132690429688}, {"text": "AIM: The coronavirus disease 2019 (COVID-19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. METHODS: A systematic literature review was carried out to identify papers on COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. RESULTS: The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%-5% of diagnosed COVID-19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID-19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. CONCLUSIONS: The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.", "title": "Systematic review of COVID-19 in children shows milder cases and a better prognosis than adults", "pid": "vij0hqsn", "bm25_score": 216.13046264648438}, {"text": "We describe the clinical course of 57 children with coronavirus disease 2019 (COVID-19) cared for through a single hospital system. Most children were mildly symptomatic, and only a few patients with underlying medical conditions required hospitalization. System-wide patient evaluation processes allowed for prompt identification and management of COVID-19 patients.", "title": "Coronavirus Disease 2019 in Children Cared for at Texas Children's Hospital: Initial Clinical Characteristics and Outcomes", "pid": "zb42aitl", "bm25_score": 216.11195373535156}, {"text": "Pediatric coronavirus disease - 19 (COVID-19) infection is relatively mild when compared to adults, and children are reported to have a better prognosis Mortality in children appears rare Clinical features of COVID-19 in children include fever and cough, but a large proportion of infected children appears to be asymptomatic and may contribute to transmission It remains unclear why children and young adults are less severely affected than older individuals, but this might involve differences in immune system function in the elderly and/or differences in the expression/function of the cellular receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) - Angiotensin converting enzyme 2 (ACE2) Laboratory findings and chest imaging may not be specific in children with COVID-19 Diagnosis is by Reverse transcriptase-Polymerase chain reaction (RT-PCR) testing of upper or lower respiratory tract secretions This review additionally considers COVID-19 in immunosuppressed children, and also suggests a management algorithm for the few children who appear to present with life threatening infection, including the potential use of antiviral and immunomodulatory treatment The most significant threat to global child health from SARS-CoV-2 is unlikely to be related to COVID 19 in children, but rather the socio-economic consequences of a prolonged pandemic", "title": "Coronavirus Disease (COVID-19) in Children - What We Know So Far and What We Do Not?", "pid": "03vy3uaj", "bm25_score": 216.10543823242188}, {"text": "We describe the clinical course of 57 children with coronavirus disease 2019 (COVID-19) cared for through a single hospital system. Most children were mildly symptomatic, and only a few patients with underlying medical conditions required hospitalization. Systemwide patient evaluation processes allowed for prompt identification and management of patients with COVID-19.", "title": "Coronavirus Disease 2019 in Children Cared for at Texas Children’s Hospital: Initial Clinical Characteristics and Outcomes", "pid": "dxykh8k0", "bm25_score": 216.09475708007812}, {"text": "The new pandemic coronavirus disease (COVID-19) has affected children, including neonates, who mostly comprise of approximately 2% of total confirmed cases. Most children are asymptomatic or have mild disease and much lower mortality compared to adults for yet unknown reasons. Recovery from illness has largely been universal and <2% have severe disease requiring intensive care. Standardised guidelines from initial studies are now available for diagnosis, treatment, and prevention. Treatment is mostly supportive with no recommendations for any specific drugs so far. As the pandemic evolves, it is expected that more children will be diagnosed and treated with evolving newer regimens. Research should now focus on early diagnosis, better drugs for children, intensive care modalities, and a universal vaccine. New developments will help in better prevention asides from the other precautionary measures already being practiced.", "title": "COVID-19 in children: Epidemiology, presentation, diagnosis and management.", "pid": "ni4ck8w4", "bm25_score": 216.081298828125}, {"text": "INTRODUCTION The recent outbreak of COVID-19 which began in Wuhan, China in December 2019 and rapidly spread worldwide evolving into a pandemic, poses a global health emergency. As of mid-April over 2 million people have been infected with over 145 thousand casualties. The disease is more severe in the older population, whereas in children lower infection rates and milder symptoms are more common. Severe symptoms in the pediatric population, although uncommon, have been reported mainly in infants younger than 1 year of age. Perinatal transmission is infrequent and associated with a relatively mild illness in the newborn.", "title": "[CURRENT KNOWLEDGE ON COVID-19 IN CHILDREN - CAUTIOUS OPTIMISM].", "pid": "9fgq8jhi", "bm25_score": 216.0653076171875}, {"text": "INTRODUCTION: The recent outbreak of COVID-19 which began in Wuhan, China in December 2019 and rapidly spread worldwide evolving into a pandemic, poses a global health emergency. As of mid-April over 2 million people have been infected with over 145 thousand casualties. The disease is more severe in the older population, whereas in children lower infection rates and milder symptoms are more common. Severe symptoms in the pediatric population, although uncommon, have been reported mainly in infants younger than 1 year of age. Perinatal transmission is infrequent and associated with a relatively mild illness in the newborn.", "title": "[current Knowledge on Covid-19 in Children - Cautious Optimism]", "pid": "a5jqttue", "bm25_score": 216.05079650878906}, {"text": "BACKGROUND Novel coronavirus disease (COVID-19) is spreading globally. Little is known about the risk factors for the clinical outcomes of COVID-19 in children. METHODS A retrospective case-control study was taken in children with severe acute respiratory syndrome coronary virus-2 infection in Wuhan Children's Hospital. Risk factors associated with the development of COVID-19 and progression were collected and analyzed. RESULTS Eight out of 260 children diagnosed with severe COVID-19 pneumonia were included in the study. Thirty-five children with COVID-19 infection matched for age, sex and date of admission, and who classified as non-severe type, were randomly selected from the hospital admissions. For cases with severe pneumonia caused by COVID-19, the most common symptoms were dyspnea (87.5%), fever (62.5%) and cough (62.5%). In laboratory, white blood cells count was significantly higher in severe children than non-severe children. Levels of inflammation bio-makers such as hsCRP, IL-6, IL-10 and D-dimer elevated in severe children compared with non-severe children on admission. The level of total bilirubin and uric acid clearly elevated in severe children compared with non-severe children on admission. All of severe children displayed the lesions on chest CT, more lung segments were involved in severe children than in non-severe children, which was only risk factor associated with severe COVID-19 pneumonia in multivariable analysis. CONCLUSIONS More than 3 lung segments involved were associated with greater risk of development of severe COVID-19 in children. Moreover, the possible risk of the elevation of IL-6, high total bilirubin and D-dimer with univariable analysis could identify patients to be severe earlier.", "title": "The Risk of Children Hospitalized With Severe COVID-19 in Wuhan.", "pid": "l5n0r5g9", "bm25_score": 216.05072021484375}, {"text": "BACKGROUND AND AIM Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its outbreak in many states of the world, forced the World Health Organization (WHO) to declare a pandemic. Currently, COVID-19 has infected 1 991 562 patients causing 130 885 deaths globally as of 16 April 2020. The aim of this review is to underline the epidemiological, clinical and management characteristics in children affected by COVID-19. METHODS We searched Pubmed, from January to April 2020, for the following search terms: \"COVID-19\", \"children\", \"SARS-COV2\", \"complications\", \"epidemiology\", \"clinical features\", focusing our attention mostly on epidemiology and symptoms of COVID-19 in children. RESULTS Usually, infants and children present milder symptoms of the disease with a better outcome than adults. Consequently, children may be considered an infection reservoir that may play a role as spreader of the infection in community.", "title": "Novel coronavirus infection and children.", "pid": "c2iibuqa", "bm25_score": 216.03915405273438}, {"text": "BACKGROUND AND AIM: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Its outbreak in many states of the world, forced the World Health Organization (WHO) to declare a pandemic. Currently, COVID-19 has infected 1 991 562 patients causing 130 885 deaths globally as of 16 April 2020. The aim of this review is to underline the epidemiological, clinical and management characteristics in children affected by COVID-19. METHODS: We searched Pubmed, from January to April 2020, for the following search terms: \"COVID-19\", \"children\", \"SARS-COV2\", \"complications\", \"epidemiology\", \"clinical features\", focusing our attention mostly on epidemiology and symptoms of COVID-19 in children. RESULTS: Usually, infants and children present milder symptoms of the disease with a better outcome than adults. Consequently, children may be considered an infection reservoir that may play a role as spreader of the infection in community.", "title": "Novel coronavirus infection and children", "pid": "uvvsiltp", "bm25_score": 216.02978515625}, {"text": "The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has spread rapidly across the globe. In contrast to initial reports, recent studies suggest that children are just as likely as adults to become infected with the virus but have fewer symptoms and less severe disease. In this review, we summarize the epidemiologic and clinical features of children infected with SARS-CoV-2 reported in pediatric case series to date. We also summarize the perinatal outcomes of neonates born to women infected with SARS-CoV-2 in pregnancy. We found 11 case series including a total of 333 infants and children. Overall, 83% of the children had a positive contact history, mostly with family members. The incubation period varied between 2 and 25 days with a mean of 7 days. The virus could be isolated from nasopharyngeal secretions for up to 22 days and from stool for more than 30 days. Co-infections were reported in up to 79% of children (mainly mycoplasma and influenza). Up to 35% of children were asymptomatic. The most common symptoms were cough (48%; range 19%-100%), fever (42%; 11%-100%) and pharyngitis (30%; 11%-100%). Further symptoms were nasal congestion, rhinorrhea, tachypnoea, wheezing, diarrhea, vomiting, headache and fatigue. Laboratory test parameters were only minimally altered. Radiologic findings were unspecific and included unilateral or bilateral infiltrates with, in some cases, ground-glass opacities or consolidation with a surrounding halo sign. Children rarely needed admission to intensive care units (3%), and to date, only a small number of deaths have been reported in children globally. Nine case series and 2 case reports described outcomes of maternal SARS-CoV-2 infection during pregnancy in 65 women and 67 neonates. Two mothers (3%) were admitted to intensive care unit. Fetal distress was reported in 30% of pregnancies. Thirty-seven percent of women delivered preterm. Neonatal complications included respiratory distress or pneumonia (18%), disseminated intravascular coagulation (3%), asphyxia (2%) and 2 perinatal deaths. Four neonates (3 with pneumonia) have been reported to be SARS-CoV-2 positive despite strict infection control and prevention procedures during delivery and separation of mother and neonates, meaning vertical transmission could not be excluded.", "title": "COVID-19 in Children, Pregnancy and Neonates: A Review of Epidemiologic and Clinical Features.", "pid": "21fnyxw7", "bm25_score": 216.01815795898438}, {"text": "Children will face many hidden negative effects from the new coronavirus– it's not too late to avert them, says Paul Ramchandani", "title": "Children and covid-19", "pid": "if6t1e5h", "bm25_score": 216.009765625}, {"text": "The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has spread rapidly across the globe. In contrast to initial reports, recent studies suggest that children are just as likely as adults to become infected with the virus but have fewer symptoms and less severe disease. In this review, we summarize the epidemiologic and clinical features of children infected with SARS-CoV-2 reported in pediatric case series to date. We also summarize the perinatal outcomes of neonates born to women infected with SARS-CoV-2 in pregnancy. We found 11 case series including a total of 333 infants and children. Overall, 83% of the children had a positive contact history, mostly with family members. The incubation period varied between 2 and 25 days with a mean of 7 days. The virus could be isolated from nasopharyngeal secretions for up to 22 days and from stool for more than 30 days. Co-infections were reported in up to 79% of children (mainly mycoplasma and influenza). Up to 35% of children were asymptomatic. The most common symptoms were cough (48%; range 19%-100%), fever (42%; 11%-100%) and pharyngitis (30%; 11%-100%). Further symptoms were nasal congestion, rhinorrhea, tachypnoea, wheezing, diarrhea, vomiting, headache and fatigue. Laboratory test parameters were only minimally altered. Radiologic findings were unspecific and included unilateral or bilateral infiltrates with, in some cases, ground-glass opacities or consolidation with a surrounding halo sign. Children rarely needed admission to intensive care units (3%), and to date, only a small number of deaths have been reported in children globally. Nine case series and 2 case reports described outcomes of maternal SARS-CoV-2 infection during pregnancy in 65 women and 67 neonates. Two mothers (3%) were admitted to intensive care unit. Fetal distress was reported in 30% of pregnancies. Thirty-seven percent of women delivered preterm. Neonatal complications included respiratory distress or pneumonia (18%), disseminated intravascular coagulation (3%), asphyxia (2%) and 2 perinatal deaths. Four neonates (3 with pneumonia) have been reported to be SARS-CoV-2 positive despite strict infection control and prevention procedures during delivery and separation of mother and neonates, meaning vertical transmission could not be excluded.", "title": "COVID-19 in Children, Pregnancy and Neonates: A Review of Epidemiologic and Clinical Features", "pid": "xkkasaza", "bm25_score": 216.00717163085938}, {"text": "The ongoing pandemic of coronavirus disease 2019 (COVID-19) has affected people from all cultures, religions, gender, and age groups around the world. In the last few months, several studies have been conducted on various aspects of COVID-19. Our goal was to see if the pediatric population is vulnerable to this infection. In this review, we conducted extensive research mainly by using the PubMed database. We used Medical Subject Headings (MeSH) and associated keywords to engage in an extensive search focussing on COVID-19 in the pediatric population. We discovered that most of the studies were from China, and some of them were in the Chinese language. However, English translations of many of the studies were available. For accessing the relevant statistical data, we relied on the World Health Organization (WHO) resources and the official website of the Ontario Government (ontario.ca). Most of the studies showed that the virus has affected the pediatric population. However, we found some differences among these studies regarding the severity of symptoms in children affected by COVID-19. While a few studies stated that the virus has presented with milder symptoms in the pediatric population, some studies have presented data of children who have suffered life-threatening complications due to COVID-19. Although the data is limited, we have been able to conclude from the studies we reviewed that COVID-19 does indeed affect children the same way as any other age group. Moreover, children can act as carriers of the virus and can endanger the lives of other individuals. Besides, neonates and infants can easily acquire the infection from family members without having any exposure to the outside world. Hence, utmost care should be taken while handling this population. More trials and studies should be conducted to analyze the impact of early diagnosis of infection in children and its management.", "title": "Coronavirus Disease 2019 (COVID-19) in Children: Vulnerable or Spared? A Systematic Review", "pid": "62cyo5kj", "bm25_score": 216.00363159179688}, {"text": "", "title": "Addressing the indirect effects of COVID-19 on the health of children and young people.", "pid": "nd81vcx0", "bm25_score": 216.00059509277344}, {"text": "The new pandemic coronavirus disease (COVID-19) has affected children, including neonates, who mostly comprise of approximately 2% of total confirmed cases. Most children are asymptomatic or have mild disease and much lower mortality compared to adults for yet unknown reasons. Recovery from illness has largely been universal and <2% have severe disease requiring intensive care. Standardised guidelines from initial studies are now available for diagnosis, treatment, and prevention. Treatment is mostly supportive with no recommendations for any specific drugs so far. As the pandemic evolves, it is expected that more children will be diagnosed and treated with evolving newer regimens. Research should now focus on early diagnosis, better drugs for children, intensive care modalities, and a universal vaccine. New developments will help in better prevention asides from the other precautionary measures already being practiced.", "title": "COVID-19 in children: Epidemiology, presentation, diagnosis and management", "pid": "yekcr5ka", "bm25_score": 215.99810791015625}, {"text": "Background: The outbreak of novel coronavirus pneumonia in China began in December 2019. Studies on novel coronavirus disease (COVID-19) were less based on pediatric patients. This study aimed to reveal the clinical characteristics of COVID-19 in children. Method: This study retrospectively analyzed the clinical symptoms, laboratory results, chest CT, and treatment of children with laboratory-confirmed COVID-19(ie, with samples that were positive for 2019 novel coronavirus[2019-nCoV]) who were admitted to Shenzhen Center of National Infectious Disease Clinical Medical Research from January 16 to February 8, 2020. Result: Nine patients had no obvious clinical symptom. 11 patients developed fever. Other symptoms, including cough(in eleven of seventeen patients), rhinorrhea(in two), diarrhea(in two), vomiting(in two), were also observed. A small minority of patients had lymphocytopenia. Alanine transaminase or transaminase increased in three cases. According to chest CT scan, 11 patients showed unilateral pneumonia, 8 patients had no pulmonary infiltration. No serious complications such as acute respiratory syndrome and acute lung injury occurred in all patients. Conclusion: The clinical characteristics of 2019-nCoV infection in children were different from adult. The overall condition of children were mild and have a good prognosis.", "title": "A retrospective study of the clinical characteristics of COVID-19 infection in 26 children", "pid": "txyf05n4", "bm25_score": 215.9740753173828}, {"text": "BACKGROUND: Novel coronavirus disease (COVID-19) is spreading globally. Little is known about the risk factors for the clinical outcomes of COVID-19 in children. METHODS: A retrospective case-control study was taken in children with severe acute respiratory syndrome coronary virus-2 infection in Wuhan Children's Hospital. Risk factors associated with the development of COVID-19 and progression were collected and analyzed. RESULTS: Eight of 260 children diagnosed with severe COVID-19 pneumonia were included in the study. Thirty-five children with COVID-19 infection matched for age, sex and date of admission, and who classified as non-severe type, were randomly selected from the hospital admissions. For cases with severe pneumonia caused by COVID-19, the most common symptoms were dyspnea (87.5%), fever (62.5%) and cough (62.5%). In laboratory, white blood cells count was significantly higher in severe children than non-severe children. Levels of inflammation bio-makers such as hsCRP, IL-6, IL-10 and D-dimer elevated in severe children compared with non-severe children on admission. The level of total bilirubin and uric acid clearly elevated in severe children compared with non-severe children on admission. All of severe children displayed the lesions on chest CT, more lung segments were involved in severe children than in non-severe children, which was only risk factor associated with severe COVID-19 pneumonia in multivariable analysis. CONCLUSIONS: More than 3 lung segments involved were associated with greater risk of development of severe COVID-19 in children. Moreover, the possible risk of the elevation of IL-6, high total bilirubin and D-dimer with univariable analysis could identify patients to be severe earlier.", "title": "Children Hospitalized With Severe COVID-19 in Wuhan", "pid": "9cr0bk2a", "bm25_score": 215.97300720214844}, {"text": "AIM: The coronavirus disease 2019 (COVID‐19) pandemic has affected hundreds of thousands of people. Data on symptoms and prognosis in children are rare. METHODS: A systematic literature review was carried out to identify papers on COVID‐19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), using the MEDLINE and Embase databases between January 1 and March 18, 2020. RESULTS: The search identified 45 relevant scientific papers and letters. The review showed that children have so far accounted for 1%‐5% of diagnosed COVID‐19 cases, they often have milder disease than adults and deaths have been extremely rare. Diagnostic findings have been similar to adults, with fever and respiratory symptoms being prevalent, but fewer children seem to have developed severe pneumonia. Elevated inflammatory markers were less common in children, and lymphocytopenia seemed rare. Newborn infants have developed symptomatic COVID‐19, but evidence of vertical intrauterine transmission was scarce. Suggested treatment included providing oxygen, inhalations, nutritional support and maintaining fluids and electrolyte balances. CONCLUSIONS: The coronavirus disease 2019 has occurred in children, but they seemed to have a milder disease course and better prognosis than adults. Deaths were extremely rare.", "title": "Systematic review of COVID‐19 in children shows milder cases and a better prognosis than adults", "pid": "sgokzw5i", "bm25_score": 215.9571075439453}, {"text": "The novel coronavirus SARS-CoV2 is a threat to the health and well-being of millions of lifes across the globe. A significant proportion of adult patients require hospitalisation and may develop severe life-threatening complications. Children, on the other hand, can carry and transmit the virus, but usually do not develop severe disease. Mortality in the paediatric age-group is relatively low. Differences in virus containment and clearance, as well as reduced inflammation-related tissue and organ damage may be caused by age-specific environmental and host factors. Since severe complications in adults are frequently caused by uncontrolled immune responses and a resulting \"cytokine storm\" that may be controlled by targeted blockade of cytokines, previously established treatment with immunosuppressive treatments may indeed protect children from complications.", "title": "COVID-19 - Considerations for the paediatric rheumatologist", "pid": "0g7ekos2", "bm25_score": 215.94961547851562}, {"text": "", "title": "Addressing the indirect effects of COVID-19 on the health of children and young people", "pid": "mr8cni62", "bm25_score": 215.9438934326172}, {"text": "", "title": "A wake-up call: COVID-19 and its impact on children's health and wellbeing", "pid": "59l40qmg", "bm25_score": 215.93304443359375}, {"text": "", "title": "Children are at risk from COVID-19", "pid": "w6ygorko", "bm25_score": 215.8947296142578}, {"text": "", "title": "Children are at Risk from COVID-19", "pid": "lhykluue", "bm25_score": 215.8947296142578}, {"text": "BACKGROUND AND OBJECTIVE: Knowledge about COVID-19 in children is limited due to the paucity of reported data. The pediatric age group comprises only less than 5% of total COVID-19 worldwide, therefore, large studies in this population are unlikely in the immediate future. Hence, we planned to synthesize the current data that will help in a better understanding of COVID-19 in children. METHODS: Four different electronic databases (MEDLINE, EMBASE, Web of Science, and CENTRAL) were searched for articles related to COVID-19 in the pediatric population. We included studies reporting disease characteristics and outcomes of COVID-19 in patients aged less than 19 years. We performed a random-effect meta-analysis to provide pooled estimates of various disease characteristics. RESULTS: 27 studies (4857 patients) fulfilling the eligibility criteria were included in this systematic review, from a total of 883 records. About half of the patients had each of fever and cough, 11% (6-17%) had fast breathing, and 6-13% had gastrointestinal manifestations. Most of the patients had mild to moderate disease, and only 4% had a severe or critical illness. Leukopenia was the commonest reported laboratory abnormality. CONCLUSION: Even among the symptomatic COVID-19 cases, severe manifestations are seen in very few children. Though fever and respiratory symptoms are most common, many children also have gastrointestinal manifestations.", "title": "Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis", "pid": "z6trtz8s", "bm25_score": 215.87533569335938}, {"text": "Although medical literature shows that children are minimally susceptible to 2019-Corona virus disease (COVID-19), they are hit the hardest by psychosocial impact of this pandemic. Being quarantined in homes and institutions may impose greater psychological burden than the physical sufferings caused by the virus. School closure, lack of outdoor activity, aberrant dietary and sleeping habits are likely to disrupt children's usual lifestyle and can potentially promote monotony, distress, impatience, annoyance and varied neuropsychiatric manifestations. Incidences of domestic violence, child abuse, adulterated online contents are on the rise. Children of single parent and frontline workers suffer unique problems. The children from marginalized communities are particularly susceptible to the infection and may suffer from extended ill-consequences of this pandemic, such as child labor, child trafficking, child marriage, sexual exploitation and death etc. Parents, pediatricians, psychologists, social workers, hospital authorities, government and non-governmental organizations have important roles to play to mitigate the psychosocial ill-effects of COVID-19 on children and adolescents. To provide the basic amenities, social security, medical care, and to minimize the educational inequities among the children of the different strata of the society are foremost priorities.", "title": "Impact of COVID -19 on children: special focus on the psychosocial aspect", "pid": "k30mv20e", "bm25_score": 215.87144470214844}, {"text": "Although medical literature shows that children are minimally susceptible to 2019-Corona virus disease (COVID-19), they are hit the hardest by psychosocial impact of this pandemic. Being quarantined in homes and institutions may impose greater psychological burden than the physical sufferings caused by the virus. School closure, lack of outdoor activity, aberrant dietary and sleeping habits are likely to disrupt children's usual lifestyle and can potentially promote monotony, distress, impatience, annoyance and varied neuropsychiatric manifestations. Incidences of domestic violence, child abuse, adulterated online contents are on the rise. Children of single parent and frontline workers suffer unique problems. The children from marginalized communities are particularly susceptible to the infection and may suffer from extended ill-consequences of this pandemic, such as child labor, child trafficking, child marriage, sexual exploitation and death etc. Parents, pediatricians, psychologists, social workers, hospital authorities, government and non-governmental organizations have important roles to play to mitigate the psychosocial ill-effects of COVID-19 on children and adolescents. To provide the basic amenities, social security, medical care, and to minimize the educational inequities among the children of the different strata of the society are foremost priorities.", "title": "Impact of COVID -19 on children: special focus on the psychosocial aspect.", "pid": "q0ubeurh", "bm25_score": 215.86883544921875}, {"text": "The novel severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) has rapidly spread worldwide with increasing hospitalization and mortality rate. Ongoing studies and accumulated data are de- tailing the features and the effects of the new coronavirus disease 19 (COVID 19) in the adult population, and cardiovascular involvement is emerging as the most significant and life-threatening complication, with an in- creased risk of morbidity and mortality in patients with underlying cardiovascular disease. At present, though the limited data on the effects of COVID 19 in pediatric patients, children seem to count for a little proportion of SARS-COV 2 infection, and present with less severe disease and effects However infants and toddlers are at risk of developing critical course. The disease has a range of clinical presentations in children, for which the potential need for further investigation of myocardial injury and cardiovascular issues should be kept in mind to avoid misdiagnosing severe clinical entities. Overlapping with Kawasaki disease is a concern, particularly the incomplete and atypical form. We aim to summarize the initial considerations and potential cardiovascular implications of COVID-19 for children and patients with congenital heart disease.", "title": "COVID19: potential cardiovascular issues in pediatric patients.", "pid": "9jr7ekbu", "bm25_score": 215.86410522460938}, {"text": "BACKGROUND AND OBJECTIVE Knowledge about COVID-19 in children is limited due to the paucity of reported data. The pediatric age group comprises only less than 5% of total COVID-19 worldwide, therefore, large studies in this population are unlikely in the immediate future. Hence, we planned to synthesize the current data that will help in a better understanding of COVID-19 in children. METHODS Four different electronic databases (MEDLINE, EMBASE, Web of Science, and CENTRAL) were searched for articles related to COVID-19 in the pediatric population. We included studies reporting disease characteristics and outcomes of COVID-19 in patients aged less than 19 years. We performed a random-effect meta-analysis to provide pooled estimates of various disease characteristics. RESULTS 27 studies (4857 patients) fulfilling the eligibility criteria were included in this systematic review, from a total of 883 records. About half of the patients had each of fever and cough, 11% (6-17%) had fast breathing, and 6-13% had gastrointestinal manifestations. Most of the patients had mild to moderate disease, and only 4% had a severe or critical illness. Leukopenia was the commonest reported laboratory abnormality. CONCLUSION Even among the symptomatic COVID-19 cases, severe manifestations are seen in very few children. Though fever and respiratory symptoms are most common, many children also have gastrointestinal manifestations.", "title": "Clinical Features and Outcome of SARS-CoV-2 Infection in Children: A Systematic Review and Meta-analysis.", "pid": "6zqp53tk", "bm25_score": 215.86343383789062}, {"text": "The novel severe acute respiratory syndrome coronavirus 2 (SARS-COV 2) has rapidly spread worldwide with increasing hospitalization and mortality rate. Ongoing studies and accumulated data are de- tailing the features and the effects of the new coronavirus disease 19 (COVID 19) in the adult population, and cardiovascular involvement is emerging as the most significant and life-threatening complication, with an in- creased risk of morbidity and mortality in patients with underlying cardiovascular disease. At present, though the limited data on the effects of COVID 19 in pediatric patients, children seem to count for a little proportion of SARS-COV 2 infection, and present with less severe disease and effects However infants and toddlers are at risk of developing critical course. The disease has a range of clinical presentations in children, for which the potential need for further investigation of myocardial injury and cardiovascular issues should be kept in mind to avoid misdiagnosing severe clinical entities. Overlapping with Kawasaki disease is a concern, particularly the incomplete and atypical form. We aim to summarize the initial considerations and potential cardiovascular implications of COVID-19 for children and patients with congenital heart disease.", "title": "COVID19: potential cardiovascular issues in pediatric patients", "pid": "18zt8b8g", "bm25_score": 215.85491943359375}, {"text": "Two epidemics-Covid-19 and opioid use disorder (OUD) -are creating short- and long-term mental and physical health risks for vulnerable children and adolescents. Information about the risks to children from exposure to the coronavirus is still fragmentary, but even many healthy children are not getting appropriate health care, such as vaccinations or monitoring of developmental milestones during the Covid-19 pandemic. Children living in poverty are at heightened risk. Youngsters who are already dealing with OUD in their families-2.2 million as of 2017-face serious consequences stemming from trauma and stress. Although not officially designated by the Centers for Disease Control and Prevention as \"adverse childhood experiences\" (\"ACEs\"), these situations meet the CDC's criteria for inclusion, such as death or separation from a parent. It is important to recognize and meet the needs of all these children now and not just when the long-term consequences become apparent.", "title": "Vulnerable Children in a Dual Epidemic.", "pid": "g8oachgn", "bm25_score": 215.83070373535156}, {"text": "Abstract Much is being learned about clinical outcomes for adult COVID-19 patients with underlying chronic conditions, however, there is less coverage on how the COVID-19 pandemic impacts the management of chronic medical conditions in children and youth, such as asthma. Asthma is a common chronic medical condition in children that is uniquely susceptible to changes brought upon by COVID-19. Sudden dramatic changes in the environment, medical practice, and medication use have altered the asthma management landscape with potential impacts on asthma outcomes. In this paper, we review how changes in transportation and travel patterns, school attendance, physical activity, and time spent indoors, along with changes in healthcare delivery since the start of the pandemic all play a contributing role in asthma control in children. We review potentially important influences of asthma control in children during the COVID-19 pandemic worthy of further study.", "title": "The Unexpected Risks of COVID-19 on Asthma Control in Children", "pid": "swcpap5h", "bm25_score": 215.775390625}, {"text": "OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n=19, 70%) were mainly neurological (n=7), respiratory, (n=4), or sickle cell disease (n=4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n=9), catecholamine (n=4), erythropheresis (n=4), renal replacement therapy (n=1), and extracorporeal membrane oxygenation (n=1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children.", "title": "Severe and fatal forms of COVID-19 in children", "pid": "zi23n8b4", "bm25_score": 215.7749786376953}, {"text": "Abstract Background At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help paediatricians To help pediatricians understand the conditions of COVID-19 in children, we conducted this study. Methods We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan children's hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes. Results As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-α nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance. Conclusions The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.", "title": "Coronavirus Disease 2019 in Children: Characteristics, Antimicrobial Treatment, and Outcomes", "pid": "11es4w0u", "bm25_score": 215.768310546875}, {"text": "BACKGROUND: At present, coronavirus disease 2019 (COVID-19) has spread in many countries. We conducted this study to help pediatricians understand the conditions of COVID-19 in children. METHODS: We retrospectively summarized the characteristics, treatment and outcomes of pediatric cases in Wuhan Children's Hospital which was the only designated hospital for children with COVID-19 in Hubei Province. A Cox proportional hazards regression analysis was used to evaluate factors associated with clinical outcomes. RESULTS: As of February 29, 75 children had been discharged, of which only one was has severe pneumonia and one was critical cases. Children younger than 2 years were more susceptible to COVID-19. All patients have received interferon-&#945; nebulization, and eight cases including the severe and critical cases were co-administrated ribavirin. Five patients with mild pneumonia were given arbidol. Twenty-three patients were given traditional Chinese medicine (TCM). The average length of stay (LOS) and the time of SARS-CoV-2 clearance were 10.57 and 6.39 days, respectively. None of the factors was associated with LOS or time of SARS-CoV-2 clearance. CONCLUSIONS: The severity of COVID-19 in pediatric cases were milder than adults. The efficacy of the antiviral therapy in children with COVID-19 remains to be evaluated.", "title": "Coronavirus disease 2019 in children: Characteristics, antimicrobial treatment, and outcomes", "pid": "t4tg0o8o", "bm25_score": 215.76669311523438}, {"text": "Objective: The novel coronavirus, COVID-19, has rapidly emerged to become a global pandemic and is known to cause a high risk to patients over the age of 70 and those with co-morbidities, such as hypertension and diabetes. Though children are at comparatively lower risk compared to adults, the Indian population has a large young demographic that is likely to be at higher risk due to exposure to pollution, malnutrition and poor access to medical care. We aimed to quantify the potential impact of COVID-19 on Indias child population. Methods: We combined district family household survey data with data from the COVID-19 outbreak in China to analyze the potential impact of COVID-19 on children under the age of 5, under three different scenarios; each of which assumed the prevalence of infection to be 0.5%, 1%, or 5%. Results: We find that in the lowest prevalence scenario, across the most populous 18 Indian states, asymptomatic, non-hospitalized symptomatic and hospitalized symptomatic cases could reach 87,200, 412,900 and 31,900, respectively. In a moderate prevalence scenario, these figures reach 174,500, 825,800, and 63,800, and in the worst case, high prevalence scenario these cases could climb as high as 872,200, 4,128,900 and 319,700. Conclusion: These estimates show COVID-19 has the potential to pose a substantial threat to Indias large population of children, particularly those suffering from malnutrition and exposure to indoor air pollution, who may have limited access to health services.", "title": "Risks to Children under-five in India from COVID-19", "pid": "jm2dtrav", "bm25_score": 215.7655029296875}, {"text": "This commentary contextualizes potential mental health outcomes for children during and after the COVID-19 pandemic within the risk and resilience literature. Individual, familial, and community-level factors that may increase risk for mental health challenges for children as well as factors associated with positive adaptation in the face of adversity are considered. We highlight the value of considering children's resilience within a systemic perspective by considering family-centered approaches including both short-term and long-term evidence-informed mental health practices. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Shifting from survival to supporting resilience in children and families in the COVID-19 pandemic: Lessons for informing U.S. mental health priorities.", "pid": "77fx5tty", "bm25_score": 215.7611541748047}, {"text": "BACKGROUND: Little is known as yet about the outcome of SARS-CoV-2 infection in children being treated for cancer. METHODS: We collected information on the clinical characteristics and outcomes of a cohort of 29 children (16 females and 13 males, median age 7 years, range [0-16]) diagnosed with SARS-CoV-2 infection while on chemotherapy/immunotherapy (N=26), or after stem cell transplantation (N=3) during the peak of the epidemic in Italy. These patients suffered from leukemia (N=16), lymphoma (N=3), solid tumors (N=10), and Langerhans cell histiocytosis (N=1). RESULTS: The course of the disease was mild in all cases, with only 12 children developing symptoms (pneumonia in 3 cases), and none needing intensive care. Fifteen patients were hospitalized, including 7 asymptomatic patients. Nine patients (including 5 with no symptoms) were given hydroxychloroquine, and 3 of them were also given lopinavir/ritonavir. CONCLUSIONS: SARS-CoV-2 infection seems to take a milder clinical course in children than in adults with cancer. Specific SARS-CoV-2 treatment seems unnecessary for most children. In the light of our findings, and albeit with the necessary caution, we suggest avoiding major changes to planned anticancer treatments in pediatric patients acquiring COVID-19.", "title": "Clinical characteristics and outcome of SARS-CoV-2 infection in Italian pediatric oncology patients: a study from the Infectious Diseases Working Group of the AIEOP", "pid": "f1697rdp", "bm25_score": 215.7606964111328}, {"text": "This study aims to analyze the different clinical characteristics between children and their families infected with severe acute respiratory syndrome coronavirus 2. Clinical data from nine children and their 14 families were collected, including general status, clinical, laboratory test, and imaging characteristics. All the children were detected positive result after their families onset. Three children had fever (22.2%) or cough (11.2%) symptoms and six (66.7%) children had no symptom. Among the 14 adult patients, the major symptoms included fever (57.1%), cough (35.7%), chest tightness/pain (21.4%), fatigue (21.4%) and sore throat (7.1%). Nearly 70% of the patients had normal (71.4%) or decreased (28.6%) white blood cell counts, and 50% (7/14) had lymphocytopenia. There were 10 adults (71.4%) showed abnormal imaging. The main manifestations were pulmonary consolidation (70%), nodular shadow (50%), and ground glass opacity (50%). Five discharged children were admitted again because their stool showed positive result in SARS-CoV-2 PCR. COVID-19 in children is mainly caused by family transmission, and their symptoms are mild and prognosis is better than adult. However, their PCR result in stool showed longer time than their families. Because of the mild or asymptomatic clinical process, it is difficult to recognize early for pediatrician and public health staff.", "title": "The different clinical characteristics of corona virus disease cases between children and their families in China – the character of children with COVID-19", "pid": "mar8zt2t", "bm25_score": 215.76051330566406}, {"text": "This study aims to analyze the different clinical characteristics between children and their families infected with severe acute respiratory syndrome coronavirus 2. Clinical data from nine children and their 14 families were collected, including general status, clinical, laboratory test, and imaging characteristics. All the children were detected positive result after their families onset. Three children had fever (22.2%) or cough (11.2%) symptoms and six (66.7%) children had no symptom. Among the 14 adult patients, the major symptoms included fever (57.1%), cough (35.7%), chest tightness/pain (21.4%), fatigue (21.4%) and sore throat (7.1%). Nearly 70% of the patients had normal (71.4%) or decreased (28.6%) white blood cell counts, and 50% (7/14) had lymphocytopenia. There were 10 adults (71.4%) showed abnormal imaging. The main manifestations were pulmonary consolidation (70%), nodular shadow (50%), and ground glass opacity (50%). Five discharged children were admitted again because their stool showed positive result in SARS-CoV-2 PCR. COVID-19 in children is mainly caused by family transmission, and their symptoms are mild and prognosis is better than adult. However, their PCR result in stool showed longer time than their families. Because of the mild or asymptomatic clinical process, it is difficult to recognize early for pediatrician and public health staff.", "title": "The different clinical characteristics of corona virus disease cases between children and their families in China - the character of children with COVID-19", "pid": "feqqdlof", "bm25_score": 215.7416229248047}, {"text": "In mid-December 2019, a disease caused by infection with severe acute respiratory syndrome coronavirus-2, which began in Wuhan, China, has spread throughout the country and many countries around the world. The number of children with coronavirus disease-2019 (COVID-19) has also increased significantly. Although information regarding the epidemiology of COVID-19 in children has accumulated, relevant comprehensive reports are lacking. The present article reviews the epidemiological characteristics of COVID-19 in children.", "title": "COVID-19 epidemic: Disease characteristics in children", "pid": "3qctslxf", "bm25_score": 215.73550415039062}, {"text": "Much is being learned about clinical outcomes for adult COVID-19 patients with underlying chronic conditions; however, there is less coverage on how the COVID-19 pandemic impacts the management of chronic medical conditions, such as asthma, in children and youth. Asthma is a common chronic medical condition in children that is uniquely susceptible to changes brought on by COVID-19. Sudden dramatic changes in the environment, medical practice, and medication use have altered the asthma management landscape with potential impacts on asthma outcomes. In this paper, we review how changes in transportation and travel patterns, school attendance, physical activity, and time spent indoors, along with changes in health care delivery since the start of the pandemic, all play a contributing role in asthma control in children. We review potentially important influences of asthma control in children during the COVID-19 pandemic worthy of further study.", "title": "The Unexpected Risks of COVID-19 on Asthma Control in Children", "pid": "ts2ryyzj", "bm25_score": 215.72573852539062}, {"text": "The COVID-19 pandemic impact on children is a growing concern. The United Nations and its agencies (the World Health Organization and UNICEF), Indian Association For Child and Adolescent Mental Health and National Institute of Mental Health and Neuroscience in India warn about the broader impacts on children and call for urgent action to support the world's children amidst the pandemic which may have lasting consequences. The COVID-19 pandemic and unprecedented control measures to prevent its spread have disrupted nearly every aspect of children's lives - their health, development, learning, behaviour and their families' economic security, including protection from violence and abuse. Given this background, there is an urgent need for action through screening to minimize the mental health issues of children in India who constitute a substantial proportion of the population.", "title": "Debate: COVID-19 and children in India", "pid": "swgb2tzx", "bm25_score": 215.70556640625}, {"text": "BACKGROUND Little is known as yet about the outcome of SARS-CoV-2 infection in children being treated for cancer. METHODS We collected information on the clinical characteristics and outcomes of a cohort of 29 children (16 females and 13 males, median age 7 years, range [0-16]) diagnosed with SARS-CoV-2 infection while on chemotherapy/immunotherapy (N=26), or after stem cell transplantation (N=3) during the peak of the epidemic in Italy. These patients suffered from leukemia (N=16), lymphoma (N=3), solid tumors (N=10), and Langerhans cell histiocytosis (N=1). RESULTS The course of the disease was mild in all cases, with only 12 children developing symptoms (pneumonia in 3 cases), and none needing intensive care. Fifteen patients were hospitalized, including 7 asymptomatic patients. Nine patients (including 5 with no symptoms) were given hydroxychloroquine, and 3 of them were also given lopinavir/ritonavir. CONCLUSIONS SARS-CoV-2 infection seems to take a milder clinical course in children than in adults with cancer. Specific SARS-CoV-2 treatment seems unnecessary for most children. In the light of our findings, and albeit with the necessary caution, we suggest avoiding major changes to planned anticancer treatments in pediatric patients acquiring COVID-19.", "title": "Clinical characteristics and outcome of SARS-CoV-2 infection in Italian pediatric oncology patients: a study from the Infectious Diseases Working Group of the AIEOP.", "pid": "rznp2fuy", "bm25_score": 215.67999267578125}, {"text": "The prevalence of coronavirus disease 2019 (COVID-19) is lower in children compared to adults. Children contribute to 1-5% of all COVID-19 cases (1) . A recent study from China reported that 171(12.3%) of 1391 children with suspected disease had confirmed COVID-19 infection (2) . As of May 15, 2020, there are 33,241 children with COVID-19 in the United States (3) . The most common symptoms in children with confirmed and suspected COVID-19 include fever and cough followed by diarrhea, and abdominal pain.", "title": "Spectrum of COVID-19 in Children", "pid": "el6cvwtk", "bm25_score": 215.6796875}, {"text": "Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered.Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. What is Known: • There is limited evidence on the clinical presentation and outcomes of children with COVID-19 in Europe, and almost no evidence on characteristics and risk factors of severe cases. What is New: • Among a case series of 130 children, mostly diagnosed at hospital level, and with a relatively high rate (26.2%) of comorbidities, about three-quarter had an asymptomatic or mild disease. • However, 57.7% were hospitalized, 11.5% needed some respiratory support, and 6.9% were treated in an intensive care unit.", "title": "Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks", "pid": "u7arfoym", "bm25_score": 215.67742919921875}, {"text": "ABSTRACT OBJECTIVES: The aim of this study was to describe severe forms of novel coronavirus disease 2019 in children, including patient characteristics, clinical, laboratory, and imaging findings, as well as the disease management and outcomes. METHODS: This was a retrospective, single-center, observational study conducted in a pediatric intensive and high-dependency care unit (PICU, HDU) in an urban hospital in Paris. All patients, aged from 1 month to 18 years, admitted for confirmed or highly suspected SARS-CoV-2 were included. RESULTS: We analyzed the data of 27 children. Comorbidities (n = 19, 70 %) were mainly neurological (n = 7), respiratory, (n = 4), or sickle cell disease (n = 4). SARS-CoV-2 PCR results were positive in 24 children (nasopharyngeal swabs). The three remaining children had a chest CT scan consistent with COVID-19. Respiratory involvement was observed in 24 patients (89%). Supportive treatments were invasive mechanical ventilation (n = 9), catecholamine (n = 4), erythropheresis (n = 4), renal replacement therapy (n = 1), and extracorporeal membrane oxygenation (n = 1). Five children died, of whom three were without past medical history. CONCLUSION: This study highlighted the large spectrum of clinical presentation and time course of disease progression as well as the non-negligible occurrence of pediatric life-threatening and fatal cases of COVID-19 mostly in patients with comorbidities. Additional laboratory investigations are needed to further analyze the mechanism underlying the variability of SARS-Cov-2 pathogenicity in children", "title": "Severe and fatal forms of COVID-19 in children", "pid": "z1wihwga", "bm25_score": 215.66806030273438}, {"text": "Abstract The novel coronavirus SARS-CoV2 is a threat to the health and well-being of millions of lifes across the globe. A significant proportion of adult patients require hospitalisation and may develop severe life-threatening complications. Children, on the other hand, can carry and transmit the virus, but usually do not develop severe disease. Mortality in the paediatric age-group is relatively low. Differences in virus containment and clearance, as well as reduced inflammation-related tissue and organ damage may be caused by age-specific environmental and host factors. Since severe complications in adults are frequently caused by uncontrolled immune responses and a resulting “cytokine storm” that may be controlled by targeted blockade of cytokines, previously established treatment with immunosuppressive treatments may indeed protect children from complications.", "title": "COVID-19 – Considerations for the paediatric rheumatologist", "pid": "sg9zelgu", "bm25_score": 215.6652374267578}, {"text": "Background. The prevalence of symptomatic COVID-19 in children remains low to date. In just a few months, COVID-19 has affected millions of people worldwide, and as of the date of this publication, the pandemic continues. Based on the current available evidence, children do not appear to be at higher risk of contracting COVID-19 than adults. However, children with neurological and neuromuscular conditions are vulnerable to the respiratory complications of other viral infections. Objectives. To assess whether children with brain-based developmental disabilities were more likely to develop COVID-19 and have complications or poorer outcomes following infection. Methods. We conducted a two-week rapid review on studies with primary data regarding children aged between zero and 18 years old with brain-based developmental disabilities, or who were at risk of developing such disabilities, with confirmed or suspected COVID-19. We performed our literature searches on April 18, 2020. Results. Our search strategy identified 538 individual records, of which four were included in our review. Of the 50 COVID-19 pediatric patients reported in the included studies, a total of seven children were at risk of developing brain-based disabilities. Symptoms ranged in severity. However, generally, patients were discharged or saw improvements in their symptoms by the end of the study period. No deaths were reported. Discussion. Our study highlights a knowledge gap regarding the impact of COVID-19 in children with brain-based developmental disabilities.", "title": "COVID-19 in Children with Brain-Based Developmental Disabilities: A Rapid Review", "pid": "wjbh1z8y", "bm25_score": 215.66427612304688}, {"text": "", "title": "COVID-19 in children: More than meets the eye", "pid": "9qsqbsxu", "bm25_score": 215.6550750732422}, {"text": "BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has spread around the world, and reports of children with COVID-19 are increasing. OBJECTIVES: To assess clinical profiles of pediatric COVID-19. STUDY DESIGN: A retrospective analysis was undertaken using clinical data of sixteen children (11 months-14 years) diagnosed with COVID-19 between January 1, 2020 and March 17, 2020 at Xiangyang Central Hospital, Hubei province, China. RESULTS: All children had positive epidemiologic histories, 12 (12/16, 75 %) involving family units. The illnesses were either mild (5/16, 31.3 %) or ordinary (11/16, 68.8 %), presenting as follows: asymptomatic (8/16, 50 %), fever and/or cough (8/16, 50 %). Four asymptomatic patients (4/16, 25 %) in ordinary cases had chest computed tomography (CT) abnormalities. Leukocyte counts were normal in 14 cases(88 %), but 2 patients (12.5 %) had leukopenia, and 1 (6.3 %) was lymphopenic. There were 11 patients with chest CT abnormalities, some nodular, others small patchy and others ground-glass opacities. In asymptomatic children, the median time to SRAS-CoV-2 nucleic acid test(NAT) positivity once exposed to a family member with confirmed infection was 15.5 days (range, 10-26 days). The median time to first NAT-negative conversion was 5.5 days (range, 1-23 days). CONCLUSIONS: COVID-19 in children of Xiangyang city is often family acquired and not serious, with favorable outcomes. Asymptomatic children can be diagnosed as pneumonia because of chest CT abnormalities. It is essential to actively screen this segment of the population.", "title": "Clinical features of pediatric patients with coronavirus disease (COVID-19)", "pid": "feujr1vv", "bm25_score": 215.6475372314453}, {"text": "Detailed data on clinical presentations and outcomes of children with COVID-19 in Europe are still lacking. In this descriptive study, we report on 130 children with confirmed COVID-19 diagnosed by 28 centers (mostly hospitals), in 10 regions in Italy, during the first months of the pandemic. Among these, 67 (51.5%) had a relative with COVID-19 while 34 (26.2%) had comorbidities, with the most frequent being respiratory, cardiac, or neuromuscular chronic diseases. Overall, 98 (75.4%) had an asymptomatic or mild disease, 11 (8.5%) had moderate disease, 11 (8.5%) had a severe disease, and 9 (6.9%) had a critical presentation with infants below 6 months having significantly increased risk of critical disease severity (OR 5.6, 95% CI 1.3 to 29.1). Seventy-five (57.7%) children were hospitalized, 15 (11.5%) needed some respiratory support, and nine (6.9%) were treated in an intensive care unit. All recovered. Conclusion:This descriptive case series of children with COVID-19, mostly encompassing of cases enrolled at hospital level, suggest that COVID-19 may have a non-negligible rate of severe presentations in selected pediatric populations with a relatively high rates of comorbidities. More studies are needed to further understand the presentation and outcomes of children with COVID-19 in children with special needs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00431-020-03683-8) contains supplementary material, which is available to authorized users.", "title": "Characteristic of COVID-19 infection in pediatric patients: early findings from two Italian Pediatric Research Networks", "pid": "62ic8r0s", "bm25_score": 215.64271545410156}, {"text": "We reported the clinical characteristics of a case series of 10 patients with coronavirus disease 2019 (COVID-19) aged from 1 year to 18 years. Seven patients had contact with confirmed COVID-19 family members before onset. Fever (4 [40.0%]) and cough (3 [30.0%]) were the most common symptoms. No patient showed leucopenia and lymphopenia on admission. Pneumonia was observed in chest CT images in 5 (50.0%) patients. Five (50.0%) patients received antiviral treatment. No patient had severe complications or developed a severe illness in our study. Our study indicated that COVID-19 children present less severe symptoms and have better outcomes.", "title": "Clinical characteristics of a case series of children with coronavirus disease 2019", "pid": "nb08i303", "bm25_score": 215.63258361816406}, {"text": "This commentary contextualizes potential mental health outcomes for children during and after the COVID-19 pandemic within the risk and resilience literature. Individual, familial, and community-level factors that may increase risk for mental health challenges for children as well as factors associated with positive adaptation in the face of adversity are considered. We highlight the value of considering children's resilience within a systemic perspective by considering family-centered approaches including both short-term and long-term evidence-informed mental health practices. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Shifting from survival to supporting resilience in children and families in the COVID-19 pandemic: Lessons for informing U.S. mental health priorities", "pid": "5xbyqkpt", "bm25_score": 215.62957763671875}, {"text": "Perhaps when China reported its first cases of the novel coronavirus in December 2019, few would predict that it would overwhelm the majority of the global community The first reports conveyed that the rate of infection and death from this virus among children is rare However, evidence showed that there is no particular age range for the disease and children, infants and even neonates may be infected Although COVID-19 primarily targets the host's respiratory system, complications in other organs such as heart, kidney and liver have been observed as well This mini-review attempts to consider the publications focused on the COVID-19 infection among children with emphasis on renal involvement and the treatment approach of this complication", "title": "Renal involvement in children with COVID-19 infection", "pid": "dd69ms7k", "bm25_score": 215.6268310546875}, {"text": "INTRODUCTION: World Health Organization has declared COVID-19 a pandemic and a global health emergency. Thus, it is necessary to clearly characterize clinical manifestations and management of COVID-19 infection in children to provide accurate information for healthcare workers. Accordingly, the present study was designed to review articles published on clinical manifestations and characteristics of children and infants with COVID-19. METHODS: In this systematic review, medical databases including Cochrane Library, Web of Science, Embase, Scopus, SID, Medline, WHO and LitCovid were searched using English and Persian keywords including COVID-19, Pediatrics, Newborn, Coronavirus 2019, 2019-nCoV, SARS-CoV-2. Finally, data of 14 related articles were included in the study. RESULTS: A total of 2228 children, newborns and infants were studied. Clinical manifestation in children may be mild (72%), moderate (22%) or severe (6%), and the most common symptoms include dry cough (91%) and fever (96%). According to the included articles, two children had died, one of which was a 14-year-old boy and his exposure history and underlying disease were unclear, and the other was a male newborn with gestational age of 35 weeks and 5 days, birth weight of 2200, Apgar score of 8, 8 (1 min and 5 min) and his first symptom was increased heart rate. No differences were found between male and female children regarding infection with COVID-19. CONCLUSION: Most pediatrics were infected with COVID-19 due to family cluster or history of close contact. Infected children have relatively milder clinical symptoms compared to infected adults. We should pay special attention to early diagnosis and early treatment in children infected with COVID-19.", "title": "Clinical Characteristics of COVID-19 Infection in Newborns and Pediatrics: A Systematic Review", "pid": "33ixlhxc", "bm25_score": 215.6183624267578}, {"text": "The new coronavirus disease outbreak in 2019 (COVID-19) represents a dramatic challenge for healthcare systems worldwide. As to viral tropism, lungs are not the only COVID-19 target but also the heart may be involved in a not negligible percentage of the infected patients. Myocarditis-related cardiac dysfunction and potentially life-threatening arrhythmias are the main aftermaths. A few studies showed that myocardial injury in adult patients is often linked with a fatal outcome. Conversely, scientific evidence in children is sparse, although several reports were published with the description of a cardiac involvement in COVID-19 paediatric patients. In these young subjects, a background of surgically treated congenital heart disease seems to be a predisposing factor.Conclusion: This systematic review is aimed at summarizing all COVID-19 cases with a cardiac involvement published in paediatric age and trying to explain the underlying mechanisms responsible for COVID-19-related myocardial damage.What is Known:• Coronaviruses proved to be able to jump from animals to humans.• The outbreak of COVID-19 started from China (Dec 2019) and became pandemic.What is New:• Even in childhood, COVID-19 is not without the risk of cardiac involvement.• Myocarditis, heart failure, and arrhythmias are among the possible manifestations.", "title": "Children's heart and COVID-19: Up-to-date evidence in the form of a systematic review", "pid": "b1roq671", "bm25_score": 215.611328125}, {"text": "", "title": "What Are the Newest Effects of COVID-19 in Children?", "pid": "d5pic2ws", "bm25_score": 215.599365234375}, {"text": "IMPORTANCE: A surge in severe cases of COVID-19 (coronavirus disease 2019) in children would present unique challenges for hospitals and public health preparedness efforts in the United States. OBJECTIVE: To provide evidence-based estimates of children infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and projected cumulative numbers of severely ill pediatric COVID-19 cases requiring hospitalization during the US 2020 pandemic. DESIGN: Empirical case projection study. MAIN OUTCOMES AND MEASURES: Adjusted pediatric severity proportions and adjusted pediatric criticality proportions were derived from clinical and spatiotemporal modeling studies of the COVID-19 epidemic in China for the period January-February 2020. Estimates of total children infected with SARS-CoV-2 in the United States through April 6, 2020, were calculated using US pediatric intensive care unit (PICU) cases and the adjusted pediatric criticality proportion. Projected numbers of severely and critically ill children with COVID-19 were derived by applying the adjusted severity and criticality proportions to US population data, under several scenarios of cumulative pediatric infection proportion (CPIP). RESULTS: By April 6, 2020, there were 74 children who had been reported admitted to PICUs in 19 states, reflecting an estimated 176 190 children nationwide infected with SARS-CoV-2 (52 381 infants and toddlers younger than 2 years, 42 857 children aged 2-11 years, and 80 952 children aged 12-17 years). Under a CPIP scenario of 5%, there would be 3.7 million children infected with SARS-CoV-2, 9907 severely ill children requiring hospitalization, and 1086 critically ill children requiring PICU admission. Under a CPIP scenario of 50%, 10 865 children would require PICU admission, 99 073 would require hospitalization for severe pneumonia, and 37.0 million would be infected with SARS-CoV-2. CONCLUSIONS AND RELEVANCE: Because there are 74.0 million children 0 to 17 years old in the United States, the projected numbers of severe cases could overextend available pediatric hospital care resources under several moderate CPIP scenarios for 2020 despite lower severity of COVID-19 in children than in adults.", "title": "COVID-19 in Children in the United States: Intensive Care Admissions, Estimated Total Infected, and Projected Numbers of Severe Pediatric Cases in 2020", "pid": "hdvb2aed", "bm25_score": 215.59539794921875}, {"text": "Abstract Background Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has spread around the world, and reports of children with COVID-19 are increasing. Objectives To assess clinical profiles of pediatric COVID-19. Study design A retrospective analysis was undertaken using clinical data of sixteen children (11 months-14 years) diagnosed with COVID-19 between January 1, 2020 and March 17, 2020 at Xiangyang Central Hospital, Hubei province, China. Results All children had positive epidemiologic histories, 12 (12/16, 75 %) involving family units. The illnesses were either mild (5/16, 31.3 %) or ordinary (11/16, 68.8 %), presenting as follows: asymptomatic (8/16, 50 %), fever and/or cough (8/16, 50 %). Four asymptomatic patients (4/16, 25 %) in ordinary cases had chest computed tomography (CT) abnormalities. Leukocyte counts were normal in 14 cases(88 %), but 2 patients (12.5 %) had leukopenia, and 1 (6.3 %) was lymphopenic. There were 11 patients with chest CT abnormalities, some nodular, others small patchy and others ground-glass opacities. In asymptomatic children, the median time to SRAS-CoV-2 nucleic acid test(NAT) positivity once exposed to a family member with confirmed infection was 15.5 days (range, 10–26 days). The median time to first NAT-negative conversion was 5.5 days (range, 1–23 days). Conclusions COVID-19 in children of Xiangyang city is often family acquired and not serious, with favorable outcomes. Asymptomatic children can be diagnosed as pneumonia because of chest CT abnormalities. It is essential to actively screen this segment of the population.", "title": "Clinical features of pediatric patients with coronavirus disease (COVID-19)", "pid": "53xjbu8i", "bm25_score": 215.59230041503906}, {"text": "OBJECTIVE: To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with COVID-19. STUDY DESIGN: Children 1 month to 21 years with COVID-19 from a single tertiary care children's hospital between March 15-April 13, 2020 were included. Demographic and clinical data were collected. RESULTS: 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (p=0.99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (p<0.05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (p=0.0001) and were more likely to have received Remdesivir through compassionate release (p<0.05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) PICU patients. Acute respiratory distress syndrome (ARDS) was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer. CONCLUSIONS: We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.", "title": "Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City", "pid": "t5fpm082", "bm25_score": 215.5867156982422}, {"text": "There is a current outbreak of coronavirus disease 2019 (COVID-19), with a global spread. With the rapid increase in the number of infections, an increase is observed in the number of children with COVID-19. Most research findings are regarding adult cases, which are not always transferrable to children. Evidence-based studies are still expected to formulate clinical decisions for pediatric patients. In this review, we included 2597 pediatric patients that reported recently and evaluated the demographic, clinical, laboratory, and imaging features of children with COVID-19. We found that even lymphopenia was the most common lab finding in adults; it infrequently occurred in children (9.8%). Moreover, elevated creatine kinase MB isoenzyme was much more commonly observed in children (27.0%) than that in adults, suggesting that heart injury would be more likely to occur in pediatric patients. Our analysis may contribute to determine the spectrum of disease in children and to develop strategies to control the disease transmission.", "title": "Children with coronavirus disease 2019: A review of demographic, clinical, laboratory, and imaging features in pediatric patients", "pid": "8jfsrsmf", "bm25_score": 215.58108520507812}, {"text": "AIM: This aim of this systematic review and meta‐analysis was to evaluate the clinical characteristics of COVID‐19 in neonates and children under one year of age. METHODS: A systematic literature review of the MEDLINE, PubMed, CINAHL, Embase and EBSCO databases was carried out for studies from 1 January to 7 April 2020. We included all papers that addressed clinical manifestations, laboratory results, imaging findings and outcomes in infants and neonates. RESULTS: Our search identified 77 peer‐reviewed papers and 18 papers covering 160 infants were reviewed. One paper was from Vietnam and the other 17 were from China: eight were cross‐sectional studies, eight were case reports, one was a case series and one was a prospective cohort study. The most common clinical symptoms were fever (54%) and cough (33%). Most infants were treated symptomatically, with frequent use of various empirical medications. Infants and neonates tended to have more severe COVID‐19 disease than older children: 11 (7%) were admitted to intensive care and one infant died. The mortality rate was 0.006%, with favourable outcomes in most cases. CONCLUSION: Infants and neonates were more vulnerable to more severe COVID‐19 disease than older children, but morbidity and mortality were low.", "title": "Novel Coronavirus Infection (COVID‐19) in Children Younger Than One Year: A Systematic Review of Symptoms, Management and Outcomes", "pid": "y8lctk6k", "bm25_score": 215.57565307617188}, {"text": "Background: There is evolving evidence of significant differences in severity and outcomes of coronavirus disease 2019 (COVID-19) in children compared to adults. Underlying medical conditions associated with increased risk of severe disease are based on adult data, but have been applied across all ages resulting in large numbers of families undertaking social shielding (vulnerable group). We conducted a retrospective analysis of children with suspected COVID-19 at a Specialist Childrens Hospital to determine outcomes based on COVID-19 testing status and underlying health vulnerabilities. Methods: Routine clinical data were extracted retrospectively from the Institutions Electronic Health Record system and Digital Research Environment for patients with suspected and confirmed COVID-19 diagnoses. Data were compared between Sars-CoV-2 positive and negative patients (CoVPos / CoVNeg respectively), and in relation to presence of underlying health vulnerabilities based on Public Health England guidance. Findings: Between 1st March and 15th May 2020, 166 children (<18 years of age) presented to a specialist childrens hospital with clinical features of possible COVID-19 infection. 65 patients (39.2%) tested positive for SARS-CoV-2 virus. CoVPos patients were older (median 9 [0.9-14] years vs median 1 [0.1-5.7.5] years respectively, p<0.001). There was a significantly reduced proportion of vulnerable cases (47.7% vs 72.3%, p=0.002), but no difference in proportion of vulnerable patients requiring ventilation (61% vs 64.3%, p = 0.84) between CoVPos and CoVNeg groups. However, a significantly lower proportion of CoVPos patients required mechanical ventilation support compared to CoVNeg patients (27.7 vs 57.4%, p<0.001). Mortality was not significantly different between CoVPos and CoVNeg groups (1.5 vs 4% respectively, p=0.67) although there were no direct COVID-19 related deaths in this highly preselected paediatric population. Interpretation: COVID-19 infection may be associated with severe disease in childhood presenting to a specialist hospital, but does not appear significantly different in severity to other causes of similar clinical presentations. In children presenting with pre-existing COVID-19 vulnerable medical conditions at a specialist centre, there does not appear to be significantly increased risk of either contracting COVID-19 or severe complications, apart from those undergoing chemotherapy, who are over-represented.", "title": "Coronavirus (COVID-19) infection in children at a specialist centre: outcome and implications of underlying high-risk comorbidities in a paediatric population", "pid": "15zj660u", "bm25_score": 215.56309509277344}, {"text": "OBJECTIVE: To describe the clinical profiles and risk factors for critical illness in hospitalized children and adolescents with COVID-19. STUDY DESIGN: Children 1 month to 21 years with COVID-19 from a single tertiary care children’s hospital between March 15-April 13, 2020 were included. Demographic and clinical data were collected. RESULTS: 67 children tested positive for COVID-19; 21 (31.3%) were managed as outpatients. Of 46 admitted patients, 33 (72%) were admitted to the general pediatric medical unit and 13 (28%) to the pediatric intensive care unit (PICU). Obesity and asthma were highly prevalent but not significantly associated with PICU admission (p=0.99). Admission to the PICU was significantly associated with higher C-reactive protein, procalcitonin, and pro-B type natriuretic peptide levels and platelet counts (p<0.05 for all). Patients in the PICU were more likely to require high-flow nasal cannula (p=0.0001) and were more likely to have received Remdesivir through compassionate release (p<0.05). Severe sepsis and septic shock syndromes were observed in 7 (53.8%) PICU patients. Acute respiratory distress syndrome (ARDS) was observed in 10 (77%) PICU patients, 6 of whom (46.2%) required invasive mechanical ventilation for a median of 9 days. Of the 13 patients in the PICU, 8 (61.5%) were discharged home, and 4 (30.7%) patients remain hospitalized on ventilatory support at day 14. One patient died after withdrawal of life-sustaining therapy because of metastatic cancer. CONCLUSIONS: We describe a higher than previously recognized rate of severe disease requiring PICU admission in pediatric patients admitted to the hospital with COVID-19.", "title": "Clinical Characteristics and Outcomes of Hospitalized and Critically Ill Children and Adolescents with Coronavirus Disease 2019 (COVID-19) at a Tertiary Care Medical Center in New York City", "pid": "0ifsyct7", "bm25_score": 215.56234741210938}, {"text": "Two epidemics-Covid-19 and opioid use disorder (OUD) -are creating short- and long-term mental and physical health risks for vulnerable children and adolescents. Information about the risks to children from exposure to the coronavirus is still fragmentary, but even many healthy children are not getting appropriate health care, such as vaccinations or monitoring of developmental milestones during the Covid-19 pandemic. Children living in poverty are at heightened risk. Youngsters who are already dealing with OUD in their families-2.2 million as of 2017-face serious consequences stemming from trauma and stress. Although not officially designated by the Centers for Disease Control and Prevention as \"adverse childhood experiences\" (\"ACEs\"), these situations meet the CDC's criteria for inclusion, such as death or separation from a parent. It is important to recognize and meet the needs of all these children now and not just when the long-term consequences become apparent.", "title": "Vulnerable Children in a Dual Epidemic", "pid": "i16tiot6", "bm25_score": 215.55223083496094}, {"text": "Abstract The 2019 novel coronavirus (COVID-19) has been reported to cause significant morbidity in adults with reportedly a lesser impact on children. Cardiac dysfunction has only been described in adults thus far. We describe three cases of previously healthy children presenting with shock and COVID-19 related cardiac inflammation.", "title": "Cardiac dysfunction and shock in pediatric patients with COVID-19", "pid": "clhbtjr9", "bm25_score": 215.5511474609375}, {"text": "The COVID‐19 pandemic impact on children is a growing concern. The United Nations and its agencies (the World Health Organization and UNICEF), Indian Association For Child and Adolescent Mental Health and National Institute of Mental Health and Neuroscience in India warn about the broader impacts on children and call for urgent action to support the world’s children amidst the pandemic which may have lasting consequences. The COVID‐19 pandemic and unprecedented control measures to prevent its spread have disrupted nearly every aspect of children’s lives – their health, development, learning, behaviour and their families’ economic security, including protection from violence and abuse. Given this background, there is an urgent need for action through screening to minimize the mental health issues of children in India who constitute a substantial proportion of the population.", "title": "Debate: COVID‐19 and children in India", "pid": "8bu6xadf", "bm25_score": 215.54266357421875}, {"text": "COVID-19 is a coronavirus responsible for a global pandemic that started in China in December 2019 and has quickly spread to almost all countries. Approximately 2% of cases are diagnosed in children. There is increasing evidence for transmission by asymptomatic or presymptomatic adults and children. The clinical features do not differ from those of other respiratory viral infections, although rare cases manifest an unusual rash involving the digits. Disease is generally mild in children but deaths have been reported. Risk groups for severe disease in children are yet to be delineated. All treatments remain experimental.", "title": "COVID-19 – What does a paediatrician need to know?", "pid": "828ubhzi", "bm25_score": 215.51205444335938}, {"text": "", "title": "After COVID-19, a future for the world's children?", "pid": "dhs8olij", "bm25_score": 215.5099334716797}, {"text": "", "title": "The intriguing features of COVID-19 in children and its impact on the pandemic", "pid": "dtpj9bz2", "bm25_score": 215.5055694580078}, {"text": "BACKGROUND: Few paediatric cases of COVID-19 have been reported and we know little about the epidemiology in children, though more is known about other coronaviruses. We aimed to understand the infection rate, clinical presentation, clinical outcomes and transmission dynamics for SARS-CoV-2, in order to inform clinical and public health measures. METHODS: We undertook a rapid systematic review and narrative synthesis of all literature relating to SARS-CoV-2 in paediatric populations. The search terms also included SARS-CoV and MERS-CoV. We searched three databases and the COVID-19 resource centres of eleven major journals and publishers. English abstracts of Chinese language papers were included. Data were extracted and narrative syntheses conducted. RESULTS: 24 studies relating to COVID-19 were included in the review. Children appear to be less affected by COVID-19 than adults by observed rate of cases in large epidemiological studies. Limited data on attack rate indicate that children are just as susceptible to infection. Data on clinical outcomes are scarce but include several reports of asymptomatic infection and a milder course of disease in young children, though radiological abnormalities are noted. Severe cases are not reported in detail and there are little data relating to transmission. CONCLUSIONS: Children appear to have a low observed case rate of COVID-19 but may have similar rates to adults of infection with SARS-CoV-2. This discrepancy may be because children are asymptomatic or too mildly infected to draw medical attention, be tested and counted in observed cases of COVID-19.", "title": "SARS-CoV-2 (COVID-19): What do we know about children? A systematic review", "pid": "998lscmk", "bm25_score": 215.49691772460938}, {"text": "", "title": "COVID-19 virus and children: What do we know?", "pid": "om7gigcb", "bm25_score": 215.49462890625}, {"text": "AIM: The aim of this systematic review was to evaluate the clinical characteristics of COVID-19 in neonates and children under one year of age. METHODS: A systematic literature review of the MEDLINE, PubMed, CINAHL, Embase and EBSCO databases was carried out for studies from January 1, 2020, to April 7, 2020. We included all papers that addressed clinical manifestations, laboratory results, imaging findings and outcomes in infants and neonates. RESULTS: Our search identified 77 peer-reviewed papers, and 18 papers covering 160 infants were reviewed. One paper was from Vietnam, and the other 17 were from China: eight were cross-sectional studies, eight were case reports, one was a case series, and one was a prospective cohort study. The most common clinical symptoms were fever (54%) and cough (33%). Most infants were treated symptomatically, with frequent use of various empirical medications. Infants and neonates tended to have more severe COVID-19 disease than older children: 11 (7%) were admitted to intensive care and one infant died. The mortality rate was 0.006%, with favourable outcomes in most cases. CONCLUSION: Infants and neonates were more vulnerable to more severe COVID-19 disease than older children, but morbidity and mortality were low.", "title": "Novel coronavirus infection (COVID-19) in children younger than one year: A systematic review of symptoms, management and outcomes", "pid": "1n3t23ag", "bm25_score": 215.4894256591797}, {"text": "A recent outbreak of a novel Coronavirus responsible for a Severe Acute Respiratory Syndrome (SARS-CoV-2) is spreading globally. The aim of this study was to systematically review main clinical characteristics and outcomes of SARS-CoV-2 infections in pediatric age. An electronic search was conducted in PubMed database. Papers published between 1 January and 1 May 2020 including children aged 0–18 years were selected. Sixty-two studies and three reviews were included, with a total sample size of 7480 children (2428/4660 males, 52.1%; weighted mean age 7.6 years). Patients showed mainly mild (608/1432, 42.5%) and moderate (567/1432, 39.6%) signs of the infection. About 2% of children were admitted to the pediatric intensive care unit. The most commonly described symptoms were fever (51.6%) and cough (47.3%). Laboratory findings were often unremarkable. Children underwent a chest CT scan in 73.9% of all cases, and 32.7% resulted normal. Overall, the estimated mortality was 0.08%. A higher proportion of newborns was severely ill (12%) and dyspnea was the most common reported sign (40%). Conclusion: SARS-CoV-2 affects children less severely than adults. Laboratory and radiology findings are mainly nonspecific. Larger epidemiological and clinical cohort studies are needed to better understand possible implications of COVID-19 infection in children. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00431-020-03684-7) contains supplementary material, which is available to authorized users.", "title": "SARS-COV-2 infection in children and newborns: a systematic review", "pid": "6d6yzece", "bm25_score": 215.48582458496094}, {"text": "OBJECTIVES: To investigate the clinical and epidemiological characteristics of paediatric patients with coronavirus disease-19 (COVID-19). METHODS: Paediatric patients diagnosed with COVID-19 between January 15 and March 15, 2020, from seven hospitals in Zhejiang Province, China, were collected retrospectively and analysed. RESULTS: Thirty-two children with COVID-19, ranging in age from 3 months to 18 years, were enrolled. Family aggregation occurred in 87.5% of infant and preschool-aged children (7/8), and also school-aged children (14/16), but in only 12.5% (1/8) of adolescents (p < 0.05, p < 0.001). Most of these patients had mild symptoms: mainly fever (20/32) followed by cough (10/32) and fatigue (4/32). The average durations of viral RNA in respiratory samples and gastrointestinal samples were 15.8 d and 28.9 d, respectively. Detox duration in faeces decreased with age: 39.8 d, 27.5 d and 20.4 d in infants and preschool children, school children, and adolescents respectively (p0-6, -18 <0.01, p0-6, -14 <0.05). Pneumonia was found in 14 children, but there was no statistical significance in the incidence of pneumonia between different age groups. Thirty patients were treated with antiviral drugs, and all patients were stable and gradually improved after admission. CONCLUSIONS: Most children with COVID-19 had a mild process and a good prognosis. More attention should be paid to investigation of household contact history in the diagnosis of COVID-19 in young children. Viral RNA lasts longer in the gastrointestinal system than in the respiratory tract, especially in younger children.", "title": "Childhood COVID-19: a multicentre retrospective study", "pid": "v6kh517q", "bm25_score": 215.48483276367188}, {"text": "BACKGROUND: In December 2019, the infection caused by 2019 novel coronavirus (COVID-19) led to an outbreak in Wuhan, situated in the Hubei Province of China. Following this, there has been a rapid increase in the number of cases. On 12th March 2020, there were over 100,000 confirmed cases and almost 4,300 deaths worldwide. The clinical profile of children with COVID-19 is unknown due to the few number of cases reported. Currently, available data suggest they may have a milder form of illness. METHODS: A review of the literature published from June 2019 to March 2020 was undertaken to evaluate the clinical presentation, management and outcomes of COVID-19 in in children. Data sources included EMBASE, MEDLINE, Cochrane library, ISI Web of Knowledge and references within identified articles. RESULTS: We identified 303 potential studies, and 295 were excluded for reasons including duplicates, experimental studies and case reports. Eight studies were eligible for inclusion, including a total of 820 paediatric cases of COVID-19. Asymptomatic cases represented 14.3% (n = 117) of the total number of cases identified, and thus the remaining 85.7% (n = 703) experienced symptoms. Fever was the commonest symptom in 53.9% (n = 48) of cases, followed by cough in 39.3% (n = 35) of cases, and rhinorrhoea or pharyngeal congestion in 13.5% (n = 12) of cases. Diarrhoea and sore throats were less common symptoms, 7.9% (n = 7) and 9.0% (n = 8) respectively. Other symptoms, including fatigue, headache and dizziness were rare. CONCLUSION: Children are disproportionately affected by COVID-19 and are more likely to run a milder cause of illness following this infection compared to adults. This outbreak only started 3 months ago, therefore, further population wide studies are needed to validate these findings.", "title": "Clinical Characteristics of Children with COVID-19", "pid": "fg0lcl64", "bm25_score": 215.4820098876953}, {"text": "BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has made widespread impact recently. We aim to investigate the clinical characteristics of COVID-19 children with different severities and allergic status. METHODS: Data extracted from the electronical medical records, including demographics, clinical manifestations, comorbidities, laboratory and immunological results and radiological images of 182 hospitalized COVID-19 children were summarized and analyzed. RESULTS: The median age was 6 years old, ranging from 3 days to 15 years, and there were more boys (male-female ratio about 2:1) within the studied 182 patients. Most of the children were infected by family members. Fever (43.4%) and dry cough (44.5%) were common symptoms, and gastrointestinal manifestations accounted for 11.0%, including diarrhea, abdominal discomfort and vomiting. 71.4% had abnormal chest computed tomography (CT) scan images, and typical signs of pneumonia were ground-glass opacity and local patchy shadowing on admission. Laboratory results were mostly within normal ranges, and only a small ratio of lymphopenia (3.9%) and eosinopenia (29.5%) were observed. The majority (97.8%) of infected children were not severe, and 24 (13.2%) of them had asymptomatic infections. Compared to children without pneumonia(manifested as asymptomatic and acute upper respiratory infection), children with pneumonia were associated with higher percentages of the comorbidity history, symptoms of fever and cough, and increased levels of serum procalcitonin, alkaline phosphatase and serum interleukins (IL)-2, IL-4, IL-6, IL-10 and TNF-&#945;.There were no differences of treatments, duration of hospitalization, time from first positive to first negative nucleic acid testing and outcomes between children with mild pneumonia and without pneumonia. All the hospitalized COVID-19 children had recovered except one death due to intussusception and sepsis. In 43 allergic children with COVID-19, allergic rhinitis (83.7%) was the major disease, followed by drug allergy, atopic dermatitis, food allergy and asthma. Demographics and clinical features were not significantly different between allergic and non-allergic groups. Allergic patients showed less increase in acute phase reactants, procalcitonin, D-dimer and aspartate aminotransferase levels compared to all patients. Immunological profiles including circulating T, B and NK lymphocyte subsets, total immunoglobulin and complement levels and serum cytokines did not show any difference in allergic and pneumonia groups. Neither eosinophil counts nor serum total immunoglobulin E (IgE) levels showed a significant correlation with other immunological measures, such as other immunoglobulins, complements, lymphocyte subsets numbers and serum cytokine levels. CONCLUSION: Pediatric COVID-19 patients tended to have a mild clinical course. Patients with pneumonia had higher proportion of fever and cough and increased inflammatory biomarkers than those without pneumonia. There was no difference between allergic and non-allergic COVID-19 children in disease incidence, clinical features, laboratory and immunological findings. Allergy was not a risk factor for developing and severity of SARS-CoV-2 infection and hardly influenced the disease course of COVID-19 in children.", "title": "Clinical characteristics of 182 pediatric COVID-19 patients with different severities and allergic status", "pid": "m63b9ekk", "bm25_score": 215.46408081054688}, {"text": "", "title": "Children with COVID-19 at a specialist centre: initial experience and outcome", "pid": "lz711hew", "bm25_score": 215.46133422851562}, {"text": "We reported the clinical characteristics of a case series of 10 patients with coronavirus disease 2019 (COVID‐19) aged from 1 year to 18 years. Seven patients had contact with confirmed COVID‐19 family members before onset. Fever (4 [40.0%]) and cough (3 [30.0%]) were the most common symptoms. No patient showed leucopenia and lymphopenia on admission. Pneumonia was observed in chest CT images in 5 (50.0%) patients. Five (50.0%) patients received antiviral treatment. No patient had severe complications or developed a severe illness in our study. Our study indicated that COVID‐19 children present less severe symptoms and have better outcomes.", "title": "Clinical characteristics of a case series of children with coronavirus disease 2019", "pid": "gmo6big4", "bm25_score": 215.45516967773438}, {"text": "Children are not indifferent to the significant psychological impact of the COVID-19 Pandemic. They experience fears, uncertainties, substantial changes to their routines, physical and social isolation alongside high level of parental stress. Understanding their emotions and responses is essential to properly address their needs during this pandemic. In this article, we highlight children’s vulnerability, provide an overview of common symptoms of distress in different age groups, and summarize the interventions and resources available to promote child mental health and wellbeing during these challenging times. We advocate that prioritizing mental health including child & adolescent mental health is an essential component of any universal, community led response to COVID-19 Pandemic.", "title": "Mental health considerations for children & adolescents in COVID-19 Pandemic", "pid": "6iuekyie", "bm25_score": 215.45516967773438}, {"text": "We first described the 2019 novel coronavirus infection in 10 children occurring in areas other than Wuhan. The coronavirus diseases in children are usually mild and epidemiological exposure is a key clue to recognize pediatric case. Prolonged virus shedding is observed in respiratory tract and feces at the convalescent stage.", "title": "A Case Series of children with 2019 novel coronavirus infection: clinical and epidemiological features", "pid": "qbazis0e", "bm25_score": 215.44644165039062}, {"text": "BACKGROUND: Although people of all ages are susceptible to the novel coronavirus infection, which is presently named \"Coronavirus Disease 2019\" (COVID-19), there has been relatively few cases reported among children. Therefore, it is necessary to understand the clinical characteristics of COVID-19 in children and the differences from adults. CASE PRESENTATION: We report one pediatric case of COVID-19. A 14-month-old boy was admitted to the hospital with a symptom of fever, and was diagnosed with a mild form of COVID-19. The child's mother and grandmother also tested positive for SARS-CoV-2 RNA. However, the lymphocyte counts were normal. The chest computed tomography (CT) revealed scattered ground glass opacities in the right lower lobe close to the pleura and resorption after the treatment. The patient continued to test positive for SARS-CoV-2 RNA in the nasopharyngeal swabs and stool at 17 days after the disappearance of symptoms. CONCLUSION: The present pediatric case of COVID-19 was acquired through household transmission, and the symptoms were mild. Lymphocyte counts did not significantly decrease. The RNA of SARS-CoV-2 in stool and nasopharyngeal swabs remained positive for an extended period of time after the disappearance of symptoms. This suggests that attention should be given to the potential contagiousness of pediatric COVID-19 cases after clinical recovery.", "title": "A child with household transmitted COVID-19", "pid": "qhvyzpli", "bm25_score": 215.4459228515625}, {"text": "BACKGROUND: Although people of all ages are susceptible to the novel coronavirus infection, which is presently named “Coronavirus Disease 2019” (COVID-19), there has been relatively few cases reported among children. Therefore, it is necessary to understand the clinical characteristics of COVID-19 in children and the differences from adults. CASE PRESENTATION: We report one pediatric case of COVID-19. A 14-month-old boy was admitted to the hospital with a symptom of fever, and was diagnosed with a mild form of COVID-19. The child’s mother and grandmother also tested positive for SARS-CoV-2 RNA. However, the lymphocyte counts were normal. The chest computed tomography (CT) revealed scattered ground glass opacities in the right lower lobe close to the pleura and resorption after the treatment. The patient continued to test positive for SARS-CoV-2 RNA in the nasopharyngeal swabs and stool at 17 days after the disappearance of symptoms. CONCLUSION: The present pediatric case of COVID-19 was acquired through household transmission, and the symptoms were mild. Lymphocyte counts did not significantly decrease. The RNA of SARS-CoV-2 in stool and nasopharyngeal swabs remained positive for an extended period of time after the disappearance of symptoms. This suggests that attention should be given to the potential contagiousness of pediatric COVID-19 cases after clinical recovery.", "title": "A child with household transmitted COVID-19", "pid": "txhtw2la", "bm25_score": 215.43362426757812}, {"text": "", "title": "COVID-19 disease in children: not as mild as we have been led to believe", "pid": "6tabiuhc", "bm25_score": 215.4257049560547}, {"text": "", "title": "COVID-19: children on the front line", "pid": "en22n5vp", "bm25_score": 215.41677856445312}, {"text": "In mid‐December 2019, a disease caused by infection with severe acute respiratory syndrome coronavirus‐2, which began in Wuhan, China, has spread throughout the country and many countries around the world. The number of children with coronavirus disease‐2019 (COVID‐19) has also increased significantly. Although information regarding the epidemiology of COVID‐19 in children has accumulated, relevant comprehensive reports are lacking. The present article reviews the epidemiological characteristics of COVID‐19 in children.", "title": "COVID‐19 epidemic: Disease characteristics in children", "pid": "dq5dnjmn", "bm25_score": 215.41506958007812}, {"text": "BACKGROUND: Estimates of pediatric morbidity and mortality from COVID-19 are vital for planning optimal use of human and material resources throughout this pandemic. METHODS: Government websites from countries with minimum 1000 cases in adults and children on April 13, 2020 were searched to find the number of cases confirmed in children, the age range, and the number leading to hospitalization, intensive care unit (ICU) admission or death. A systematic literature search was performed April 13, 2020 to find additional data from cases series. RESULTS: Data on pediatric cases were available from government websites for 23 of the 70 countries with minimum 1000 cases by April 13, 2020. Of 424 978 cases in these 23 countries, 8113 (1.9%) occurred in children. Nine publications provided data from 4251 cases in 4 additional countries. Combining data from the websites and the publications, 330 of 2361 cases required admission (14%). The ICU admission rate was 2.2 % of confirmed cases (44 of 2031) and 7.2% of admitted children (23 of 318). Death was reported for 15 cases. CONCLUSION: Children accounted for 1.9% of confirmed cases. The true incidence of pediatric infection and disease will only be known once testing is expanded to individuals with less severe or no symptoms. Admission rates vary from 0.3 to 10% of confirmed cases (presumably varying with the threshold for testing) with about 7% of admitted children requiring ICU care. Death is rare in middle and high income countries.", "title": "COVID- 19 Infection in Children: Estimating Pediatric Morbidity and Mortality", "pid": "71uvferq", "bm25_score": 215.4143524169922}, {"text": "OBJECTIVE: To study the clinical features of coronavirus disease 2019 (COVID-19) in children aged <18 years. METHODS: A retrospective analysis was performed from the medical data of 23 children, aged from 3 months to 17 years and 8 months, who were diagnosed with COVID-19 in Jiangxi, China from January 21 to February 29, 2020. RESULTS: Of the 23 children with COVID-19, 17 had family aggregation. Three children (13%) had asymptomatic infection, 6 (26%) had mild type, and 14 (61%) had common type. Among these 23 children, 16 (70%) had fever, 11 (48%) had cough, 8 (35%) had fever and cough, and 8 (35%) had wet rales in the lungs. The period from disease onset or the first nucleic acid-positive detection of SARS-CoV-2 to the virus nucleic acid negative conversion was 6-24 days (median 12 days). Of the 23 children, 3 had a reduction in total leukocyte count, 2 had a reduction in lymphocytes, 2 had an increase in C-reactive protein, and 2 had an increase in D-dimer. Abnormal pulmonary CT findings were observed in 12 children, among whom 9 had patchy ground-glass opacities in both lungs. All 23 children received antiviral therapy and were recovered. CONCLUSIONS: COVID-19 in children aged <18 years often occurs with family aggregation, with no specific clinical manifestation and laboratory examination results. Most of these children have mild symptoms and a good prognosis. Epidemiological history is of particular importance in the diagnosis of COVID-19 in children aged <18 years.", "title": "[Clinical features of coronavirus disease 2019 in children aged <18 years in Jiangxi, China: an analysis of 23 cases]", "pid": "4qjklght", "bm25_score": 215.41310119628906}]}
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concerns about the risks to students and staff.", "title": "Back to school: Safe for children with underlying medical conditions.", "pid": "6gn2seix", "bm25_score": 219.228759765625}, {"text": "", "title": "Re-Opening Schools Safely: The Case for Collaboration, Constructive Disruption of Pre-COVID Expectations, and Creative Solutions", "pid": "101aqyd5", "bm25_score": 219.0606689453125}, {"text": "", "title": "Covid-19: Push to reopen schools risks new wave of infections, says Independent SAGE", "pid": "sx4yih5m", "bm25_score": 219.0045166015625}, {"text": "", "title": "Reopening schools after the COVID-19 lockdown", "pid": "bgjpfby7", "bm25_score": 218.85081481933594}, {"text": "The epidemic of coronavirus disease 2019 (COVID-19) broke out in Wuhan, China, in December 2019 and rapidly spread across the world. In order to counter this epidemic, several countries put in place different restrictive measures, such as the school's closure and a total lockdown. However, as the knowledge on the disease progresses, clinical evidence showed that children mainly have asymptomatic or mild disease and it has been suggested that they are also less likely to spread the virus. Moreover, the lockdown and the school closure could have negative consequences on children, affecting their social life, their education and their mental health. As many countries have already entered or are planning a phase of gradual lifting of the containment measures of social distancing, it seems plausible that the re-opening of nursery schools and primary schools could be considered a policy to be implemented at an early stage of recovery efforts, putting in place measures to do it safely, such as the maintenance of social distance, the reorganisation of classes into smaller groups, the provision of adequate sanitization of spaces, furniture and toys, the prompt identification of cases in the school environment and their tracing. Therefore, policy makers have the task of balancing pros and cons of the school re-opening strategy, taking into account psychological, educational and social consequences for children and their families. Another issue to be considered is represented by socio-economic disparities and inequalities which could be amplified by school's closure.", "title": "COVID-19 and the re-opening of schools: a policy maker's dilemma", "pid": "5eg7hf6r", "bm25_score": 218.76544189453125}, {"text": "The epidemic of coronavirus disease 2019 (COVID-19) broke out in Wuhan, China, in December 2019 and rapidly spread across the world. In order to counter this epidemic, several countries put in place different restrictive measures, such as the school’s closure and a total lockdown. However, as the knowledge on the disease progresses, clinical evidence showed that children mainly have asymptomatic or mild disease and it has been suggested that they are also less likely to spread the virus. Moreover, the lockdown and the school closure could have negative consequences on children, affecting their social life, their education and their mental health. As many countries have already entered or are planning a phase of gradual lifting of the containment measures of social distancing, it seems plausible that the re-opening of nursery schools and primary schools could be considered a policy to be implemented at an early stage of recovery efforts, putting in place measures to do it safely, such as the maintenance of social distance, the reorganisation of classes into smaller groups, the provision of adequate sanitization of spaces, furniture and toys, the prompt identification of cases in the school environment and their tracing. Therefore, policy makers have the task of balancing pros and cons of the school re-opening strategy, taking into account psychological, educational and social consequences for children and their families. Another issue to be considered is represented by socio-economic disparities and inequalities which could be amplified by school’s closure.", "title": "COVID-19 and the re-opening of schools: a policy maker’s dilemma", "pid": "22y5ewq6", "bm25_score": 218.6571502685547}, {"text": "", "title": "Covid-19: Delaying school reopening by two weeks would halve risks to children, says iSAGE.", "pid": "k9kq0uir", "bm25_score": 218.60617065429688}, {"text": "", "title": "Covid-19: Delaying school reopening by two weeks would halve risks to children, says iSAGE", "pid": "f0izfja8", "bm25_score": 218.60293579101562}, {"text": "The COVID-19 pandemic is causing substantial morbidity and mortality, straining health care systems, shutting down economies, and closing school districts. While it is a priority to mitigate its immediate impact, we want to call attention to the pandemic's longer-term effect on children's health: COVID-19, via these school closures, may exacerbate the epidemic of childhood obesity and increase disparities in obesity risk. In many areas of the U.S., the COVID-19 pandemic has closed schools and some of these school systems are not expected to re-open this school year. The experiences in Hong Kong, Taiwan and Singapore suggest that social distancing orders, if lifted after short periods, will have to be periodically re-instated to control COVID-19 flare ups. In short, we anticipate that the COVID-19 pandemic will likely double out-of-school time this year for many children in the U.S. and will exacerbate the risk factors for weight gain associated with summer recess.", "title": "COVID-19 Related School Closings and Risk of Weight Gain Among Children.", "pid": "x6x6a35w", "bm25_score": 218.57440185546875}, {"text": "Objective: School reopening has not yet started in China where the COVID-19 outbreak has reached ending stage, largely due to a great concern about COVID-19 infections on students. We attempted to quantitatively evaluate the risk of COVID-19 infections on students caused by school reopening. Study design: We collected the data of the numbers of teachers, population size and newly confirmed COVID-19 cases in the past 14 days in typical provinces/cities of China, and then analyzed the risk of COVID-19 infections in schools with respect to each province/city. Methods: A step-by-step procedure was explored to calculate the probability of COVID-19 infections on students as transmitted from infected teachers. Two critical assumptions for analysis were proposed: (i) only locally generated cases were counted while imported cases were omitted; (ii) the secondary attack rate of the COVID-19 virus in schools is similar to that in households in China, ranging from 3-10%. Results: The probability of COVID-19 resurgence within one week on students of primary, middle and high schools in China (outside Hubei) is extremely low (<0.2%) in each province/city, and such probability can be updated daily and weekly based on the newly confirmed cases in the past 14 days. In some areas without newly confirmed cases in the past 14 days, the risk is zero. Conclusions: Our work provides guidance for local governments to make risk level-based policies for school reopening. Currently, the risk of COVID-19 infections on students is extremely low in China (outside Hubei) and therefore school reopening can be initiated without the endanger of infections on students.", "title": "Little Risk of the COVID-19 Resurgence on Students in China (outside Hubei) Caused by School Reopening", "pid": "7en6cog7", "bm25_score": 218.57225036621094}, {"text": "", "title": "Pandemic school closures: risks and opportunities", "pid": "ewah8x7m", "bm25_score": 218.51513671875}, {"text": "As schools reopen as a result of low community transmission rates of COVID-19, parents and teachers will have understandable concerns about the risks to students and staff.", "title": "Back to school: Safe for children with underlying medical conditions", "pid": "xu7bazzw", "bm25_score": 218.33871459960938}, {"text": "As several countries around the world are planning exit strategies to progressively lift the rigid social restrictions implemented with lockdown, different options are being chosen regarding the closure or reopening of schools. We evaluate the expected impact of reopening schools in lIe-de-France region after the withdrawal of lockdown currently scheduled for May 11, 2020. We explore several scenarios of partial, progressive, or full school reopening, coupled with moderate social distancing interventions and large-scale tracing, testing, and isolation. Accounting for current uncertainty on the role of children in COVID-19 epidemic, we test different hypotheses on children's transmissibility distinguishing between younger children (pre-school and primary school age) and adolescents (middle and high school age). Reopening schools after lifting lockdown will likely lead to an increase in the number of COVID-19 cases in the following 2 months, even with lower transmissibility of children, yet protocols exist that would allow maintaining the epidemic under control without saturating the healthcare system. With pre-schools and primary schools in session starting May 11, ICU occupation would reach at most 72% [55,83]% (95% probability ranges) of a 1,500-bed capacity (here foreseen as the routine capacity restored in the region post-first wave) if no other school level reopens before summer or if middle and high schools reopen one month later through a progressive protocol (increasing attendance week by week). Full attendance of adolescents at school starting in June would overwhelm the ICU system (138% [118,159]% occupation). Reopening all schools on May 11 would likely lead to a second wave similar to the one recently experienced, except if maximum attendance is limited to 50% for both younger children and adolescents. Based on the estimated situation on May 11, no substantial difference in the epidemic risk is predicted between progressive and prompt reopening of pre-schools and primary schools, thus allowing full attendance of younger children mostly in need of resuming learning and development. Reopening would require however large-scale trace and testing to promptly isolate cases, in addition to moderate social distancing interventions. Full attendance in middle and high schools is instead not recommended. Findings are consistent across different assumptions on the relative transmissibility of younger children and for small increase of the reproductive number possibly due to decreasing compliance to lockdown.", "title": "Expected impact of reopening schools after lockdown on COVID-19 epidemic in Ile-de-France", "pid": "qnlf5qfd", "bm25_score": 218.22425842285156}, {"text": "", "title": "Reopening Schools in the Time of Pandemic: Look to the School Nurses.", "pid": "sdoxki4n", "bm25_score": 218.18698120117188}, {"text": "As a result of the COVID-19 pandemic, many school districts have closed for the remainder of the academic year. These closures are unfortunate because, for many students, schools are their only source of trauma-informed care and supports. When schools reopen, they must develop a comprehensive plan to address the potential mental health needs of their students. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Children and the COVID-19 pandemic.", "pid": "4nv1kedt", "bm25_score": 218.16136169433594}, {"text": "", "title": "Reopening Schools in the Time of Pandemic: Look to the School Nurses", "pid": "mlf8369r", "bm25_score": 218.1333770751953}, {"text": "In response to the coronavirus disease (COVID-19) pandemic, most countries implemented school closures. In Norway, schools closed on 13 March 2020. The evidence of effect on disease transmission was limited, while negative consequences were evident. Before reopening, risk-assessment for paediatric risk groups was performed, concluding that most children can attend school with few conditions requiring preventative homeschooling. We here present infection prevention and control guidelines for primary schools and recommendations for paediatric risk groups.", "title": "Infection prevention guidelines and considerations for paediatric risk groups when reopening primary schools during COVID-19 pandemic, Norway, April 2020", "pid": "k36e2sob", "bm25_score": 217.93373107910156}, {"text": "Reopening colleges and universities during the coronavirus disease 2019 (COVID-19) pandemic poses a special challenge worldwide. Taiwan is one of the few countries where schools are functioning normally. To secure the safety of students and staff, the Ministry of Education in Taiwan established general guidelines for college campuses. The guidelines delineated creation of a task force at each university; school-based risk screening based on travel history, occupation, contacts, and clusters; measures on self-management of health and quarantine; general hygiene measures (including wearing masks indoors); principles on ventilation and sanitization; regulations on school assemblies; a process for reporting suspected cases; and policies on school closing and make-up classes. It also announced that a class should be suspended if 1 student or staff member in it tested positive and that a school should be closed for 14 days if it had 2 or more confirmed cases. As of 18 June 2020, there have been 7 confirmed cases in 6 Taiwanese universities since the start of the pandemic. One university was temporarily closed, adopted virtual classes, and quickly reopened after 14 days of contact tracing and quarantine of possible contacts. Taiwan's experience suggests that, under certain circumstances, safely reopening colleges and universities this fall may be feasible with a combination of strategies that include containment (access control with contact tracing and quarantine) and mitigation (hygiene, sanitation, ventilation, and social distancing) practices.", "title": "How to Safely Reopen Colleges and Universities During COVID-19: Experiences From Taiwan", "pid": "vgbhyzb9", "bm25_score": 217.89735412597656}, {"text": "As a result of the COVID-19 pandemic, many school districts have closed for the remainder of the academic year. These closures are unfortunate because, for many students, schools are their only source of trauma-informed care and supports. When schools reopen, they must develop a comprehensive plan to address the potential mental health needs of their students. (PsycInfo Database Record (c) 2020 APA, all rights reserved).", "title": "Children and the COVID-19 pandemic", "pid": "17a70tu9", "bm25_score": 217.88125610351562}, {"text": "Although there has been consistent evidence indicating that school closures have only limited efficacy in reducing community transmission of coronavirus disease 2019 (COVID-19), the question of whether children should be kept home from school has attracted extensive and often divisive public debate in Australia. In this article we analyse the factors that drove high levels of concern among parents, teachers and the public and led to both demands for school closures in late March 2020, and to many parents' reluctance to return their children to school in May 2020. We discuss how the use of well-established principles of risk communication might have reduced much of this community concern. Then we set out a range of practical suggestions for communication practices that build trust and hence diminish concerns in relation to managing schools over the long term of the COVID-19 pandemic.", "title": "How risk communication could have reduced controversy about school closures in Australia during the COVID-19 pandemic.", "pid": "u3isdii7", "bm25_score": 217.88059997558594}, {"text": "Although there has been consistent evidence indicating that school closures have only limited efficacy in reducing community transmission of coronavirus disease 2019 (COVID-19), the question of whether children should be kept home from school has attracted extensive and often divisive public debate in Australia. In this article we analyse the factors that drove high levels of concern among parents, teachers and the public and led to both demands for school closures in late March 2020, and to many parents' reluctance to return their children to school in May 2020. We discuss how the use of well-established principles of risk communication might have reduced much of this community concern. Then we set out a range of practical suggestions for communication practices that build trust and hence diminish concerns in relation to managing schools over the long term of the COVID-19 pandemic.", "title": "How risk communication could have reduced controversy about school closures in Australia during the COVID-19 pandemic", "pid": "pvus33s7", "bm25_score": 217.82525634765625}, {"text": "The coronavirus disease 2019 pandemic has affected nearly 70% of children and teenagers around the world due to school closure policies. School closure is implemented widely in order to prevent viral transmission and its impact on the broader community, based on preliminary recommendations and evidence from influenza. However, there is debate with regard to the effectiveness of school closures. Growing evidence suggests that a child's SARS-CoV-2 infection is often mild or asymptomatic and that children may not be major SARS-CoV-2 transmitters; thus, it is questionable if school closures prevent transmission significantly. This question is important as a majority of children in low- and middle-income countries depend on free school meals; unexpected long-term school closure may adversely impact nutrition and educational outcomes. Food insecurity is expected to be higher during the pandemic. In this viewpoint, we argue for a more thorough exploration of potential adverse impacts of school closures in low- and middle-income countries and recommend actions to ensure that the health and learning needs of vulnerable populations are met in this time of crisis.", "title": "School closure, COVID-19 and lunch programme: Unprecedented undernutrition crisis in low-middle income countries", "pid": "7ty971vj", "bm25_score": 217.79449462890625}, {"text": "We investigate the effect of school closure and subsequent reopening on the transmission of COVID-19, by considering Denmark, Norway, Sweden, and German states as case studies. By comparing the growth rates in daily hospitalisations or confirmed cases under different interventions, we provide evidence that the effect of school closure is visible as a reduction in the growth rate approximately 9 days after implementation. Limited school attendance, such as older students sitting exams or the partial return of younger year groups, does not appear to significantly affect community transmission. A large-scale reopening of schools while controlling or suppressing the epidemic appears feasible in countries such as Denmark or Norway, where community transmission is generally low. However, school reopening can contribute to significant increases in the growth rate in countries like Germany, where community transmission is relatively high. Our findings underscore the need for a cautious evaluation of reopening strategies that ensure low classroom occupancy and a solid infrastructure to quickly identify and isolate new infections.", "title": "Shut and re-open: the role of schools in the spread of COVID-19 in Europe", "pid": "r2x3awlw", "bm25_score": 217.72897338867188}, {"text": "Coronavirus disease 2019 (COVID-19), which was first identified in Wuhan, China, in late December of 2019 is rapidly spreading across the globe. The South Korean government has ordered the closure of all schools, as part of its attempts to use social distancing measures to prevent the spread of COVID-19. The effects of the school closures on reducing contagion are generally positive; however, the measure is controversial because of the socioeconomic ripple effect that accompanies it. The author briefly reviewed the existing literature on the mental health aspects of disasters and presents the issues related to school closures due to pandemics, from medical and socioeconomic perspectives and in terms of children’s mental health. The results of this review suggest that research on children’s mental health in relation to the adoption of school closures as a pandemic mitigation strategy is urgently needed.", "title": "Coronavirus Disease 2019, School Closures, and Children’s Mental Health", "pid": "y0ufxwhq", "bm25_score": 217.723876953125}, {"text": "The shift to the postpandemic school environment will cause dramatic changes and is likely to increase separation problems. In this article, we look at the anxiety problems that some parents and their children might experience when school reopens after the COVID-19 lockdown. Using a behavioral theory of development, we provide suggestions for how to handle the departure and separation problems that may emerge as parents drop their children off at school. Many parents are unsure about how to handle anxiety or fear as their children return to school or have to visit other environments outside their homes. Social distancing has caused families to develop stronger dependencies at home and to create new routines that vary, in many instances greatly, from their prepandemic routines. Families are adjusting to the new “normal.” They are keeping their children busy with schoolwork as best they can. In particular, families have likely developed close attachment relationships. Families have been struggling with an unprecedented lockdown, and for many parents and their children, this extended period of family confinement and severe restrictions has been especially stressful, and the timing for returning to school is uncertain. We emphasize here that parents can be responsive to their children’s needs, plan ahead, provide reassurance, and depart firmly without vacillating, and we provide other tips to avoid inadvertently shaping children’s negative or anxiety behaviors as they go back to school. We offer some specific advice for parents and teachers to follow to prevent the departure and separation problems that typically develop during challenging behavioral interactions in school settings.", "title": "Returning to School: Separation Problems and Anxiety in the Age of Pandemics", "pid": "66c2qobr", "bm25_score": 217.6614532470703}, {"text": "Countries throughout the world are counting the health and socioeconomic costs of the COVID-19 pandemic, including the strategies necessary to contain it. Profound consequences from social isolation are beginning to emerge, and there is an urgency about charting a path to recovery, albeit to a 'new normal' that mitigates them. Children have not suffered as much from the direct effects of COVID-19 infection as older adults. Still, there is mounting evidence that their health and welfare are being adversely affected. Closure of schools has been a critical component of social isolation but has a far broader impact than the diminution of educational opportunities, as important as these are. Reopening of schools is therefore essential to recovery, with some countries already tentatively implementing it. Children's interests are vital considerations in any recovery plan, but the question remains as to how to address them within the context of how society views children; should they be regarded as pawns, pathfinders or partners in this enterprise?", "title": "Children of COVID-19: pawns, pathfinders or partners?", "pid": "gyilcbr7", "bm25_score": 217.58448791503906}, {"text": "Countries throughout the world are counting the health and socioeconomic costs of the COVID-19 pandemic, including the strategies necessary to contain it. Profound consequences from social isolation are beginning to emerge, and there is an urgency about charting a path to recovery, albeit to a ‘new normal’ that mitigates them. Children have not suffered as much from the direct effects of COVID-19 infection as older adults. Still, there is mounting evidence that their health and welfare are being adversely affected. Closure of schools has been a critical component of social isolation but has a far broader impact than the diminution of educational opportunities, as important as these are. Reopening of schools is therefore essential to recovery, with some countries already tentatively implementing it. Children’s interests are vital considerations in any recovery plan, but the question remains as to how to address them within the context of how society views children; should they be regarded as pawns, pathfinders or partners in this enterprise?", "title": "Children of COVID-19: pawns, pathfinders or partners?", "pid": "gdz63spj", "bm25_score": 217.5712890625}, {"text": "Background: In the UK, cases of COVID-19 have been declining since mid-April and there is good evidence to suggest that the effective reproduction number has dropped below 1, leading to a multi-phase relaxation plan for the country to emerge from lockdown. As part of this staggered process, primary schools are scheduled to partially reopen on 1st June. Evidence from a range of sources suggests that children are, in general, only mildly affected by the disease and have low mortality rates, though there is less certainty regarding children's role in transmission. Therefore, there is wide discussion on the impact of reopening schools. Methods: We compare eight strategies for reopening primary and secondary schools in England from 1st June, focusing on the return of particular year groups and the associated epidemic consequences. This is assessed through model simulation, modifying a previously developed dynamic transmission model for SARS-CoV-2. We quantify how the process of reopening schools affected contact patterns and anticipated secondary infections, the relative change in R according to the extent of school reopening, and determine the public health impact via estimated change in clinical cases and its sensitivity to decreases in adherence post strict lockdown. Findings: Whilst reopening schools, in any form, results in more mixing between children, an increase in R and hence transmission of the disease, the magnitude of that increase can be low dependent upon the age-groups that return to school and the behaviour of the remaining population. We predict that reopening schools in a way that allows half class sizes or that is focused on younger children is unlikely to push R above one, although there is noticeable variation between the regions of the country. Given that older children have a greater number of social contacts and hence a greater potential for transmission, our findings suggest reopening secondary schools results in larger increases in case burden than only reopening primary schools; reopening both generates the largest increase and could push R above one in some regions. The impact of less social-distancing in the rest of the population, generally has far larger effects than reopening schools and exacerbates the impacts of reopening. Discussion: Our work indicates that any reopening of schools will result in increased mixing and infection amongst children and the wider population, although the opening of schools alone is unlikely to push the value of R above one. However, impacts of other recent relaxations of lockdown measures are yet to be quantified, suggesting some regions may be closer to the critical threshold that would lead to a growth in cases. Given the uncertainties, in part due to limited data on COVID-19 in children, school reopening should be carefully monitored. Ultimately, the decision about reopening classrooms is a difficult trade-off between increased epidemiological consequences and the emotional, educational and developmental needs of children.", "title": "The impact of school reopening on the spread of COVID-19 in England", "pid": "xhyqg5u2", "bm25_score": 217.53927612304688}, {"text": "School closures are an important strategy to mitigate the impacts of a pandemic. But an optimal approach to transitioning from in-person to distance learning approaches is lacking. We analyzed a convenience sample of public K-12 schools in the early weeks of the COVID-19 pandemic in the United States. This initial snapshot provides some insights to inform future research into the variation of strategies across school districts, and would benefit from more rigorous methods to determine true correlations between demographic and geographic factors. Additionally, many of these strategies have evolved in response to ongoing and prolonged public health social distancing measures implemented after this analysis was conducted.", "title": "Initial Coronavirus Disease-2019 Closure Strategies Adopted by a Convenience Sample of US School Districts: Directions for Future Research", "pid": "xecvlxhg", "bm25_score": 217.42156982421875}, {"text": "School closures are an important strategy to mitigate the impacts of a pandemic. But an optimal approach to transitioning from in-person to distance learning approaches is lacking. We analyzed a convenience sample of public K-12 schools in the early weeks of the COVID-19 pandemic in the United States. This initial snapshot provides some insights to inform future research into the variation of strategies across school districts, and would benefit from more rigorous methods to determine true correlations between demographic and geographic factors. Additionally, many of these strategies have evolved in response to ongoing and prolonged public health social distancing measures implemented after this analysis was conducted.", "title": "Initial Coronavirus Disease–2019 Closure Strategies Adopted by a Convenience Sample of US School Districts: Directions for Future Research", "pid": "6n0ce55n", "bm25_score": 217.3789825439453}, {"text": "In response to the novel coronavirus disease 2019 (COVID-19) pandemic, most states in the United States enacted statewide school closures, ranging in duration from 1 month to the remainder of the academic year. The extended durations of these closures present unique challenges, as many families rely on the school as a source of physical activity, mental health services, psychosocial support, child care, and food security. While the school doors may be closed, the school nurse can still play a vital role in emergency management. This article discusses challenges and proposes solutions to maintaining student health and wellness during extended school closures due to the COVID-19 pandemic. Furthermore, it is inevitable that until a vaccine for coronavirus is developed and readily available, many schools will continue to see future closures, though likely for shorter periods of time, as they respond to local outbreaks.", "title": "School Nurses on the Front Lines of Healthcare: The Approach to Maintaining Student Health and Wellness During COVID-19 School Closures", "pid": "xqmxyz7u", "bm25_score": 217.37191772460938}, {"text": "", "title": "COVID-19 and Schools Closure: Implications for School Nurses.", "pid": "w9se87mt", "bm25_score": 217.34759521484375}, {"text": "In the COVID-19 crisis, the science of learning has two different responsibilities: first, to offer guidance about how best to deal with the impact of the current situation, including lockdown and home-schooling; and second, to consider bigger questions about what this large-scale educational experiment might mean for the future. The first part of this Viewpoint summarises advice for parents on mental health, and on becoming stand-in-teachers. The second part, taking the longer view, considers the potential negative impact of the COVID-19 crisis in increasing inequality in education; but also the potential positive impact of driving innovations in technology use for educating children.", "title": "Education, the science of learning, and the COVID-19 crisis", "pid": "v83dwt6k", "bm25_score": 217.34429931640625}, {"text": "The coronavirus disease 2019 pandemic has affected nearly 70% of children and teenagers around the world due to school closure policies. School closure is implemented widely in order to prevent viral transmission and its impact on the broader community, based on preliminary recommendations and evidence from influenza. However, there is debate with regard to the effectiveness of school closures. Growing evidence suggests that a child's SARS‐CoV‐2 infection is often mild or asymptomatic and that children may not be major SARS‐CoV‐2 transmitters; thus, it is questionable if school closures prevent transmission significantly. This question is important as a majority of children in low‐ and middle‐income countries depend on free school meals; unexpected long‐term school closure may adversely impact nutrition and educational outcomes. Food insecurity is expected to be higher during the pandemic. In this viewpoint, we argue for a more thorough exploration of potential adverse impacts of school closures in low‐ and middle‐income countries and recommend actions to ensure that the health and learning needs of vulnerable populations are met in this time of crisis.", "title": "School closure, COVID‐19 and lunch programme: Unprecedented undernutrition crisis in low‐middle income countries", "pid": "zc2u3hqv", "bm25_score": 217.22979736328125}, {"text": "We found the publication on \"COVID-19 Related School Closings and Risk of Weight Gain Among Children\" to be interesting.1 Rundle et al. noted that \"we anticipate that the COVID-19 pandemic will likely double out-of-school time this year for many children in the U.S. and will exacerbate the risk factors for weight gain associated with summer recess.\"1 In fact, there are several factors relating to nutritional status of the children. We would like to share observations from Thailand, the second country in the timeline of COVID-19.2 In Thailand, school aged children in rural areas where COVID-19 disease outbreak exists are usually underweight.3 Thus, school closing means the children have to live with poor parents adding to economic problems of the family.", "title": "COVID-19 , School Closings and Weight Gain.", "pid": "qz6w094y", "bm25_score": 217.22857666015625}, {"text": "", "title": "School Closure During the Coronavirus Disease 2019 (COVID-19) Pandemic: An Effective Intervention at the Global Level?", "pid": "zlcv5zjv", "bm25_score": 217.22555541992188}, {"text": "", "title": "Covid-19: Government must plan for schools to reopen, say paediatricians.", "pid": "9kgs0ztn", "bm25_score": 217.197021484375}, {"text": "", "title": "Children returning to schools following COVID-19: A balance of probabilities - Letter to the Editor", "pid": "bsxmnn6v", "bm25_score": 217.16262817382812}, {"text": "", "title": "Children returning to schools following COVID-19: A balance of probabilities – Letter to the Editor", "pid": "s4o9tehm", "bm25_score": 217.10853576660156}, {"text": "", "title": "COVID-19 and Schools Closure: Implications for School Nurses", "pid": "jr7d0igd", "bm25_score": 217.10464477539062}, {"text": "", "title": "Covid-19: Government must plan for schools to reopen, say paediatricians", "pid": "cnrx9kxy", "bm25_score": 217.0636749267578}, {"text": "More than one billion students are out of school because of Covid-19, forced to a remote learning that has several drawbacks and has been hurriedly arranged; in addition, most countries are currently uncertain on how to plan school activities for the 2020-2021 school year; all of this makes learning and education some of the biggest world issues of the current pandemic. Unfortunately, due to the length of the incubation period of Covid-19, full opening of schools seems to be impractical till a vaccine is available. In order to support the possibility of some in-person learning, we study a mathematical model of the diffusion of the epidemic due to school opening, and evaluate plans aimed at containing the extra Covid-19 cases due to school activities while ensuring an adequate number of in-class learning periods. We consider a SEAIR model with an external source of infection and a suitable loss function; after a realistic parameter selection, we numerically determine optimal school opening strategies by simulated annealing. It turns out that blended models, with almost periodic alternations of in-class and remote teaching days or weeks, are generally optimal. Besides containing Covid-19 diffusion, these solutions could be pedagogically acceptable, and could also become a driving model for the society at large. In a prototypical example, the optimal strategy results in the school opening 90 days out of 200 with the number of Covid-19 cases among the individuals related to the school increasing by about 66%, instead of the about 250% increase that would have been a consequence of full opening.", "title": "Planning of School Teaching during COVID-19", "pid": "rd8dqeot", "bm25_score": 217.04273986816406}, {"text": "", "title": "Covid-19: local implementation of tracing and testing programmes could enable some schools to reopen.", "pid": "7080eivg", "bm25_score": 217.0045623779297}, {"text": "In response to the coronavirus disease 2019 (COVID-19) pandemic, 107 countries had implemented national school closures by March 18, 2020. It is unknown whether school measures are effective in coronavirus outbreaks (eg, due to severe acute respiratory syndrome [SARS], Middle East respiratory syndrome, or COVID-19). We undertook a systematic review by searching three electronic databases to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks. We included 16 of 616 identified articles. School closures were deployed rapidly across mainland China and Hong Kong for COVID-19. However, there are no data on the relative contribution of school closures to transmission control. Data from the SARS outbreak in mainland China, Hong Kong, and Singapore suggest that school closures did not contribute to the control of the epidemic. Modelling studies of SARS produced conflicting results. Recent modelling studies of COVID-19 predict that school closures alone would prevent only 2-4% of deaths, much less than other social distancing interventions. Policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and that combinations of social distancing measures should be considered. Other less disruptive social distancing interventions in schools require further consideration if restrictive social distancing policies are implemented for long periods.", "title": "School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review", "pid": "wsn7y3wr", "bm25_score": 216.96730041503906}, {"text": "In response to the coronavirus disease 2019 (COVID-19) pandemic, 107 countries had implemented national school closures by March 18, 2020. It is unknown whether school measures are effective in coronavirus outbreaks (eg, due to severe acute respiratory syndrome [SARS], Middle East respiratory syndrome, or COVID-19). We undertook a systematic review by searching three electronic databases to identify what is known about the effectiveness of school closures and other school social distancing practices during coronavirus outbreaks. We included 16 of 616 identified articles. School closures were deployed rapidly across mainland China and Hong Kong for COVID-19. However, there are no data on the relative contribution of school closures to transmission control. Data from the SARS outbreak in mainland China, Hong Kong, and Singapore suggest that school closures did not contribute to the control of the epidemic. Modelling studies of SARS produced conflicting results. Recent modelling studies of COVID-19 predict that school closures alone would prevent only 2–4% of deaths, much less than other social distancing interventions. Policy makers need to be aware of the equivocal evidence when considering school closures for COVID-19, and that combinations of social distancing measures should be considered. Other less disruptive social distancing interventions in schools require further consideration if restrictive social distancing policies are implemented for long periods.", "title": "School closure and management practices during coronavirus outbreaks including COVID-19: a rapid systematic review", "pid": "y2zcwcic", "bm25_score": 216.95265197753906}, {"text": "", "title": "Covid-19: Papers justifying government's plans to reopen schools are \"inconclusive,\" say union bosses.", "pid": "l6iqniif", "bm25_score": 216.9455108642578}, {"text": "", "title": "Reopening Colleges and Universities During the COVID-19 Pandemic", "pid": "i5sk772y", "bm25_score": 216.93325805664062}, {"text": "", "title": "Should Schools Reopen Early or Late? - Transmission Dynamics of COVID-19 in Children", "pid": "udv9tdi4", "bm25_score": 216.8722686767578}, {"text": "", "title": "Covid-19: Papers justifying government's plans to reopen schools are \"inconclusive,\" say union bosses", "pid": "a5o6yev9", "bm25_score": 216.83352661132812}, {"text": "BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is leading to social (physical) distancing policies worldwide, including in the USA. Some of the first actions taken by governments are the closing of schools. The evidence that mandatory school closures reduce the number of cases and, ultimately, mortality comes from experience with influenza or from models that do not include the effect of school closure on the health-care labour force. The potential benefits from school closures need to be weighed against costs of health-care worker absenteeism associated with additional child-care obligations. In this study, we aimed to measure child-care obligations for US health-care workers arising from school closures when these are used as a social distancing measure. We then assessed how important the contribution of health-care workers would have to be in reducing mortality for their absenteeism due to child-care obligations to undo the benefits of school closures in reducing the number of cases. METHODS: For this modelling analysis, we used data from the monthly releases of the US Current Population Survey to characterise the family structure and probable within-household child-care options of US health-care workers. We accounted for the occupation within the health-care sector, state, and household structure to identify the segments of the health-care workforce that are most exposed to child-care obligations from school closures. We used these estimates to identify the critical level at which the importance of health-care labour supply in increasing the survival probability of a patient with COVID-19 would undo the benefits of school closures and ultimately increase cumulative mortality. FINDINGS: Between January, 2018, and January, 2020, the US Current Population Survey included information on more than 3·1 million individuals across 1·3 million households. We found that the US health-care sector has some of the highest child-care obligations in the USA, with 28·8% (95% CI 28·5-29·1) of the health-care workforce needing to provide care for children aged 3-12 years. Assuming non-working adults or a sibling aged 13 years or older can provide child care, 15·0% (14·8-15·2) of the health-care workforce would still be in need of child care during a school closure. We observed substantial variation within the health-care system. We estimated that, combined with reasonable parameters for COVID-19 such as a 15·0% case reduction from school closings and 2·0% baseline mortality rate, a 15·0% decrease in the health-care labour force would need to decrease the survival probability per percent health-care worker lost by 17·6% for a school closure to increase cumulative mortality. Our model estimates that if the infection mortality rate of COVID-19 increases from 2·00% to 2·35% when the health-care workforce declines by 15·0%, school closures could lead to a greater number of deaths than they prevent. INTERPRETATION: School closures come with many trade-offs, and can create unintended child-care obligations. Our results suggest that the potential contagion prevention from school closures needs to be carefully weighted with the potential loss of health-care workers from the standpoint of reducing cumulative mortality due to COVID-19, in the absence of mitigating measures. FUNDING: None.", "title": "Impact of school closures for COVID-19 on the US health-care workforce and net mortality: a modelling study", "pid": "xgjd961x", "bm25_score": 216.77899169921875}, {"text": "The massive damages of COVID-19 may be incalculable. But in the spirit of never wasting a good crisis, COVID-19 represents an opportunity to rethink education. The rethinking should not be about improving schooling, but should focus on the what, how, and where of learning. This article highlights some of the questions that schools can ask as they reimagine post-COVID education.", "title": "COVID-19 as a catalyst for educational change", "pid": "w3ohzxn5", "bm25_score": 216.72789001464844}, {"text": "The COVID-19 pandemic quickly led to the closure of universities and colleges around the world, in hopes that public health officials’ advice of social distancing could help to flatten the infection curve and reduce total fatalities from the disease. Drawing on Copenhagen school securitization theory and analyzing 25 declarations of emergency eLearning at American universities, I argue that in addition to COVID-19 being framed as a general threat, face-to-face schooling was also presented as a threat through these policies. A review of securitization theory—with particular attention to the question of advocacy and the relationship of desecuritization to emancipation—grounds the investigation theoretically. I argue that securitization theory is an important tool for educators not only for observing (and understanding) the phenomenon of emergency eLearning, but also for advocating the desecuritization of schooling after the COVID-19 crisis passes.", "title": "COVID-19 and emergency eLearning: Consequences of the securitization of higher education for post-pandemic pedagogy", "pid": "v3mt8cd5", "bm25_score": 216.7164306640625}, {"text": "Asymptomatic infection occurs for numerous respiratory viral diseases, including influenza and COVID-19. We seek to clarify confusion in three areas: age-specific risks of transmission and/or disease; various definitions for the COVID-19 “mortality rate”, each useful for specific purposes; and implications for student return strategies from pre-school through university settings.", "title": "Asymptomatic transmission and the infection fatality risk for COVID-19: Implications for school reopening", "pid": "e995ev2w", "bm25_score": 216.70870971679688}, {"text": "Asymptomatic infection occurs for numerous respiratory viral diseases, including influenza and COVID-19. We seek to clarify confusion in three areas: age-specific risks of transmission and/or disease; various definitions for the COVID-19 \"mortality rate\", each useful for specific purposes; and implications for student return strategies from pre-school through university settings.", "title": "Asymptomatic transmission and the infection fatality risk for COVID-19: Implications for school reopening", "pid": "401kxcmi", "bm25_score": 216.6674041748047}, {"text": "", "title": "Should Schools Reopen Early or Late? – Transmission Dynamics of COVID-19 in Children", "pid": "1n2ebcwp", "bm25_score": 216.63145446777344}, {"text": "BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is leading to social (physical) distancing policies worldwide, including in the USA. Some of the first actions taken by governments are the closing of schools. The evidence that mandatory school closures reduce the number of cases and, ultimately, mortality comes from experience with influenza or from models that do not include the effect of school closure on the health-care labour force. The potential benefits from school closures need to be weighed against costs of health-care worker absenteeism associated with additional child-care obligations. In this study, we aimed to measure child-care obligations for US health-care workers arising from school closures when these are used as a social distancing measure. We then assessed how important the contribution of health-care workers would have to be in reducing mortality for their absenteeism due to child-care obligations to undo the benefits of school closures in reducing the number of cases. METHODS: For this modelling analysis, we used data from the monthly releases of the US Current Population Survey to characterise the family structure and probable within-household child-care options of US health-care workers. We accounted for the occupation within the health-care sector, state, and household structure to identify the segments of the health-care workforce that are most exposed to child-care obligations from school closures. We used these estimates to identify the critical level at which the importance of health-care labour supply in increasing the survival probability of a patient with COVID-19 would undo the benefits of school closures and ultimately increase cumulative mortality. FINDINGS: Between January, 2018, and January, 2020, the US Current Population Survey included information on more than 3·1 million individuals across 1·3 million households. We found that the US health-care sector has some of the highest child-care obligations in the USA, with 28·8% (95% CI 28·5–29·1) of the health-care workforce needing to provide care for children aged 3–12 years. Assuming non-working adults or a sibling aged 13 years or older can provide child care, 15·0% (14·8–15·2) of the health-care workforce would still be in need of child care during a school closure. We observed substantial variation within the health-care system. We estimated that, combined with reasonable parameters for COVID-19 such as a 15·0% case reduction from school closings and 2·0% baseline mortality rate, a 15·0% decrease in the health-care labour force would need to decrease the survival probability per percent health-care worker lost by 17·6% for a school closure to increase cumulative mortality. Our model estimates that if the infection mortality rate of COVID-19 increases from 2·00% to 2·35% when the health-care workforce declines by 15·0%, school closures could lead to a greater number of deaths than they prevent. INTERPRETATION: School closures come with many trade-offs, and can create unintended child-care obligations. Our results suggest that the potential contagion prevention from school closures needs to be carefully weighted with the potential loss of health-care workers from the standpoint of reducing cumulative mortality due to COVID-19, in the absence of mitigating measures. FUNDING: None.", "title": "Impact of school closures for COVID-19 on the US health-care workforce and net mortality: a modelling study", "pid": "517s290b", "bm25_score": 216.5889129638672}, {"text": "According to the United Nations Educational, Science and Cultural Organization, 194 countries had implemented country‐wide school closures by April 1(st) 2020 in an effort to combat the COVID‐19 pandemic. It’s estimated that those closures affected 91.3% of students across the globe. However, Sweden adopted a different approach to the strict lockdowns imposed elsewhere and day care centres and schools for children up to 15 years of age remained open. The strategy decision to shift schools to distance learning only for children aged 16 years and older was influenced by multiple factors, including the potential impact on school closures on the availability of the healthcare work force, the increasing evidence of mainly mild infections among children and the potential negative consequences of school closures for younger children.", "title": "Paediatric COVID‐19 admissions in a region with open schools during the two first months of the pandemic", "pid": "555e3ndo", "bm25_score": 216.55149841308594}, {"text": "The COVID-19 pandemic is a huge challenge to education systems. This Viewpoint offers guidance to teachers, institutional heads, and officials on addressing the crisis. What preparations should institutions make in the short time available and how do they address students’ needs by level and field of study? Reassuring students and parents is a vital element of institutional response. In ramping up capacity to teach remotely, schools and colleges should take advantage of asynchronous learning, which works best in digital formats. As well as the normal classroom subjects, teaching should include varied assignments and work that puts COVID-19 in a global and historical context. When constructing curricula, designing student assessment first helps teachers to focus. Finally, this Viewpoint suggests flexible ways to repair the damage to students’ learning trajectories once the pandemic is over and gives a list of resources.", "title": "Education and the COVID-19 pandemic", "pid": "744a3hga", "bm25_score": 216.5138397216797}, {"text": "BACKGROUND There remains substantial debate over the impact of school closure as a mitigation strategy during an influenza pandemic. The ongoing 2009 H1N1 influenza pandemic has provided an unparalleled opportunity to test interventions with the most up-to-date simulations. METHODS To assist the Allegheny County Health Department during the 2009 H1N1 influenza pandemic, the University of Pittsburgh Models of Infectious Disease Agents Study group employed an agent-based computer simulation model (ABM) of Allegheny County, Pennsylvania, to explore the effects of various school closure strategies on mitigating influenza epidemics of different reproductive rates (R0). RESULTS Entire school system closures were not more effective than individual school closures. Any type of school closure may need to be maintained throughout most of the epidemic (ie, at least 8 weeks) to have any significant effect on the overall serologic attack rate. In fact, relatively short school closures (ie, 2 weeks or less) may actually slightly increase the overall attack rate by returning susceptible students back into schools in the middle of the epidemic. Varying the illness threshold at which school closures are triggered did not seem to have substantial impact on the effectiveness of school closures, suggesting that short delays in closing schools should not cause concern. CONCLUSIONS School closures alone may not be able to quell an epidemic but, when maintained for at least 8 weeks, could delay the epidemic peak for up to a week, providing additional time to implement a second more effective intervention such as vaccination.", "title": "Simulating school closure strategies to mitigate an influenza epidemic.", "pid": "qac68abi", "bm25_score": 216.50914001464844}, {"text": "Summary In response to WHO raising the influenza pandemic alert level from phase five to phase six, health officials around the world are carefully reviewing pandemic mitigation protocols. School closure (also called class dismissal in North America) is a non-pharmaceutical intervention that is commonly suggested for mitigating influenza pandemics. Health officials taking the decision to close schools must weigh the potential health benefits of reducing transmission and thus case numbers against high economic and social costs, difficult ethical issues, and the possible disruption of key services such as health care. Also, if schools are expected to close as a deliberate policy option, or just because of high levels of staff absenteeism, it is important to plan to mitigate the negative features of closure. In this context, there is still debate about if, when, and how school closure policy should be used. In this Review, we take a multidisciplinary and holistic perspective and review the multiple aspects of school closure as a public health policy. Implications for the mitigation of the swine-origin influenza A H1N1 pandemic are also discussed.", "title": "Closure of schools during an influenza pandemic", "pid": "xv3k0irk", "bm25_score": 216.48809814453125}, {"text": "The COVID-19 pandemic is the largest social and economic shock of our lifetimes. As governments grapple with their responses to the virus, more than half the world’s countries have closed their schools and severely limited almost all forms of public life. This will have a profound impact on children, both now and in the decade to come. As many countries start to send children back to school, a question arises: who should go back to school first? This Viewpoint addresses that question in the context of a middle-income country, South Africa. Based on a review of much of the evidence available at the time of publication, it concludes that the youngest children are least susceptible to harm from COVID-19, are less likely to spread the virus than adults, and also have the most to lose by being out of school. Hence, they should be the ones to return to school first.", "title": "COVID-19 and schooling in South Africa: Who should go back to school first?", "pid": "rmefwih2", "bm25_score": 216.48171997070312}, {"text": "The COVID-19 pandemic is a huge challenge to education systems. This Viewpoint offers guidance to teachers, institutional heads, and officials on addressing the crisis. What preparations should institutions make in the short time available and how do they address students' needs by level and field of study? Reassuring students and parents is a vital element of institutional response. In ramping up capacity to teach remotely, schools and colleges should take advantage of asynchronous learning, which works best in digital formats. As well as the normal classroom subjects, teaching should include varied assignments and work that puts COVID-19 in a global and historical context. When constructing curricula, designing student assessment first helps teachers to focus. Finally, this Viewpoint suggests flexible ways to repair the damage to students' learning trajectories once the pandemic is over and gives a list of resources.", "title": "Education and the COVID-19 pandemic", "pid": "06mqd6vg", "bm25_score": 216.477783203125}, {"text": "In their article, Cheng and colleagues present the plan for reopening colleges and universities in Taiwan. There are important differences between Taiwan and other countries, but residential colleges and universities present similar challenges to pandemic control for all. Considering how well Taiwan has managed COVID-19 overall, the editorialists believe that the plan for safely reopening colleges and universities in Taiwan offers important principles.", "title": "Reopening Colleges and Universities During the COVID-19 Pandemic", "pid": "hn4wg94k", "bm25_score": 216.4448699951172}, {"text": "Australian schools, like schools elsewhere, have been through a period of closure. The closure creates both threats and opportunities for teachers and students. In the context of a project exploring approaches to teaching in early years, we outline some considerations and offer advice to teachers and educators on strategies for welcoming students back to school.", "title": "Threats and opportunities in remote learning of mathematics: implication for the return to the classroom", "pid": "kj3v3fd1", "bm25_score": 216.43429565429688}, {"text": "", "title": "Mental health effects of school closures during COVID-19", "pid": "orc4c5lb", "bm25_score": 216.42172241210938}, {"text": "BACKGROUND: There is currently considerable international debate around school closures/openings and the role of children in the transmission of coronavirus disease 2019 (COVID-19). Whilst evidence suggests that children are not impacted by COVID-19 as severely as adults, little is still known about their transmission potential, and with a lot of asymptomatic cases they may be silent transmitters (i.e. infectious without showing clinical signs of disease), albeit at a lower level than adults. In relation to this, it is somewhat concerning that in many countries children are cared for, or are often in close contact with, older individuals such as grandparents ─ the age group most at risk of acquiring serious respiratory complications resulting in death. MAIN TEXT: We emphasise that in the absence of a vaccine or an effective therapeutic drug, preventive measures such as good hygiene practices ─ hand washing, cough etiquette, disinfection of surfaces and social distancing represent the major (in fact only) weapons that we have against COVID-19. Accordingly, we stress that there is a pressing need to develop specific COVID-19 prevention messages for schoolchildren. CONCLUSION: An entertainment education intervention for schoolchildren systematically implemented in schools would be highly effective and fill this need. With such measures in place there would be greater confidence around the opening of schools.", "title": "Health-education to prevent COVID-19 in schoolchildren: a call to action", "pid": "ynaum52m", "bm25_score": 216.40859985351562}, {"text": "BACKGROUND: There is currently considerable international debate around school closures/openings and the role of children in the transmission of coronavirus disease 2019 (COVID-19). Whilst evidence suggests that children are not impacted by COVID-19 as severely as adults, little is still known about their transmission potential, and with a lot of asymptomatic cases they may be silent transmitters (i.e. infectious without showing clinical signs of disease), albeit at a lower level than adults. In relation to this, it is somewhat concerning that in many countries children are cared for, or are often in close contact with, older individuals such as grandparents ─ the age group most at risk of acquiring serious respiratory complications resulting in death. MAIN TEXT: We emphasise that in the absence of a vaccine or an effective therapeutic drug, preventive measures such as good hygiene practices ─ hand washing, cough etiquette, disinfection of surfaces and social distancing represent the major (in fact only) weapons that we have against COVID-19. Accordingly, we stress that there is a pressing need to develop specific COVID-19 prevention messages for schoolchildren. CONCLUSION: An entertainment education intervention for schoolchildren systematically implemented in schools would be highly effective and fill this need. With such measures in place there would be greater confidence around the opening of schools.", "title": "Health-education to prevent COVID-19 in schoolchildren: a call to action", "pid": "ccx9klxa", "bm25_score": 216.40560913085938}, {"text": "The crisis caused by the COVID-19 virus has far-reaching effects in the field of education, as schools were closed in March 2020 in many countries around the world. In this article, we present and discuss the School Barometer, a fast survey (in terms of reaction time, time to answer and dissemination time) that was conducted in Germany, Austria and Switzerland during the early weeks of the school lockdown to assess and evaluate the current school situation caused by COVID-19. Later, the School Barometer was extended to an international survey, and some countries conducted the survey in their own languages. In Germany, Austria and Switzerland, 7116 persons participated in the German language version: 2222 parents, 2152 students, 1949 school staff, 655 school leaders, 58 school authority and 80 members of the school support system. The aim was to gather, analyse and present data in an exploratory way to inform policy, practice and further research. In this article, we present some exemplary first results and possible implications for policy, practice and research. Furthermore, we reflect on the strengths and limitations of the School Barometer and fast surveys as well as the methodological options for data collection and analysis when using a short monitoring survey approach. Specifically, we discuss the methodological challenges associated with survey data of this kind, including challenges related to hypothesis testing, the testing of causal effects and approaches to ensure reliability and validity. By doing this, we reflect on issues of assessment, evaluation and accountability in times of crisis.", "title": "COVID-19 and schooling: evaluation, assessment and accountability in times of crises—reacting quickly to explore key issues for policy, practice and research with the school barometer", "pid": "zwhbzdm2", "bm25_score": 216.36207580566406}, {"text": "BACKGROUND: According to UNESCO's monitoring, more than 160 countries implemented nationwide closures, which impacted over 87% of the world's student population. Several other countries implemented localized school closures; should these closures become nationwide, millions of additional learners will experience education disruption. Universities from around the world have been uncertain about how long the coronavirus crisis will last and how it might affect the mental health of students and faculty. The psychological impact has been a critical disruptor, creating anxiety and uncertainty. METHOD: The data were cross-checked with information from the main international newspapers. RESULTS: By discussing online and distance education, the coronavirus opens an important and urgent issue that affects mental health - these are virtually unexplored topics, and their results have not been validated yet. Online education is not limited to distance education, as it regards a grouping of learning/teaching procedures completed in cyberspace. Blended learning was, thus, introduced as a tool in personalized learning to adjust to new realities. These are unprecedented circumstances, and we understand they create stress, favoring anguish and a fierce search for new knowledge acquisition. CONCLUSIONS: Current research highlights that anxiety and depression, exacerbated by uncertainties and intensification of the information flow, will grow extensively. Negative physiological consequences of stress will manifest. For instance, loneliness, which will increase under these circumstances, seems to have a negative impact on education and, therefore, on psychological pain and suffering.", "title": "Impact Of Sars-Cov-2 And Its Reverberation In Global Higher Education And Mental Health", "pid": "3unwyjdq", "bm25_score": 216.33987426757812}, {"text": "A vast majority of the relief and rehabilitation packages announced in the months following the nationwide lockdown in India have focused on economic rehabilitation. However, the education sector has remained absent from this effort, including in India’s central government’s 250 billion dollar stimulus package. In this paper, we discuss the implications of lockdown-induced school and rural child-care center closures on education and health outcomes for the urban and rural poor. We especially focus on food and nutritional security of children who depend on school feeding and supplementary nutrition programs. We argue that the impacts are likely to be much more severe for girls as well as for children from already disadvantaged ethnic and caste groups. We also discuss ways in which existing social security programs can be leveraged and strengthened to ameliorate these impacts.", "title": "Learning in times of lockdown: how Covid-19 is affecting education and food security in India", "pid": "6mutnwid", "bm25_score": 216.32130432128906}, {"text": "Background In order to slow down the spread of SARS-CoV-2, the virus causing the COVID-19 pandemic, the UK government has imposed strict physical distancing (lockdown) measures including school 'dismissals' since 23 March 2020. As evidence is emerging that these measures may have slowed the spread of the pandemic, it is important to assess the impact of any changes in strategy, including scenarios for school reopening and broader relaxation of social distancing. This work uses an individual-based model to predict the impact of a suite of possible strategies to reopen schools in the UK, including that currently proposed by the UK government. Methods We use Covasim, a stochastic agent-based model for transmission of COVID-19, calibrated to the UK epidemic. The model describes individuals' contact networks stratified as household, school, work and community layers, and uses demographic and epidemiological data from the UK. We simulate a range of different school reopening strategies with a society-wide relaxation of lockdown measures and in the presence of different non-pharmaceutical interventions, to estimate the number of new infections, cumulative cases and deaths, as well as the effective reproduction number with different strategies. To account for uncertainties within the stochastic simulation, we also simulated different levels of infectiousness of children and young adults under 20 years old compared to older ages. Findings We found that with increased levels of testing of people (between 25% and 72% of symptomatic people tested at some point during an active COVID-19 infection depending on scenarios) and effective contact-tracing and isolation for infected individuals, an epidemic rebound may be prevented across all reopening scenarios, with the effective reproduction number (R) remaining below one and the cumulative number of new infections and deaths significantly lower than they would be if testing did not increase. If UK schools reopen in phases from June 2020, prevention of a second wave would require testing 51% of symptomatic infections, tracing of 40% of their contacts, and isolation of symptomatic and diagnosed cases. However, without such measures, reopening of schools together with gradual relaxing of the lockdown measures are likely to induce a secondary pandemic wave, as are other scenarios for reopening. When infectiousness of <20 year olds was varied from 100% to 50% of that of older ages, our findings remained unchanged. Interpretation To prevent a secondary COVID-19 wave, relaxation of social distancing including reopening schools in the UK must be implemented alongside an active large-scale population-wide testing of symptomatic individuals and effective tracing of their contacts, followed by isolation of symptomatic and diagnosed individuals. Such combined measures have a greater likelihood of controlling the transmission of SARS-CoV-2 and preventing a large number of COVID-19 deaths than reopening schools and society with the current level of implementation of testing and isolation of infected individuals.", "title": "Determining the optimal strategy for reopening schools, work and society in the UK: balancing earlier opening and the impact of test and trace strategies with the risk of occurrence of a secondary COVID-19 pandemic wave", "pid": "4sxsyr6k", "bm25_score": 216.28875732421875}, {"text": "The novel coronavirus disease 2019 (COVID-19), originated in Wuhan city of China, has spread rapidly around the world, sending billions of people into lockdown. The World Health Organization (WHO) declared the coronavirus epidemic a pandemic. In light of rising concern about the current COVID-19 pandemic, a growing number of universities across the world have either postponed or canceled all campus events such as workshops, conferences, sports, and other activities. Universities are taking intensive measures to prevent and protect all students and staff members from the highly infectious disease. Faculty members are already in the process of transitioning to online teaching platforms. In this review, the author will highlight the potential impact of the terrible COVID-19 outbreak on the education and mental health of students and academic staff.", "title": "Closure of Universities Due to Coronavirus Disease 2019 (COVID-19): Impact on Education and Mental Health of Students and Academic Staff", "pid": "gz1yqaun", "bm25_score": 216.27064514160156}, {"text": "BACKGROUND: : According to UNESCO's monitoring, more than 160 countries implemented nationwide closures, which impacted over 87% of the world's student population. Several other countries implemented localized school closures; should these closures become nationwide, millions of additional learners will experience education disruption. Universities from around the world have been uncertain about how long the coronavirus crisis will last and how it might affect the mental health of students and faculty. The psychological impact has been a critical disruptor, creating anxiety and uncertainty. METHOD: : The data were cross-checked with information from the main international newspapers. RESULTS: : By discussing online and distance education, the coronavirus opens an important and urgent issue that affects mental health – these are virtually unexplored topics, and their results have not been validated yet. Online education is not limited to distance education, as it regards a grouping of learning/teaching procedures completed in cyberspace. Blended learning was, thus, introduced as a tool in personalized learning to adjust to new realities. These are unprecedented circumstances, and we understand they create stress, favoring anguish and a fierce search for new knowledge acquisition. CONCLUSIONS: : Current research highlights that anxiety and depression, exacerbated by uncertainties and intensification of the information flow, will grow extensively. Negative physiological consequences of stress will manifest. For instance, loneliness, which will increase under these circumstances, seems to have a negative impact on education and, therefore, on psychological pain and suffering.", "title": "Impact Of Sars-Cov-2 And Its Reverberation In Global Higher Education And Mental Health", "pid": "64nq8qk3", "bm25_score": 216.25193786621094}, {"text": "In a recent paper entitled, \"COVID-19 Related School Closings and Risk of Weight Gain Among Children\" Rundle et al. (2020) proposed the COVID-19 pandemic may increase obesity among American children because the pandemic, \"will likely double out-of-school time this year for many children in the United States and will exacerbate the risk factors for weight gain associated with summer recess\" (pg. 1). I add support to Rundle et al.'s argument by demonstrating that doubling of out-of-school time alone may lead to a sizable increase in childhood obesity.", "title": "How Much May COVID-19 School Closures Increase Childhood Obesity?", "pid": "8ew7rv5q", "bm25_score": 216.24969482421875}, {"text": "Background With the exposure to the COVID-19 pandemic, countries swiftly implemented a variety of health policies. In this work we examine how rapid countries responded to this pandemic using two events: the day in which the first case of COVID-19 was reported, and first day in which countries used school closure as one of the measures to avoid outbreaks. Methods We compiled information from multiple sources, from December 31st 2019 to June 1st 2020, to trace when 172 countries reported their first COVID-19 case and implemented school closure to contain outbreaks. We applied cross-national Weibull survival analysis to evaluate the global speed of detection of first COVID-19 reported cases and school closure. We also assessed how health systems, globalization, economic development, political systems, and economic integration to China, Republic of Korea and Italy increased the speed of adoption. Results Ten days after the World Health Organization (WHO) declared COVID-19 to be an international emergency, countries were 28 (95% CI: 12,77) times more likely to report first COVID-19 cases and 42 (95% CI: 22,90) times more likely to close schools. One standard deviation increase in the epidemic security index rises the rate of report first cases by 37% (Hazard Ratio (HR) 1.37 (95% CI: 1.09,1.72) and delays the adoption for school closures by 36% (HR 0.64 (95% CI:0.50,0.82). One standard deviation increase in the globalization index augments the adoption for school closures by 74% (HR 1.74 (95% CI:1.34,2.24). Conclusion. After the WHO declared a global emergency, countries were unprecedently acting very rapidly. While countries more globally integrated were swifter in closing schools, countries with better designed health systems to tackle epidemics were slower in adopting it. More studies are needed to assess how the speed of school closures and other policies will affect the development of the pandemic.", "title": "The global viralization of policies to contain the spreading of the COVID-19 pandemic: analyses of school closures and first reported cases.", "pid": "5kbrsos9", "bm25_score": 216.21697998046875}, {"text": "BackgroundEmergency school closures are often used as public health interventions during infectious disease outbreaks to minimise the spread of infection. However, if children continue mixing with others outside the home during closures, the effect of these measures may be limited.AimThis review aimed to summarise existing literature on children's activities and contacts made outside the home during unplanned school closures.MethodsIn February 2020, we searched four databases, MEDLINE, PsycInfo, Embase and Web of Science, from inception to 5 February 2020 for papers published in English or Italian in peer-reviewed journals reporting on primary research exploring children's social activities during unplanned school closures. Main findings were extracted.ResultsA total of 3,343 citations were screened and 19 included in the review. Activities and social contacts appeared to decrease during closures, but contact remained common. All studies reported children leaving the home or being cared for by non-household members. There was some evidence that older child age (two studies) and parental disagreement (two studies) with closure were predictive of children leaving the home, and mixed evidence regarding the relationship between infection status and such. Parental agreement with closure was generally high, but some disagreed because of perceived low risk of infection and issues regarding childcare and financial impact.ConclusionEvidence suggests that many children continue to leave home and mix with others during school closures despite public health recommendations to avoid social contact. This review of behaviour during unplanned school closures could be used to improve infectious disease modelling.", "title": "The impact of unplanned school closure on children's social contact: rapid evidence review", "pid": "13qtfl0t", "bm25_score": 216.179931640625}, {"text": "OBJECTIVE: During COVID-19 pandemic, the institutions in Pakistan have started online learning. This study explores the perception of teachers and students regarding its advantages, limitations and recommendations. METHODS: This qualitative case study was conducted from March to April 2020. Using maximum variation sampling, 12 faculty members and 12 students from University College of Medicine and University College of Dentistry, Lahore were invited to participate. Four focus group interviews, two each with the faculty and students of medicine and dentistry were carried out. Data were transcribed verbatim and thematically analyzed using Atlas Ti. RESULTS: The advantages included remote learning, comfort, accessibility, while the limitations involved inefficiency and difficulty in maintaining academic integrity. The recommendations were to train faculty on using online modalities and developing lesson plan with reduced cognitive load and increased interactivities. CONCLUSION: The current study supports the use of online learning in medical and dental institutes, considering its various advantages. Online learning modalities encourage student-centered learning and they are easily manageable during this lockdown situation.", "title": "Advantages, Limitations and Recommendations for online learning during COVID-19 pandemic era", "pid": "m33zddwe", "bm25_score": 216.17572021484375}, {"text": "COVID-19 has disrupted education for millions of children across the globe. The education community is re-imagining and re-designing to build back better. This Viewpoint takes the principles behind UNESCO’s Futures of Education initiative to highlight their importance in post-COVID-19 recovery. The pandemic has shown how communities can come together to educate children. The article argues that, post-COVID-19, education systems should recognize community-driven support systems, use technology to overcome the digital divide in learning, and focus more on SDG 4.7 and its links to climate crises.", "title": "Education as the path to a sustainable recovery from COVID-19", "pid": "gneuzgts", "bm25_score": 216.17237854003906}, {"text": "", "title": "Rethinking the role of the school after COVID-19", "pid": "71enat3h", "bm25_score": 216.16651916503906}, {"text": "The COVID-19 pandemic has resulted in widespread closure of schools and universities. These institutions have turned to distance learning to provide educational continuity. Schools now face the challenge of how to reopen safely and resume in-class learning. However, there is little empirical evidence to guide decision-makers on how this can be achieved. Here, we show that selectively deploying e-learning for larger classes is highly effective at decreasing campus-wide opportunities for student-to-student contact, while allowing most in-class learning to continue uninterrupted. We conducted a natural experiment at a large university that implemented a series of e-learning interventions during the COVID-19 outbreak. Analyses of >24 million student connections to the university Wi-Fi network revealed that population size can be manipulated by e-learning in a targeted manner according to class size characteristics. Student mixing showed accelerated growth with population size according to a power law distribution. Therefore, a small e-learning dependent decrease in population size resulted in a large reduction in student clustering behaviour. Our results show that e-learning interventions can decrease potential for disease transmission while minimizing disruption to university operations. Universities should consider targeted e-learning a viable strategy for providing educational continuity during early or late stages of a disease outbreak.", "title": "A targeted e-learning approach to reduce student mixing during a pandemic", "pid": "f70a2twc", "bm25_score": 216.16004943847656}, {"text": "BACKGROUND: Emergency school closures are often used as public health interventions during infectious disease outbreaks to minimise the spread of infection. However, if children continue mixing with others outside the home during closures, the effect of these measures may be limited. AIM: This review aimed to summarise existing literature on children’s activities and contacts made outside the home during unplanned school closures. METHODS: In February 2020, we searched four databases, MEDLINE, PsycInfo, Embase and Web of Science, from inception to 5 February 2020 for papers published in English or Italian in peer-reviewed journals reporting on primary research exploring children’s social activities during unplanned school closures. Main findings were extracted. RESULTS: A total of 3,343 citations were screened and 19 included in the review. Activities and social contacts appeared to decrease during closures, but contact remained common. All studies reported children leaving the home or being cared for by non-household members. There was some evidence that older child age (two studies) and parental disagreement (two studies) with closure were predictive of children leaving the home, and mixed evidence regarding the relationship between infection status and such. Parental agreement with closure was generally high, but some disagreed because of perceived low risk of infection and issues regarding childcare and financial impact. CONCLUSION: Evidence suggests that many children continue to leave home and mix with others during school closures despite public health recommendations to avoid social contact. This review of behaviour during unplanned school closures could be used to improve infectious disease modelling.", "title": "The impact of unplanned school closure on children’s social contact: rapid evidence review", "pid": "cf5srzrv", "bm25_score": 216.15174865722656}, {"text": "", "title": "Advocating for Children During the COVID-19 School Closures.", "pid": "6vuzhu9v", "bm25_score": 216.12698364257812}, {"text": "BACKGROUND: Nonpharmaceutical intervention strategy is significantly important to mitigate the coronavirus disease 2019 (COVID-19) spread. One of the interventions implemented by the government is a school closure. The Ministry of Education decided to postpone the school opening from March 2 to April 6 to minimize epidemic size. We aimed to quantify the school closure effect on the COVID-19 epidemic. METHODS: The potential effects of school opening were measured using a mathematical model considering two age groups: children (aged 19 years and younger) and adults (aged over 19). Based on susceptible-exposed-infectious-recovered model, isolation and behavior-changed susceptible individuals are additionally considered. The transmission parameters were estimated from the laboratory confirmed data reported by the Korea Centers for Disease Control and Prevention from February 16 to March 22. The model was extended with estimated parameters and estimated the expected number of confirmed cases as the transmission rate increased after school opening. RESULTS: Assuming the transmission rate between children group would be increasing 10 fold after the schools open, approximately additional 60 cases are expected to occur from March 2 to March 9, and approximately additional 100 children cases are expected from March 9 to March 23. After March 23, the number of expected cases for children is 28.4 for 7 days and 33.6 for 14 days. CONCLUSION: The simulation results show that the government could reduce at least 200 cases, with two announcements by the Ministry of education. After March 23, although the possibility of massive transmission in the children's age group is lower, group transmission is possible to occur.", "title": "School Opening Delay Effect on Transmission Dynamics of Coronavirus Disease 2019 in Korea: Based on Mathematical Modeling and Simulation Study", "pid": "x0yiv35v", "bm25_score": 216.0774688720703}, {"text": "In a recent paper entitled, “COVID‐19 Related School Closings and Risk of Weight Gain Among Children” Rundle et al. (2020) proposed the COVID‐19 pandemic may increase obesity among American children because the pandemic, “will likely double out‐of‐school time this year for many children in the United States and will exacerbate the risk factors for weight gain associated with summer recess” (pg. 1). I add support to Rundle et al.’s argument by demonstrating that doubling of out‐of‐school time alone may lead to a sizable increase in childhood obesity.", "title": "How Much May COVID‐19 School Closures Increase Childhood Obesity?", "pid": "1rw80tde", "bm25_score": 216.04745483398438}, {"text": "Aim This narrative review aims to report on the impacts of COVID-19 on the provision of dental education in the 67 dental schools in the United States (US). Having set the scene and current challenges, it aims to suggest some strategies to overcome the issues facing dental schools going forward.Background In the US the Occupational Safety and Health Administration classified dentists in the very high risk category because of the potential for exposure to the virus as a result of aerosol generating procedures (AGP). In the last 20 years there have been two previous outbreaks of coronaviruses (severe acute respiratory syndrome and Middle East respiratory syndrome) which resulted in no long-term changes in the provision of dental education. The recent paper from Wuhan, China described action in the height of the infection but no sustainable actions to deliver dental education going forward.Challenges The challenges identified include: protecting the health of students, faculty and staff; ensuring the continuity and quality of dental education; ensuring confidence in health and safety measures; and keeping up with guidance. There is some variation across the US but most schools have suspended clinical teaching and implemented stay at home policies. Others have implemented social distancing in laboratories including clinical skills. The final challenge is ensuring that students have the teaching, experience and are assessed to ensure the competency of the graduating student.Solutions Technology in teaching and learning offers many opportunities. For didactic teaching distance learning has been implemented. There are 'off the shelf' programmes for teaching and assessment. The development of bespoke content is time consuming and one solution is for schools to share material. Although still requiring social distancing, manikins and haptics offer some opportunities for skills training. The need for excellent information sharing with faculty and students is emphasised.Conclusion Schools should re-evaluate their policies and curricula and incorporate appropriate methods of distance learning permanently into their teaching. Students should have outreach and multi-professional support in order to allow them to assist in the community during public health crises. Finally, gaps have been identified in US dental schools preparedness for pandemics.", "title": "The COVID-19 pandemic: implications for dental education", "pid": "d4tu2k7s", "bm25_score": 216.03970336914062}, {"text": "Aim This narrative review aims to report on the impacts of COVID-19 on the provision of dental education in the 67 dental schools in the United States (US). Having set the scene and current challenges, it aims to suggest some strategies to overcome the issues facing dental schools going forward. Background In the US the Occupational Safety and Health Administration classified dentists in the very high risk category because of the potential for exposure to the virus as a result of aerosol generating procedures (AGP). In the last 20 years there have been two previous outbreaks of coronaviruses (severe acute respiratory syndrome and Middle East respiratory syndrome) which resulted in no long-term changes in the provision of dental education. The recent paper from Wuhan, China described action in the height of the infection but no sustainable actions to deliver dental education going forward. Challenges The challenges identified include: protecting the health of students, faculty and staff; ensuring the continuity and quality of dental education; ensuring confidence in health and safety measures; and keeping up with guidance. There is some variation across the US but most schools have suspended clinical teaching and implemented stay at home policies. Others have implemented social distancing in laboratories including clinical skills. The final challenge is ensuring that students have the teaching, experience and are assessed to ensure the competency of the graduating student. Solutions Technology in teaching and learning offers many opportunities. For didactic teaching distance learning has been implemented. There are 'off the shelf' programmes for teaching and assessment. The development of bespoke content is time consuming and one solution is for schools to share material. Although still requiring social distancing, manikins and haptics offer some opportunities for skills training. The need for excellent information sharing with faculty and students is emphasised. Conclusion Schools should re-evaluate their policies and curricula and incorporate appropriate methods of distance learning permanently into their teaching. Students should have outreach and multi-professional support in order to allow them to assist in the community during public health crises. Finally, gaps have been identified in US dental schools preparedness for pandemics.", "title": "The COVID-19 pandemic: implications for dental education", "pid": "nrumr61g", "bm25_score": 216.03970336914062}, {"text": "", "title": "Gendered effects of school closures during the COVID-19 pandemic", "pid": "wc7u3hau", "bm25_score": 216.00526428222656}, {"text": "In the early days of the COVID-19 outbreak, school district leaders’ most immediate priority was to ensure that students have access to regular meals. However, efforts to provide a range of other social services must follow close behind. As a start, superintendents can look to their data systems to help them identify those students and families that are most likely to need social services to make it through this phase and beyond. But even while racing to ensure students’ health and safety, they cannot afford to ignore the longer-term challenges that their districts will face, given not just the need to move instruction online but also given that COVID-19 is all but guaranteed to do serious damage to state and local economies.", "title": "On Leadership: Responding to COVID-19: Short- and long-term challenges", "pid": "o56km9qw", "bm25_score": 215.99063110351562}, {"text": "", "title": "Health measures for the reopening of schools, colleges, high schools and nurseries", "pid": "whg6wn4n", "bm25_score": 215.9867401123047}, {"text": "BACKGROUND: School closure is a non-pharmaceutical intervention that was considered in many national pandemic plans developed prior to the start of the influenza A(H1N1)pdm09 pandemic, and received considerable attention during the event. Here, we retrospectively review and compare national and local experiences with school closures in several countries during the A(H1N1)pdm09 pandemic. Our intention is not to make a systematic review of country experiences; rather, it is to present the diversity of school closure experiences and provide examples from national and local perspectives. METHODS: Data were gathered during and following a meeting, organized by the European Centres for Disease Control, on school closures held in October 2010 in Stockholm, Sweden. A standard data collection form was developed and sent to all participants. The twelve participating countries and administrative regions (Bulgaria, China, France, Hong Kong Special Administrative Region (SAR), Italy, Japan, New Zealand, Serbia, South Africa, Thailand, United Kingdom, and United States) provided data. RESULTS: Our review highlights the very diverse national and local experiences on school closures during the A(H1N1)pdm09 pandemic. The processes including who was in charge of making recommendations and who was in charge of making the decision to close, the school-based control strategies, the extent of school closures, the public health tradition of responses and expectations on school closure varied greatly between countries. Our review also discusses the many challenges associated with the implementation of this intervention and makes recommendations for further practical work in this area. CONCLUSIONS: The single most important factor to explain differences observed between countries may have been the different public health practises and public expectations concerning school closures and influenza in the selected countries.", "title": "School closures during the 2009 influenza pandemic: national and local experiences", "pid": "3amxb7qr", "bm25_score": 215.98155212402344}, {"text": "", "title": "Considering inequalities in the school closure response to COVID-19", "pid": "0wj9k97j", "bm25_score": 215.97816467285156}, {"text": "The consequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus have been devastating to the healthcare system. As the positive effects of social distancing, mandatory masking, and societal lockdown on the spread of the disease and its incidence in the community were documented, societal and financial pressures mounted worldwide, prompting efforts to “re-open” countries, states, communities, businesses, and schools. The same happened with hospital, which had to start developing strategies to resume elective surgery activities. This manuscript describes the pre-requisites as well as the strategies for resuming surgical activity, be it in the outpatient or inpatient setting.", "title": "Resuming elective surgical services in times of COVID-19 infection", "pid": "f0frlpwh", "bm25_score": 215.93699645996094}, {"text": "", "title": "Covid-19: Researchers question policy of closing schools after finding under 20s have low susceptibility to virus.", "pid": "hnzmj7t6", "bm25_score": 215.90159606933594}, {"text": "As many countries begin to lift some of the restrictions to contain COVID-19 spread, lack of evidence of transmission in the school setting remains. We examined Irish notifications of SARS-CoV2 in the school setting before school closures on 12 March 2020 and identified no paediatric transmission. This adds to current evidence that children do not appear to be drivers of transmission, and we argue that reopening schools should be considered safe accompanied by certain measures.", "title": "No evidence of secondary transmission of COVID-19 from children attending school in Ireland, 2020", "pid": "i804iorq", "bm25_score": 215.8791961669922}, {"text": "Background Emergency school closures are often used as public health interventions during infectious disease outbreaks in an attempt to minimise the spread of infection. However, if children continue to mix with others outside the home during the closures, these measures are unlikely to be effective. Objectives This review aimed to summarise existing literature on children's activities and contacts made outside the home during unplanned school closures. Methods We searched four databases from inception to February 2020 for relevant literature. Main findings were extracted. Results 3,343 citations were screened and 19 included in the review. Activities and social contacts appeared to decrease during closures but contact was still common. All studies reported children leaving the house or being looked after by non-household members. There was some evidence that older child age and parental disagreement with closure were predictive of children leaving the house, and mixed evidence regarding the relationship between infection status and leaving the home. Parental agreement with closure was generally high, but some parents disagreed due to perceived low risk of infection and practical issues regarding childcare and financial impact. Conclusions Evidence suggests that many children continue to leave the house and mix with others during school closures despite public health recommendations to avoid social contact. This review of behaviour during unplanned school closures could be used to improve infectious disease modelling.", "title": "The impact of unplanned school closure on children's social contact: Rapid evidence review", "pid": "us7d19p5", "bm25_score": 215.87855529785156}, {"text": "", "title": "Covid-19: school closures and bans on mass gatherings will need to be considered, says England's CMO", "pid": "74txzvou", "bm25_score": 215.8518524169922}, {"text": "With the coronavirus (COVID-19) outbreak in China, the Chinese government decided to ban any type of face-to-face teaching, disrupting classes and resulting in over 270 million students being unable to return to their universities/schools. Therefore, the Ministry of Education (MoE) launched an initiative titled ‘Ensuring learning undisrupted when classes are disrupted’ by reforming the entire educational system and including an online education component. However, this quick reform in this unexpected critical situation of widespread COVID-19 cases harbours several challenges, such as the lack of time and teacher/student isolation. This paper discusses the possibility of using open educational resources (OER) and open educational practices (OEP) as an effective educational solution to overcome these challenges. Particularly, this study presents a generic OEP framework built on existing open-practice definitions. It then presents, based on this framework and based on the challenges reported by several Chinese education specialists during two national online seminars, a set of guidelines for the effective use of OER and OEP for both teaching and learning. Finally, this study presents some recommendations for the better adoption of OER and OEP in the future. The findings of this study can help researchers and educators apply OER and OEP for better learning experiences and outcomes during the COVID-19 outbreak.", "title": "Disrupted classes, undisrupted learning during COVID-19 outbreak in China: application of open educational practices and resources", "pid": "heil4572", "bm25_score": 215.83343505859375}, {"text": "COVID-19 confronts the education system with a new and massive crisis. What should a “new normal” look like for future generations? How can countries use the innovativeness of the recovery period to “build back better”? This Viewpoint highlights the UNESCO-led Global Coalition for Education initiative, which is seeking solutions to support learners and teachers, as well as governments throughout the recovery process, with a principal focus on inclusion, equity, and gender equality. The Viewpoint also argues that the current crisis is an opportunity for stronger international collaboration, which might provide a better focus and deliver solutions, including digital tools. Resilience and adaptability will be crucial for the next generations to navigate through the present—and any future—pandemic.", "title": "COVID-19 causes unprecedented educational disruption: Is there a road towards a new normal?", "pid": "zg51e060", "bm25_score": 215.82940673828125}, {"text": "", "title": "Advocating for Children During the COVID-19 School Closures", "pid": "v0wnlru2", "bm25_score": 215.80393981933594}]}
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concern. However, to date, there was hardly any study in characterizing the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. In this study, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and analyzed their SARS-CoV-2-specific antibody and T cell responses. We observed SARS-CoV-2-specific humoral and cellular immunity in the patients. Both were detected in newly discharged patients, suggesting both participate in immune-mediated protection to viral infection. However, follow-up patients (2 weeks post discharge) exhibited high titers of IgG antibodies, but with low levels of virus-specific T cells, suggesting that they may enter a quiescent state. Our work has thus provided a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in designing an effective vaccine to protect and treat SARS-CoV-2 infection.", "title": "Characterization of anti-viral immunity in recovered individuals infected by SARS-CoV-2", "pid": "dptgg05n", "bm25_score": 220.35775756835938}, {"text": "We report the kinetics of the immune response in relation to clinical and virological features of a patient with mild-to-moderate coronavirus disease-19 (COVID-19) requiring hospitalisation. Increased antibody-secreting cells, follicular T-helper cells, activated CD4+ and CD8+ T-cells and IgM/IgG SARS-CoV-2-binding antibodies were detected in blood, prior to symptomatic recovery. These immunological changes persisted for at least 7 days following full resolution of symptoms, indicating substantial anti-viral immunity in this non-severe COVID-19.", "title": "Breadth of concomitant immune responses underpinning viral clearance and patient recovery in a non-severe case of COVID-19", "pid": "kqanoog7", "bm25_score": 220.01467895507812}, {"text": "In the current SARS-CoV-2 pandemic a key unsolved question is the quality and duration of acquired immunity in recovered individuals. This is crucial to solve, however SARS-CoV-2 has circulated for under five months, precluding a direct study. We therefore monitored 10 subjects over a time span of 35 years (1985-2020), providing a total of 2473 follow up person-months, and determined a) their antibody levels following infection by any of the four seasonal human coronaviruses, and b) the time period after which reinfections by the same virus can occur. An alarmingly short duration of protective immunity to coronaviruses was found by both analyses. We saw frequent reinfections at 12 months post-infection and a substantial reduction in antibody levels as soon as 6 months post-infection.", "title": "Human coronavirus reinfection dynamics: lessons for SARS-CoV-2", "pid": "u5nxm9tu", "bm25_score": 219.0730438232422}, {"text": "To date, understanding whether acquired immunity and presence of anti SARS‐Cov2 antibodies protects against reinfection is one the most important focus of the scientific community [1‐2]. Several studies suggest that acquired immunity may protect upon further exposure to SARS‐COV2 [3‐6]. Contrary to this picture, we describe a case of a patient recovered from COVID‐19 pneumonia with positive serology, followed up by 6 negative nasopharyngeal swab‐PCR tests performed along 1 month, who later on, after exposure to the virus, presented another positive RT‐PCR test and a second IgM seroconversion. This report opens up several possible interpretations. This article is protected by copyright. All rights reserved.", "title": "New IgM seroconversion and positive RT‐PCR test after exposure to the virus in recovered COVID‐19 patient", "pid": "38mhmxvd", "bm25_score": 218.98858642578125}, {"text": "SARS-CoV-2-specific memory T cells will likely prove critical for long-term immune protection against COVID-19. We systematically mapped the functional and phenotypic landscape of SARS-CoV-2-specific T cell responses in a large cohort of unexposed individuals as well as exposed family members and individuals with acute or convalescent COVID-19. Acute phase SARS-CoV-2-specific T cells displayed a highly activated cytotoxic phenotype that correlated with various clinical markers of disease severity, whereas convalescent phase SARS-CoV-2-specific T cells were polyfunctional and displayed a stem-like memory phenotype. Importantly, SARS-CoV-2-specific T cells were detectable in antibody-seronegative family members and individuals with a history of asymptomatic or mild COVID-19. Our collective dataset shows that SARS-CoV-2 elicits robust memory T cell responses akin to those observed in the context of successful vaccines, suggesting that natural exposure or infection may prevent recurrent episodes of severe COVID-19 also in seronegative individuals.", "title": "Robust T cell immunity in convalescent individuals with asymptomatic or mild COVID-19", "pid": "wdfzrzkt", "bm25_score": 218.972412109375}, {"text": "Background: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. Methods: 90 individuals were enrolled in this study, 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC). Using two comprehensive 11-color flow cytometric panels conforming to Good Laboratory Practice (GLP) and approved for clinical diagnostics, we longitudinally examined cell count differences in lymphocyte populations and T cell activation in COVID-19 patients. Findings: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and {gamma}{delta} T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Interestingly, follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. Interpretation: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Our data imply that the presence of SARS-CoV-2 responsive T cells contributes to convalescence in MD. Thus, understanding the T cell-response in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control.", "title": "Reappearance of Effector T Cells Predicts Successful Recovery from COVID-19", "pid": "5lhvix51", "bm25_score": 218.94122314453125}, {"text": "The World Health Organization has declared SARS-CoV-2 virus outbreak a worldwide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free, and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in eight newly discharged patients. Follow-up analysis on another cohort of six patients 2 weeks post discharge also revealed high titers of immunoglobulin G (IgG) antibodies. In all 14 patients tested, 13 displayed serum-neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It also has implications in developing an effective vaccine to SARS-CoV-2 infection.", "title": "Detection of SARS-CoV-2-Specific Humoral and Cellular Immunity in COVID-19 Convalescent Individuals", "pid": "53j3ly3v", "bm25_score": 218.9342041015625}, {"text": "Summary The World Health Organization has declared SARS-CoV-2 virus outbreak a world-wide pandemic. However, there is very limited understanding on the immune responses, especially adaptive immune responses to SARS-CoV-2 infection. Here, we collected blood from COVID-19 patients who have recently become virus-free and therefore were discharged, and detected SARS-CoV-2-specific humoral and cellular immunity in 8 newly discharged patients. Follow-up analysis on another cohort of 6 patients 2 weeks post discharge also revealed high titers of IgG antibodies. In all 14 patients tested, 13 displayed serum neutralizing activities in a pseudotype entry assay. Notably, there was a strong correlation between neutralization antibody titers and the numbers of virus-specific T cells. Our work provides a basis for further analysis of protective immunity to SARS-CoV-2, and understanding the pathogenesis of COVID-19, especially in the severe cases. It has also implications in developing an effective vaccine to SARS-CoV-2 infection.", "title": "Detection of SARS-CoV-2-specific humoral and cellular immunity in COVID-19 convalescent individuals", "pid": "0tn06al2", "bm25_score": 218.87588500976562}, {"text": "Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "title": "Protective immunity after COVID-19 has been questioned: what can we do without SARS-CoV-2-IgG detection?", "pid": "rsz7ch2a", "bm25_score": 218.8585662841797}, {"text": "BACKGROUND: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. METHODS: 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC) participated in this study. We used two comprehensive 11-colour flow cytometric panels conforming to Good Laboratory Practice and approved for clinical diagnostics. FINDINGS: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and γδ T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. INTERPRETATION: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Understanding T cell-responses in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control. FUNDING: Funded by State of Lower Saxony grant 14-76,103-184CORONA-11/20 and German Research Foundation, Excellence Strategy - EXC2155\"RESIST\"-Project ID39087428, and DFG-SFB900/3-Project ID158989968, grants SFB900-B3, SFB900-B8.", "title": "Reappearance of effector T cells is associated with recovery from COVID-19", "pid": "871812f7", "bm25_score": 218.8278045654297}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a severe acute respiratory syndrome that is called COVID-19. Clinical manifestations of COVID-19 include diarrhea, pneumonia, lymphopenia, exhausted lymphocytes, and pro-inflammatory cytokine production. Immunology is part of the process of clinical evolution, but there are some questions around immunity-based protection: (1) why some infected people have only mild symptoms of the disease or are asymptomatic; (2) why delayed and weak antibody responses are associated with severe outcomes; and (3) why positivity in molecular tests does not represent protective antibody IgG. Perhaps T cell responses may be the key to solving those questions. SARS-CoV-2-specific memory T cells persist in peripheral blood and may be capable of providing effective information about protective immunity. The T cells studies can be helpful in elucidating the pathways for development of vaccines, therapies, and diagnostics for COVID-19 and for filling these immunology knowledge gaps.", "title": "Protective immunity after COVID-19 has been questioned: What can we do without SARS-CoV-2-IgG detection?", "pid": "rs79r7kc", "bm25_score": 218.82337951660156}, {"text": "BACKGROUND: Elucidating the role of T cell responses in COVID-19 is of utmost importance to understand the clearance of SARS-CoV-2 infection. METHODS: 30 hospitalized COVID-19 patients and 60 age- and gender-matched healthy controls (HC) participated in this study. We used two comprehensive 11-colour flow cytometric panels conforming to Good Laboratory Practice and approved for clinical diagnostics. FINDINGS: Absolute numbers of lymphocyte subsets were differentially decreased in COVID-19 patients according to clinical severity. In severe disease (SD) patients, all lymphocyte subsets were reduced, whilst in mild disease (MD) NK, NKT and γδ T cells were at the level of HC. Additionally, we provide evidence of T cell activation in MD but not SD, when compared to HC. Follow up samples revealed a marked increase in effector T cells and memory subsets in convalescing but not in non-convalescing patients. INTERPRETATION: Our data suggest that activation and expansion of innate and adaptive lymphocytes play a major role in COVID-19. Additionally, recovery is associated with formation of T cell memory as suggested by the missing formation of effector and central memory T cells in SD but not in MD. Understanding T cell-responses in the context of clinical severity might serve as foundation to overcome the lack of effective anti-viral immune response in severely affected COVID-19 patients and can offer prognostic value as biomarker for disease outcome and control. FUNDING: Funded by State of Lower Saxony grant 14–76,103–184CORONA-11/20 and German Research Foundation, Excellence Strategy – EXC2155“RESIST”–Project ID39087428, and DFG-SFB900/3–Project ID158989968, grants SFB900-B3, SFB900-B8.", "title": "Reappearance of effector T cells is associated with recovery from COVID-19", "pid": "9iuesnxo", "bm25_score": 218.71832275390625}, {"text": "Most of the individuals infected with SARS coronavirus (SARS-CoV) spontaneously recovered without clinical intervention. However, the immunological correlates associated with patients' recovery are currently unknown. In this report, we have sequentially monitored 30 recovered patients over a two-year period to characterize temporal changes in SARS-CoV-specific antibody responses as well as cytotoxic T cell (CTL) responses. We have found persistence of robust antibody and CTL responses in all of the study subjects throughout the study period, with a moderate decline one year after the onset of symptoms. We have also identified two potential major CTL epitopes in N proteins based on ELISPOT analysis of pooled peptides. However, despite the potent immune responses and clinical recovery, peripheral lymphocyte counts in the recovered patients have not yet been restored to normal levels. In summary, our study has, for the first time, characterized the temporal and dynamic changes of humoral and CTL responses in the natural history of SARS-recovered individuals, and strongly supports the notion that high and sustainable levels of immune responses correlate strongly with the disease outcome. Our findings have direct implications for future design and development of effective therapeutic agents and vaccines against SARS-CoV infection.", "title": "Long-Term Persistence of Robust Antibody and Cytotoxic T Cell Responses in Recovered Patients Infected with SARS Coronavirus", "pid": "itu39mln", "bm25_score": 218.65245056152344}, {"text": "A multiple sclerosis patient infected by SARS-CoV-2 during fingolimod therapy was hospitalized with moderate clinical features, and recovered in 15 days. High levels of CCL5 and CCL10 chemokines and of antibody-secreting B cells were detected, while the levels other B- and T-cell subsets were comparable to that of appropriate controls. However, CD4+ and CD8+ cells were oligoclonally expanded and prone to apoptosis when stimulated in vitro. This study suggests that fingolimod-immunosuppressed patients, despite the low circulating lymphocytes, may rapidly expand antibody-secreting cells and mount an effective immune response that favors COVID-19 recovery after discontinuation.", "title": "Immunologic characterization of a immunosuppressed multiple sclerosis patient that recovered from SARS-CoV-2 infection", "pid": "03dzqten", "bm25_score": 218.55384826660156}, {"text": "A multiple sclerosis patient infected by SARS-CoV-2 during fingolimod therapy was hospitalized with moderate clinical features, and recovered in 15 days. High levels of CCL5 and CCL10 chemokines and of antibody-secreting B cells were detected, while the levels other B- and T-cell subsets were comparable to that of appropriate controls. However, CD4+ and CD8+ cells were oligoclonally expanded and prone to apoptosis when stimulated in vitro. This study suggests that fingolimod-immunosuppressed patients, despite the low circulating lymphocytes, may rapidly expand antibody-secreting cells and mount an effective immune response that favors COVID-19 recovery after drug discontinuation.", "title": "Immunologic characterization of a immunosuppressed multiple sclerosis patient that recovered from SARS-CoV-2 infection", "pid": "5mk4jcn6", "bm25_score": 218.5258026123047}, {"text": "Since December 2019, COVID-19, the clinical syndrome associated with SARS-CoV-2 infection, has infected more than 6.2 million people and brought the function of the global community to a halt. As the number of patients recovered from COVID-19 rises and the world transitions toward reopening, the question of acquired immunity versus the possibility of reinfection are critical to anticipating future viral spread. Here, we present a case of a patient previously recovered from COVID-19 who re-presents with new respiratory, radiographical, laboratory, and RT-PCR findings concerning for re-infection. We review this case in the context of the evolving discussion and theories surrounding dynamic RT-PCR results, prolonged viral shedding, and the possibility of developed immunity.", "title": "A case report of possible novel coronavirus 2019 reinfection", "pid": "aed6psww", "bm25_score": 218.33750915527344}, {"text": "An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.", "title": "SARS-CoV-2 infection protects against rechallenge in rhesus macaques", "pid": "t3sjv4hv", "bm25_score": 218.26171875}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causing coronavirus disease 2019 (COVID-19) has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS-CoV-2 infection needs to be determined. Here, 26 cases of COVID-19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms, and no case of severe symptoms was found among these patients. Strikingly, a subset of these patients had SARS-CoV-2 and virus-specific IgG coexist for an unexpectedly long time, with two cases for up to 50 days. One COVID-19 patient who did not produce any SARS-CoV-2-bound IgG successfully cleared SARS-CoV-2 after 46 days of illness, revealing that without antibody-mediated adaptive immunity, innate immunity alone may still be powerful enough to eliminate SARS-CoV-2. This report may provide a basis for further analysis of both innate and adaptive immunity in SARS-CoV-2 clearance, especially in nonsevere cases.", "title": "Long-term coexistence of SARS-CoV-2 with antibody response in COVID-19 patients", "pid": "x1k6ao9h", "bm25_score": 218.2504119873047}, {"text": "The global fight against coronavirus disease 2019 (COVID-19) is largely based on strategies to boost immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and prevent its severe course and complications. The human defence may include antibodies which interact with SARS-CoV-2 and neutralize its aggressive actions on multiple organ systems. Protective cross-reactivity of antibodies against measles and other known viral infections has been postulated, primarily as a result of the initial observations of asymptomatic and mild COVID-19 in children. Uncontrolled case series have demonstrated virus-neutralizing effect of convalescent plasma, supporting its efficiency at early stages of contracting SARS-CoV-2. Given the variability of the virus structure, the utility of convalescent plasma is limited to the geographic area of its preparation, and for a short period of time. Intravenous immunoglobulin may also be protective in view of its nonspecific antiviral and immunomodulatory effects. Finally, human monoclonal antibodies may interact with some SARS-CoV-2 proteins, inhibiting the virus-receptor interaction and prevent tissue injury. The improved understanding of the host antiviral responses may help develop safe and effective immunotherapeutic strategies against COVID-19 in the foreseeable future.", "title": "Perspectives of Immune Therapy in Coronavirus Disease 2019", "pid": "0l86swz1", "bm25_score": 218.2257537841797}, {"text": "SARS-CoV-2, the virus that causes COVID-19, has been unclear Now, two studies reveal that infected people harbor T cells that target the virus—and may help them recover Both studies also found that some people never infected with SARS-CoV-2 have these cellular defenses, most likely because they were previously infected with other coronaviruses “This is encouraging data,” says virologist Angela Rasmussen of Columbia University Although the studies don’t clarify whether people who clear a SARS-CoV-2 infection can ward off the virus in the future, both identified strong T cell responses to it, which “bodes well for the development of long-term protective immunity,” Rasmussen says The findings could also help researchers create better vaccines", "title": "T cells found in COVID-19 patients ‘bode well’ for long-term immunity", "pid": "88px7oq2", "bm25_score": 218.2232666015625}, {"text": "An understanding of protective immunity to SARS-CoV-2 is critical for vaccine and public health strategies aimed at ending the global COVID-19 pandemic. A key unanswered question is whether infection with SARS-CoV-2 results in protective immunity against re-exposure. We developed a rhesus macaque model of SARS-CoV-2 infection and observed that macaques had high viral loads in the upper and lower respiratory tract, humoral and cellular immune responses, and pathologic evidence of viral pneumonia. Following initial viral clearance, animals were rechallenged with SARS-CoV-2 and showed 5 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa compared with primary infection. Anamnestic immune responses following rechallenge suggested that protection was mediated by immunologic control. These data show that SARS-CoV-2 infection induced protective immunity against re-exposure in nonhuman primates.", "title": "SARS-CoV-2 infection protects against rechallenge in rhesus macaques", "pid": "car394ou", "bm25_score": 218.1803741455078}, {"text": "We determined and compared the humoral immune response in severe, hospitalized and mild, non-hospitalized COVID-19 patients. Severe patients (n=38) develop a robust antibody response to SARS-CoV-2, including IgG and IgA antibodies. The geometric mean 50% virus neutralization titer is 1:240. SARS-CoV-2 infected hospital personnel (n=24), who developed mild symptoms necessitating leave of absence, self-isolation, but not hospitalization, 75 % develop antibodies, but with low/absent virus neutralization (60% < 1:20). While severe COVID-19 patients develop a strong antibody response, mild SARS-CoV-2 infections induce a modest antibody response. Long term monitoring will show whether these responses predict protection against future infections.", "title": "Differences in antibody kinetics and functionality between severe and mild SARS-CoV-2 infections.", "pid": "yuwrr4vg", "bm25_score": 218.07472229003906}, {"text": "The emerging coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic, and brings formidable challenges to public health, society and the economy worldwide. Currently, the antibody responses against SARS-CoV-2 remains largely unknown. We herein estimated the longevity of specific antibodies against SARS-CoV-2, and reported that antibodies waned over substantially in COVID-19 patients after recovery. This article is protected by copyright. All rights reserved.", "title": "Antibody responses against SARS-CoV-2 in COVID-19 patients", "pid": "6n26bw7v", "bm25_score": 218.07090759277344}, {"text": "For the first 3 months of COVID-19 pandemic, COVID-19 was expected to be an immunizing non-relapsing disease. We report a national case series of 11 virologically-confirmed COVID-19 patients having experienced a second clinically- and virologically-confirmed acute COVID-19 episode. According to the clinical history, we discuss either re-infection or reactivation hypothesis. Larger studies including further virological, immunological and epidemiologic data are needed to understand the mechanisms of these recurrences.", "title": "Clinical recurrences of COVID-19 symptoms after recovery: viral relapse, reinfection or inflammatory rebound?", "pid": "qg01p4bq", "bm25_score": 218.042724609375}, {"text": "Since emerging in China in December 2019, the infection caused by SARS-CoV-2, COVID-19, has infected more than 3 million people worldwide (Johns Hopkins University and Medicine: Coronavirus Resource Center). Since then, clusters of infections have emerged in Singapore, particularly among younger workers in communal living environments. The spectrum of COVID-19 infection ranges from mild respiratory illness, to viral pneumonia and life-threatening acute respiratory distress syndrome in up 15-20% (Huang, et al 2020, Wu and McGoogan 2020).", "title": "Temporal changes in immune blood cell parameters in COVID‐19 infection and recovery from severe infection", "pid": "o6k81dcc", "bm25_score": 217.99606323242188}, {"text": "During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-2(1–5). Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal neutralizing titers ranging from undetectable in 33% to below 1:1000 in 79%, while only 1% showed titers >1:5000. Antibody cloning revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titers, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC(50)s) as low as single digit ng/mL. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.", "title": "Convergent Antibody Responses to SARS-CoV-2 Infection in Convalescent Individuals", "pid": "nhkd88yv", "bm25_score": 217.96783447265625}, {"text": "CD4 T follicular helper (Tfh) cells are important for the generation of long-lasting and specific humoral protection against viral infections. The degree to which SARS-CoV-2 infection generates Tfh cells and stimulates the germinal center response is an important question as we investigate vaccine options for the current pandemic. Here we report that, following infection with SARS-CoV-2, adult rhesus macaques exhibited transient accumulation of activated, proliferating Tfh cells in their peripheral blood on a transitory basis. The CD4 helper cell responses were skewed predominantly toward a Th1 response in blood, lung, and lymph nodes, reflective of the interferon-rich cytokine environment following infection. We also observed the generation of germinal center Tfh cells specific for the SARS-CoV-2 spike (S) and nucleocapsid (N) proteins, and a corresponding early appearance of antiviral serum IgG antibodies but delayed or absent IgA antibodies. Our data suggest that a vaccine promoting Th1-type Tfh responses that target the S protein may lead to protective immunity.", "title": "SARS-CoV-2 infection induces germinal center responses with robust stimulation of CD4 T follicular helper cells in rhesus macaques", "pid": "l7lqn4js", "bm25_score": 217.91360473632812}, {"text": "Background. In the background of the current COVID-19 pandemic, serological tests are being used to assess past infection and immunity against SARS-CoV-2. This knowledge is paramount to determine the transmission dynamics of SARS-CoV-2 through the post pandemic period. Several individuals belonging to households with an index COVID-19 patient, reported symptoms of COVID-19 but discrepant serology results. Methods. Here we investigated the humoral and cellular immune responses against SARS-CoV-2 in seven families, including nine index patients and eight contacts, who had evidence of serological discordances within the households. Ten unexposed healthy donors were enrolled as controls. Results. All index patients recovered from a mild COVID-19. They all developed anti-SARS-CoV-2 antibodies and a significant T cell response detectable up to 69 days after symptom onset. Six of the eight contacts reported COVID-19 symptoms within 1 to 7 days after the index patients but all were SARS-CoV-2 seronegative. Six out of eight contacts developed a SARS-CoV-2-specific T cell response against structural and/or accessory proteins that lasts up to 80 days post symptom onset suggesting a past SARS-CoV-2 infection. Conclusion. Exposure to SARS-CoV-2 can induce virus-specific T cell responses without seroconversion. T cell responses may be more sensitive indicators of SARS-Co-V-2 exposure than antibodies. Our results indicate that epidemiological data relying only on the detection of SARS-CoV-2 antibodies may lead to a substantial underestimation of prior exposure to the virus", "title": "Intrafamilial Exposure to SARS-CoV-2 Induces Cellular Immune Response without Seroconversion", "pid": "eml8uilb", "bm25_score": 217.85679626464844}, {"text": "During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21-5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres: less than 1:50 in 33% and below 1:1,000 in 79%, while only 1% showed titres above 1:5,000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50 values) as low as single digit nanograms per millitre. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.", "title": "Convergent antibody responses to SARS-CoV-2 in convalescent individuals", "pid": "79891dfu", "bm25_score": 217.83074951171875}, {"text": "The duration and nature of immunity generated in response to SARS-CoV-2 infection is unknown. Many public health responses and modeled scenarios for COVID-19 outbreaks caused by SARSCoV-2 assume that infection results in an immune response that protects individuals from future infections or illness for some amount of time. The timescale of protection is a critical determinant of the future impact of the pathogen. The presence or absence of protective immunity due to infection or vaccination (when available) will affect future transmission and illness severity. The dynamics of immunity and nature of protection are relevant to discussions surrounding therapeutic use of convalescent sera as well as efforts to identify individuals with protective immunity. Here, we review the scientific literature on antibody immunity to coronaviruses, including SARS-CoV-2 as well as the related SARS-CoV-1, MERS-CoV and human endemic coronaviruses (HCoVs). We reviewed 1281 abstracts and identified 322 manuscripts relevant to 5 areas of focus: 1) antibody kinetics, 2) correlates of protection, 3) immunopathogenesis, 4) antigenic diversity and cross-reactivity, and 5) population seroprevalence. While studies of SARS-CoV-2 are necessary to determine immune responses to it, evidence from other coronaviruses can provide clues and guide future research.", "title": "A systematic review of antibody mediated immunity to coronaviruses: antibody kinetics, correlates of protection, and association of antibody responses with severity of disease", "pid": "yzffm05r", "bm25_score": 217.8262481689453}, {"text": "Summary We profiled adaptive immunity in COVID-19 patients with active infection or after recovery and created a repository of currently >14 million B and T cell receptor (BCR, TCR) sequences from blood of these patients. The B cell response showed converging IGHV3-driven BCR clusters closely associated with SARS-CoV-2 antibodies. Clonality and skewing of TCR repertoires was associated with interferon type I and III responses, early CD4+ and CD8+ T cell activation and counterregulation by the coreceptors BTLA, Tim-3, PD-1, TIGIT and CD73. Tfh, Th17-like and nonconventional (but not classical anti-viral) Th1 cell polarizations were induced. SARS-CoV-2-specific T cell responses were driven by TCR clusters shared between patients with a characteristic trajectory of clonotypes and traceability over the disease course. Our data provide fundamental insight into adaptive immunity to SARS-CoV-2 with the actively updated repository providing a resource for the scientific community urgently needed to inform therapeutic concepts and vaccine development.", "title": "Next Generation Sequencing of T and B cell receptor repertoires from COVID-19 patients showed signatures associated with severity of disease", "pid": "tb8k979g", "bm25_score": 217.80517578125}, {"text": "COVID‐19 pandemic is an emerging new human disease, where no vaccines, or monoclonal antibodies (mAbs), or drugs are currently available for therapy. Active vaccination requires the induction of an immune response against a given agent to a susceptible individual for the purpose of preventing or treating an infectious disease and this usually takes time to develop. Thus, the use of existing autologous Ab administration, obtainable from recovered COVID 19 patients, after 2 weeks recovery, is the best and the most practical strategy for providing immediate passive immunity to susceptible recipients in need.", "title": "Reflection on passive immunotherapy in those who need most: some novel strategic arguments for obtaining safer therapeutic plasma or autologous antibodies from recovered COVID ‐19 infected patients", "pid": "w8c3ma8l", "bm25_score": 217.79371643066406}, {"text": "Deciphering the dynamic changes of antibodies against SARS-CoV-2 is essential for understanding the immune response in COVID-19 patients. By comprehensively analyzing the laboratory findings of 1,850 patients, we describe the dynamic changes of the total antibody, spike protein (S)-, receptor-binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels during SARS-CoV-2 infection and recovery. Our results indicate that the S-, RBD-, and N- specific IgG generation of severe/critical COVID-19 patients is one week later than mild/moderate cases, while the levels of these antibodies are 1.5-fold higher in severe/critical patients during hospitalization (P<0.01). The decrease of these IgG levels indicates the poor outcome of severe/critical patients. The RBD- and S-specific IgG levels are 2-fold higher in virus-free patients (P<0.05). Notably, we found that the patients who got re-infected had a low level of protective antibody on discharge. Therefore, our evidence proves that the dynamic changes of antibodies could provide an important reference for diagnosis, monitoring, and treatment, and shed new light on the precise management of COVID-19.", "title": "The Dynamic Changes of Antibodies against SARS-CoV-2 during the Infection and Recovery of COVID-19", "pid": "q5i8lpan", "bm25_score": 217.79095458984375}, {"text": "The severe acute respiratory syndrome (SARS) epidemic started in late 2002 and swiftly spread across 5 continents with a mortality rate of around 10%. Although the epidemic was eventually controlled through the implementation of strict quarantine measures, there continues a need to investigate the SARS coronavirus (SARS-CoV) and develop interventions should it re-emerge. Numerous studies have shown that neutralizing antibodies against the virus can be found in patients infected with SARS-CoV within days upon the onset of illness and lasting up to several months. In contrast, there is little data on the kinetics of T cell responses during SARS-CoV infection and little is known about their role in the recovery process. However, recent studies in mice suggest the importance of T cells in viral clearance during SARS-CoV infection. Moreover, a growing number of studies have investigated the memory T cell responses in recovered SARS patients. This review covers the available literature on the emerging importance of T cell responses in SARS-CoV infection, particularly on the mapping of cytotoxic T lymphocyte (CTL) epitopes, longevity, polyfunctionality and human leukocyte antigen (HLA) association as well as their potential implications on treatment and vaccine development.", "title": "Understanding the T cell immune response in SARS coronavirus infection", "pid": "5uoepd0r", "bm25_score": 217.76441955566406}, {"text": "Motivated by historical and present clinical observations, we discuss the possible unfavorable evolution of the immunity (similar to documented antibody-dependent enhancement scenarios) after a first infection with COVID-19. More precisely we ask the question of how the epidemic outcomes are affected if the initial infection does not provide immunity but rather sensitization to future challenges. We first provide background comparison with the 2003 SARS epidemic. Then we use a compartmental epidemic model structured by immunity level (taken here as age classes) that we fit on available data; this allows to derive quantitative insights into the future number of severe cases and deaths.", "title": "Immunity after COVID-19: protection or sensitization ?", "pid": "g6g34uvh", "bm25_score": 217.7497100830078}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current coronavirus disease 2019 (COVID-19) pandemic. Understanding both the immunological processes providing specific immunity and potential immunopathology underlying the pathogenesis of this disease may provide valuable insights for potential therapeutic interventions. Here, we quantified SARS-CoV-2 specific immune responses in patients with different clinical courses. Compared to individuals with a mild clinical presentation, CD4+ T cell responses were qualitatively impaired in critically ill patients. Strikingly, however, in these patients the specific IgG antibody response was remarkably strong. The observed disparate T and B cell responses could be indicative of a deregulated immune response in critically ill COVID-19 patients.", "title": "Divergent SARS-CoV-2-specific T and B cell responses in severe but not mild COVID-19", "pid": "hpbjdytv", "bm25_score": 217.7387237548828}, {"text": "During the COVID-19 pandemic, SARS-CoV-2 infected millions of people and claimed hundreds of thousands of lives. Virus entry into cells depends on the receptor binding domain (RBD) of the SARS-CoV-2 spike protein (S). Although there is no vaccine, it is likely that antibodies will be essential for protection. However, little is known about the human antibody response to SARS-CoV-21-5. Here we report on 149 COVID-19 convalescent individuals. Plasmas collected an average of 39 days after the onset of symptoms had variable half-maximal pseudovirus neutralizing titres: less than 1:50 in 33% and below 1:1,000 in 79%, while only 1% showed titres above 1:5,000. Antibody sequencing revealed expanded clones of RBD-specific memory B cells expressing closely related antibodies in different individuals. Despite low plasma titres, antibodies to three distinct epitopes on RBD neutralized at half-maximal inhibitory concentrations (IC50 values) as low as single digit nanograms per millitre. Thus, most convalescent plasmas obtained from individuals who recover from COVID-19 do not contain high levels of neutralizing activity. Nevertheless, rare but recurring RBD-specific antibodies with potent antiviral activity were found in all individuals tested, suggesting that a vaccine designed to elicit such antibodies could be broadly effective.", "title": "Convergent antibody responses to SARS-CoV-2 in convalescent individuals.", "pid": "gof2of9o", "bm25_score": 217.737548828125}, {"text": "The emergency represented by the COVID-19 pandemic represents a new challenge for clinicians who deal with autoimmune diseases because of patients undergoing immunosuppressive therapy. Few cases of Multiple Sclerosis (MS) patients receiving ocrelizumab who contracted COVID-19 with a benign course have recently been published. We present the case of a MS patient with mild COVID-19 who developed SARS-CoV-2 specific IgA without IgG ten weeks after infection. Patients on B-cell depleting drugs have a reduced antibody immune response to viral neoantigens. A relative sparing of mucosal-associated lymphoid tissues (MALT) could be responsible for IgA response in our patient.", "title": "Is serological response to SARS-CoV-2 preserved in MS patients on ocrelizumab treatment? A case report", "pid": "z2lzgubi", "bm25_score": 217.73268127441406}, {"text": "Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.", "title": "Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques", "pid": "tdorhy8x", "bm25_score": 217.6385498046875}, {"text": "Six years have passed since the outbreak of severe acute respiratory syndrome (SARS). Previous studies indicated that specific Abs to SARS-related coronavirus (SARS-CoV) waned over time in recovered SARS patients. It is critical to find out whether a potential anamnestic response, as seen with other viral infections, exists to protect a person from reinfection in case of another SARS outbreak. Recovered SARS patients were followed up to 6 y to estimate the longevity of specific Ab. The specific memory B cell and T cell responses to SARS-CoV Ags were measured by means of ELISPOT assay. Factors in relation to humoral and cellular immunity were investigated. Six years postinfection, specific IgG Ab to SARS-CoV became undetectable in 21 of the 23 former patients. No SARS-CoV Ag-specific memory B cell response was detected in either 23 former SARS patients or 22 close contacts of SARS patients. Memory T cell responses to a pool of SARS-CoV S peptides were identified in 14 of 23 (60.9%) recovered SARS patients, whereas there was no such specific response in either close contacts or healthy controls. Patients with more severe clinical manifestations seemed to present a higher level of Ag-specific memory T cell response. SARS-specific IgG Ab may eventually vanish and peripheral memory B cell responses are undetectable in recovered SARS patients. In contrast, specific T cell anamnestic responses can be maintained for at least 6 y. These findings have applications in preparation for the possible reemergence of SARS.", "title": "Lack of peripheral memory B cell responses in recovered patients with severe acute respiratory syndrome: a six-year follow-up study.", "pid": "xdpxkxkc", "bm25_score": 217.63482666015625}, {"text": "The emergence of the novel coronavirus in Wuhan, China, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern. Most coronaviruses infect animals but can evolve into strains that cross the species barrier and infect humans. At the present, there is no single specific vaccine or efficient antiviral therapy against COVID-19. Recently, we showed that intravenous immunoglobulin (IVIg) treatment reduces inflammation of intestinal epithelial cells and eliminates overgrowth of the opportunistic human fungal pathogen Candida albicans in the murine gut. Immunotherapy with IVIg could be employed to neutralize COVID-19. However, the efficacy of IVIg would be better if the immune IgG antibodies were collected from patients who have recovered from COVID-19 in the same city, or the surrounding area, in order to increase the chance of neutralizing the virus. These immune IgG antibodies will be specific against COVID-19 by boosting the immune response in newly infected patients. Different procedures may be used to remove or inactivate any possible pathogens from the plasma of recovered coronavirus patient derived immune IgG, including solvent/detergent, 60 °C heat-treatment, and nanofiltration. Overall, immunotherapy with immune IgG antibodies combined with antiviral drugs may be an alternative treatment against COVID-19 until stronger options such as vaccines are available.", "title": "Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients?", "pid": "ix4zo0ha", "bm25_score": 217.62344360351562}, {"text": "Coronavirus disease 2019 (COVID-19), which is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic. It currently remains unclear whether convalescing patients have a risk of reinfection. We generated a rhesus macaque model of SARS-CoV-2 infection that was characterized by interstitial pneumonia and systemic viral dissemination mainly in the respiratory and gastrointestinal tracts. Rhesus macaques reinfected with the identical SARS-CoV-2 strain during the early recovery phase of the initial SARS-CoV-2 infection did not show detectable viral dissemination, clinical manifestations of viral disease, or histopathological changes. Comparing the humoral and cellular immunity between primary infection and rechallenge revealed notably enhanced neutralizing antibody and immune responses. Our results suggest that primary SARS-CoV-2 exposure protects against subsequent reinfection in rhesus macaques.", "title": "Primary exposure to SARS-CoV-2 protects against reinfection in rhesus macaques.", "pid": "5dbuxvc4", "bm25_score": 217.59371948242188}, {"text": "The emergence of the novel coronavirus in Wuhan, China, which causes severe respiratory tract infections in humans (COVID-19), has become a global health concern Most coronaviruses infect animals but can evolve into strains that cross the species barrier and infect humans At the present, there is no single specific vaccine or efficient antiviral therapy against COVID-19 Recently, we showed that intravenous immunoglobulin (IVIg) treatment reduces inflammation of intestinal epithelial cells and eliminates overgrowth of the opportunistic human fungal pathogen Candida albicans in the murine gut Immunotherapy with IVIg could be employed to neutralize COVID-19 However, the efficacy of IVIg would be better if the immune IgG antibodies were collected from patients who have recovered from COVID-19 in the same city, or the surrounding area, in order to increase the chance of neutralizing the virus These immune IgG antibodies will be specific against COVID-19 by boosting the immune response in newly infected patients Different procedures may be used to remove or inactivate any possible pathogens from the plasma of recovered coronavirus patient derived immune IgG, including solvent/detergent, 60 &deg;C heat-treatment, and nanofiltration Overall, immunotherapy with immune IgG antibodies combined with antiviral drugs may be an alternative treatment against COVID-19 until stronger options such as vaccines are available", "title": "Could Intravenous Immunoglobulin Collected from Recovered Coronavirus Patients Protect against COVID-19 and Strengthen the Immune System of New Patients?", "pid": "d4sjferd", "bm25_score": 217.5736083984375}, {"text": "We read with deep interest the report by Tepasse and colleagues1 , concerning two cases of persisting viremia in Covid-19 with fatal outcome. Whilst SARS-CoV-2 infection in the early stages of infection has been well described, less is known about the development of antibodies to SARS-CoV-2, clearance of RNA shedding and clinical outcome of COVID-19.", "title": "Convalescent plasma for persisting Covid-19 following therapeutic lymphocyte depletion: a report of rapid recovery", "pid": "p2226xuz", "bm25_score": 217.5572052001953}, {"text": "We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.", "title": "Antibody responses to SARS-CoV-2 in patients with COVID-19", "pid": "zw1f1s16", "bm25_score": 217.55445861816406}, {"text": "SARS-CoV infection of human results in antigen-specific cellular and humoral immune responses. However, it is critical to determine whether SARS-CoV-specific memory T cells can persist for long periods of time. In this study, we analyzed the cellular immune response from 21 SARS-recovered individuals who had been diagnosed with SARS in 2003 by using ELISA, CBA, ELISpot and multiparameter flow cytometry assays. Our results demonstrated that low levels of specific memory T cell responses to SARS-CoV S, M, E and N peptides were detected in a proportion of SARS-recovered patients, and IFN-γ was the predominant cytokine produced by T cells after stimulation with peptides. Cytometry analysis indicated that the majority of memory CD8(+) T cells produced IFN-γ, whereas memory CD4(+) T cells produced IFN-γ, IL-2 or TNF-α. These results might provide valuable information on the cellular immune response in recovered SARS-CoV patients for the rational design of vaccines against SARS-CoV infection.", "title": "Characterization of SARS-CoV-specific memory T cells from recovered individuals 4 years after infection", "pid": "anaqgzvi", "bm25_score": 217.55203247070312}, {"text": "We report dynamics of seroconversion to SARS-CoV-2 infections detected by IgG ELISA in 177 individuals diagnosed by RT-PCR. Longitudinal analysis identifies 2-7% of individuals who do not seroconvert even weeks after infection. They are younger and less severely affected than seroconverters. Higher antibody responses are associated with symptomatic disease, older age, ethnicity, increased co-morbidity and higher inflammatory markers such as C Reactive Protein. Antibody responses do not decline during follow up almost to 2 months. Serological assays increase understanding of disease severity. Their application in regular surveillance will clarify the duration and protective nature of humoral responses to SARS-CoV.", "title": "Dynamics of IgG seroconversion and pathophysiology of COVID-19 infections", "pid": "pkr3immj", "bm25_score": 217.54238891601562}, {"text": "We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.", "title": "Antibody responses to SARS-CoV-2 in patients with COVID-19.", "pid": "40fvjskj", "bm25_score": 217.47488403320312}, {"text": "A close interaction between the virus SARS-CoV-2 and the immune system of an individual results in a diverse clinical manifestation of the COVID-19 disease While adaptive immune responses are essential for SARS-CoV-2 virus clearance, the innate immune cells, such as macrophages, may contribute, in some cases, to the disease progression Macrophages have shown a significant production of IL-6 suggesting they may contribute to the excessive inflammation in COVID-19 disease Macrophage Activation Syndrome may further explain the high serum levels of CRP, which are normally lacking in viral infections In adaptive immune responses, it has been revealed that cytotoxic CD8+ T cells exhibit functional exhaustion patterns, such as the expression of NKG2A, PD-1, and TIM-3 Since SARS-CoV-2 restrains antigen presentation by downregulating MHC class I and II molecules and, therefore, inhibits the T cell-mediated immune responses, humoral immune responses also play a substantial role Specific IgA response appears to be stronger and more persistent than IgM response Moreover, IgM and IgG antibodies show similar dynamics in COVID-19 disease", "title": "COVID-19 and the immune system", "pid": "p6h7k7ty", "bm25_score": 217.4656524658203}, {"text": "Coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, has rapidly spread to most of countries in the world, threatening the health and lives of many people. Unfortunately, information regarding the immunological characteristics in COVID-19 patients remains limited. Here we collected the blood samples from 18 healthy donors (HD) and 38 COVID-19 patients to analyze changes in the adaptive immune cell populations and phenotypes. In comparison to HD, the lymphocyte percentage was slightly decreased, the percentages of CD4 and CD8 T cells in lymphocytes are similar, whereas B cell percentage increased in COVID-19 patients. T cells, especially CD8 T cells, showed an enhanced expression of late activation marker CD25 and exhaustion marker PD-1. Importantly, SARS-CoV-2 induced an increased percentage of T follicular helpher (Tfh)- and germinal center B-like (GCB-like) cells in the blood. However, the parameters in COVD-19 patients remained unchanged across various age groups. Therefore, we demonstrated that the T and B cells can be activated normally and exhibit functional features. These data provide a clue that the adaptive immunity in most people could be primed to induce a significant immune response against SARS-CoV-2 infection upon receiving standard medical care.", "title": "Analysis of adaptive immune cell populations and phenotypes in the patients infected by SARS-CoV-2", "pid": "zjgswsjj", "bm25_score": 217.45999145507812}, {"text": "COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. T cell response is a critical part of both individual and herd immunity to SARS-CoV-2 and the efficacy of developed vaccines. However neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immune memory are well understood. In this study we use longitudinal high-throughput T cell receptor sequencing to track changes in the T cell repertoire following two mild cases of COVID-19 infection. In both donors we identified SARS-CoV-2-responding CD4+ and CD8+ T cell clones. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones, suggesting the existence of immunodominant epitopes. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain CD4+ clones were detected in the memory fraction at the pre-infection timepoint, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.", "title": "Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection", "pid": "fglyfz8p", "bm25_score": 217.44210815429688}, {"text": "The novel SARS-CoV-2 is a recently emerging virus causing a human pandemic. A great variety of symptoms associated with COVID-19 disease, ranging from mild to severe symptoms, eventually leading to death. Specific SARS-CoV-2 RT-PCR is the standard method to screen symptomatic people; however, asymptomatic subjects and subjects with undetectable viral load escape from the screening, contributing to viral spread. Currently, the lock down imposed by many governments is an important measure to contain the spread, as there is no specific antiviral therapy or a vaccine and the main treatments are supportive. Therefore, there is urgent need to characterize the virus and the viral-mediated responses, in order to develop specific diagnostic and therapeutic tools to prevent viral transmission and efficiently cure COVID-19 patients. Here, we review the current studies on two viral mediated-responses, specifically the cytokine storm occurring in a subset of patients and the antibody response triggered by the infection. Further studies are needed to explore both the dynamics and the mechanisms of the humoral immune response in COVID-19 patients, in order to guide future vaccine design and antibody-based therapies for the management of the disease.", "title": "Humoral Immune Responses in COVID-19 Patients: A Window on the State of the Art", "pid": "3tgvvq4o", "bm25_score": 217.44004821777344}, {"text": "Severe acute respiratory syndrome coronavirus 2 infection causing coronavirus disease 2019 has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS-CoV-2 infection needs to be determined. Here, 26 cases of COVID-19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms and no cases of severe symptoms were found among these patients. A striking feature of some patients is that SARS-CoV-2 could exist in patients who have virus-specific IgG antibodies for a very long period, with one case for up to 36 days. One COVID-19 patient who did not produce any SARS-CoV-2-bound IgG successfully cleared SARS-CoV-2 after 46 days of illness, revealing that without antibody-mediated adaptive immunity, innate immunity may still be powerful enough to eliminate SARS-CoV-2. Overall, this report may provide a basis for further analysis of both innate and adaptive immunity in SARS-CoV-2 clearance, especially in non-severe cases. This study also has implications for understanding the pathogenesis and treatment of SARS-CoV-2.", "title": "Long-term Co-existence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) with Antibody Response in Non-severe Coronavirus Disease 2019 (COVID-19) Patients", "pid": "12edypl7", "bm25_score": 217.42176818847656}, {"text": "Abstract The role of cell-mediated immunity in human SARS-CoV infection is still not well understood. In this study, we found that memory T-cell responses against the spike (S) protein were persistent for more than 1 year after SARS-CoV infection by detecting the production of IFN-γ using ELISA and ELISpot assays. Flow cytometric analysis showed that both CD4+ and CD8+ T cells were involved in cellular responses against SARS-CoV infection. Interestingly, most of SARS-CoV S-specific memory CD4+ T cells were central memory cells expressing CD45RO+ CCR7+ CD62L−. However, the majority of memory CD8+ T cells revealed effector memory phenotype expressing CD45RO− CCR7− CD62L−. Thus, our study provides the evidence that SARS-CoV infection in humans can induce cellular immune response that is persistent for a long period of time. These data may have an important implication in the possibility of designing effective vaccine against SARS-CoV infection, specifically in defining T-cell populations that are implicated in protective immunity.", "title": "Long-lived effector/central memory T-cell responses to severe acute respiratory syndrome coronavirus (SARS-CoV) S antigen in recovered SARS patients", "pid": "yhdj5m0e", "bm25_score": 217.41360473632812}, {"text": "While individuals infected with coronavirus disease 2019 (COVID-19) manifested a broad range in susceptibility and severity to the disease, the pre-existing immune memory of related pathogens can influence the disease outcome. Here, we investigated the potential extent of T cell cross-reactivity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be conferred by other coronaviruses and influenza virus, and generated a map of public and private predicted CD8+ T cell epitopes between coronaviruses. Moreover, to assess the potential risk of self-reactivity and/or diminished T cell response for peptides identical or highly similar to the host, we identified predicted epitopes with high sequence similarity with human proteome. Lastly, we compared predicted epitopes from coronaviruses with epitopes from influenza virus deposited in IEDB to support vaccine development against different virus strains. We believe the comprehensive in silico profile of private and public predicted epitopes across coronaviruses and influenza viruses will facilitate design of vaccines capable of protecting against various viral infections.", "title": "CD8+ T cell cross-reactivity against SARS-CoV-2 conferred by other coronavirus strains and influenza virus", "pid": "x8asawcv", "bm25_score": 217.41236877441406}, {"text": "BACKGROUND: The rapid spread of coronavirus disease 2019 (COVID-19) was declared as an emerging public health threat by the World Health Organization. As various measures have been taken successfully to combat the epidemic caused by SARS-CoV-2, a growing number of fully recovered patients have been discharged from hospitals. However, some of them have relapsed. Little is known about the causes that triggered the relapse. CASE PRESENTATION: We report a case of a 40 years old man who suffered from recurrent pulmonary infection with progression of lesions on chest computed tomography (CT), elevated levels of ferritin and IL2R, reduced lymphocyte count and positive oropharyngeal swab test for SARS-CoV-2 again after 5 days discharge from hospital. The anti-SARS-CoV-2 antibody level of this patient was very low at the time of relapse, suggesting a weak humoral immune response to the virus. Total exon sequencing revealed mutations in TRNT1 gene, which may be responsible for B cell immunodeficiency. Therefore, uncleared SARS-CoV-2 at his first discharge was likely to lead to his recurrence. However, viral superinfection and non-infectious organizing pneumonia could not be completely excluded. CONCLUSION: COVID-19 relapse may occur in a part of discharged patients with low titers of anti-SARS-CoV-2 antibodies. These patients should be maintained in isolation for longer time even after discharge. A more sensitive method to detect SARS-CoV-2 needs to be established and serological testing for specific antibodies may be used as a reference to determine the duration of isolation.", "title": "Recurrent pneumonia in a patient with new coronavirus infection after discharge from hospital for insufficient antibody production: a case report", "pid": "vsh9rdct", "bm25_score": 217.41159057617188}, {"text": "The Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pneumonia. MERS was recently identified as a candidate for vaccine development, but most efforts focus on antibody responses, which are often transient after CoV infections. CoV-specific T cells are generally long-lived, but the virus-specific T cell response has not been addressed in MERS patients. We obtained peripheral blood mononuclear cells and/or sera from 21 MERS survivors. We detected MERS-CoV-specific CD4+ and CD8+ T cell responses in all MERS survivors and demonstrated functionality by measuring cytokine expression after peptide stimulation. Neutralizing (PRNT50) antibody titers measured in vitro predicted serum protective ability in infected mice and correlated with CD4+ but not CD8+ T cell responses; patients with higher PRNT50 and CD4+ T cell responses had longer intensive care unit stays and prolonged virus shedding and required ventilation. Survivors with undetectable MERS-CoV-specific antibody responses mounted CD8+ T cell responses comparable with those of the whole cohort. There were no correlations between age, disease severity, comorbidities, and virus-specific CD8+ T cell responses. In conclusion, measurements of MERS-CoV-specific T cell responses may be useful for predicting prognosis, monitoring vaccine efficacy, and identifying MERS patients with mild disease in epidemiological studies and will complement virus-specific antibody measurements.", "title": "Recovery from the Middle East respiratory syndrome is associated with antibody and T-cell responses.", "pid": "345fmq8h", "bm25_score": 217.41159057617188}, {"text": "We compared levels of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in recovery plasma from 7 completely asymptomatic coronavirus disease patients with those in symptomatic patients in South Korea. We found that serologic diagnostic testing was positive for 71% (5/7) of completely asymptomatic patients, but neutralizing antibody response occurred in all 7 patients.", "title": "Antibody Responses to SARS-CoV-2 at 8 Weeks Postinfection in Asymptomatic Patients", "pid": "cu52j6tq", "bm25_score": 217.4055938720703}, {"text": "BACKGROUND: : SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: : To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: : Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm appears to contribute to the damage in ARDS. IMPLICATIONS: : In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.", "title": "The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic.", "pid": "mpf6lxxr", "bm25_score": 217.395751953125}, {"text": "We compared levels of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in recovery plasma from 7 completely asymptomatic coronavirus disease patients with those in symptomatic patients in South Korea. We found that serologic diagnostic testing was positive for 71% (5/7) of completely asymptomatic patients, but neutralizing antibody response occurred in all 7 patients.", "title": "Antibody Responses to SARS-CoV-2 at 8 Weeks Postinfection in Asymptomatic Patients.", "pid": "q7mm4nwm", "bm25_score": 217.38259887695312}, {"text": "We performed a retrospective study of Covid-19 in people with HIV (PWH). PWH with Covid-19 demonstrated severe lymphopenia and decreased CD4+ T cell counts. Levels of inflammatory markers, including C-reactive protein, fibrinogen, D-dimer, interleukin-6, interleukin-8, and TNF-alpha were commonly elevated. In all, 19/72 hospitalized individuals (26.4%) died and 53 (73.6%) recovered. PWH who died had higher levels of inflammatory markers and more severe lymphopenia than those who recovered. These findings suggest that PWH remain at risk for severe manifestations of Covid-19 despite ART and that those with increased markers of inflammation and immune dysregulation are at risk for worse outcomes.", "title": "Clinical outcomes and immunologic characteristics of Covid-19 in people with HIV", "pid": "qyo9x78w", "bm25_score": 217.35414123535156}, {"text": "A global pandemic of Corona Virus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is ongoing spread. It remains unclear whether the convalescing patients have a risk of reinfection. Rhesus macaques were rechallenged with SARS-CoV-2 during an early recovery phase from initial infection characterized by weight loss, interstitial pneumonia and systemic viral dissemination mainly in respiratory and gastrointestinal tracts. The monkeys rechallenged with the identical SARS-CoV-2 strain have failed to produce detectable viral dissemination, clinical manifestations and histopathological changes. A notably enhanced neutralizing antibody response might contribute the protection of rhesus macaques from the reinfection by SARS-CoV-2. Our results indicated that primary SARS-CoV-2 infection protects from subsequent reinfection. One Sentence Summary Neutralizing antibodies against SARS-CoV-2 might protect rhesus macaques which have undergone an initial infection from reinfection during early recovery days.", "title": "Lack of Reinfection in Rhesus Macaques Infected with SARS-CoV-2", "pid": "q4m2uj6r", "bm25_score": 217.3514404296875}, {"text": "Most patients with COVID-19 lack antibody to SARS-CoV-2 in the first 10 days of illness while the virus drives disease pathogenesis. SARS-CoV-2 antibody deficiency in the setting of a tissue viral burden suggests that using an antibody as a therapeutic agent would augment the antiviral immune response. In this issue of the JCI, Wang and collaborators describe the kinetics of viral load and antibody responses of 23 individuals with COVID-19 with mild and severe disease. The researchers found: 1) individuals with mild and severe disease produced neutralizing IgG to SARS-CoV-2 10 days after disease onset; 2) SARS-CoV-2 persisted longer in those with severe disease; and 3) there was cross-reactivity between antibodies to SARS-CoV-1 and SARS-CoV-2, but only antibodies from patients with COVID-19 neutralized SARS-CoV-2. These observations provide important information on the serological response to SARS-CoV-2 of hospitalized patients with COVID-19 that can inform the use of convalescent plasma therapy.", "title": "SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy", "pid": "tckjc7os", "bm25_score": 217.3429412841797}, {"text": "A close interaction between the virus SARS-CoV-2 and the immune system of an individual results in a diverse clinical manifestation of the COVID-19 disease. While adaptive immune responses are essential for SARS-CoV-2 virus clearance, the innate immune cells, such as macrophages, may contribute, in some cases, to the disease progression. Macrophages have shown a significant production of IL-6 suggesting they may contribute to the excessive inflammation in COVID-19 disease. Macrophage Activation Syndrome may further explain the high serum levels of CRP, which are normally lacking in viral infections. In adaptive immune responses, it has been revealed that cytotoxic CD8+ T cells exhibit functional exhaustion patterns, such as the expression of NKG2A, PD-1, and TIM-3. Since SARS-CoV-2 restrains antigen presentation by downregulating MHC class I and II molecules and, therefore, inhibits the T cell-mediated immune responses, humoral immune responses also play a substantial role. Specific IgA response appears to be stronger and more persistent than IgM response. Moreover, IgM and IgG antibodies show similar dynamics in COVID-19 disease.", "title": "COVID-19 and the immune system.", "pid": "2o3dvi2d", "bm25_score": 217.33860778808594}, {"text": "COVID-19 is a global pandemic caused by the SARS-CoV-2 coronavirus. The T cell response is a critical part of both individual and herd immunity to SARS-CoV-2 and the efficacy of developed vaccines. However neither the dynamics and cross-reactivity of the SARS-CoV-2-specific T cell response nor the diversity of resulting immune memory are well understood. In this study we use longitudinal high-throughput T cell receptor sequencing to track changes in the T cell repertoire following two mild cases of COVID-19 infection. In both donors we identified SARS-CoV-2-responding CD4+ and CD8+ T cell clones. We describe characteristic motifs in TCR sequences of COVID-19-reactive clones, suggesting the existence of immunodominant epitopes. We show that in both donors the majority of infection-reactive clonotypes acquire memory phenotypes. Certain CD4+ clones were detected in the memory fraction at the pre-infection timepoint, suggesting participation of pre-existing cross-reactive memory T cells in the immune response to SARS-CoV-2.", "title": "Longitudinal high-throughput TCR repertoire profiling reveals the dynamics of T cell memory formation after mild COVID-19 infection", "pid": "4akxfetl", "bm25_score": 217.33828735351562}, {"text": "Both cellular and humoral immunities are critically important to control COVID19 infection but little is known about the kinetics of those responses and, in particular, in patients who will go on to develop a severe form of the disease over several weeks. We herein report the first set of data of our prospective cohort study of 90 hospitalized cases. Serological surveys were thoroughly performed over 2 month period by assessing IgG and IgM responses by immunofluorescence, immunoblot, Western blot and conventional ELISA using clinical RUN isolates of SARS-CoV-2 immobilized on 96 well plates. While the IgM and, unexpectedly, the IgG responses were readily detected early during the course of the disease (5-7 days post-first symptoms), our results (n=3-5 and over the full dilution set of the plasma 1/200 to 1/12800) demonstrated a significant decrease (over 2.5-fold) of IgG levels in severe (ICU) hospitalized patients (exemplified in patient 1) by WB and ELISA. In contrast, mild non-ICU patients had a steady and yet robust rise in their specific IgG levels against the virus. Interestingly, both responses (IgM and IgG) were initially against the nucleocapsid (50kDa band on the WB) and spreading to other major viral protein S and domains (S1 and S2. In conclusion, serological testing may be helpful for the diagnosis of patients with negative RT-PCR results and for the identification of asymptomatic cases. Moreover, medical care and protections should be maintained particularly for recovered patients (severe cases) who may remain at risk of relapsing or reinfection. Experiments to ascertain T cell responses but although their kinetics overtime are now highly warranted. All in all, these studies will help to delineate the best routes for vaccination.", "title": "Serological surveys in Reunion Island of the first hospitalized patients revealed that long-lived immunoglobulin G antibodies specific against SARS-CoV2 virus are rapidly vanishing in severe cases", "pid": "4aawkp8p", "bm25_score": 217.31710815429688}, {"text": "Abstract Validation studies of serological antibody tests must be properly designed for clinical, epidemiological and Public Health objectives such as confirmation of suspected COVID-19 cases, certification of seroconversion after infection, and epidemiological surveillance. We evaluated the kinetics of IgM, IgA and IgG SARS-CoV-2 antibodies in COVID-19 patients with confirmed (rRT-PCR) infection. We found that the IgA response appears and grows early, peaks at week 3, and it is stronger and more persistent than the IgM response. Further longitudinal investigations of virus-specific antibodies functions and of their protective efficacy over time are needed.", "title": "IgA-Ab response to spike glycoprotein of SARS-CoV-2 in patients with COVID-19: A longitudinal study", "pid": "kzz4sx1j", "bm25_score": 217.3151397705078}, {"text": "Here we report the clinical features of 25 discharged patients with COVID-19 recovery. Our analysis indicated that there was a significant inverse correlation existed between serum D-Dimer level and the duration of antiviral treatment, while lymphocyte concentration significantly positively correlated with the duration of virus reversal.", "title": "Clinical Characteristics on 25 Discharged Patients with COVID-19 Virus Returning", "pid": "jarnavwl", "bm25_score": 217.30337524414062}, {"text": "Coronavirus disease-2019 (COVID-19) is caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was recently declared as a pandemic by the World Health Organization. In its severe form, the disease is characterized by acute respiratory distress syndrome, and there are no targeted intervention strategies to treat or prevent it. The immune response is thought to both contribute to the pathogenesis of disease and provide protection during its resolution. Thus, understanding the immune response to SARS-CoV-2 is of the utmost importance for developing and testing vaccines and therapeutics. In this review, we discuss the earliest knowledge and hypotheses of the mechanisms of immune pathology in the lung during acute infection as well at the later stages of disease resolution, recovery, and immune memory formation.", "title": "Early Insights into Immune Responses during COVID-19", "pid": "pp71jaau", "bm25_score": 217.30335998535156}, {"text": "T cell reactivity against SARS-CoV-2 was observed in unexposed people; however, the source and clinical relevance of the reactivity remains unknown. It is speculated that this reflects T cell memory to circulating ‘common cold’ coronaviruses. It will be important to define specificities of these T cells and assess their association with COVID-19 disease severity and vaccine responses.", "title": "Pre-existing immunity to SARS-CoV-2: the knowns and unknowns", "pid": "bw6a5gmy", "bm25_score": 217.28778076171875}, {"text": "Understanding the determinants of adaptive immune response to SARS-CoV-2 is critical for fighting the ongoing COVID-19 pandemic. Here we assayed both antibody and T-cell reactivity to SARS-CoV-2 antigens in COVID-19 convalescent patients and healthy donors sampled before and during the pandemic. Our results show that while anti-SARS-CoV-2 antibodies can distinguish convalescent patients from healthy donors, the magnitude of T-cell response was more pronounced in healthy donors sampled during COVID-19 pandemic than in donors sampled before the outbreak. This hints at the possibility that some individuals have encountered the virus but were protected by T-cell cross-reactivity observed. A public and diverse T-cell response was observed for two A*02-restricted SARS-CoV-2 epitopes, revealing a set of T-cell receptor motifs displaying germline-encoded features. Bulk CD4+ and CD8+ T-cell response to SARS-CoV-2 glycoprotein S is characterized by multiple groups of homologous T-cell receptor sequences some of which are shared across multiple donors, indicating the existence of immunodominant epitopes. Overall, our findings indicate that T cells form an efficient response to SARS-CoV-2 and alongside the antibodies can serve as a useful biomarker for surveying SARS-CoV-2 exposure and immunity. We hope that data, including the set of specific T-cell receptors identified in this study can serve as a basis for future developments of SARS-CoV-2 vaccinations and monitoring.", "title": "SARS-CoV-2 epitopes are recognized by a public and diverse repertoire of human T-cell receptors", "pid": "ioihqf0r", "bm25_score": 217.28355407714844}, {"text": "Most patients with COVID-19 lack antibody to SARS-CoV-2 in the first 10 days of illness while the virus drives disease pathogenesis. SARS-CoV-2 antibody deficiency in the setting of a tissue viral burden suggests that using an antibody as a therapeutic agent would augment the antiviral immune response. In this issue of the JCI, Wang and collaborators describe the kinetics of viral load and antibody responses of 23 individuals with COVID-19 with mild and severe disease. The researchers found: 1) individuals with mild and severe disease produced neutralizing IgG to SARS-CoV-2 10 days after disease onset; 2) SARS-CoV-2 persisted longer in those with severe disease; and 3) there was cross-reactivity between antibodies to SARS-CoV-1 and SARS-CoV-2, but only antibodies from patients with COVID-19 neutralized SARS-CoV-2. These observations provide important information on the serological response to SARS-CoV-2 of hospitalized patients with COVID-19 that can inform the use of convalescent plasma therapy.", "title": "SARS-CoV-2 viral load and antibody responses: the case for convalescent plasma therapy.", "pid": "xp09u1tq", "bm25_score": 217.2758026123047}, {"text": "Over the past decade, we have seen an alarming number of high-profile outbreaks of newly emerging and re-emerging viruses. Recent outbreaks of avian influenza viruses, Middle East respiratory syndrome coronaviruses, Zika virus and Ebola virus present great threats to global health. Considering the pivotal role of host T-cell immunity in the alleviation of symptoms and the clearance of viruses in patients, there are three issues to be primarily concerned about T-cell immunity when a new virus emerges: first, does the population possess pre-existing T-cells against the new virus through previous infections of genetically relevant viruses; second, does a proper immune response arise in the patients to provide protection through an immunopathogenic effect; lastly, how long can the virus-specific immune memory persist. Herein, we summarize the current updates on the characteristics of human T-cell immunological responses against recently emerged or re-emerged viruses, and emphasize the necessity for timely investigation on the T-cell features of these viral diseases, which may provide beneficial recommendations for clinical diagnosis and vaccine development.", "title": "Human T-cell immunity against the emerging and re-emerging viruses", "pid": "tp606gp1", "bm25_score": 217.2537078857422}, {"text": "We studied plasma antibody responses of 35 patients about 1 month after SARS-CoV-2 infection. Titers of antibodies binding to the viral nucleocapsid and spike proteins were significantly higher in patients with severe disease. Likewise, mean antibody neutralization titers against SARS-CoV-2 pseudovirus and live virus were higher in the sicker patients, by ~5-fold and ~7-fold, respectively. These findings have important implications for those pursuing plasma therapy, isolation of neutralizing monoclonal antibodies, and determinants of immunity.", "title": "SARS-CoV-2 Neutralizing Antibody Responses Are More Robust in Patients with Severe Disease", "pid": "z4tio66h", "bm25_score": 217.2438201904297}, {"text": "Public health measures are needed to resolve the novel coronavirus disease (COVID-19) pandemic, although a looming economic fallout merits close attention. Early safe reintroduction of immune individuals into the workforce may be essential to protecting the economic welfare of communities. Reverse transcriptase–polymerase chain reaction testing, our primary diagnostic tool to date, has sensitivity and timing concerns, owing to sampling/handling errors, as well as a complex virus–host interaction. Reverse transcriptase–polymerase chain reaction assays do not establish immune status once the virus has been cleared. Targeted serosurveillance for the determination of individuals’ potential for transmissibility, particularly if paired with direct pathogen testing, may aid in “cleared for business” decision-making.", "title": "COVID-19 Serosurveillance May Facilitate Return-to-Work Decisions", "pid": "30k8o31p", "bm25_score": 217.23545837402344}, {"text": "Public health measures are needed to resolve the novel coronavirus disease (COVID-19) pandemic, although a looming economic fallout merits close attention. Early safe reintroduction of immune individuals into the workforce may be essential to protecting the economic welfare of communities. Reverse transcriptase-polymerase chain reaction testing, our primary diagnostic tool to date, has sensitivity and timing concerns, owing to sampling/handling errors, as well as a complex virus-host interaction. Reverse transcriptase-polymerase chain reaction assays do not establish immune status once the virus has been cleared. Targeted serosurveillance for the determination of individuals' potential for transmissibility, particularly if paired with direct pathogen testing, may aid in \"cleared for business\" decision-making.", "title": "COVID-19 Serosurveillance May Facilitate Return-to-Work Decisions", "pid": "npxxm5cz", "bm25_score": 217.23304748535156}, {"text": "RATIONALE A high proportion of influenza infections are asymptomatic. Animal and human challenge studies and observational studies suggest T cells protect against disease among those infected, but the impact of T-cell immunity at the population level is unknown. OBJECTIVES To investigate whether naturally preexisting T-cell responses targeting highly conserved internal influenza proteins could provide cross-protective immunity against pandemic and seasonal influenza. METHODS We quantified influenza A(H3N2) virus-specific T cells in a population cohort during seasonal and pandemic periods between 2006 and 2010. Follow-up included paired serology, symptom reporting, and polymerase chain reaction (PCR) investigation of symptomatic cases. MEASUREMENTS AND MAIN RESULTS A total of 1,414 unvaccinated individuals had baseline T-cell measurements (1,703 participant observation sets). T-cell responses to A(H3N2) virus nucleoprotein (NP) dominated and strongly cross-reacted with A(H1N1)pdm09 NP (P < 0.001) in participants lacking antibody to A(H1N1)pdm09. Comparison of paired preseason and post-season sera (1,431 sets) showed 205 (14%) had evidence of infection based on fourfold influenza antibody titer rises. The presence of NP-specific T cells before exposure to virus correlated with less symptomatic, PCR-positive influenza A (overall adjusted odds ratio, 0.27; 95% confidence interval, 0.11-0.68; P = 0.005, during pandemic [P = 0.047] and seasonal [P = 0.049] periods). Protection was independent of baseline antibodies. Influenza-specific T-cell responses were detected in 43%, indicating a substantial population impact. CONCLUSIONS Naturally occurring cross-protective T-cell immunity protects against symptomatic PCR-confirmed disease in those with evidence of infection and helps to explain why many infections do not cause symptoms. Vaccines stimulating T cells may provide important cross-protective immunity.", "title": "Natural T Cell-mediated Protection against Seasonal and Pandemic Influenza. Results of the Flu Watch Cohort Study.", "pid": "mtm5xocw", "bm25_score": 217.231689453125}, {"text": "Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel strain of coronavirus. Examination of the immune responses of patients who have recovered from SARS should provide important information for design of a safe and effective vaccine. We determined the continuous viral epitopes targeted by antibodies in plasma samples from convalescent SARS patients through biopanning with a vast M13 phage display dodecapeptide library. These epitopes converged to very short peptide fragments, one on each of the structural proteins spike and nucleocapsid and the nonstructural proteins 3a, 9b, and nsp 3. Immunoassays found that most of the patients who had recovered from SARS developed complementary antibodies to the epitope-rich region on the spike S2 protein, indicating that this is an immunodominant site on the viral envelope comprising the spike, matrix, and small envelope glycoproteins. These S2-targeting antibodies were shown to effectively neutralize the coronavirus, indicating that they provided protective immunity to help the patients recover from the viral infection. These results suggest that the SARS coronavirus might have an antigenic profile distinct from those of other human or animal coronaviruses. Due to the tested safety and protective effects of the convalescent-phase serological antibodies, identification of their complementary antigens may enable the design of an epitope-based vaccine to prevent potential antibody-mediated immunopathology.", "title": "B-cell responses in patients who have recovered from severe acute respiratory syndrome target a dominant site in the S2 domain of the surface spike glycoprotein.", "pid": "m16xmyv0", "bm25_score": 217.22869873046875}, {"text": "BACKGROUND: SARS-CoV-2 viral infection causes COVID-19 that can result in severe acute respiratory distress syndrome (ARDS), which can cause significant mortality, leading to concern that immunosuppressive treatments for multiple sclerosis and other disorders have significant risks for both infection and ARDS. OBJECTIVE: To examine the biology that potentially underpins immunity to the SARS-Cov-2 virus and the immunity-induced pathology related to COVID-19 and determine how this impinges on the use of current disease modifying treatments in multiple sclerosis. OBSERVATIONS: Although information about the mechanisms of immunity are scant, it appears that monocyte/macrophages and then CD8 T cells are important in eliminating the SARS-CoV-2 virus. This may be facilitated via anti-viral antibody responses that may prevent re-infection. However, viral escape and infection of leucocytes to promote lymphopenia, apparent CD8 T cell exhaustion coupled with a cytokine storm and vascular pathology appears to contribute to the damage in ARDS. IMPLICATIONS: In contrast to ablative haematopoietic stem cell therapy, most multiple-sclerosis-related disease modifying therapies do not particularly target the innate immune system and few have any major long-term impact on CD8 T cells to limit protection against COVID-19. In addition, few block the formation of immature B cells within lymphoid tissue that will provide antibody-mediated protection from (re)infection. However, adjustments to dosing schedules may help de-risk the chance of infection further and reduce the concerns of people with MS being treated during the COVID-19 pandemic.", "title": "The underpinning biology relating to multiple sclerosis disease modifying treatments during the COVID-19 pandemic", "pid": "j67b1leq", "bm25_score": 217.2216796875}, {"text": "During virus infection B cells are critical for the production of antibodies and protective immunity. Here we show that the human B cell compartment in patients with diagnostically confirmed SARS-CoV-2 and clinical COVID-19 is rapidly altered with the early recruitment of B cells expressing a limited subset of IGHV genes, progressing to a highly polyclonal response of B cells with broader IGHV gene usage and extensive class switching to IgG and IgA subclasses with limited somatic hypermutation in the initial weeks of infection. We identify extensive convergence of antibody sequences across SARS-CoV-2 patients, highlighting stereotyped naïve responses to this virus. Notably, sequence-based detection in COVID-19 patients of convergent B cell clonotypes previously reported in SARS-CoV infection predicts the presence of SARS-CoV/SARS-CoV-2 cross-reactive antibody titers specific for the receptor-binding domain. These findings offer molecular insights into shared features of human B cell responses to SARS-CoV-2 and other zoonotic spillover coronaviruses.", "title": "Human B cell clonal expansion and convergent antibody responses to SARS-CoV-2", "pid": "bv66depf", "bm25_score": 217.21612548828125}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection causing coronavirus disease 2019 (COVID‐19) has spread worldwide. Whether antibodies are important for the adaptive immune responses against SARS‐CoV‐2 infection needs to be determined. Here, 26 cases of COVID‐19 in Jinan, China, were examined and shown to be mild or with common clinical symptoms, and no case of severe symptoms was found among these patients. Strikingly, a subset of these patients had SARS‐CoV‐2 and virus‐specific IgG coexist for an unexpectedly long time, with two cases for up to 50 days. One COVID‐19 patient who did not produce any SARS‐CoV‐2–bound IgG successfully cleared SARS‐CoV‐2 after 46 days of illness, revealing that without antibody‐mediated adaptive immunity, innate immunity alone may still be powerful enough to eliminate SARS‐CoV‐2. This report may provide a basis for further analysis of both innate and adaptive immunity in SARS‐CoV‐2 clearance, especially in nonsevere cases.", "title": "Long‐term coexistence of SARS‐CoV‐2 with antibody response in COVID‐19 patients", "pid": "y6a4u0vh", "bm25_score": 217.2110137939453}, {"text": "The emerging coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has become a global pandemic, and brings formidable challenges to public health, society and the economy worldwide. Currently, the antibody responses against SARS‐CoV‐2 remains largely unknown. We herein estimated the longevity of specific antibodies against SARS‐CoV‐2, and reported that antibodies waned over substantially in COVID‐19 patients after recovery. This article is protected by copyright. All rights reserved.", "title": "Antibody responses against SARS‐CoV‐2 in COVID‐19 patients", "pid": "vuym41xv", "bm25_score": 217.2088623046875}, {"text": "Coronavirus disease-2019 (COVID-19) is caused by the newly emerged virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was recently declared as a pandemic by the World Health Organization. In its severe form, the disease is characterized by acute respiratory distress syndrome, and there are no targeted intervention strategies to treat or prevent it. The immune response is thought to both contribute to the pathogenesis of disease and provide protection during its resolution. Thus, understanding the immune response to SARS-CoV-2 is of the utmost importance for developing and testing vaccines and therapeutics. In this review, we discuss the earliest knowledge and hypotheses of the mechanisms of immune pathology in the lung during acute infection as well at the later stages of disease resolution, recovery, and immune memory formation.", "title": "Early Insights into Immune Responses during COVID-19.", "pid": "1mhxy9hh", "bm25_score": 217.18978881835938}, {"text": "The current pandemic is caused by the SARS-CoV-2 virus and large progress in understanding the pathology of the virus has been made since its emergence in late 2019. Several reports indicate short lasting immunity against endemic coronaviruses, which contrasts repeated reports that biobanked venous blood contains SARS-CoV-2 reactive T cells even before the outbreak in Wuhan. This suggests there exists a preformed T cell memory in individuals not exposed to the pandemic virus. Given the similarity of SARS-CoV-2 to other members of the Coronaviridae family, the endemic coronaviruses appear likely candidates to generate this T cell memory. However, given the apparent poor immunological memory created by the endemic coronaviruses, other immunity against other common pathogens might offer an alternative explanation. Here, we utilize a combination of epitope prediction and similarity to common human pathogens to identify potential sources of the SARS-CoV-2 T cell memory. We find that no common human virus, other than beta-coronaviruses, can explain the pre-existing SARS-CoV-2 reactive T cells in uninfected individuals. Our study suggests OC43 and HKU1 are the most likely pathogens giving rise to SARS-CoV-2 preformed immunity.", "title": "SARS-CoV-2 reactive T cells in uninfected individuals are likely expanded by beta-coronaviruses", "pid": "guzohu7y", "bm25_score": 217.1807861328125}, {"text": "In many parts of the United States, SARS-CoV-2 cases have reached peak infection rates, prompting administrators to create protocols to resume elective cases. As elective procedures and surgeries get scheduled, ASCs must implement some form of widespread testing in order to ensure the safety of both the ASC staff as well as the patients being seen. The CDC recently announced the approval of new serological testing for SARS-CoV-2, a test that can indicate the presence of IgM and IgG antibodies in the serum against viral particles. However, the possibility for reinfection raises questions about the utility of this new serological test, as the presence of IgG may not correspond to long-term immunity. The coronavirus has been known to form escape mutations, which may correspond to reduction in immunoglobulin binding capacity. Patients who develop more robust immune responses with formation of memory CD8+ T-cells and helper CD4+ T-cells will be the most equipped if exposed to the virus, but unfortunately the serology test will not help us in distinguishing those individuals. Given the inherent disadvantages of serological testing, antibody testing alone should not be used when deciding patient care and should be combined with PCR testing.", "title": "Efficacy of Serology Testing in Predicting Reinfection in Patients with SARS-CoV-2.", "pid": "g1dij8ty", "bm25_score": 217.1799774169922}, {"text": "After preliminary trials, the detailed changes in the concentration of specific circulating and local antibodies were followed in 15 volunteers inoculated with coronavirus 229E. Ten of them, who had significantly lower concentrations of pre-existing antibody than the rest, became infected and eight of these developed colds. A limited investigation of circulating lymphocyte populations showed some lymphocytopenia in infected volunteers. In this group, antibody concentrations started to increase 1 week after inoculation and reached a maximum about 1 week later. Thereafter antibody titres slowly declined. Although concentrations were still slightly raised 1 year later, this did not always prevent reinfection when volunteers were then challenged with the homologous virus. However, the period of virus shedding was shorter than before and none developed a cold. All of the uninfected group were infected on re-challenge although they also appeared to show some resistance to disease and in the extent of infection. These results are discussed with reference to natural infections with coronavirus and with other infections, such as rhinovirus infections.", "title": "The time course of the immune response to experimental coronavirus infection of man.", "pid": "dgizpo1z", "bm25_score": 217.17965698242188}, {"text": "Since the first case of COVID-19 was detected in Wuhan, China in December 2019, COVID-19 has become a pandemic causing a global economic and public health emergency. There is no known treatment or vaccine available for COVID-19 to date. Immunotherapy and plasma therapy has been used with satisfactory efficacy over the past two decades in many viral infections like SARS (Systemic Acute Respiratory Syndrome), MERS (Middle East Respiratory Syndrome), and H1N1. Limited data from China show clinical benefit, radiological resolution, reduction in viral loads, and improved survival. Our aim is to create a mathematical model for COVID-19 transmission and then apply various control parameters to see their effects on recovery from COVID-19 disease. We have formulated a system of non-linear ordinary differential equations, calculated basic reproduction R0, and applied five different controls (self-isolation, quarantine, herd immunity, immunotherapy, plasma therapy) to test the effectiveness of control strategy. Control optimality was checked by Lagrangian functions. Numerical simulations and bifurcation analyses were carried out. The study concludes that the COVID-19 outbreak can be controlled up to a significant level three weeks after applying all the control strategies together. These strategies lead to a reduction in hospitalization and a rise in recovery from infection. Immunotherapy is highly effective initially in hospitalized infected individuals however better results were seen in the long term with plasma therapy.", "title": "Modelling the impact of Plasma Therapy and Immunotherapy for Recovery of COVID-19 Infected Individuals", "pid": "a4khopb5", "bm25_score": 217.17840576171875}, {"text": "The immune system protects us from viruses and diseases. It produces an antibody to kill pathogen. This review shows a brief picture about the immune system to protect us from COVID-19. It illustrates the process of the immune system, how it works, and mechanism of the immune system to fight virus. It also provides information on recent COVID-19 treatment and experimental data. Various types of potential challenges are also discussed for the immunes system. At the end, some foods have been suggested and some are discouraged. Physical exercise is also encouraged. This article can be used as a state of the art at this critical moment to the globe for a promising alternative solutions related to the survival of people from coronavirus.", "title": "Immune Response in COVID-19: A Review", "pid": "bqhml1yo", "bm25_score": 217.1765594482422}, {"text": "Convalescing COVID-19 patients mount robust T cell responses against SARS-CoV-2, suggesting an important role for T cells in viral clearance. To date, the phenotypes of SARS-CoV-2-specific T cells remain poorly defined. Using 38-parameter CyTOF, we phenotyped longitudinal specimens of SARS-CoV-2-specific CD4+ and CD8+ T cells from four individuals who recovered from mild COVID-19. SARS-CoV-2-specific CD4+ T cells were exclusively Th1 cells, and predominantly Tcm with phenotypic features of robust helper function. SARS-CoV-2-specific CD8+ T cells were predominantly atypical Temra cells in a state of less terminal differentiation and therefore capable of expansion. Subsets of SARS-CoV-2-specific T cells exhibit features of being long-lived and capable of homeostatic proliferation consistent with their persistence for over two months. Our results suggest that long-lived and robust T cell immunity is generated following natural SARS-CoV-2 infection, and support an important role for SARS-CoV-2-specific T cells in host control of COVID-19.", "title": "SARS-CoV-2-specific T cells exhibit unique features characterized by robust helper function, lack of terminal differentiation, and high proliferative potential", "pid": "lec1kplh", "bm25_score": 217.1747589111328}, {"text": "Clinical manifestations of COVID-19 caused by the novel coronavirus SARS-CoV-2 are associated with age. While children are largely spared from severe respiratory disease, they can present with a SARS-CoV-2-associated multisystem inflammatory syndrome (MIS-C) similar to Kawasaki's disease. Here, we show distinct antibody (Ab) responses in children with MIS-C compared to adults with severe COVID-19 causing acute respiratory distress syndrome (ARDS), and those who recovered from mild disease. There was a reduced breadth and specificity of anti-SARS-CoV-2-specific antibodies in MIS-C patients compared to the COVID patient groups; MIS-C predominantly generated IgG Abs specific for the Spike (S) protein but not for the nucleocapsid (N) protein, while both COVID-19 cohorts had anti-S IgG, IgM and IgA Abs, as well as anti-N IgG Abs. Moreover, MIS-C patients had reduced neutralizing activity compared to COVID-19 cohorts, indicating a reduced protective serological response. These results suggest a distinct infection course and immune response in children and adults who develop severe disease, with implications for optimizing treatments based on symptom and age.", "title": "Antibody responses to SARS-CoV2 are distinct in children with MIS-C compared to adults with COVID-19", "pid": "1bmu7tis", "bm25_score": 217.1676025390625}, {"text": "Validation studies of serological antibody tests must be properly designed for clinical, epidemiological and Public Health objectives such as confirmation of suspected COVID-19 cases, certification of seroconversion after infection, and epidemiological surveillance. We evaluated the kinetics of IgM, IgA and IgG SARS-CoV-2 antibodies in COVID-19 patients with confirmed (rRT-PCR) infection. We found that the IgA response appears and grows early, peaks at week 3, and it is stronger and more persistent than the IgM response. Further longitudinal investigations of virus-specific antibodies functions and of their protective efficacy over time are needed.", "title": "IgA-Ab response to spike glycoprotein of SARS-CoV-2 in patients with COVID-19: A longitudinal study", "pid": "g9ef7e7g", "bm25_score": 217.14883422851562}, {"text": "Coronavirus disease 2019 (COVID-19) has caused over 220,000 deaths so far and is still an ongoing global health problem. However, the immunopathological changes of key types of immune cells during and after virus infection remain unclear. Here, we enriched CD3+ and CD19+ lymphocytes from peripheral blood mononuclear cells of COVID-19 patients (severe patients and recovered patients at early or late stages) and healthy people (SARS-CoV-2 negative) and revealed transcriptional profiles and changes in these lymphocytes by comprehensive single-cell transcriptome and V(D)J recombination analyses. We found that although the T lymphocytes were decreased in the blood of patients with virus infection, the remaining T cells still highly expressed inflammatory genes and persisted for a while after recovery in patients. We also observed the potential transition from effector CD8 T cells to central memory T cells in recovered patients at the late stage. Among B lymphocytes, we analyzed the expansion trajectory of a subtype of plasma cells in severe COVID-19 patients and traced the source as atypical memory B cells (AMBCs). Additional BCR and TCR analyses revealed a high level of clonal expansion in patients with severe COVID-19, especially of B lymphocytes, and the clonally expanded B cells highly expressed genes related to inflammatory responses and lymphocyte activation. V-J gene usage and clonal types of higher frequency in COVID-19 patients were also summarized. Taken together, our results provide crucial insights into the immune response against patients with severe COVID-19 and recovered patients and valuable information for the development of vaccines and therapeutic strategies.", "title": "Single-cell RNA-seq and V(D)J profiling of immune cells in COVID-19 patients", "pid": "yrfcqf4b", "bm25_score": 217.14132690429688}, {"text": "A newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 2019 (COVID-19) across the world. An understanding of the antibody responses to the viral components is very important for diagnosis and vaccine development. We herein estimated the longevity of specific antibodies against SARS-CoV-2, and reported antibodies disappeared in a moderate COVID-19 patient within 3 months after the onset of the symptoms.", "title": "Disappearance of antibodies to SARS-CoV-2 in a Covid-19 patient after recovery", "pid": "lp4uwdm2", "bm25_score": 217.13104248046875}, {"text": "[This corrects the article DOI: 10.1038/s41421-020-0168-9.].", "title": "Author Correction: Immune cell profiling of COVID-19 patients in the recovery stage by single-cell sequencing", "pid": "5qh2inc1", "bm25_score": 217.11534118652344}, {"text": "Background Lymphopenia is a typical symptom in the COVID-19 patients. While millions of patients are clinical recovered, little is known about the immune status of lymphocytes in these individuals. Methods A clinical recovered cohort (CR) of 55 COVID-19 individuals (discharged from hospital 4 to 11 weeks), and 55 age and sex matched healthy donors cohort (HD) were recruited. Detailed analysis on phenotype of the lymphocytes in peripheral blood mononuclear cells (PBMCs) was performed by flow cytometry. Findings Compared with cohort HD, the CD8+ T cells in cohort CR had higher Teff and Tem, but lower Tc1 (IFN-{gamma}+), Tc2 (IL-4+) and Tc17 (IL-17A+) frequencies. The CD4+ T cells of CR had decreased frequency, especially on the Tcm subset. Moreover, CD4+ T cells of CR expressed lower PD-1 and had lower frequencies of Th1 (IFN-{gamma}+), Th2 (IL-4+), Th17 (IL-17A+) as well as circulating Tfh (CXCR5+PD-1+). Accordingly, isotype-switched memory B cell (IgM-CD20hi) in CR had significantly lower proportion in B cells, though level of activation marker CD71 elevated. For CD3-HLA-DRlo lymphocytes of CR, besides levels of IFN-{gamma}, Granzyme B and T-bet were lower, the correlation between T-bet and IFN-{gamma} became irrelevant. In addition, taken into account of discharged days, all the lowered function associated phenotypes showed no recovery tendency within whole observation period. Interpretation The CR COVID-19 individuals still showed remarkable phenotypic alterations in lymphocytes after clinical recovery 4 to 11 weeks. This suggests SARS-CoV-2 infection imprints profoundly on lymphocytes and results in long-lasting potential dysfunctions.", "title": "Broad phenotypic alterations and potential dysfunctions of lymphocytes in COVID-19 recovered individuals", "pid": "avhxj8jk", "bm25_score": 217.11102294921875}, {"text": "Seroconversion appeared early after COVID-19 onset, and convalescent sera therapy benefit some critical patients. However, neutralizing antibody (nAb) in convalescents is largely unknown. We found that 97.01% (65/67) of COVID-19 convalescents maintained IgG antibodies with high binding and avidity to SARS-CoV-2 spike subunits S1 and S2, and 95.52% (64/67) had neutralization activity against SARS-CoV-2 pesudovirus, one month after discharge (median ID50, 2.75; IQR, 2.34-3.08). Some sera exhibited cross-neutralization against SARS-CoV (76.12%), MERS-CoV (17.91%), or both (10.45%). Interestingly, individuals recovered from severe disease (severe group) had nAbs with binding and neutralization titers higher than non-severe group. Severe group appeared a rapid increase of lymphocytes and a high proportion of circulating CXCR3+ Tfh cells. Interestingly, the later were spike-specific and positively correlated with SARS-CoV-2 nAb titers. All subjects had no autoimmunity. Our findings provide novel insights into nAb responses in COVID-19 convalescents and facilitate treatment and vaccine development for SARS-CoV-2 infection.", "title": "Cross-reactivity of neutralizing antibody and its correlation with circulating T follicular cells in recovered COVID-19 individuals", "pid": "70jg65o2", "bm25_score": 217.10682678222656}, {"text": "BACKGROUND: The long-term pulmonary function and related physiological characteristics of COVID-19 survivors have not been studied in depth, thus many aspects are not understood. METHODS: COVID-19 survivors were recruited for high resolution computed tomography (HRCT) of the thorax, lung function and serum levels of SARS-CoV-2 IgG antibody tests 3 months after discharge. The relationship between the clinical characteristics and the pulmonary function or CT scores were investigated. FINDINGS: Fifty-five recovered patients participated in this study. SARS-CoV-2 infection related symptoms were detected in 35 of them and different degrees of radiological abnormalities were detected in 39 patients. Urea nitrogen concentration at admission was associated with the presence of CT abnormalities (P = 0.046, OR 7.149, 95% CI 1.038 to 49.216). Lung function abnormalities were detected in 14 patients and the measurement of D-dimer levels at admission may be useful for prediction of impaired diffusion defect (P = 0.031, OR 1.066, 95% CI 1.006 to 1.129). Of all the subjects, 47 of 55 patients tested positive for SARS-CoV-2 IgG in serum, among which the generation of Immunoglobulin G (IgG) antibody in female patients was stronger than male patients in infection rehabilitation phase. INTERPRETATION: Radiological and physiological abnormalities were still found in a considerable proportion of COVID-19 survivors without critical cases 3 months after discharge. Higher level of D-dimer on admission could effectively predict impaired DLCO after 3 months discharge. It is necessary to follow up the COVID-19 patients to appropriately manage any persistent or emerging long-term sequelae. FUNDING: Key Scientific Research Projects of Henan Higher Education Institutions", "title": "Follow-up study of the pulmonary function and related physiological characteristics of COVID-19 survivors three months after recovery", "pid": "9cnuxusj", "bm25_score": 217.10464477539062}, {"text": "The intriguing aspects of SARS-CoV-2 virus are the high rate of spread and rapid progression of pneumonitis. Confronted with thousands of deaths daily worldwide, we have to build quickly the rationale behind the treatment, taking advantage from past analogues. When a new virus strikes, T-cell receptor (TCR) gamma/delta cells are in the first line of defence, activated by stress molecules and recognising some epitopes in a process that is major histocompatibility complex (MHC) independent but still specific, e.g. cytomegalovirus (CMV), as well as participating in the regulatory mechanism - both characteristics are useful in fighting SARS-CoV-2. The fatalities are mostly due to pneumonitis, in the course of which an overwhelming inflammatory process impairs blood oxygenation, calling for artificial ventilation. In fatal COVID-19 cases the balance between the immune response and the inflammatory outcome fails, due to which the patients at risk, mostly aged, have higher levels of anti-SARS-CoV-2 antibodies and an enhanced inflammatory process in the lung. Apparently there is no feedback control over the antibody production. The investigational use of convalescent plasma, providing antibodies taken from patients who have recovered, was shown to be effective, likely through exerting idiotype associated negative control of antibody production. Similarly, the use of mesenchymal stem cells (MSC) may assist the body regulatory mechanisms, knowing the anti-inflammatory potential of these cells. The use of these two immunotherapeutic tools is understandable on the grounds of basic immunology, whose knowledge may direct the medical community in efforts to fight the virus.", "title": "Ability of the immune system to fight viruses highlighted by cytometry and TCR clonotype assessments: lessons taken prior to COVID-19 virus pandemic outbreak.", "pid": "euzh18tq", "bm25_score": 217.09007263183594}, {"text": "In the ongoing pandemic of coronavirus disease 2019 (COVID-19), the novel virus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is infecting a naïve population. The innate immunity of the infected patient is unable to mount an effective defense, resulting in a severe illness with substantial morbidity and mortality. As most treatment modalities including antivirals and anti-inflammatory agents are mostly ineffective, an immunological approach is needed. The mechanism of innate immunity to this viral illness is not fully understood. Passive immunity becomes an important avenue for the management of these patients. In this article, the immune responses of COVID-19 patients are reviewed. As SARS-CoV-2 has many characteristics in common with two other viruses, SARS-CoV that cause severe acute respiratory syndrome (SARS) and MERS-CoV (Middle East respiratory syndrome coronavirus) that causes Middle East respiratory syndrome (MERS), the experiences learned from the use of passive immunity in treatment can be applied to COVID-19. The immune response includes the appearance of immunoglobulin M followed by immunoglobulin G and neutralizing antibodies. Convalescent plasma obtained from patients recovered from the illness with high titers of neutralizing antibodies was successful in treating many COVID-19 patients. The factors that determine responses as compared with those seen in SARS and MERS are also reviewed. As there are no approved vaccines against all three viruses, it remains a challenge in the ongoing development for an effective vaccine for COVID-19.", "title": "Passive Immunity for Coronavirus Disease 2019: A Commentary on Therapeutic Aspects Including Convalescent Plasma.", "pid": "y8fmls6v", "bm25_score": 217.0795135498047}, {"text": "Background: The efficacy of the humoral and cellular immunity determines the outcome of viral infections. An appropriate immune response mediates protection, whereas an overwhelming immune response has been associated with immune-mediated pathogenesis in viral infections. The current study explored the general and SARS-CoV-2 specific cellular and humoral immune status in patients with different COVID-19 severities. Methods: In this prospective study, we included 53 patients with moderate, severe, and critical COVID-19 manifestations comparing their quantitative, phenotypic, and functional characteristics of circulating immune cells, SARS-CoV-2 antigen specific T-cells, and humoral immunity. Results: Significantly diminished frequencies of CD8+T-cells, CD4+ and CD8+T-cell subsets with activated differentiated memory/effector phenotype and migratory capacity were found in circulation in patients with severe and/or critical COVID-19 as compared to patients with moderate disease. Importantly, the improvement of the clinical courses from severe to moderate was accompanied by an improvement in the T-cell subset alterations. Furthermore, we surprisingly observed a detectable SARS-CoV-2-reactive T-cell response in all three groups after stimulation with SARS-CoV-2 S-protein overlapping peptide pool already at the first visit. Of note, patients with a critical COVID-19 demonstrated a stronger response of SARS-CoV-2-reactive T-cells producing Th1 associated inflammatory cytokines. Furthermore, clear correlation between antibody titers and SARS-CoV-2-reactive CD4+ frequencies underscore the role of specific immunity in disease progression. Conclusion: Our data demonstrate that depletion of activated memory phenotype circulating T-cells and a strong SARS-CoV-2-specific cellular and humoral immunity are associated with COVID-19 disease severity. This counter-intuitive finding may have important implications for diagnostic, therapeutic and prophylactic COVID-19 management.", "title": "A possible role of immunopathogenesis in COVID-19 progression", "pid": "in91dr4g", "bm25_score": 217.06959533691406}]}
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Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins. Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in a Phase 2 clinical trial with a trajectory towards Phase 3 efficacy evaluation.", "title": "SARS-CoV-2 mRNA Vaccine Development Enabled by Prototype Pathogen Preparedness", "pid": "1v0f2dtx", "bm25_score": 221.93682861328125}, {"text": "SARS-CoV-2 has rapidly become a pandemic worldwide; therefore, an effective vaccine is urgently needed. Recently, messenger RNAs (mRNAs) have emerged as a promising platform for vaccination. Here, we systematically investigated the untranslated regions (UTRs) of mRNAs in order to enhance protein production. Through a comprehensive analysis of endogenous gene expression and de novo design of UTRs, we identified the optimal combination of 5’ and 3’ UTR, termed as NASAR, which was five to ten-fold more efficient than the tested endogenous UTRs. More importantly, NASAR mRNAs delivered by lipid-derived nanoparticles showed dramatic expression of potential SARS-CoV-2 antigens both in vitro and in vivo. These NASAR mRNAs merit further development as alternative SARS-CoV-2 vaccines.", "title": "Leveraging mRNAs sequences to express SARS-CoV-2 antigens in vivo", "pid": "aju2nr9x", "bm25_score": 221.3359375}, {"text": "", "title": "mRNA Vaccines: Possible Tools to Combat SARS-CoV-2", "pid": "6emy92i5", "bm25_score": 221.0347442626953}, {"text": "", "title": "Preclinical data from SARS-CoV-2 mRNA vaccine", "pid": "bchcy4hn", "bm25_score": 220.80552673339844}, {"text": "The first outbreak of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) occurred in Wuhan, Hubei Province, China, in late 2019. The subsequent COVID-19 pandemic rapidly affected the health and economy of the world. The global approach to the pandemic was to isolate populations to reduce the spread of this deadly virus while vaccines began to be developed. In March 2020, the first phase I clinical trial of a novel lipid nanoparticle (LNP)-encapsulated mRNA-based vaccine, mRNA-1273, which encodes the spike protein (S protein) of SARS-CoV-2, began in the United States (US). The production of mRNA-based vaccines is a promising recent development in the production of vaccines. However, there remain significant challenges in the development and testing of vaccines as rapidly as possible to control COVID-19, which requires international collaboration. This review aims to describe the background to the rationale for the development of mRNA-based SARS-CoV-2 vaccines and the current status of the mRNA-1273 vaccine.", "title": "An Evidence Based Perspective on mRNA-SARS-CoV-2 Vaccine Development", "pid": "xbze5s3c", "bm25_score": 220.77438354492188}, {"text": "SARS-CoV-2 is the deadly virus behind COVID-19, the disease that went on to ravage the world and caused the biggest pandemic 21st century has witnessed so far. On the face of ongoing death and destruction, the urgent need for the discovery of a vaccine against the virus is paramount. This study resorted to the emerging discipline of immunoinformatics in order to design a multi-epitope mRNA vaccine against the spike glycoprotein of SARS-CoV-2. Various immunoinformatics tools were utilized to predict T and B lymphocyte epitopes. The epitopes were channeled through a filtering pipeline comprised of antigenicity, toxicity, allergenicity, and cytokine inducibility evaluation with the goal of selecting epitopes capable of generating both T and B cell-mediated immune responses. Molecular docking simulation between the epitopes and their corresponding MHC molecules was carried out. 13 epitopes, a highly immunogenic adjuvant, elements for proper sub-cellular trafficking, a secretion booster, and appropriate linkers were combined for constructing the vaccine. The vaccine was found to be antigenic, almost neutral at physiological pH, non-toxic, non-allergenic, capable of generating a robust immune response and had a decent worldwide population coverage. Based on these parameters, this design can be considered a promising choice for a vaccine against SARS-CoV-2.", "title": "Designing a novel mRNA vaccine against SARS-CoV-2: An immunoinformatics approach", "pid": "q77da2y3", "bm25_score": 220.12705993652344}, {"text": "The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-γ production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.", "title": "Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice", "pid": "oiu80002", "bm25_score": 219.50123596191406}, {"text": "The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle (LNP) as a vaccine. We observe remarkably high and dose-dependent SARS-CoV-2 specific antibody titers in mouse sera, as well as robust neutralization of both a pseudo-virus and wild-type virus. Upon further characterization we find that the neutralization is proportional to the quantity of specific IgG and of higher magnitude than recovered COVID-19 patients. saRNA LNP immunizations induce a Th1-biased response in mice, and there is no antibody-dependent enhancement (ADE) observed. Finally, we observe high cellular responses, as characterized by IFN-γ production, upon re-stimulation with SARS-CoV-2 peptides. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.", "title": "Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine candidate induces high neutralizing antibody titers in mice", "pid": "1c15qxb8", "bm25_score": 219.476318359375}, {"text": "The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log(10) reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.", "title": "DNA vaccine protection against SARS-CoV-2 in rhesus macaques", "pid": "w9zyshzb", "bm25_score": 219.419921875}, {"text": "The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.", "title": "DNA vaccine protection against SARS-CoV-2 in rhesus macaques", "pid": "pfjq2m42", "bm25_score": 219.4075927734375}, {"text": "The ongoing COVID-19 pandemic, caused by infection with SARS-CoV-2, is having a dramatic and deleterious impact on health services and the global economy. Grim public health statistics highlight the need for vaccines that can rapidly confer protection after a single dose and be manufactured using components suitable for scale-up and efficient distribution. In response, we have rapidly developed repRNA-CoV2S, a stable and highly immunogenic vaccine candidate comprised of an RNA replicon formulated with a novel Lipid InOrganic Nanoparticle (LION) designed to enhance vaccine stability, delivery and immunogenicity. We show that intramuscular injection of LION/repRNA-CoV2S elicits robust anti-SARS-CoV-2 spike protein IgG antibody isotypes indicative of a Type 1 T helper response as well as potent T cell responses in mice. Importantly, a single-dose administration in nonhuman primates elicited antibody responses that potently neutralized SARS-CoV-2. These data support further development of LION/repRNA-CoV2S as a vaccine candidate for prophylactic protection from SARS-CoV-2 infection.", "title": "Single-dose replicating RNA vaccine induces neutralizing antibodies against SARS-CoV-2 in nonhuman primates", "pid": "wzv8n34v", "bm25_score": 219.1698760986328}, {"text": "The coronavirus family member, SARS-CoV-2 has been identified as the causal agent for the pandemic viral pneumonia disease, COVID-19. At this time, no vaccine is available to control further dissemination of the disease. We have previously engineered a synthetic DNA vaccine targeting the MERS coronavirus Spike (S) protein, the major surface antigen of coronaviruses, which is currently in clinical study. Here we build on this prior experience to generate a synthetic DNA-based vaccine candidate targeting SARS-CoV-2 S protein. The engineered construct, INO-4800, results in robust expression of the S protein in vitro. Following immunization of mice and guinea pigs with INO-4800 we measure antigen-specific T cell responses, functional antibodies which neutralize the SARS-CoV-2 infection and block Spike protein binding to the ACE2 receptor, and biodistribution of SARS-CoV-2 targeting antibodies to the lungs. This preliminary dataset identifies INO-4800 as a potential COVID-19 vaccine candidate, supporting further translational study.", "title": "Immunogenicity of a DNA vaccine candidate for COVID-19", "pid": "f5xs0tv2", "bm25_score": 219.13824462890625}, {"text": "Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for which a vaccine is urgently needed to control its spreading. To facilitate the representation of a native-like immunogen without being infectious, here, we reported a SARS-CoV-2 vaccine candidate (designated ShaCoVacc) by incorporating spike-encoding mRNA inside and decorating spike protein on the surface of the virus simulating particles (VSPs) derived from lentiviral particles. We characterized the mRNA copy number, glycosylation status, transduction efficiency, and innate immune property of the new vaccine platform. Importantly, we showed the ShaCoVacc induced strong spike-specific humoral immune responses and potent neutralizing activities by a single injection. Additionally, we disclosed the epitopes of spike-specific antibodies using peptide microarray and revealed epitopes susceptible to specific neutralizing antibodies. These results support further development of ShaCoVacc as a candidate vaccine for COVID-19 and VSP may serve as a new vaccine platform for emerging infectious diseases.", "title": "A single dose SARS-CoV-2 simulating particle vaccine induces potent neutralizing activities", "pid": "ptvsie6m", "bm25_score": 219.12733459472656}, {"text": "The spread of the SARS-CoV-2 into a global pandemic within a few months of onset motivates the development of a rapidly scalable vaccine. Here, we present a self-amplifying RNA encoding the SARS-CoV-2 spike protein encapsulated within a lipid nanoparticle as a vaccine and demonstrate induction of robust neutralization of a pseudo-virus, proportional to quantity of specific IgG and of higher quantities than recovered COVID-19 patients. These data provide insight into the vaccine design and evaluation of immunogenicity to enable rapid translation to the clinic.", "title": "Self-amplifying RNA SARS-CoV-2 lipid nanoparticle vaccine induces equivalent preclinical antibody titers and viral neutralization to recovered COVID-19 patients", "pid": "6ubk3rv7", "bm25_score": 218.88319396972656}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused millions of human infections and hundreds of thousands of deaths. Accordingly, an effective vaccine is of critical importance in mitigating coronavirus induced disease 2019 (COVID-19) and curtailing the pandemic. We developed a replication-competent vesicular stomatitis virus (VSV)-based vaccine by introducing a modified form of the SARS-CoV-2 spike gene in place of the native glycoprotein gene (VSV-eGFP-SARS-CoV-2). Immunization of mice with VSV-eGFP-SARS-CoV-2 elicits high titers of antibodies that neutralize SARS-CoV-2 infection and target the receptor binding domain that engages human angiotensin converting enzyme-2 (ACE2). Upon challenge with a human isolate of SARS-CoV-2, mice expressing human ACE2 and immunized with VSV-eGFP-SARS-CoV-2 show profoundly reduced viral infection and inflammation in the lung indicating protection against pneumonia. Finally, passive transfer of sera from VSV-eGFP-SARS-CoV-2-immunized animals protects naïve mice from SARS-CoV-2 challenge. These data support development of VSV-eGFP-SARS-CoV-2 as an attenuated, replication-competent vaccine against SARS-CoV-2.", "title": "Replication-competent vesicular stomatitis virus vaccine vector protects against SARS-CoV-2-mediated pathogenesis", "pid": "enli9n34", "bm25_score": 218.8170928955078}, {"text": "As the SARS-CoV-2 pandemic is rapidly progressing, the need for the development of an effective vaccine is critical. A promising approach for vaccine development is to generate, through codon pair deoptimization, an attenuated virus. This approach carries the advantage that it only requires limited knowledge specific to the virus in question, other than its genome sequence. Therefore, it is well suited for emerging viruses for which we may not have extensive data. We performed comprehensive in silico analyses of several features of SARS-CoV-2 genomic sequence (e.g., codon usage, codon pair usage, dinucleotide/junction dinucleotide usage, RNA structure around the frameshift region) in comparison with other members of the coronaviridae family of viruses, the overall human genome, and the transcriptome of specific human tissues such as lung, which are primarily targeted by the virus. Our analysis identified the spike (S) and nucleocapsid (N) proteins as promising targets for deoptimization and suggests a roadmap for SARS-CoV-2 vaccine development, which can be generalizable to other viruses.", "title": "Sequence analysis of SARS-CoV-2 genome reveals features important for vaccine design", "pid": "2fn25l6m", "bm25_score": 218.70994567871094}, {"text": "SARS-CoV-2 is spreading globally at a rapid pace. To contain its spread and prevent further fatalities, the development of a vaccine against SARS-CoV-2 is an urgent prerequisite. Thus, in this article, by utilizing the in silico approach, a vaccine candidate for SARS-CoV-2 has been proposed. Moreover, the effectiveness and safety measures of our proposed epitopic vaccine candidate have been evaluated by in silico tools and servers (AllerTOP and AllergenFP servers). We observed that the vaccine candidate has no allergenicity and successfully combined with Toll-like receptor (TLR) protein to elicit an inflammatory immune response. Stable, functional mobility of the vaccine-TLR protein binding interface was confirmed by the Normal Mode Analysis. The in silico cloning model demonstrated the efficacy of the construct vaccine along with the identified epitopes against SARS-CoV-2. Taken together, our proposed in silico vaccine candidate has potent efficacy against COVID-19 infection, and successive research work might validate its effectiveness in in vitro and in vivo models.", "title": "A SARS-CoV-2 vaccine candidate: In silico cloning and validation", "pid": "du2zxq96", "bm25_score": 218.6836395263672}, {"text": "Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.", "title": "Development of a Synthetic Poxvirus-Based SARS-CoV-2 Vaccine", "pid": "nper7qes", "bm25_score": 218.65640258789062}, {"text": "Abstract The SARS-CoV spike glycoprotein (S) is the main target of the protective immune response in humans and animal models of SARS. Here, we demonstrated that efficient expression of S from the wild-type spike gene in cultured cells required the use of improved plasmid vectors containing donor and acceptor splice sites, as well as heterologous viral RNA export elements, such as the CTE of Mazon-Pfizer monkey virus or the PRE of Woodchuck hepatitis virus (WPRE). The presence of both splice sites and WPRE markedly improved the immunogenicity of S-based DNA vaccines against SARS. Upon immunization of mice with low doses (2 μg) of naked DNA, only intron and WPRE-containing vectors could induce neutralizing anti-S antibodies and provide protection against challenge with SARS-CoV. Our observations are likely to be useful for the construction of plasmid and viral vectors designed for optimal expression of intronless genes derived from cytoplasmic RNA viruses.", "title": "Heterologous viral RNA export elements improve expression of severe acute respiratory syndrome (SARS) coronavirus spike protein and protective efficacy of DNA vaccines against SARS", "pid": "7del8d2p", "bm25_score": 218.5836944580078}, {"text": "The outbreak of 2019-novel coronavirus disease (COVID-19) that is caused by SARS-CoV-2 has spread rapidly in China, and has developed to be a Public Health Emergency of International Concern. However, no specific antiviral treatments or vaccines are available yet. This work aims to share strategies and candidate antigens to develop safe and effective vaccines against SARS-CoV-2.", "title": "The outbreak of SARS-CoV-2 pneumonia calls for viral vaccines", "pid": "zn182czp", "bm25_score": 218.56919860839844}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. There are currently no SARS-CoV-2-specific treatments or vaccines available due to the novelty of the virus. Hence, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against SARS-CoV-2 strains. Three immunizations using two different doses (3 μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support clinical development of SARS-CoV-2 vaccines for humans.", "title": "Development of an inactivated vaccine candidate for SARS-CoV-2", "pid": "f5s0ntps", "bm25_score": 218.54006958007812}, {"text": "The 2019-novel coronavirus disease (COVID-19) is caused by SARS-CoV-2 is transmitted from human to human has recently reported in China. Now COVID-19 has been spread all over the world and declared epidemics by WHO. It has caused a Public Health Emergency of International Concern. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Due to the rapid increase of SARS-CoV-2 infections and unavailability of antiviral therapeutic agents, developing an effective SAR-CoV-2 vaccine is urgently required. SARS-CoV-2 which is genetically similar to SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV) is an enveloped, single and positive-stranded RNA virus with a genome comprising 29,891 nucleotides, which encode the 12 putative open reading frames responsible for the synthesis of viral structural and nonstructural proteins which are very similar to SARS-CoV and MERS-CoV proteins. In this review we have summarized various vaccine candidates i.e., nucleotide, subunit and vector based as well as attenuated and inactivated forms, which have already been demonstrated their prophylactic efficacy against MERS-CoV and SARS-CoV, so these candidates could be used as a potential tool for the development of a safe and effective vaccine against SARS-CoV-2.", "title": "Vaccination strategies to combat novel corona virus SARS-CoV-2", "pid": "eq2ahtlc", "bm25_score": 218.523681640625}, {"text": "The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in an unprecedented public health crisis. Because of the novelty of the virus, there are currently no SARS-CoV-2-specific treatments or vaccines available. Therefore, rapid development of effective vaccines against SARS-CoV-2 are urgently needed. Here, we developed a pilot-scale production of PiCoVacc, a purified inactivated SARS-CoV-2 virus vaccine candidate, which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats, and nonhuman primates. These antibodies neutralized 10 representative SARS-CoV-2 strains, suggesting a possible broader neutralizing ability against other strains. Three immunizations using two different doses, 3 or 6 micrograms per dose, provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without observable antibody-dependent enhancement of infection. These data support the clinical development and testing of PiCoVacc for use in humans.", "title": "Development of an inactivated vaccine candidate for SARS-CoV-2", "pid": "5bftuzw5", "bm25_score": 218.46424865722656}, {"text": "SARS-CoV-2, the causal agent of COVID-19, first emerged in late 2019 in China. It has since infected more than 870,000 individuals and caused more than 43,000 deaths globally. Here, we discuss therapeutic and prophylactic interventions for SARS-CoV-2 with a focus on vaccine development and its challenges. Vaccines are being rapidly developed but will likely come too late to affect the first wave of a potential pandemic. Nevertheless, critical lessons can be learned for the development of vaccines against rapidly emerging viruses. Importantly, SARS-CoV-2 vaccines will be essential to reducing morbidity and mortality if the virus establishes itself in the population.", "title": "SARS-CoV-2 Vaccines: Status Report", "pid": "7yq8zqxq", "bm25_score": 218.41017150878906}, {"text": "The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) caused an ongoing unprecedented global public health crises of coronavirus disease in 2019 (CoVID-19). The precipitously increased death rates, its impact on livelihood and trembling economies warrant the urgent development of SARS-CoV-2 vaccine which would be safe, efficacious and scalable. Owing to unavailability of the vaccine, we propose a de novo synthesised avian orthoavulavirus 1 (AOaV-1)-based topical respiratory vaccine candidate against CoVID-19. Avirulent strain of Newcastle disease virus, proto-type virus of AOaV-1, was engineered to express full length spike (S) glycoprotein which is highly neutralizing and major protective antigen of the SARS-CoV-2. Broad-scale in vitro characterization of recombinant vaccine candidate demonstrated efficient co-expression of the hemagglutinin-neuraminidase (HN) of AOaV-1 and S protein of SARS-CoV-2, and comparable replication kinetics were observed in cell culture model. The recombinant vaccine candidate virus actively replicated and spread within cells independently of exogenous trypsin. Interestingly, incorporation of S protein of SARS-CoV-2 into the recombinant AOaV-1 particles attributed the sensitivity to anti-SARS-CoV-2 antiserum and more prominently to anti-AOaV-1 antiserum. Finally, our results demonstrated that the recombinant vaccine vector stably expressed S protein after multiple propagation in chicken embryonated eggs, and this expression did not significantly impact the in vitro growth characteristics of the recombinant. Taken together, the presented respiratory vaccine candidate is highly attenuated in primates per se, safe and lacking pre-existing immunity in human, and carries the potential for accelerated vaccine development against CoVID-19 for clinical studies.", "title": "A Scalable Topical Vectored Vaccine Candidate Against SARS-CoV-2", "pid": "v9ndmjzm", "bm25_score": 218.39064025878906}, {"text": "Summary Here we propose a SARS-CoV-2 vaccine design concept based on identification of highly conserved regions of the viral genome and newly acquired adaptations, both predicted to generate epitopes presented on MHC class I and II across the vast majority of the population. We further prioritize genomic regions that generate highly dissimilar peptides from the human proteome, and are also predicted to produce B cell epitopes. We propose sixty-five 33mer peptide sequences, a subset of which can be tested using DNA or mRNA delivery strategies. These include peptides that are contained within evolutionarily divergent regions of the spike protein reported to increase infectivity through increased binding to the ACE2 receptor and within a newly evolved furin cleavage site thought to increase membrane fusion. Validation and implementation of this vaccine concept could specifically target specific vulnerabilities of SARS-CoV-2 and should engage a robust adaptive immune response in the vast majority of the population.", "title": "Identification of SARS-CoV-2 Vaccine Epitopes Predicted to Induce Long-term Population-Scale Immunity", "pid": "4ab3d00h", "bm25_score": 218.3799285888672}, {"text": "Abstract A novel approach modifying cells to express viral markers to elicit protective immunity responses (decoy cellular vaccination) in the prevention of COVID-19 disease is currently being explored. Our approach entails utilizing SARS-CoV-2 Spike antigen-expressing, non-replicating cells as carriers and presenters of immunogenic antigens, so called “I-cells”. By using irradiated cells as presenting vehicles of SARS-CoV-2 viral antigens(s) in a cellular context, these presented viral proteins can be recognized by the host immune system, thus, an efficient protective immune response might be elicited. Another advantage of this strategy is that the manufacturing process is scalable and yields uniform cell products allowing for “off-the-shelf” frozen supply availability. To prevent engraftment and proliferation of the cells after administration, the cells will be irradiated post-harvesting abolishing in vivo replication potential. Specifically, immunoreactive Spike-1 proteins from SARS-CoV-2 are expressed on the surface of irradiated target I-cells. Utilizing this innovative strategy, these viral antigen-displaying decoy cells will be developed as a vaccine to protect against COVID-19 disease.", "title": "Novel decoy cellular vaccine strategy utilizing transgenic antigen-expressing cells as immune presenter and adjuvant in vaccine prototype against SARS-CoV-2 virus", "pid": "2kwfcgz9", "bm25_score": 218.37786865234375}, {"text": "The COVID-19 pandemic caused by SARS-CoV-2 has brought about an unprecedented crisis, taking a heavy toll on human health, lives as well as the global economy. There are no SARS-CoV-2-specific treatments or vaccines available due to the novelty of this virus. Hence, rapid development of effective vaccines against SARS-CoV-2 is urgently needed. Here we developed a pilot-scale production of a purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc), which induced SARS-CoV-2-specific neutralizing antibodies in mice, rats and non-human primates. These antibodies potently neutralized 10 representative SARS-CoV-2 strains, indicative of a possible broader neutralizing ability against SARS-CoV-2 strains circulating worldwide. Immunization with two different doses (3μg or 6 μg per dose) provided partial or complete protection in macaques against SARS-CoV-2 challenge, respectively, without any antibody-dependent enhancement of infection. Systematic evaluation of PiCoVacc via monitoring clinical signs, hematological and biochemical index, and histophathological analysis in macaques suggests that it is safe. These data support the rapid clinical development of SARS-CoV-2 vaccines for humans. One Sentence Summary A purified inactivated SARS-CoV-2 virus vaccine candidate (PiCoVacc) confers complete protection in non-human primates against SARS-CoV-2 strains circulating worldwide by eliciting potent humoral responses devoid of immunopathology", "title": "Rapid development of an inactivated vaccine for SARS-CoV-2", "pid": "m1bvurwi", "bm25_score": 218.3769989013672}, {"text": "The COVID-19 pandemic continues to spread throughout the world with an urgent need for a safe and protective vaccine to effectuate herd immunity to control the spread of SARS-CoV-2. Here, we report the development of a SARS-CoV-2 subunit vaccine (NVX-CoV2373) produced from the full-length spike (S) protein, stabilized in the prefusion conformation. Purified NVX-CoV2373 S form 27.2nm nanoparticles that are thermostable and bind with high affinity to the human angiotensin-converting enzyme 2 (hACE2) receptor. In mice and baboons, low-dose NVX-CoV2373 with saponin-based Matrix-M adjuvant elicits high titer anti-S IgG that is associated with blockade of hACE2 receptor binding, virus neutralization, and protection against SARS-CoV-2 challenge in mice with no evidence of vaccine-associated enhanced respiratory disease (VAERD). NVX-CoV2373 vaccine also elicits multifunctional CD4+ and CD8+ T cells, CD4+ T follicular helper T cells (Tfh), and the generation of antigen-specific germinal center (GC) B cells in the spleen. These results support the ongoing phase 1/2 clinical evaluation of the safety and immunogenicity of NVX-CoV2327 with Matrix-M (NCT04368988).", "title": "SARS-CoV-2 spike glycoprotein vaccine candidate NVX-CoV2373 elicits immunogenicity in baboons and protection in mice", "pid": "2nruf2g7", "bm25_score": 218.3701934814453}, {"text": "The development of vaccines against SARS-CoV-2 is progressing at an unparalleled speed. As of the 29th of March, there were at least 68 vaccine candidates comprising several different vaccine designs, including whole killed virus, subunit, attenuated, viral vector, DNA and mRNA vaccines. Whilst it usually takes 10-15 years to develop a vaccine, it has only taken just over 9 weeks from the publication of the viral genetic sequence for the first vaccine candidate to reach clinical testing. Development has been expediated by using existing technological platforms and by performing preclinical and clinical testing simultaneously.", "title": "[At least 68 vaccine candidates under development].", "pid": "l9l6z1o0", "bm25_score": 218.30821228027344}, {"text": "Spike, Envelope and Membrane proteins from the SARS CoV-2 virus surface coat are important vaccine targets. We hereby report recombinant co-expression of the three proteins (Spike, Envelope and Membrane) in a engineered Saccharomyces cerevisiae platform (D-Crypt™) and their self-assembly as Virus-like particle (VLP). This design as a multi-antigenic VLP for SARS CoV-2 has the potential to be a scalable vaccine candidate. The VLP is confirmed by transmission electron microscopy (TEM) images of the SARS CoV-2, along with supportive HPLC, Dynamic Light Scattering (DLS) and allied analytical data. The images clearly outline the presence of a “Corona” like morphology, and uniform size distribution.", "title": "Multi-Antigenic Virus-like Particle of SARS CoV-2 produced in Saccharomyces cerevisiae as a vaccine candidate", "pid": "1q71gjwt", "bm25_score": 218.20948791503906}, {"text": "There is a great need for the development of vaccines for preventing SARS-CoV-2 infection and mitigating the COVID-19 pandemic. Here, we developed two modified vaccinia Ankara (MVA) based vaccines which express either a membrane anchored full-length spike protein (MVA/S) stabilized in a prefusion state or the S1 region of the spike (MVA/S1) which forms trimers and is secreted. Both immunogens contained the receptor-binding domain (RBD) which is a known target of antibody-mediated neutralization. Following immunizations with MVA/S or MVA/S1, both spike protein recombinants induced strong IgG antibodies to purified full-length SARS-CoV-2 spike protein. The MVA/S induced a robust antibody response to purified RBD, S1 and S2 whereas MVA/S1 induced an antibody response to the S1 region outside of the RBD region. Both vaccines induced an antibody response in the lung and that was associated with induction of bronchus-associated lymphoid tissue. MVA/S but not MVA/S1 vaccinated mice generated robust neutralizing antibody responses against SARS-CoV-2 that strongly correlated with RBD antibody binding titers. Mechanistically, S1 binding to ACE-2 was strong but reduced following prolonged pre-incubation at room temperature suggesting confirmation changes in RBD with time. These results demonstrate MVA/S is a potential vaccine candidate against SARS-CoV-2 infection.", "title": "Modified Vaccinia Ankara Based SARS-CoV-2 Vaccine Expressing Full-Length Spike Induces Strong Neutralizing Antibody Response", "pid": "byt52ym3", "bm25_score": 218.20921325683594}, {"text": "With an increasing fatality rate, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has emerged as a promising threat to human health worldwide. SARS-CoV-2 is a member of the Coronaviridae family, which is transmitted from animal to human and because of being contagious, further it transmitted human to human. Recently, the World Health Organization (WHO) has announced the infectious disease caused by SARS-CoV-2, which is known as coronavirus disease-2019 (COVID-2019) as a global pandemic. But, no specific medications are available for the treatment of COVID-19 so far. As a corollary, there is a need for a potential vaccine to impede the progression of the disease. Lately, it has been documented that the nucleocapsid (N) protein of SARS-CoV-2 is responsible for viral replication as well as interferes with host immune responses. We have comparatively analyzed the sequences of N protein of SARS-CoV-2 for the identification of core attributes and analyzed the ancestry through phylogenetic analysis. Subsequently, we have predicted the most immunogenic epitope for T-cell as well as B-cell. Importantly, our investigation mainly focused on major histocompatibility complex (MHC) class I potential peptides and NTASWFTAL interacted with most human leukocyte antigen (HLA) that are encoded by MHC class I molecules. Further, molecular docking analysis unveiled that NTASWFTAL possessed a greater affinity towards HLA and also available in a greater range of the population. Our study provides a consolidated base for vaccine design and we hope that this computational analysis will pave the way for designing novel vaccine candidates.", "title": "Epitope-Based Peptide Vaccine Against Severe Acute Respiratory Syndrome-Coronavirus-2 Nucleocapsid Protein: An in silico Approach", "pid": "6m9llyta", "bm25_score": 218.16897583007812}, {"text": "The spike (S) protein, a main surface antigen of the SARS coronavirus (SARS-CoV), is considered to be one of the most important protective antigen candidates for targets for vaccine design against the virus. In this study, a secreted recombinant expression plasmid, pVAX-S1, encoding the partial S protein with a signal peptide, was constructed and used to immunize BALB/c mice through electroporation. It was demonstrated that the eukaryotic expression vector pVAX-S1 was successfully constructed by restriction enzyme and sequence analysis. The expressed protein could be detected specifically by Western blot analysis. The serum IgG level of the vaccine group mice was significantly higher than that of the corresponding control group at day 14 after vaccination (P < 0.05). The vaccine group demonstrated significantly higher S1 protein lymphocyte proliferation index (LPI) than the control groups (P < 0.05). Furthermore, in the experimental group, a decrease in the ratio of CD4(+) to CD8(+) T-lymphocytes and an increase level of IFN-gamma in serum were observed. However, interleukin-4 (IL-4) was not detectable in two groups. These results strongly demonstrated that the pVAX-S1 plasmid could induce humoral and cellular immune responses in mice, and may be a potential candidate for a DNA vaccine against the SARS coronavirus.", "title": "Construction of a eukaryotic expression plasmid encoding partial S gene fragments of the SARS-CoV and its potential utility as a DNA vaccine.", "pid": "521zj5u2", "bm25_score": 218.16314697265625}, {"text": "The spike (S) protein, a main surface antigen of SARS-coronavirus (SARS-CoV), is one of the most important antigen candidates for vaccine design. In the present study, three fragments of the truncated S protein were expressed in E. coli, and analyzed with pooled sera of convalescence phase of SARS patients. The full length S gene DNA vaccine was constructed and used to immunize BALB/c mice. The mouse serum IgG antibody against SARS-CoV was measured by ELISA with E. coli expressed truncated S protein or SARS-CoV lysate as diagnostic antigen. The results showed that all the three fragments of S protein expressed by E. coli was able to react with sera of SARS patients and the S gene DNA candidate vaccine could induce the production of specific IgG antibody against SARS-CoV efficiently in mice with seroconversion ratio of 75% after 3 times of immunization. These findings lay some foundations for further understanding the immunology of SARS-CoV and developing SARS vaccines.", "title": "DNA Vaccine of SARS-Cov S Gene Induces Antibody Response in Mice", "pid": "65iwx5nv", "bm25_score": 218.11465454101562}, {"text": "Since the first appearance of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS- CoV-2) in China on December 2019, the world has now witnessed the emergence of the SARS- CoV-2 outbreak. Therefore, due to the high transmissibility rate of virus, there is an urgent need to design and develop vaccines against SARS-CoV-2 to prevent more cases affected by the virus. In this study, a computational approach is proposed for vaccine design against the envelope (E) protein of SARS-CoV-2, which contains a conserved sequence feature. First, we sought to gain potential B-cell and T-cell epitopes for vaccine designing against SARS-CoV-2. Second, we attempted to develop a multi-epitope vaccine. Immune targeting of such epitopes could theoretically provide defense against SARS-CoV-2. Finally, we evaluated the affinity of the vaccine to major histocompatibility complex (MHC) molecules to stimulate the immune system response to this vaccine. We also identified a collection of B-cell and T-cell epitopes derived from E proteins that correspond identically to SARS-CoV-2 E proteins. The in-silico design of our potential vaccine against E protein of SARS-CoV-2 demonstrated a high affinity to MHC molecules, and it can be a candidate to make a protection against this pandemic event.", "title": "An in-silico approach to develop of a multi-epitope vaccine candidate against SARS-CoV-2 envelope (E) protein", "pid": "l5ojx3jw", "bm25_score": 218.10789489746094}, {"text": "PURPOSE OF REVIEW: The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19). RECENT FINDINGS: Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS-CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID-19 epidemic in China. Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS-CoV vaccines, it is expected that all COVID-19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID-19 vaccine target product profile must address vaccinating at-risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. SUMMARY: Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time.", "title": "The SARS-CoV-2 Vaccine Pipeline: an Overview", "pid": "rl2qxd03", "bm25_score": 218.10455322265625}, {"text": "Purpose of Review: The goal of this review is to provide a timely overview on efforts to develop a vaccine for the 2019 novel coronavirus SARS-CoV-2, the causative agent of coronavirus disease (COVID-19). Recent Findings: Previous research efforts to develop a severe acute respiratory syndrome coronavirus (SARS-CoV) vaccine in the years following the 2003 pandemic have opened the door for investigators to design vaccine concepts and approaches for the COVID-19 epidemic in China. Both SARS-CoV and SARS-CoV-2 exhibit a high degree of genetic similarity and bind to the same host cell ACE2 receptor. Based on previous experience with SARS-CoV vaccines, it is expected that all COVID-19 vaccines will require careful safety evaluations for immunopotentiation that could lead to increased infectivity or eosinophilic infiltration. Besides this, a COVID-19 vaccine target product profile must address vaccinating at-risk human populations including frontline healthcare workers, individuals over the age of 60, and those with underlying and debilitating chronic conditions. Among the vaccine technologies under evaluation are whole virus vaccines, recombinant protein subunit vaccines, and nucleic acid vaccines. Summary: Each current vaccine strategy has distinct advantages and disadvantages. Therefore, it is paramount that multiple strategies be advanced quickly and then evaluated for safety and efficacy. Ultimately, the safety studies to minimize undesired immunopotentiation will become the most significant bottleneck in terms of time.", "title": "The SARS-CoV-2 Vaccine Pipeline: an Overview", "pid": "7jsponjx", "bm25_score": 218.10455322265625}, {"text": "The immunogenicity of SARS-CoV nucleocapsid DNA vaccine and the immunoregulatory activity of interleukin-2 (IL-2) were investigated. DNA vaccine plasmids, pcDNA-N and pcDNA-IL2, were constructed and inoculated into BALB/c mice with or without pcDNA-IL2 by intramuscular injection. Cellular and humoral immune responses were assessed by indirect ELISA, lymphocyte proliferation assays, ELISPOT and FACS. The nucleocapsid DNA vaccine had good immunogenicity and can induce specific humoral and cellular immunity in BALB/c mice, while IL-2 plays an immunoadjuvant role and enhances specific immune responses. This study provides a frame of reference for the design of DNA vaccines against SARS-CoV.", "title": "Enhancing immune responses against SARS-CoV nucleocapsid DNA vaccine by co-inoculating interleukin-2 expressing vector in mice", "pid": "gi7ktelw", "bm25_score": 218.0828399658203}, {"text": "Severe acute respiratory syndrome (SARS) is a serious threat to public health and the economy on a global scale. The SARS coronavirus (SARS-CoV) has been identified as the etiological agent for SARS. Thus, vaccination against SARS-CoV may represent an effective approach to controlling SARS. DNA vaccines are an attractive approach for SARS vaccine development, as they offer many advantages over conventional vaccines, including stability, simplicity, and safety. Our investigators have previously shown that DNA vaccination with antigen linked to calreticulin (CRT) dramatically enhances major histocompatibility complex class I presentation of linked antigen to CD8(+) T cells. In this study, we have employed this CRT-based enhancement strategy to create effective DNA vaccines using SARS-CoV nucleocapsid (N) protein as a target antigen. Vaccination with naked CRT/N DNA generated the most potent N-specific humoral and T-cell-mediated immune responses in vaccinated C57BL/6 mice among all of the DNA constructs tested. Furthermore, mice vaccinated with CRT/N DNA were capable of significantly reducing the titer of challenging vaccinia virus expressing the N protein of the SARS virus. These results show that a DNA vaccine encoding CRT linked to a SARS-CoV antigen is capable of generating strong N-specific humoral and cellular immunity and may potentially be useful for control of infection with SARS-CoV.", "title": "Generation and characterization of DNA vaccines targeting the nucleocapsid protein of severe acute respiratory syndrome coronavirus.", "pid": "0vjrewb6", "bm25_score": 218.0797119140625}, {"text": "Here we propose a vaccination strategy for SARS-CoV-2 based on identification of both highly conserved regions of the virus and newly acquired adaptations that are presented by MHC class I and II across the vast majority of the population, are highly dissimilar from the human proteome, and are predicted B cell epitopes. We present 65 peptide sequences that we expect to result in a safe and effective vaccine which can be rapidly tested in DNA, mRNA, or synthetic peptide constructs. These include epitopes that are contained within evolutionarily divergent regions of the spike protein reported to increase infectivity through increased binding to the ACE2 receptor, and within a novel furin cleavage site thought to increase membrane fusion. This vaccination strategy specifically targets unique vulnerabilities of SARS-CoV-2 and should engage a robust adaptive immune response in the vast majority of the human population.", "title": "A SARS-CoV-2 Vaccination Strategy Focused on Population-Scale Immunity", "pid": "qq22z25y", "bm25_score": 218.0430450439453}, {"text": "The spike protein (S), a membrane component of severe acute respiratory syndrome coronavirus (SARS-CoV) is anticipated to be an important component of candidate vaccines. We constructed recombinant forms of the highly attenuated modified vaccinia virus Ankara (MVA) containing the gene encoding full-length SARS-CoV S with and without a C-terminal epitope tag called MVA/S-HA and MVA/S, respectively. Cells infected with MVA/Sor MVA/S-HA synthesized a 200-kDa protein, which was recognized by antibody raised against a synthetic peptide of SARS-CoV S or the epitope tag in Western blot analyses. Further studies indicated that S was N-glycosylated and migrated in SDS polyacrylamide gels with an apparent mass of approximately 160 kDa after treatment with peptide N-glycosidase F. The acquisition of resistance to endoglycosidase H indicated trafficking of S to the medial Golgi compartment, and confocal microscopy showed that S was transported to the cell surface. Intranasal or intramuscular inoculations of BALB/c mice with MVA/S produced serum antibodies that recognized the SARS S in ELISA and neutralized SARS-CoV in vitro. Moreover, MVA/S administered by either route elicited protective immunity, as shown by reduced titers of SARS-CoV in the upper and lower respiratory tracts of mice after challenge. Passive transfer of serum from mice immunized with MVA/S to naïve mice also reduced the replication of SARS-CoV in the respiratory tract after challenge, demonstrating a role for antibody to S in protection. The attenuated nature of MVA and the ability of MVA/S to induce neutralizing antibody that protects mice support further development of this candidate vaccine.", "title": "Severe acute respiratory syndrome coronavirus spike protein expressed by attenuated vaccinia virus protectively immunizes mice.", "pid": "d92o8djm", "bm25_score": 218.03082275390625}, {"text": "In December 2019, the outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a serious pandemic in China and other countries worldwide. So far, more than 460,000 confirmed cases were diagnosed in nearly 190 countries, causing globally over 20,000 deaths. Currently, the epidemic is still spreading and there is no effective means to prevent the infection. Vaccines are proved to be the most effective and economical means to prevent and control infectious diseases. Several countries, companies, and institutions announced their programs and progress on vaccine development against the virus. While most of the vaccines are under design and preparation, there are some that have entered efficacy evaluation in animals and initial clinical trials. This review mainly focused on the progress and our prospects on field of vaccine development against SARS-CoV-2.", "title": "Progress and Prospects on Vaccine Development against SARS-CoV-2", "pid": "gl0wiyt2", "bm25_score": 218.02191162109375}, {"text": "SARS Coronavirus-2 (SARS-CoV-2) pandemic has become a global issue which has raised the concern of scientific community to design and discover a counter-measure against this deadly virus which has caused deaths of numerous infected people upon infection and spreading. To date, no effective vaccine is available which can combat the infection caused by this virus. This study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against SARS-CoV-2. Thereafter, molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. This study should contribute to uphold the present efforts of the researches to secure a definitive treatment for this lethal disease.", "title": "Immunoinformatics-guided designing of epitope-based subunit vaccine against the SARS Coronavirus-2 (SARS-CoV-2)", "pid": "s9k5ej8l", "bm25_score": 218.00840759277344}, {"text": "Novel SARS coronavirus (SARS-CoV-2) has caused a pandemic condition world-wide and has been declared as public health emergency of International concern by WHO in a very short span of time. The community transmission of this highly infectious virus has severely affected various parts of China, Italy, Spain and USA among others. The prophylactic solution against SARS-CoV-2 infection is challenging due to the high mutation rate of its RNA genome. Herein, we exploited a next generation vaccinology approach to construct a multi-epitope vaccine candidate against SARS-CoV-2 with high antigenicity, safety and efficacy to combat this deadly infectious agent. The whole proteome was scrutinized for the screening of highly conserved, antigenic, non-allergen and non-toxic epitopes having high population coverage that can elicit both humoral and cellular mediated immune response against COVID-19 infection. These epitopes along with four different adjuvants were utilized to construct a multi-epitope vaccine candidate that can generate strong immunological memory response having high efficacy in humans. Various physiochemical analyses revealed the formation of a stable vaccine product having a high propensity to form a protective solution against the detrimental SARS-CoV-2 strain with high efficacy. The vaccine candidate interacted with immunological receptor TLR3 with high affinity depicting the generation of innate immunity. Further, the codon optimization and in silico expression show the plausibility of the high expression and easy purification of the vaccine product. Thus, this present study provides an initial platform of the rapid generation of an efficacious protective vaccine for combating COVID-19.", "title": "Scrutinizing the SARS-CoV-2 protein information for the designing an effective vaccine encompassing both the T-cell and B-cell epitopes", "pid": "lmstdmyb", "bm25_score": 217.98312377929688}, {"text": "A novel Coronavirus (SARS-COV-2) has now become a global pandemic. Considering the severity of infection and the associated mortalities, there is an urgent need to develop an effective preventive measure against this virus. In this study, we have designed a novel vaccine construct using computational strategies. Spike (S) glycoprotein is the major antigenic component that trigger the host immune responses. Detailed investigation of S protein with various immunoinformatics tools enabled us to identify 5 MHC I and 5 MHC II B-cell derived T-cell epitopes with VaxiJen score > 1 and IC50 value < 100nM. These epitopes were joined with a suitable adjuvant and appropriate linkers to form a multi-epitope based vaccine construct. Further, in silico testing of the vaccine construct for its antigenicity, allergenicity, solubility, and other physicochemical properties showed it to be safe and immunogenic. Suitable tertiary structure of the vaccine protein was generated using 3Dpro of SCRATCH suite, refined with GalaxyRefine, and validated with ProSA, PROCHECK, and ERRAT server. Finally, molecular docking studies were performed to ensure a favorable binding affinity between the vaccine construct and TLR3 receptor. The designed multi-epitope vaccine showed potential to elicit specific immune responses against the SARS-COV-2. However, further wet lab validation is necessary to confirm the actual effectiveness, safety and immunogenic potency of the vaccine construct against derived in this study.", "title": "In silico approach for designing of a multi-epitope based vaccine against novel Coronavirus (SARS-COV-2)", "pid": "xjg2e8be", "bm25_score": 217.96888732910156}, {"text": "The explosively expanding COVID-19 pandemic urges the development of safe, efficacious and fast-acting vaccines to quench the unrestrained spread of SARS-CoV-2. Several promising vaccine platforms, developed in recent years, are leveraged for a rapid emergency response to COVID-191. We employed the live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express the prefusion form of the SARS-CoV-2 Spike antigen. In mice, the vaccine candidate, tentatively named YF-S0, induces high levels of SARS-CoV-2 neutralizing antibodies and a favorable Th1 cell-mediated immune response. In a stringent hamster SARS-CoV-2 challenge model2, vaccine candidate YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose confers protection from lung disease in most vaccinated animals even within 10 days. These results warrant further development of YF-S0 as a potent SARS-CoV-2 vaccine candidate.", "title": "A single-dose live-attenuated YF17D-vectored SARS-CoV2 vaccine candidate", "pid": "zwsvlnwe", "bm25_score": 217.88980102539062}, {"text": "Public health measures have successfully identified and contained outbreaks of the severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV)(1,2,3,4,5), but concerns remain over the possibility of future recurrences. Finding a vaccine for this virus therefore remains a high priority. Here, we show that a DNA vaccine encoding the spike (S) glycoprotein of the SARS-CoV induces T cell and neutralizing antibody responses, as well as protective immunity, in a mouse model. Alternative forms of S were analysed by DNA immunization. These expression vectors induced robust immune responses mediated by CD4 and CD8 cells, as well as significant antibody titres, measured by enzyme-linked immunosorbent assay. Moreover, antibody responses in mice vaccinated with an expression vector encoding a form of S that includes its transmembrane domain elicited neutralizing antibodies. Viral replication was reduced by more than six orders of magnitude in the lungs of mice vaccinated with these S plasmid DNA expression vectors, and protection was mediated by a humoral but not a T-cell-dependent immune mechanism. Gene-based vaccination for the SARS-CoV elicits effective immune responses that generate protective immunity in an animal model. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nature02463) contains supplementary material, which is available to authorized users.", "title": "A DNA vaccine induces SARS coronavirus neutralization and protective immunity in mice", "pid": "7k088cqv", "bm25_score": 217.88705444335938}, {"text": "The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its impact on global health have made imperative the development of effective and safe vaccines for this lethal strain. SARS-CoV-2 now adds to the list of coronavirus diseases that have threatened global health, along with the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses that emerged in 2002/2003 and 2012, respectively. As of April 2020, no vaccine is commercially available for these coronavirus strains. Nevertheless, the knowledge obtained from the vaccine development efforts for MERS and SARS can be of high value for COVID-19 (coronavirus disease 2019). Here, we review the past and ongoing vaccine development efforts for clinically relevant coronavirus strains with the intention that this information helps in the development of effective and safe vaccines for COVID-19. In addition, information from naturally exposed individuals and animal models to coronavirus strains is described for the same purpose of helping into the development of effective vaccines against COVID-19.", "title": "Vaccines for SARS-CoV-2: Lessons from Other Coronavirus Strains.", "pid": "qu7ddcw9", "bm25_score": 217.8802490234375}, {"text": "Vaccination efficacy is enhanced by targeting the antigen-presenting cell compartment. Here, we show that S1-Fc antigen delivery targeting the FcγR+ antigen-presenting cell compartment elicits anti-SARS-CoV-2 S1-antigen specific IgG production in vivo exerting biologically functional and protective activity against live virus infection, assessed in a stringent experimental virus challenge assay in vitro. The S1-domain of the SARS-CoV-2 spike protein was genetically fused to a human immunoglobulin Fc moiety, which contributes to mediate S1-Fc cellular internalization by FcγR+ antigen-presenting cells. Immediately upon administration intramuscularly, our novel vaccine candidate recombinant rS1-Fc homes to lymph nodes in vivo where FcγR+ antigen-presenting cells reside. Seroconversion is achieved as early as day 7, mounting considerably increased levels of anti-S1 IgGs in vivo. Interestingly, immunization at elevated doses with non-expiring S1-Fc encoding dsDNA favors the education of a desired antigen-specific adaptive T cell response. However, low-dose immunization, safeguarding patient safety, using recombinant rS1-Fc, elicits a considerably elevated protection amplitude against live SARS-CoV-2 infection. Our promising findings on rS1-Fc protein immunization prompted us to further develop an affordable and safe product for delivery to our communities in need for COVID-19 vaccinations.", "title": "A Targeted Vaccine against COVID-19: S1-Fc Vaccine Targeting the Antigen-Presenting Cell Compartment Elicits Protection against SARS-CoV-2 Infection", "pid": "l3bbl5i7", "bm25_score": 217.86270141601562}, {"text": "Abstract Epitope-based vaccines designed to induce antibody responses specific for severe acute respiratory syndrome-associated coronavirus (SARS-CoV) are being developed as a means for increasing vaccine potency. In this study, we identified four B cell epitopes from the spike (S) and membrane (M) protein through bioinformatics analysis and constructed a multi-epitope DNA vaccine. Intramuscular immunization of mice with this vaccine was sufficient to induce specific prime as well as a long-term memory humoral immune response to at least two candidate epitopes, S437–459 and M1–20. A DNA prime–protein boost strategy greatly enhanced the antibody generation and the immune sera not only reacted with the lysates of SARS-CoV-infected Vero cells but also neutralized the cytopathic effect of SARS by 75% at 1:160 dilution. The novel immunogenic S protein peptide revealed in this study provides new target for SARS vaccine design; and our work indicated multi-epitope DNA vaccine as an effective means for eliciting polyvalent humoral immune response against SARS-CoV.", "title": "A chimeric multi-epitope DNA vaccine elicited specific antibody response against severe acute respiratory syndrome-associated coronavirus which attenuated the virulence of SARS-CoV in vitro", "pid": "ivmpbuwf", "bm25_score": 217.83135986328125}, {"text": "The Spike (S) protein of the severe acute respiratory syndrome-associated coronavirus (SARS-CoV) plays important roles in viral pathogenesis and potentially in the development of an effective vaccine against this virulent infectious disease. In this study, the codon-optimized S gene of SARS-CoV was synthesized to construct DNA vaccine plasmids expressing either the full-length or segments of the S protein. High titer S-specific immunoglobulin G antibody responses were elicited in rabbits immunized with DNA against various segments of the S protein. Two neutralizing domains were identified on the S protein, one at the N terminus (Ser12-Thr535) and the other near the C terminus (Arg797-Ile1192).", "title": "Identification of two neutralizing regions on the severe acute respiratory syndrome coronavirus spike glycoprotein produced from the mammalian expression system.", "pid": "pfp36t93", "bm25_score": 217.8074951171875}, {"text": "We have investigated novel vaccine strategies against severe acute respiratory syndrome (SARS) CoV using cDNA constructs encoding the structural antigens: (S), (M), (E), or (N) protein, derived from SARS CoV. PBL from healthy human volunteers were administered i.p. into IL-2 receptor γ-chain disrupted SCID mice, and SCID-PBL/hu mice were constructed. These mice can be used to analyze the human immune response in vivo. SARS M DNA vaccine and N DNA vaccine induced human CTL specific for SARS CoV antigens. Alternatively, SARS M DNA vaccines inducing human neutralizing antibodies and human monoclonal antibodies against SARS CoV are now being developed. These results show that these vaccines can induce virus-specific immune responses and should provide a useful tool for development of protective and therapeutic vaccines.", "title": "Development of vaccines and passive immunotherapy against SARS corona virus using SCID-PBL/hu mouse models", "pid": "bdse9o26", "bm25_score": 217.8006591796875}, {"text": "The non-structural protein 1 (Nsp1), also referred to as the host shutoff factor, is the first viral protein that is synthesized in SARS-CoV-2 infected human cells to suppress host innate immune functions1,2. By combining cryo-electron microscopy and biochemical experiments, we show that SARS-CoV-2 Nsp1 binds to the human 40S subunit in ribosomal complexes including the 43S pre-initiation complex. The protein inserts its C-terminal domain at the entrance to the mRNA channel where it interferes with mRNA binding. We observe potent translation inhibition in the presence of Nsp1 in lysates from human cells. Based on the high-resolution structure of the 40S-Nsp1 complex, we identify residues of Nsp1 crucial for mediating translation inhibition. We further show that the full-length 5’ untranslated region of the genomic viral mRNA stimulates translation in vitro, suggesting that SARS-CoV-2 combines inhibition of translation by Nsp1 with efficient translation of the viral mRNA to achieve expression of viral genes3.", "title": "SARS-CoV-2 Nsp1 binds ribosomal mRNA channel to inhibit translation", "pid": "ofpna4k1", "bm25_score": 217.79783630371094}, {"text": "The emergence of the strain of coronavirus SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) and its impact on global health have made imperative the development of effective and safe vaccines for this lethal strain. SARS-CoV-2 now adds to the list of coronavirus diseases that have threatened global health, along with the SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses that emerged in 2002/2003 and 2012, respectively. As of April 2020, no vaccine is commercially available for these coronavirus strains. Nevertheless, the knowledge obtained from the vaccine development efforts for MERS and SARS can be of high value for COVID-19 (coronavirus disease 2019). Here, we review the past and ongoing vaccine development efforts for clinically relevant coronavirus strains with the intention that this information helps in the development of effective and safe vaccines for COVID-19. In addition, information from naturally exposed individuals and animal models to coronavirus strains is described for the same purpose of helping into the development of effective vaccines against COVID-19.", "title": "Vaccines for SARS-CoV-2: Lessons from Other Coronavirus Strains", "pid": "ri91u0f1", "bm25_score": 217.78997802734375}, {"text": "In the past two decades, 7 coronaviruses have infected the human population, with two major outbreaks caused by SARS-CoV and MERS-CoV in the year 2002 and 2012, respectively. Currently, the entire world is facing a pandemic of another coronavirus, SARS-CoV-2, with a high fatality rate. The spike glycoprotein of SARS-CoV-2 mediates entry of virus into the host cell and is one of the most important antigenic determinants, making it a potential candidate for a vaccine. In this study, we have computationally designed a multi-epitope vaccine using spike glycoprotein of SARS-CoV-2. The overall quality of the candidate vaccine was validated in silico and Molecular Dynamics Simulation confirmed the stability of the designed vaccine. Docking studies revealed stable interactions of the vaccine with Toll-Like Receptors and MHC Receptors. The in silico cloning and codon optimization supported the proficient expression of the designed vaccine in E. coli expression system. The efficiency of the candidate vaccine to trigger an effective immune response was assessed by an in silico immune simulation. The computational analyses suggest that the designed multi-epitope vaccine is structurally stable which can induce specific immune responses and thus, can be a potential vaccine candidate against SARS-CoV-2.", "title": "A candidate multi-epitope vaccine against SARS-CoV-2", "pid": "0razl9qf", "bm25_score": 217.76754760742188}, {"text": "The current appearance of the new SARS coronavirus 2 (SARS-CoV-2) and it quickly spreading across the world poses a global health emergency. The serious outbreak position is affecting people worldwide and requires rapid measures to be taken by healthcare systems and governments. Vaccinations represent the most effective strategy to prevent the epidemic of the virus and to further reduce morbidity and mortality with long-lasting effects. Nevertheless, currently there are no licensed vaccines for the novel coronaviruses. Researchers and clinicians from all over the world are advancing the development of a vaccine against novel human SARS-CoV-2 using various approaches. Herein, we aim to present and discuss the progress and prospects in the field of vaccine research towards SARS-CoV-2 using adenovirus (AdV) replication deficient-based strategies, with a comprehension that may support research and combat this recent world health emergency.", "title": "Prospects of Replication-Deficient Adenovirus Based Vaccine Development against SARS-CoV-2.", "pid": "gw6po8qg", "bm25_score": 217.76170349121094}, {"text": "Clinical development of the COVID-19 vaccine candidate ChAdOx1 nCoV-19, a replication-deficient simian adenoviral vector expressing the full-length SARS-CoV-2 spike (S) protein was initiated in April 2020 following non-human primate studies using a single immunisation. Here, we compared the immunogenicity of one or two doses of ChAdOx1 nCoV-19 in both mice and pigs. Whilst a single dose induced antigen-specific antibody and T cells responses, a booster immunisation enhanced antibody responses, particularly in pigs, with a significant increase in SARS-CoV-2 neutralising titres.", "title": "Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19", "pid": "jgbjxgh1", "bm25_score": 217.71595764160156}, {"text": "Severe acute respiratory syndrome coronavirus (SARS-CoV) first appeared in Southern China in November 2002, and then quickly spread to 33 countries on five continents along international air travel routes. Although the SARS epidemic has been contained, there is a clear need for a safe and effective vaccine should an outbreak of a SARS-CoV infection reappear in human population. In this study, we tested four DNA-vaccine constructs: (1) pLL70, containing cDNA for the SARS-CoV spike (S) gene; (2) pcDNA-SS, containing codon-optimized S gene for SARS-CoV S protein (residues 12-1255) fused with a leader sequence derived from the human CD5 gene; (3) pcDNA-St, containing the gene encoding the N-portion of the codon-optimized S gene (residues 12-532) with the CD5 leader sequence; (4) pcDNA-St-VP22C, containing the gene encoding the N-portion of the codon-optimized S protein with the CD5 leader sequence fused with the C-terminal 138 amino acids of the bovine herpesvirus-1 (BHV-1) major tegument protein VP22. Each of these plasmids was intradermally administered to C57BL/6 mice in three separate immunizations. Analysis of humoral and cellular immune responses in immunized mice demonstrated that pcDNA-SS and pcDNA-St-VP22C are the most immunogenic SARS vaccine candidates.", "title": "Optimization of a DNA vaccine against SARS.", "pid": "6derrgno", "bm25_score": 217.71527099609375}, {"text": "Here, Cas13a has been used to target and mitigate influenza virus A (IAV) and SARS-CoV-2 using a synthetic mRNA-based platform. CRISPR RNAs (crRNA) against PB1 and highly conserved regions of PB2 were screened in conjunction with mRNA-encoded Cas13a. Screens were designed such that only guides that decreased influenza RNA levels in a Cas13-mediated fashion, were valid. Cas13a mRNA and validated guides, delivered post-infection, simulating treatment, were tested in combination and across multiplicities of infection. Their function was also characterized over time. Similar screens were performed for guides against SARS-CoV-2, yielding multiple guides that significantly impacted cytopathic effect. Last, the approach was utilized in vivo, demonstrating the ability to degrade influenza RNA in a mouse model of infection, using polymer-formulated, nebulizer-based mRNA delivery. Our findings demonstrate the applicability of Cas13a in mitigating respiratory infections both in vitro and in a mouse model, paving the way for future therapeutic use.", "title": "Treating Influenza and SARS-CoV-2 via mRNA-encoded Cas13a", "pid": "a4rmtphx", "bm25_score": 217.70159912109375}, {"text": "Abstract Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. A possibility of a resurgence of COVID-19 in places where lockdowns have already worked is also developing. Thus, for controlling COVID-19, vaccines may be a better option than drugs. An mRNA-based anti-COVID-19 candidate vaccine has entered a phase 1 clinical trial. However, its efficacy and potency have to be evaluated and validated. Since vaccines have high failure rates, as an alternative, we are presenting a new, designed multi-peptide subunit-based epitope vaccine against COVID-19. The recombinant vaccine construct comprises an adjuvant, cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes joined by linkers. The computational data suggest that the vaccine is non-toxic, non-allergenic, thermostable, with the capability to elicit a humoral and cell-mediated immune response. The stabilization of the vaccine construct is validated with molecular dynamics simulation studies. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host-receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as a public health priority.", "title": "Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2", "pid": "d2j9wpqk", "bm25_score": 217.6814727783203}, {"text": "Dutta and co-workers suggest in a recent letter (1) that the SARS-CoV-2 nucleoprotein (N) might be a good vaccine target.….", "title": "The SARS-CoV-2 N protein is a good component in a vaccine.", "pid": "gwz0yhty", "bm25_score": 217.677001953125}, {"text": "The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.", "title": "Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies", "pid": "ojs5e7n9", "bm25_score": 217.65988159179688}, {"text": "COVID-19 is the pandemic outbreak that is caused by SARS-CoV-2 virus from December, 2019. Human race do not know the curative measure of this devastating disease. In today’s era of nanotechnology, it may use its knowledge to develop molecular vaccine to combat this disease. In this article we are intended to propose a hypothesis on the development of a vaccine that is molecular in nature to work against COVID-19. The nanoconjugate may comprise with the inorganic nanoparticle layered double hydroxide intercalated with shRNA-plasmid that have a sequence targeting towards the viral genome or viral mRNA. This nanoconjugate may be used as a nasal spray to deliver the shRNA-plasmid to the target site. The nanoconjugate will have several advantages such as they are biocompatible, they forms as stable knockdown to the target cells and they are stable in the nasal mucosa.", "title": "Prospective vaccination of COVID-19 using shRNA-plasmid-LDH nanoconjugate", "pid": "4nv059p1", "bm25_score": 217.6400146484375}, {"text": "The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally-determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the available SARS-CoV-2 sequences (as of 9 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.", "title": "Preliminary identification of potential vaccine targets for the COVID-19 coronavirus (SARS-CoV-2) based on SARS-CoV immunological studies", "pid": "7i52vltp", "bm25_score": 217.635986328125}, {"text": "The current appearance of the new SARS coronavirus 2 (SARS-CoV-2) and it quickly spreading across the world poses a global health emergency. The serious outbreak position is affecting people worldwide and requires rapid measures to be taken by healthcare systems and governments. Vaccinations represent the most effective strategy to prevent the epidemic of the virus and to further reduce morbidity and mortality with long-lasting effects. Nevertheless, currently there are no licensed vaccines for the novel coronaviruses. Researchers and clinicians from all over the world are advancing the development of a vaccine against novel human SARS-CoV-2 using various approaches. Herein, we aim to present and discuss the progress and prospects in the field of vaccine research towards SARS-CoV-2 using adenovirus (AdV) replication deficient-based strategies, with a comprehension that may support research and combat this recent world health emergency.", "title": "Prospects of Replication-Deficient Adenovirus Based Vaccine Development against SARS-CoV-2", "pid": "cofi4cue", "bm25_score": 217.61767578125}, {"text": "COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development.", "title": "Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus.", "pid": "sdtiyrab", "bm25_score": 217.61065673828125}, {"text": "Severe acute respiratory syndrome coronavirus (SARS-CoV) has been identified as the aetiological agent of SARS. Thus, vaccination against SARS-CoV may represent an effective approach towards controlling SARS. The nucleocapsid (N) protein is thought to play a role in induction of cell-mediated immunity to SARS-CoV and thus it is important to characterize this protein. In the present study, an E1/partially E3-deleted, replication-defective human adenovirus 5 (Ad5) vector (Ad5-N-V) expressing the SARS-CoV N protein was constructed. The N protein, expressed in vitro by Ad5-N-V, was of the expected molecular mass of 50 kDa and was phosphorylated. Vaccination of C57BL/6 mice with Ad5-N-V generated potent SARS-CoV-specific humoral and T cell-mediated immune responses. These results show that Ad5-N-V may potentially be used as a SARS-CoV vaccine.", "title": "Severe acute respiratory syndrome coronavirus nucleocapsid protein expressed by an adenovirus vector is phosphorylated and immunogenic in mice.", "pid": "ezavo1sk", "bm25_score": 217.59825134277344}, {"text": "SARS Coronavirus-2 (SARS-CoV-2) pandemic has become a global issue which has raised the concern of scientific community to design and discover a counter-measure against this deadly virus. So far, the pandemic has caused the death of hundreds of thousands of people upon infection and spreading. To date, no effective vaccine is available which can combat the infection caused by this virus. Therefore, this study was conducted to design possible epitope-based subunit vaccines against the SARS-CoV-2 virus using the approaches of reverse vaccinology and immunoinformatics. Upon continual computational experimentation, three possible vaccine constructs were designed and one vaccine construct was selected as the best vaccine based on molecular docking study which is supposed to effectively act against the SARS-CoV-2. Thereafter, the molecular dynamics simulation and in silico codon adaptation experiments were carried out in order to check biological stability and find effective mass production strategy of the selected vaccine. This study should contribute to uphold the present efforts of the researches to secure a definitive preventative measure against this lethal disease.", "title": "Immunoinformatics-guided designing of epitope-based subunit vaccines against the SARS Coronavirus-2 (SARS-CoV-2)", "pid": "fr536bc9", "bm25_score": 217.58416748046875}, {"text": "Background To date, no specific vaccine or drug has been proven to be effective for SARS-CoV-2 infection. Therefore, we implemented immunoinformatics approach to design an efficient multi-epitopes vaccine against SARS-CoV-2. Results The designed vaccine construct has several immunodominant epitopes from structural proteins of Spike, Nucleocapsid, Membrane and Envelope. These peptides promote cellular and humoral immunity and Interferon gamma responses. In addition, these epitopes have antigenicity ability and no allergenicity probability. To enhance the vaccine immunogenicity, we used three potent adjuvants; Flagellin, a driven peptide from high mobility group box 1 as HP-91 and human beta defensin 3 protein. The physicochemical and immunological properties of the vaccine structure were evaluated. Tertiary structure of the vaccine protein was predicted and refined by I-Tasser and galaxi refine and validated using Rampage and ERRAT. Results of Ellipro showed 242 residues from vaccine might be conformational B cell epitopes. Docking of vaccine with Toll-Like Receptors 3, 5 and 8 proved an appropriate interaction between the vaccine and receptor proteins. In silico cloning demonstrated that the vaccine can be efficiently expressed in Escherichia coli. Conclusions The designed multi epitope vaccine is potentially antigenic in nature and has the ability to induce humoral and cellular immune responses against SARS-CoV-2. This vaccine can interact appropriately with the TLR3, 5, and 8. Also, this vaccine has high quality structure and suitable characteristics such as high stability and potential for expression in Escherichia coli.", "title": "Design an efficient multi-epitope peptide vaccine candidate against SARS-CoV-2: An in silico analysis", "pid": "p9507cwx", "bm25_score": 217.5754852294922}, {"text": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of the ongoing pandemic of coronavirus disease 2019 (COVID-19), a public health emergency of international concern declared by the World Health Organization (WHO). An immuno-informatics approach along with comparative genomic was applied to design a multi-epitope-based peptide vaccine against SARS-CoV-2 combining the antigenic epitopes of the S, M and E proteins. The tertiary structure was predicted, refined and validated using advanced bioinformatics tools. The candidate vaccine showed an average of ≥ 90.0% world population coverage for different ethnic groups. Molecular docking of the chimeric vaccine peptide with the immune receptors (TLR3 and TLR4) predicted efficient binding. Immune simulation predicted significant primary immune response with increased IgM and secondary immune response with high levels of both IgG1 and IgG2. It also increased the proliferation of T-helper cells and cytotoxic T-cells along with the increased INF-γ and IL-2 cytokines. The codon optimization and mRNA secondary structure prediction revealed the chimera is suitable for high-level expression and cloning. Overall, the constructed recombinant chimeric vaccine candidate demonstrated significant potential and can be considered for clinical validation to fight against this global threat, COVID-19.", "title": "Epitope-based chimeric peptide vaccine design against S, M and E proteins of SARS-CoV-2 etiologic agent of global pandemic COVID-19: an in silico approach", "pid": "0yqyclxk", "bm25_score": 217.57241821289062}, {"text": "The outbreak of the 2019 novel coronavirus (SARS-CoV-2) has infected millions of people with a large number of deaths across the globe. The existing therapies are limited in dealing with SARS-CoV-2 due to the sudden appearance of the virus. Therefore, vaccines and antiviral medicines are in desperate need. We took immune-informatics approaches to identify B- and T-cell epitopes for surface glycoprotein (S), membrane glycoprotein (M) and nucleocapsid protein (N) of SARS-CoV-2, followed by estimating their antigenicity and interactions with the human leukocyte antigen (HLA) alleles. Allergenicity, toxicity, physiochemical properties analysis and stability were examined to confirm the specificity and selectivity of the epitope candidates. We identified a total of five B cell epitopes in RBD of S protein, seven MHC class-I, and 18 MHC class-II binding T-cell epitopes from S, M and N protein which showed non-allergenic, non-toxic and highly antigenic features and non-mutated in 55,179 SARS-CoV-2 virus strains until June 25, 2020. The epitopes identified here can be a potentially good candidate repertoire for vaccine development.", "title": "Epitope-based peptide vaccines predicted against novel coronavirus disease caused by SARS-CoV-2", "pid": "3a16i8l9", "bm25_score": 217.5662384033203}, {"text": "Foreign viral proteins expressed by rabies virus (RV) have been shown to induce potent humoral and cellular immune responses in immunized animals. In addition, highly attenuated and, therefore, very safe RV-based vectors have been constructed. Here, an RV-based vaccine vehicle was utilized as a novel vaccine against severe acute respiratory syndrome coronavirus (SARS-CoV). For this approach, the SARS-CoV nucleocapsid protein (N) or envelope spike protein (S) genes were cloned between the RV glycoprotein G and polymerase L genes. Recombinant vectors expressing SARS-CoV N or S protein were recovered and their immunogenicity was studied in mice. A single inoculation with the RV-based vaccine expressing SARS-CoV S protein induced a strong SARS-CoV-neutralizing antibody response. The ability of the RV-SARS-CoV S vector to confer immunity after a single inoculation makes this live vaccine a promising candidate for eradication of SARS-CoV in animal reservoirs, thereby reducing the risk of transmitting the infection to humans.", "title": "A single immunization with a rhabdovirus-based vector expressing severe acute respiratory syndrome coronavirus (SARS-CoV) S protein results in the production of high levels of SARS-CoV-neutralizing antibodies.", "pid": "a5sg617l", "bm25_score": 217.55189514160156}, {"text": "Immunization with an inactivated virus is one of the strategies currently being tested towards developing a SARS-CoV-2 vaccine. One of the methods used to inactivate viruses is exposure to high doses of ionizing radiation to damage their nucleic acids. Although gamma-rays effectively induce lesions in the RNA, envelope proteins are also highly damaged in the process. This in turn may alter their antigenic properties, affecting their capacity to induce an adaptive immune response able to confer effective protection. Here, we modelled the impact of sparsely and densely ionizing radiation on SARS-CoV-2 using the Monte Carlo toolkit Geant4-DNA. With a realistic 3D target virus model, we calculated the expected number of lesions in the spike and membrane proteins, as well as in the viral RNA. We show that gamma-rays produce significant spike protein damage, but densely ionizing charged particles induce less membrane damage for the same level of RNA lesions, because a single ion traversal through the nuclear envelope is sufficient to inactivate the virus. We propose that accelerated charged particles produce inactivated viruses with little structural damage to envelope proteins, thereby representing a new and effective tool for developing vaccines against SARS-CoV-2 and other enveloped viruses.", "title": "Monte Carlo simulation of SARS-CoV-2 radiation-induced inactivation for vaccine development", "pid": "f6ge0y6z", "bm25_score": 217.54913330078125}, {"text": "The COVID-19 outbreak has become a global pandemic responsible for over 2,000,000 confirmed cases and over 126,000 deaths worldwide. In this study, we examined the immunogenicity of CHO-expressed recombinant SARS-CoV-2 S1-Fc fusion protein in mice, rabbits, and monkeys as a potential candidate for a COVID-19 vaccine. We demonstrate that the S1-Fc fusion protein is extremely immunogenic, as evidenced by strong antibody titers observed by day 7. Strong virus neutralizing activity was observed on day 14 in rabbits immunized with the S1-Fc fusion protein using a pseudovirus neutralization assay. Most importantly, in <20 days and three injections of the S1-Fc fusion protein, two monkeys developed higher virus neutralizing titers than a recovered COVID-19 patient in a live SARS-CoV-2 infection assay. Our data strongly suggests that the CHO-expressed SARS-CoV-2 S1-Fc recombinant protein could be a strong candidate for vaccine development against COVID-19.", "title": "Recombinant SARS-CoV-2 spike S1-Fc fusion protein induced high levels of neutralizing responses in nonhuman primates", "pid": "1z0ympt6", "bm25_score": 217.54827880859375}, {"text": "The world is currently facing an unprecedented global pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Predicting the next source of the pandemic can be very challenging. As vaccination is the best way to prevent an infectious disease, the development of an effective vaccine against SARS-CoV-2 can not only reduce the morbidity and mortality associated with it, but can also lessen the economic impact. As the traditional method of vaccine development takes many years for a vaccine to be available to the society, the vaccine development for SARS-CoV-2 should be speeded up using a pandemic approach with fast-track approvals from the regulatory authorities. Various challenges associated with developing a vaccine during the pandemic such as technological hurdles, clinical development pathways, regulatory issues, and support from global funding agencies are expressed here.", "title": "Coronavirus Vaccine: Light at the End of the Tunnel", "pid": "e2g1iu39", "bm25_score": 217.54798889160156}, {"text": "There has been a collaborative global effort to construct novel therapeutic and prophylactic approaches to SARS-CoV-2 management. Although vaccine development is crucial, acute management of newly infected patients, especially those with severe acute respiratory distress syndrome, is a priority. Herein we describe the rationale and potential of repurposing a dual plasmid, Vigil (pbi-shRNA(furin)-GM-CSF), now in Phase III cancer trials, for the treatment of and, in certain circumstances, enhancement of the immune response to SARS-CoV-2.", "title": "Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection: let the virus be its own demise", "pid": "evnfvc0l", "bm25_score": 217.54542541503906}, {"text": "Abstract The COVID-19 outbreak has become a global pandemic responsible for over 2,000,000 confirmed cases and over 126,000 deaths worldwide. In this study, we examined the immunogenicity of CHO-expressed recombinant SARS-CoV-2 S1-Fc fusion protein in mice, rabbits, and monkeys as a potential candidate for a COVID-19 vaccine. We demonstrate that the S1-Fc fusion protein is extremely immunogenic, as evidenced by strong antibody titers observed by day 7. Strong virus neutralizing activity was observed on day 14 in rabbits immunized with the S1-Fc fusion protein using a pseudovirus neutralization assay. Most importantly, in less than 20 days and three injections of the S1-Fc fusion protein, two monkeys developed higher virus neutralizing titers than a recovered COVID-19 patient in a live SARS-CoV-2 infection assay. Our data strongly suggests that the CHO-expressed SARS-CoV-2 S1-Fc recombinant protein could be a strong candidate for vaccine development against COVID-19.", "title": "Recombinant SARS-CoV-2 spike S1-Fc fusion protein induced high levels of neutralizing responses in nonhuman primates", "pid": "2x4y403o", "bm25_score": 217.54278564453125}, {"text": "Abstract The immunological characteristics of SARS-CoV spike protein were investigated by administering mice with plasmids encoding various S gene fragments. We showed that the secreting forms of S1, S2 subunits and the N-terminus of S1 subunit (residues 18–495) were capable of eliciting SARS-CoV specific antibodies and the region immediate to N-terminus of matured S1 protein contained an important immunogenic determinant for elicitation of SARS-CoV specific antibodies. In addition, mice immunized with plasmids encoding S1 fragment developed a Th1-mediated antibody isotype switching. Another interesting finding was that mouse antibodies elicited separately by plasmids encoding S1 and S2 subunits cooperatively neutralized SARS-CoV but neither the S1 nor S2 specific antibodies did, suggesting the possible role of both S1 and S2 subunits in host cell docking and entry. These results provide insights into understanding the immunological characteristics of spike protein and the development of subunit vaccines against SARS-CoV.", "title": "Characterization of humoral responses in mice immunized with plasmid DNAs encoding SARS-CoV spike gene fragments", "pid": "nokybn2a", "bm25_score": 217.5318145751953}, {"text": "We have investigated to develop novel vaccines against SARS CoV using cDNA constructs encoding the structural antigen; spike protein (S), membrane protein (M), envelope protein (E), or nucleocapsid (N) protein, derived from SARS CoV. Mice vaccinated with SARS-N or -M DNA using pcDNA 3.1(+) plasmid vector showed T cell immune responses (CTL induction and proliferation) against N or M protein, respectively. CTL responses were also detected to SARS DNA-transfected type II alveolar epithelial cells (T7 cell clone), which are thought to be initial target cells for SARS virus infection in human. To determine whether these DNA vaccines could induce T cell immune responses in humans as well as in mice, SCID-PBL/hu mice was immunized with these DNA vaccines. As expected, virus-specific CTL responses and T cell proliferation were induced from human T cells. SARS-N and SARS-M DNA vaccines and SCID-PBL/hu mouse model will be important in the development of protective vaccines.", "title": "The development of vaccines against SARS corona virus in mice and SCID-PBL/hu mice", "pid": "blnn9q3r", "bm25_score": 217.52890014648438}, {"text": "Two different severe acute respiratory syndrome (SARS) vaccine strategies were evaluated for their ability to protect against live SARS coronavirus (CoV) challenge in a murine model of infection. A whole killed (inactivated by beta-propiolactone) SARS-CoV vaccine and a combination of two adenovirus-based vectors, one expressing the nucleocapsid (N) and the other expressing the spike (S) protein (collectively designated Ad S/N), were evaluated for the induction of serum neutralizing antibodies and cellular immune responses and their ability to protect against pulmonary SARS-CoV replication. The whole killed virus (WKV) vaccine given subcutaneously to 129S6/SvEv mice was more effective than the Ad S/N vaccine administered either intranasally or intramuscularly in inhibiting SARS-CoV replication in the murine respiratory tract. This protective ability of the WKV vaccine correlated with the induction of high serum neutralizing-antibody titres, but not with cellular immune responses as measured by gamma interferon secretion by mouse splenocytes. Titres of serum neutralizing antibodies induced by the Ad S/N vaccine administered intranasally or intramuscularly were significantly lower than those induced by the WKV vaccine. However, Ad S/N administered intranasally, but not intramuscularly, significantly limited SARS-CoV replication in the lungs. Among the vaccine groups, SARS-CoV-specific IgA was found only in the sera of mice immunized intranasally with Ad S/N, suggesting that mucosal immunity may play a role in protection for the intranasal Ad S/N delivery system. Finally, the sera of vaccinated mice contained antibodies to S, further suggesting a role for this protein in conferring protective immunity against SARS-CoV infection.", "title": "Comparative evaluation of two severe acute respiratory syndrome (SARS) vaccine candidates in mice challenged with SARS coronavirus.", "pid": "9k2h57q3", "bm25_score": 217.52865600585938}, {"text": "COVID-19 is an emerging infectious disease that has turned into a pandemic. It spreads through droplet transmission of the new coronavirus SARS-CoV-2. It is an RNA virus displaying a spike protein as the major surface protein with significant sequence similarity to SARS-CoV which causes severe acute respiratory syndrome. The receptor binding domain of the spike protein interacts with the human angiotensin converting enzyme 2 and is considered as the antigenic determinant for stimulating an immune response. While multiple candidate vaccines are currently under different stages of development, there are no known therapeutic interventions at the moment. This review describes the key genetic features that are being considered for generating vaccine candidates by employing innovative technologies. It also highlights the global efforts being undertaken to deliver vaccines for COVID-19 through unprecedented international cooperation and future challenges post development.", "title": "Global efforts on vaccines for COVID-19: Since, sooner or later, we all will catch the coronavirus", "pid": "z5q82rmp", "bm25_score": 217.52183532714844}, {"text": "The magnitude of the COVID-19 pandemic underscores the urgency for a safe and effective vaccine. Here we analyzed SARS-CoV-2 sequence diversity across 5,700 sequences sampled since December 2019. The Spike protein, which is the target immunogen of most vaccine candidates, showed 93 sites with shared polymorphisms; only one of these mutations was found in more than 1% of currently circulating sequences. The minimal diversity found among SARS-CoV-2 sequences can be explained by drift and bottleneck events as the virus spread away from its original epicenter in Wuhan, China. Importantly, there is little evidence that the virus has adapted to its human host since December 2019. Our findings suggest that a single vaccine should be efficacious against current global strains. One Sentence Summary The limited diversification of SARS-CoV-2 reflects drift and bottleneck events rather than adaptation to humans as the virus spread.", "title": "A SARS-CoV-2 vaccine candidate would likely match all currently circulating strains", "pid": "755ym7vl", "bm25_score": 217.5057373046875}, {"text": "Abstract Three peptides, D1 (amino acid residues 175–201), D2 (a.a. 434–467), and TM (a.a. 1128–1159), corresponding to the spike protein (S) of severe acute respiratory syndrome corona virus (SARS CoV) were synthesized and their immunological functions were investigated in three different animals models (mice, guinea pigs, and rabbits). The peptides mixture formulated either with Freund’s adjuvant or synthetic adjuvant Montanide ISA-51/oligodeoxy nucleotide CpG (ISA/CpG) could elicit antisera in immunized animals which were capable of inhibiting SARS/HIV pseudovirus entry into HepG2 cells. The neutralizing epitopes were identified using peptides to block the neutralizing effect of guinea pig antisera. The major neutralizing epitope was located on the D2 peptide, and the amino acid residue was fine mapped to 434–453. In BALB/c mice T-cell proliferation assay revealed that only D2 peptide contained T-cell epitope, the sequence of which corresponded to amino acid residue 434–448. The ISA/CpG formulation generated anti-D2 IgG titer comparable to those obtained from Freund’s adjuvant formulation, but generated fewer antibodies against D1 or TM peptides. The highly immunogenic D2 peptide contains both neutralizing and Th cell epitopes. These results suggest that synthetic peptide D2 would be useful as a component of SARS vaccine candidates.", "title": "Identification of synthetic vaccine candidates against SARS CoV infection", "pid": "zwpmx63i", "bm25_score": 217.48431396484375}, {"text": "Severe acute respiratory syndrome (SARS) is an emerging disease derived from wild animals and is highly pathogenic with a high mortality. A novel coronavirus SARS coronavirus was identified to be a causative agent for SARS. Since its discovery, many trials have been executed to establish the prophylactic and therapeutics toward SARS using laboratory animals. A number of different types of vaccines, such as inactivated virus vaccine, subunit vaccine, DNA vaccine and vaccine using viral expression vector as well as attenuated live vaccine so far reported indicate that neutralizing antibodies play an important role for protection. However, vaccine applicable to humans with the high efficacy and safety has not yet been reported.", "title": "[SARS vaccines].", "pid": "ssw85ga8", "bm25_score": 217.4794464111328}, {"text": "Coronavirus disease 2019 (COVID-19) is an emerging infectious disease that was first reported in Wuhan, China, and has subsequently spread worldwide. In the absence of any antiviral or immunomodulatory therapies, the disease is spreading at an alarming rate. A possibility of a resurgence of COVID-19 in places where lockdowns have already worked is also developing. Thus, for controlling COVID-19, vaccines may be a better option than drugs. An mRNA-based anti-COVID-19 candidate vaccine has entered a phase 1 clinical trial. However, its efficacy and potency have to be evaluated and validated. Since vaccines have high failure rates, as an alternative, we are presenting a new, designed multi-peptide subunit-based epitope vaccine against COVID-19. The recombinant vaccine construct comprises an adjuvant, cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell epitopes joined by linkers. The computational data suggest that the vaccine is non-toxic, non-allergenic, thermostable, with the capability to elicit a humoral and cell-mediated immune response. The stabilization of the vaccine construct is validated with molecular dynamics simulation studies. This unique vaccine is made up of 33 highly antigenic epitopes from three proteins that have a prominent role in host-receptor recognition, viral entry, and pathogenicity. We advocate this vaccine must be synthesized and tested urgently as a public health priority.", "title": "Design of a peptide-based subunit vaccine against novel coronavirus SARS-CoV-2", "pid": "8lktpcda", "bm25_score": 217.47808837890625}, {"text": "The S2 domain of the severe acute respiratory syndrome coronavirus (SARS-CoV) spike (S) protein is responsible for fusion between virus and target cell membranes, and is expected to be immungenic. In this study, we investigated the immune responses against the S2 subunit in BALB/c mice, which were vaccinated either with plasmid DNA encoding the S2 domain (residues 681-1120), the recombinant S2 fragment (residues 681-980) in incomplete Freund's adjuvant, or with inactivated SARS-CoV. The increased number of specific cytotoxic cells (CTLs) and the high titer of specific antibody showed stimulation of both arms of the immune system in these groups. The shift in cytokines suggested that Th1-polarized immune response was induced by plasmid pCoVS2, meanwhile the Th2-dominant response was induced by recombinant S2 fragment and inactivated vaccine. However, the titer of neutralizing antibodies was only detectable in mice immunized with inactivated virus, but not with pCoVS2 plasmid. Taken together, the S2 domain could induce specific cellular immune response and a high level of total IgG but little neutralizing antibodies against infection by SARSCoV.", "title": "Elicitation of immunity in mice after immunization with the S2 subunit of the severe acute respiratory syndrome coronavirus.", "pid": "4sxnbrd5", "bm25_score": 217.4680633544922}, {"text": "SARS-CoV-2 is the causative agent of the current COVID-19 pandemic. A major virulence factor of SARS-CoVs is the nonstructural protein 1 (Nsp1) which suppresses host gene expression by ribosome association via an unknown mechanism. Here, we show that Nsp1 from SARS-CoV-2 binds to 40S and 80S ribosomes, resulting in shutdown of capped mRNA translation both in vitro and in cells. Structural analysis by cryo-electron microscopy (cryo-EM) of in vitro reconstituted Nsp1-40S and of native human Nsp1-ribosome complexes revealed that the Nsp1 C-terminus binds to and obstructs the mRNA entry tunnel. Thereby, Nsp1 effectively blocks RIG-I-dependent innate immune responses that would otherwise facilitate clearance of the infection. Thus, the structural characterization of the inhibitory mechanism of Nsp1 may aid structure-based drug design against SARS-CoV-2.", "title": "Structural basis for translational shutdown and immune evasion by the Nsp1 protein of SARS-CoV-2", "pid": "1fbf5jcz", "bm25_score": 217.46157836914062}, {"text": "Vaccine development for severe acute respiratory syndrome coronavirus (SARS-CoV) has mainly focused on the spike (S) protein. However, the variation of the S gene between viruses may affect the efficacy of a vaccine, particularly for cross-protection against SARS-like CoV (SL-CoV). Recently, a more conserved group-specific open reading frame (ORF), the 3a gene, was found in both SARS-CoV and SL-CoV. Here, we studied the immunogenicity of human SARS-CoV 3a and bat SL-CoV 3a DNA vaccines in mice through electroporation immunization followed by enzyme-linked immunosorbent, enzyme-linked immunospot, and flow cytometry assays. Our results showed that high levels of specific humoral responses were induced by SARS-CoV 3a and SL-CoV 3a DNA vaccines. Furthermore, a strong Th1-based cellular immune response was stimulated by both DNA vaccines. The vaccines stimulated gamma interferon production mainly by CD8(+) T cells and interleukin-2 (IL-2) mainly by CD4(+) T cells. Of interest, the frequency of IL-2-positive cells elicited by the SARS-CoV 3a DNA vaccine was significantly higher than that elicited by the SL-CoV 3a DNA vaccine. In summary, our study provides a reference for designing cross-protective DNA vaccines based on the group-specific ORFs of CoVs.", "title": "Humoral and cellular immune responses induced by 3a DNA vaccines against severe acute respiratory syndrome (SARS) or SARS-like coronavirus in mice.", "pid": "2jeb1vcs", "bm25_score": 217.46124267578125}, {"text": "A double-inactivated, candidate whole virus vaccine against severe acute respiratory syndrome associated coronavirus (SARS-CoV) was developed and manufactured at large scale using fermenter cultures of serum protein free Vero cells. A two step inactivation procedure involving sequential formaldehyde and U.V. inactivation was utilised in order to ensure an extremely high safety margin with respect to residual infectivity. The immunogenicity of this double-inactivated vaccine was characterised in the mouse model. Mice that were immunised twice with the candidate SARS-CoV vaccine developed high antibody titres against the SARS-CoV spike protein and high levels of neutralising antibodies. The use of the adjuvant Al(OH)(3) had only a minor effect on the immunogenicity of the vaccine. In addition, cell mediated immunity as measured by interferon-γ and interleukin-4 stimulation, was elicited by vaccination. Moreover, the vaccine confers protective immunity as demonstrated by prevention of SARS-CoV replication in the respiratory tract of mice after intranasal challenge with SARS-CoV. Protection of mice was correlated to antibody titre against the SARS-CoV S protein and neutralising antibody titre.", "title": "A double-inactivated whole virus candidate SARS coronavirus vaccine stimulates neutralising and protective antibody responses", "pid": "ogb83fgc", "bm25_score": 217.45855712890625}, {"text": "Developing effective and safe vaccines is urgently needed to prevent infection by severe acute respiratory syndrome (SARS)–associated coronavirus (SARS-CoV). The inactivated SARS-CoV vaccine may be the first one available for clinical use because it is easy to generate; however, safety is the main concern. The spike (S) protein of SARS-CoV is the major inducer of neutralizing antibodies, and the receptor-binding domain (RBD) in the S1 subunit of S protein contains multiple conformational neutralizing epitopes. This suggests that recombinant proteins containing RBD and vectors encoding the RBD sequence can be used to develop safe and effective SARS vaccines.", "title": "SARS Vaccine Development", "pid": "c18arb6s", "bm25_score": 217.456787109375}, {"text": "Recently, a novel coronavirus (SARS-CoV-2) appeared which is conscientious for the current outbreak in China and rapidly spread worldwide Unluckily, there is no approved vaccine found against SARS-CoV-2 Therefore, there is an urgent need for designing a suitable peptide vaccine constituent against the SARS-CoV-2 In this study, we characterized the spike glycoprotein of SARS-CoV-2 to obtain immunogenic epitopes In addition, we used 58 SARS-CoV-2 isolates were retrieved from the Global Initiative on Sharing All Influenza Data (GISAID) and National Center for Biotechnology Information (NCBI), then aligned to obtain the conserved region of SARS-CoV-2 spike glycoprotein The interaction between the conserved region with ACE2 receptor, a SARS-CoV-2 receptor on the host cell, has been evaluated through molecular docking approach The B-cell epitope was identified using the immune epitope database (IEDB) web server Interestingly, we recommend Pep_4 ADHQPQTFVNTELH as a epitope-based peptide vaccine candidate to deal with the SARS-CoV-2 outbreak Pep_4 has a high level of immunogenicity and does not trigger autoimmune mechanisms Pep_4 is capable of forming BCR/Fab molecular complexes with the lowest binding energy for activation of transduction signal the direct B-cell immune response However, further study is suggested for confirmation (in vitro and in vivo)", "title": "Construction of Epitope-Based Peptide Vaccine Against SARS-CoV-2: Immunoinformatics Study", "pid": "p3aht54c", "bm25_score": 217.4566192626953}, {"text": "OBJECTIVE To study the immunological characteristics of the spike (S) protein of SARS coronavirus (SARS-CoV) and analyze the feasibility of using this protein as the component for SARS vaccine development. METHODS The two truncated fragments of S gene were separately cloned into the prokaryotic expression vector pET-15b and expressed in E.coli. The resulting recombinant proteins, rS(a) and rS(b), were purified by affinity chromatography. The full-length S gene was cloned into the eukaryotic expression plasmid pSecTagB to prepare recombinant plasmid pSecS as the DNA vaccine to immunize BALB/c mice for inducing the secretion of anti-SARS-CoV protein. The immunological effect of anti-SARS-CoV antibody was tested with purified rS(a) and rS(b) proteins by enzyme-linked immunosorbent assay (ELISA). RESULTS Both the truncated recombinant proteins were expressed in soluble forms and reacted specifically with the sera from immunized pSecS mice and clinically diagnosed SARS patients. The prokaryotically expressed recombinant truncated S protein had similar antigenicity with SARS-CoV S protein. CONCLUSION The recombinant protein could be used as an antigen for detecting the serum of SARS CoV-infected patients. The SARS-CoV S gene vaccine could induce the production of specific antibody, which offers clues for the research of SARS DNA vaccine.", "title": "[Prokaryotic expression of SARS coronavirus spike protein and construction of its DNA vaccine].", "pid": "106b6r7w", "bm25_score": 217.45590209960938}, {"text": "SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this, outbreak specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS- CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. UISS is then potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2.", "title": "In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform", "pid": "71n1tgrw", "bm25_score": 217.45281982421875}, {"text": "SARS-CoV-2 is a severe respiratory infection that infects humans. Its outburst entitled it as a pandemic emergence. To get a grip on this outbreak, specific preventive and therapeutic interventions are urgently needed. It must be said that, until now, there are no existing vaccines for coronaviruses. To promptly and rapidly respond to pandemic events, the application of in silico trials can be used for designing and testing medicines against SARS-CoV-2 and speed-up the vaccine discovery pipeline, predicting any therapeutic failure and minimizing undesired effects. Here, we present an in silico platform that showed to be in very good agreement with the latest literature in predicting SARS-CoV-2 dynamics and related immune system host response. Moreover, it has been used to predict the outcome of one of the latest suggested approach to design an effective vaccine, based on monoclonal antibody. Universal Immune System Simulator (UISS) in silico platform is potentially ready to be used as an in silico trial platform to predict the outcome of vaccination strategy against SARS-CoV-2.", "title": "In Silico Trial to test COVID-19 candidate vaccines: a case study with UISS platform", "pid": "48knj0tm", "bm25_score": 217.44149780273438}, {"text": "The extensive efforts around the globe are being made to develop a suitable vaccine against COVID-19 (Coronavirus Disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2). An effective vaccine should be able to induce high titers of neutralizing antibodies to prevent the virus from attaching to the host cell receptors. However, to elicit the protective levels of antibodies, a vaccine may require multiple doses or assistance from other immunostimulatory molecules. Further, the vaccine should be able to induce protective levels of antibodies rapidly with the least amount of antigen used. This not only decreases the cost of a vaccine and make it affordable, but also reduces the quantity of the antigen used. As the pandemic has hit most countries across the globe, there will be an overwhelming demand for the vaccine in a quick time. Incorporating a suitable adjuvant in a SARS-CoV-2 vaccine may address these requirements. This review paper will discuss the experimental results of the adjuvanted vaccine studies with similar coronaviruses (CoVs) which might be useful to select an appropriate adjuvant for a vaccine against rapidly emerging SARS-CoV-2. We also discuss the current progress in the development of adjuvanted vaccines against the disease.", "title": "Potential adjuvants for the development of a SARS-CoV-2 vaccine based on experimental results from similar coronaviruses", "pid": "npc9qdex", "bm25_score": 217.43972778320312}, {"text": "SARS CoV-2 has particularly been efficient in ensuring that many countries are brought to a standstill. With repercussions ranging from rampant mortality, fear, paranoia and economic recession, the virus has brought together countries in order to look at possible therapeutic countermeasures. With prophylactic interventions possibly months away from being particularly effective, a slew of measures and possibilities concerning the design of vaccines are being worked upon. We attempted a structure-based approach utilizing a combination of epitope prediction servers to develop a multi-epitope-based subunit vaccine that involves the two major domains of the spike glycoprotein of SARS CoV-2 (S1 and S2) coupled with a substantially effective chimeric adjuvant to create stable vaccine constructs through MD simulations. The designed constructs were evaluated based on their docking with Toll Like Receptor (TLR) 4. Our findings provide an epitope-based peptide fragment; which can be a potential candidate for the development of a vaccine against SARS-CoV-2. Recent experimental studies based on determining immunodominant regions across the spike glycoprotein of SARS-CoV-2 indicate the presence of the predicted epitopes included in this study.", "title": "Multi-epitope-based peptide vaccine design against SARS-CoV-2 using its spike protein", "pid": "i7oi7mfi", "bm25_score": 217.43386840820312}, {"text": "A recombinant adenovirus vaccine against the SARS Coronavirus (SARS-CoV) was constructed, which contains fragments from the S, N, and Orf8 genes. Rhesus Macaques immunized with the recombinant adenovirus generated antigen-specific humoral and cellular response. Furthermore, the vaccine provided significant protection against subsequent live SARS-CoV challenge. In contrast, three out of four monkeys immunized with placebo suffered severe alveolar damage and pulmonary destruction.", "title": "Protection of Rhesus Macaque from SARS-Coronavirus challenge by recombinant adenovirus vaccine", "pid": "os758lsd", "bm25_score": 217.433349609375}, {"text": "Since the outbreak of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) in December 2019 in China, there has been an upsurge in the number of deaths and infected individuals throughout the world, thereby leading to the World Health Organization declaration of a pandemic. Since no specific therapy is currently available for the same, the present study was aimed to explore the SARS-CoV-2 genome for the identification of immunogenic regions using immunoinformatics approach. A series of computational tools were applied in a systematic way to identify the epitopes that could be utilized in vaccine development. The screened-out epitopes were passed through several immune filters, such as promiscuousity, conservancy, antigenicity, nonallergenicity, population coverage, nonhomologous to human proteins, and affinity with human leukocyte antigen alleles, to screen out the best possible ones. Further, a construct comprising 11 CD4, 12 CD8, 3 B cell, and 3 interferon-γ epitopes, along with an adjuvant ß-defensin, was designed in silico, resulting in the formation of a multiepitope vaccine. The in silico immune simulation and population coverage analysis of the vaccine sequence showed its capacity to elicit cellular, humoral, and innate immune cells and to cover up a worldwide population of more than 97%. Further, the interaction analysis of the vaccine construct with Toll-like receptor 3 (immune receptor) was carried out by docking and dynamics simulations, revealing high affinity, constancy, and pliability between the two. The overall findings suggest that the vaccine may be highly effective, and is therefore required to be tested in the lab settings to evaluate its efficacy.", "title": "Excavating SARS-coronavirus 2 genome for epitope-based subunit vaccine synthesis using immunoinformatics approach", "pid": "nsdsgcmf", "bm25_score": 217.43096923828125}, {"text": "The Middle East respiratory syndrome coronavirus (MERS-CoV), is an emerging pathogen that continues to cause outbreaks in the Arabian peninsula and in travelers from this region, raising the concern that a global pandemic could occur. Here, we show that a DNA vaccine encoding the first 725 amino acids (S1) of MERS-CoV spike (S) protein induces antigen-specific humoral and cellular immune responses in mice. With three immunizations, high titers of neutralizing antibodies (up to 1: 10(4)) were generated without adjuvant. DNA vaccination with the MERS-CoV S1 gene markedly increased the frequencies of antigen-specific CD4(+) and CD8(+) T cells secreting IFN-γ and other cytokines. Both pcDNA3.1-S1 DNA vaccine immunization and passive transfer of immune serum from pcDNA3.1-S1 vaccinated mice protected Ad5-hDPP4-transduced mice from MERS-CoV challenge. These results demonstrate that a DNA vaccine encoding MERS-CoV S1 protein induces strong protective immune responses against MERS-CoV infection.", "title": "DNA Vaccine Encoding Middle East Respiratory Syndrome Coronavirus S1 Protein Induces Protective Immune Responses in Mice", "pid": "4ywrzyse", "bm25_score": 217.42770385742188}]}